bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro dose measurements in a human cadaver with abdomen/pelvis CT scans
Authors: Zhang Da , Padole Atul , Li Xinhua , Singh Sarabjeet , Khawaja Ranish Deedar Ali , Lira Diego , Liu Tianyu , Shi Jim Q. , Otrakji Alexi , Kalra Mannudeep K. , Xu X. George , Liu Bob 
Published: August 2014

Purpose:To present a study of radiation dose measurements with a human cadaver scanned on a clinical CT scanner.Methods:Multiple point dose measurements were obtained with high‐accuracy Thimble ionization chambers placed inside the stomach, liver, paravertebral gutter, ascending colon, left kidney, and urinary bladder of a human cadaver (183 cm in height and 67.5 kg in weight) whose abdomen/pelvis region was scanned repeatedly with a multidetector row CT. The flat energy response and precision of the dosimeters were verified, and the slight differences in each dosimeterˈs response were evaluated and corrected to attain high accuracy. In addition, skin doses were measured for radiosensitive organs outside the scanned region with OSL dosimeters: the right eye, thyroid, both nipples, and the right testicle. Three scan protocols were used, which shared most scan parameters but had different kVp and mA settings: 120‐kVp automA, 120‐kVp 300 mA, and 100‐kVp 300 mA. For each protocol three repeated scans were performed.Results:The tube starting angle (TSA) was found to randomly vary around two major conditions, which caused large fluctuations in the repeated point dose measurements: for the 120‐kVp 300 mA protocol this angle changed from approximately 110° to 290°, and caused 8% − 25% difference in the point dose measured at the stomach, liver, colon, and urinary bladder. When the fluctuations of the TSA were small (within 5°), the maximum coefficient of variance was approximately 3.3%. The soft tissue absorbed doses averaged from four locations near the center of the scanned region were 27.2 ± 3.3 and 16.5 ± 2.7 mGy for the 120 and 100‐kVp fixed‐mA scans, respectively. These values were consistent with the corresponding size specific dose estimates within 4%. The comparison of the per‐100‐mAs tissue doses from the three protocols revealed that: (1) dose levels at nonsuperficial locations in the TCM scans could not be accurately deduced by simply scaling the fix‐mA doses with local mA values; (2) the general power law relationship between dose and kVp varied from location to location, with the power index ranged between 2.7 and 3.5. The averaged dose measurements at both nipples, which were about 0.6 cm outside the prescribed scan region, ranged from 23 to 27 mGy at the left nipple, and varied from 3 to 20 mGy at the right nipple over the three scan protocols. Large fluctuations over repeated scans were also observed, as a combined result of helical scans of large pitch (1.375) and small active areas of the skin dosimeters. In addition, the averaged skin dose fell off drastically with the distance to the nearest boundary of the scanned region.Conclusions:This study revealed the complexity of CT dose fluctuation and variation with a human cadaver.
A study of the short‐ to long‐phantom dose ratios for CT scanning without table translation
Authors: Li Xinhua , Zhang Da , Yang Jie , Liu Bob 
Published: August 2014

Purpose:For CT scanning in the stationary‐table modes, AAPM Task Group 111 proposed to measure the midpoint dose on the central and peripheral axes of sufficiently long phantoms. Currently, a long cylindrical phantom is usually not available in many clinical facilities. The use of a long phantom is also challenging because of the heavy weight. In order to shed light on assessing the midpoint dose in CT scanning without table movement, the authors present a study of the short‐ to long‐phantom dose ratios, and perform a cross‐comparison of CT dose ratios on different scanner models.Methods:The authors performed Geant4‐based Monte Carlo simulations with a clinical CT scanner (Somatom Definition dual source CT, Siemens Healthcare), and modeled dosimetry measurements using a 0.6 cm3 Farmer type chamber and a 10‐cm long pencil ion chamber. The short (15 cm) to long (90 cm) phantom dose ratios were computed for two PMMA diameters (16 and 32 cm), two phantom axes (the center and the periphery), and a range of beam apertures (3–25 cm). The results were compared with the published data of previous studies with other multiple detector CT (MDCT) scanners and cone beam CT (CBCT) scanners.Results:The short‐ to long‐phantom dose ratios changed with beam apertures but were insensitive to beam qualities (80–140 kV, the head and body bowtie filters) and MDCT and CBCT scanner models.Conclusions:The short‐ to long‐phantom dose ratios enable medical physicists to make dosimetry measurements using the standard CT dosimetry phantoms and a Farmer chamber or a 10 cm long pencil chamber, and to assess the midpoint dose in long phantoms. This method provides an effective approach for the dosimetry of CBCT scanning in the stationary‐table modes, and is useful for perfusion and interventional CT.
Strength of stick-slip and creeping subduction megathrusts from heat flow observations
Authors: Gao Xiang , Wang Kelin 
Published: August 2014

Strong yet creeping megathrust faults
Powerful faults in subduction zones, called “megathrust faults,” produce the largest earthquakes on Earth. Gao and Wang use heat flow data to show that when the faults subduct jagged sea floor, they generate tamer earthquakes than do faults that subduct smooth sea floor. The rugged sea floor brings irregularities into the fault that cause it to deform slowly over time, which results in a comparatively higher fault strength and lower seismicity. The finding has a direct impact on assessing regional earthquake and tsunami hazards.

Science
, this issue p.
1038
Invasive Mycosis Due to Species of Blastobotrys in Immunocompromised Patients with Reduced Susceptibility to Antifungals
Authors: Kumar Anil , Babu Rachana , Bijulal Swapna , Abraham Mohan , Sasidharan P. , Kathuria Shallu , Sharma Cheshta , Meis Jacques F. , Chowdhary Anuradha 
Published: August 2014

ABSTRACT

Cases of invasive mycosis due to
Blastobotrys serpentis
and
B. proliferans
identified by sequencing in a preterm patient and a rhabdomyosarcoma patient, respectively, are reported. Both species revealed elevated fluconazole and echinocandin MICs by the CLSI broth microdilution method. Additionally,
B. serpentis
exhibited high amphotericin B MICs, thus posing serious therapeutic challenges.
Rapid Sequencing of the Mycobacterium tuberculosis
pncA
Gene for Detection of Pyrazinamide Susceptibility
Authors: Streicher Elizabeth M. , Maharaj Kashmeel , York Talita , Van Heerden Carel , Barnard Marinus , Diacon Andreas , Mendel Carl M. , Bosman Marlein E. , Hepple Juli A. , Pym Alexander S. , Warren Robin M. , van Helden Paul D. 
Published: August 2014

ABSTRACT
We developed a pyrazinamidase gene DNA-sequencing method to rapidly identify pyrazinamide resistance-causing mutations in GenoLyse-treated, smear-positive sputum specimens. The sensitivity and specificity were 90.9 and 100%, respectively, compared to those of MGIT drug susceptibility testing, after the exclusion of synonymous mutations and nonsynonymous mutations previously associated with susceptibility to pyrazinamide.
Fluorescent Tagging and Cellular Distribution of the Kaposi's Sarcoma-Associated Herpesvirus ORF45 Tegument Protein
Authors: Bergson Shir , Kalt Inna , Itzhak Inbal , Brulois Kevin F. , Jung Jae U. , Sarid Ronit 
Published: August 2014

ABSTRACT

Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is a cancer-related human virus, classified as a member of the
Gammaherpesvirinae
subfamily. We report here the construction of a dual fluorescent-tagged KSHV genome (BAC16-mCherry-ORF45), which constitutively expresses green fluorescent protein (GFP) and contains the tegument multifunctional ORF45 protein as a fusion protein with monomeric Cherry fluorescent protein (mCherry). We confirmed that this virus is properly expressed and correctly replicates and that the mCherry-ORF45 protein is incorporated into the virions. Using this labeled virus, we describe the dynamics of mCherry-ORF45 expression and localization in newly infected cells as well as in latently infected cells undergoing lytic induction and show that mCherry can be used to monitor cells undergoing the lytic viral cycle. This virus is likely to enable future studies monitoring the dynamics of viral trafficking and tegumentation during viral ingress and egress.

IMPORTANCE
The present study describes the construction and characterization of a new recombinant KSHV genome BAC16 clone which expresses mCherry-tagged ORF45. This virus enables the tracking of cells undergoing lytic infection and can be used to address issues related to the trafficking and maturation pathways of KSHV virions.
Possible Footprints of APOBEC3F and/or Other APOBEC3 Deaminases, but Not APOBEC3G, on HIV-1 from Patients with Acute/Early and Chronic Infections
Authors: Armitage Andrew E. , Deforche Koen , Welch John J. , Van Laethem Kristel , Camacho Ricardo , Rambaut Andrew , Iversen Astrid K. N. 
Published: August 2014

ABSTRACT

Members of the apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like-3 (APOBEC3) innate cellular cytidine deaminase family, particularly APOBEC3F and APOBEC3G, can cause extensive and lethal G-to-A mutations in HIV-1 plus-strand DNA (termed hypermutation). It is unclear if APOBEC3-induced mutations
in vivo
are always lethal or can occur at sublethal levels that increase HIV-1 diversification and viral adaptation to the host. The viral accessory protein Vif counteracts APOBEC3 activity by binding to APOBEC3 and promoting proteasome degradation; however, the efficiency of this interaction varies, since a range of hypermutation frequencies are observed in HIV-1 patient DNA. Therefore, we examined “footprints” of APOBEC3G and APOBEC3F activity in longitudinal HIV-1 RNA
pol
sequences from approximately 3,000 chronically infected patients by determining whether G-to-A mutations occurred in motifs that were favored or disfavored by these deaminases. G-to-A mutations were more frequent in APOBEC3G-disfavored than in APOBEC3G-favored contexts. In contrast, mutations in APOBEC3F-disfavored contexts were relatively rare, whereas mutations in contexts favoring APOBEC3F (and possibly other deaminases) occurred 16% more often than average G-to-A mutations. These results were supported by analyses of >500 HIV-1
env
sequences from acute/early infection.

IMPORTANCE
Collectively, our results suggest that APOBEC3G-induced mutagenesis is lethal to HIV-1, whereas mutagenesis caused by APOBEC3F and/or other deaminases may result in sublethal mutations that might facilitate viral diversification. Therefore, Vif-specific cytotoxic T lymphocyte (CTL) responses and drugs that manipulate the interplay between Vif and APOBEC3 may have beneficial or detrimental clinical effects depending on how they affect the binding of Vif to various members of the APOBEC3 family.
Lack of Interleukin-10-Mediated Anti-Inflammatory Signals and Upregulated Interferon Gamma Production Are Linked to Increased Intestinal Epithelial Cell Apoptosis in Pathogenic Simian Immunodeficiency Virus Infection
Authors: Pan Diganta , Kenway-Lynch Carys S. , Lala Wendy , Veazey Ronald S. , Lackner Andrew A. , Das Arpita , Pahar Bapi 
Published: August 2014

ABSTRACT
Interleukin-10 (IL-10) is an immunomodulatory cytokine that is important for maintenance of epithelial cell (EC) survival and anti-inflammatory responses (AIR). The majority of HIV infections occur through the mucosal route despite mucosal epithelium acting as a barrier to human immunodeficiency virus (HIV). Therefore, understanding the role of IL-10 in maintenance of intestinal homeostasis during HIV infection is of interest for better characterization of the pathogenesis of HIV-mediated enteropathy. We demonstrated here changes in mucosal IL-10 signaling during simian immunodeficiency virus (SIV) infection in rhesus macaques. Disruption of the epithelial barrier was manifested by EC apoptosis and loss of the tight-junction protein ZO-1. Multiple cell types, including a limited number of ECs, produced IL-10. SIV infection resulted in increased levels of IL-10; however, this was associated with increased production of mucosal gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), suggesting that IL-10 was not able to regulate AIR. This observation was supported by the downregulation of STAT3, which is necessary to inhibit production of IFN-γ and TNF-α, and the upregulation of SOCS1 and SOCS3, which are important regulatory molecules in the IL-10-mediated AIR. We also observed internalization of the IL-10 receptor (IL-10R) in mucosal lymphocytes, which could limit cellular availability of IL-10 for signaling and contribute to the loss of a functional AIR. Collectively, these findings demonstrate that internalization of IL-10R with the resultant impact on IL-10 signaling and dysregulation of the IL-10-mediated AIR might play a crucial role in EC damage and subsequent SIV/HIV pathogenesis.

IMPORTANCE
Interleukin-10 (IL-10), an important immunomodulatory cytokine plays a key role to control inflammatory function and homeostasis of the gastrointestinal mucosal immune system. Despite recent advancements in the study of IL-10 and its role in HIV infection, the role of mucosal IL-10 in SIV/HIV infection in inducing enteropathy is not well understood. We demonstrated changes in mucosal IL-10 signaling during SIV infection in rhesus macaques. Disruption of the intestinal epithelial barrier was evident along with the increased levels of mucosal IL-10 production. Increased production of mucosal IFN-γ and TNF-α during SIV infection suggested that the increased level of mucosal IL-10 was not able to regulate anti-inflammatory responses. Our findings demonstrate that internalization of IL-10R with the resultant impact on IL-10 signaling and dysregulation of the IL-10-mediated anti-inflammatory responses might play a crucial role in epithelial cell damage and subsequent SIV/HIV pathogenesis.
Emergence of Individual HIV-Specific CD8 T Cell Responses during Primary HIV-1 Infection Can Determine Long-Term Disease Outcome
Authors: Streeck Hendrik , Lu Richard , Beckwith Noor , Milazzo Mark , Liu Michelle , Routy Jean-Pierre , Little Susan , Jessen Heiko , Kelleher Anthony D. , Hecht Frederick , Sekaly Rafick-Pierre , Alter Galit , Heckerman David , Carrington Mary , Rosenberg Eric S. , Altfeld Marcus 
Published: August 2014

ABSTRACT

Events during primary HIV-1 infection have been shown to be critical for the subsequent rate of disease progression. Early control of viral replication, resolution of clinical symptoms and development of a viral set point have been associated with the emergence of HIV-specific CD8 T cell responses. Here we assessed which particular HIV-specific CD8 T cell responses contribute to long-term control of HIV-1. A total of 620 individuals with primary HIV-1 infection were screened by gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay for HLA class I-restricted, epitope-specific CD8 T cell responses using optimally defined epitopes approximately 2 months after initial presentation. The cohort was predominantly male (97%) and Caucasian (83%) (Fiebig stages II/III [
n
= 157], IV [
n
= 64], V [
n
= 286], and VI [
n
= 88] and Fiebig stage not determined [
n
= 25]). Longitudinal viral loads, CD4 count, and time to ART were collected for all patients. We observed strong associations between viral load at baseline (initial viremia) and the established early viral set points (
P
< 0.0001). Both were significantly associated with HLA class I genotypes (
P
= 0.0009). While neither the breadth nor the magnitude of HIV-specific CD8 T cell responses showed an influence on the early viral set point, a broader HIV-specific CD8 T cell response targeting epitopes within HIV-1 Gag during primary HIV-1 infection was associated with slower disease progression. Moreover, the induction of certain HIV-specific CD8 T cell responses—but not others—significantly influenced the time to ART initiation. Individual epitope-specific CD8 T cell responses contribute significantly to HIV-1 disease control, demonstrating that the specificity of the initial HIV-specific CD8 T cell response rather than the restricting HLA class I molecule alone is a critical determinant of antiviral function.

IMPORTANCE
Understanding which factors are involved in the control of HIV-1 infection is critical for the design of therapeutic strategies for patients living with HIV/AIDS. Here, using a cohort of over 600 individuals with acute and early HIV-1 infection, we assessed in unprecedented detail the individual contribution of epitope-specific CD8 T cell responses directed against HIV-1 to control of viremia and their impact on the overall course of disease progression.
Acupuncture Decreases Matrix Metalloproteinase-2 Activity in Patients with Migraine
Authors: Cayir Yasemin , Ozdemir Gokhan , Celik Mine , Aksoy Hulya , Akturk Zekeriya , Laloglu Esra , Akcay Fatih 
Published: August 2014

Objective To evaluate the effect of acupuncture on the serum matrix metalloproteinase-2 (MMP-2) level and activity in patients with migraine. Methods After baseline testing, eligible patients with migraine according to the criteria of the International Headache Society who volunteered to join the study were included (n=27). The patients received 10 sessions of acupuncture treatment. The points selected were bilateral ST8, ST44, LI4, LI11, LIV3, SP6, GB1, GB14, GB20, GV14, GV20, Yintang, Taiyang and ear Shenmen. Pain was measured using a visual analogue scale (VAS). Short form-36 (SF-36) was used to determine their quality of life. Blood samples were taken before treatment and after the first and last sessions of acupuncture for measurement of MMP-2 concentration and activity. Results The mean VAS was 85.5±16.6 before acupuncture and was significantly decreased to 39.8±20.6 after 10 sessions of acupuncture (p<0.0001). There was a significant increase in all SF-36 scores after acupuncture compared with values before treatment (p<0.0001). No significant differences were found in MMP-2 concentrations before treatment and after the first and last sessions (p>0.05). However, there were significant changes in MMP-2 activity (p<0.0001). Conclusions The results of this study showed a clinically relevant decrease in MMP-2 activity in patients with migraine treated with acupuncture. The mechanism underlying the effect of acupuncture in alleviating pain may be associated with a decrease in MMP-2 activity.
Prevalence, determinants and impact of unawareness about the health consequences of tobacco use among 17 929 school personnel in 29 African countries
Authors: Agaku Israel T , Filippidis Filippos T 
Published: August 2014

ObjectivesTo assess prevalence, determinants and impact of unawareness about the health consequences of tobacco use among school personnel in Africa.DesignCross-sectional surveys.SettingTwenty-nine African countries.ParticipantsRepresentative samples of school personnel from 29 African countries (n=17 929), using data from the 2006–2011 Global School Personnel Surveys.OutcomeWe assessed if school personnel were aware of the following five facts about tobacco use: (1) tobacco use is addictive; (2) secondhand smoke exposure is harmful; (3) smoking causes lung cancer; (4) smoking causes heart disease and (5) smoking does not cause malaria. Using multivariate logistic regression, we measured the impact of unawareness of the health consequences of tobacco use on behaviour and attitudes towards tobacco control.ResultsA median of 62.6% of school personnel were unaware of at least one health consequence of tobacco use. School personnel in countries with mandatory cigarette health warning labels had lower odds of being unaware of any health consequence of tobacco use than countries where health warning labels were not mandatory (adjusted OR [aOR]=0.51; 95% CI 0.37 to 0.71). A significant dose–response relationship was seen between being ignorant of 1; 2; or ≥3 tobacco use health consequences respectively (compared with not being ignorant of any), and the odds of the following outcomes: non-support of bans on tobacco industry sponsorship of school or extracurricular activities (aOR=1.47; 1.91; and 2.98); non-support of bans on all tobacco advertisements (aOR=1.24; 1.78; and 2.68) and non-support of policies prohibiting tobacco use by school personnel on campus (aOR=1.79; 4.45; and 4.56).ConclusionsUnawareness of the health consequences of tobacco use was associated with poor support for tobacco control policies. Intensified efforts are needed in African countries to warn about the dangers of tobacco use.
Do the eyes have it? Performance of molecular detection of tuberculosis on fresh and paraffin embedded tissues, including those with no visible tissue
Authors: McKew Genevieve L , Dubedat Sally M , Chan Raymond C 
Published: August 2014

BackgroundLittle has been published on the performance of tuberculosis PCR with respect to the quality of tissue specimens. Laboratories often receive liquid samples from fine-needle aspirates with no visible tissue for testing. The sensitivity of tuberculosis (TB) PCR on these specimens is unknown.MethodsTB PCR was compared to culture or a combination of clinical and histopathological evidence of tuberculosis; a separate analysis excluded patients with current or previous treatment.ResultsSixty-five patients had 81 positive samples; 69 by PCR and 43 by culture. Excluding those on treatment, 51 of 57 (89%) were PCR positive versus 43 of 61 (70%) by culture. 44 samples had ‘no visible tissue’ noted. Five were PCR positive; only one was culture positive. At least two samples were falsely negative.ConclusionsSensitivity of TB PCR is superior to culture on tissue. Five of seven TB cases with no visible tissue were PCR positive. The quality of the specimen deserves comment, as the two (5%) known false negatives are of concern.
HMGB1 Enhances Immune Suppression by Facilitating the Differentiation and Suppressive Activity of Myeloid-Derived Suppressor Cells
Authors: Parker Katherine H. , Sinha Pratima , Horn Lucas A. , Clements Virginia K. , Yang Huan , Li Jianhua , Tracey Kevin J. , Ostrand-Rosenberg Suzanne 
Published: August 2014

Abstract
Chronic inflammation often precedes malignant transformation and later drives tumor progression. Likewise, subversion of the immune system plays a role in tumor progression, with tumoral immune escape now well recognized as a crucial hallmark of cancer. Myeloid-derived suppressor cells (MDSC) are elevated in most individuals with cancer, where their accumulation and suppressive activity are driven by inflammation. Thus, MDSCs may define an element of the pathogenic inflammatory processes that drives immune escape. The secreted alarmin HMGB1 is a proinflammatory partner, inducer, and chaperone for many proinflammatory molecules that MDSCs develop. Therefore, in this study, we examined HMGB1 as a potential regulator of MDSCs. In murine tumor systems, HMGB1 was ubiquitous in the tumor microenvironment, activating the NF-κB signal transduction pathway in MDSCs and regulating their quantity and quality. We found that HMGB1 promotes the development of MDSCs from bone marrow progenitor cells, contributing to their ability to suppress antigen-driven activation of CD4+ and CD8+ T cells. Furthermore, HMGB1 increased MDSC-mediated production of IL-10, enhanced crosstalk between MDSCs and macrophages, and facilitated the ability of MDSCs to downregulate expression of the T-cell homing receptor L-selectin. Overall, our results revealed a pivotal role for HMGB1 in the development and cancerous contributions of MDSCs. Cancer Res; 74(20); 5723–33. ©2014 AACR.