bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased risk of deep neck infection among HIV-infected patients in the era of highly active antiretroviral therapy—a population-based follow-up study
Authors: Liu Ching-Feng , Weng Shih-Feng , Lin Yung-Song , Lin Chih-Sheng , Lien Ching-Feng , Wang Jhi-Joung 
Published: April 2013

Abstract

Background
Deep neck infections (DNIs) in HIV-infected patients often produce severe complications, even death. Data on the incidence rates and risks of DNI among HIV-infected patients are scarce, particularly with the widespread use of highly active antiretroviral therapy (HAART). We evaluated the incidence rates and risks for DNI among HIV-infected patients and observed the long-term trends.

Methods
A total of 9888 new HIV-infected patients diagnosed in 2001–2007 were included and matched with 49440 randomly selected subjects. The HIV-infected subjects were offered free access to HAART. All subjects were traced until December 2009. A Kaplan-Meier analysis generated the cumulative DNI incidence rate. The adjusted hazard ratio was computed using Cox proportional hazard regressions.

Results
From the HIV-infected and comparison cohorts, 222 individuals (57.01 cases per 10000 person-years) and 735 individuals (35.54 cases per 10000 person-years) developed DNI, respectively. The log rank test indicated that patients with HIV had a significantly higher 8-year incidence rate of DNI than the control group (P < 0.0001). The adjusted hazard ratio for developing DNI after an HIV attack during the mean 3.94 years follow-up period was 1.59. The incidence rate and relative risk of DNI were 74.58 (per 10000 person-years) and 2.05 (P < 0.0001). Both figures were highest in the first follow-up year and decreased year-by-year thereafter.

Conclusion
The risk of developing DNI is significantly elevated among HIV-infected patients, even with free access to HAART. Additional research is needed to examine the role of HAART in reducing the risk.
In vitro and in vivo effects of geranylgeranyltransferase I inhibitor P61A6 on non-small cell lung cancer cells
Authors: Zimonjic Drazen B , Chan Lai N , Tripathi Veenu , Lu Jie , Kwon Ohyun , Popescu Nicholas C , Lowy Douglas R , Tamanoi Fuyuhiko 
Published: April 2013

Abstract

Background
Lung cancer is the leading cause of cancer-related mortality. Therapies against non-small cell lung cancer (NSCLC) are particularly needed, as this type of cancer is relatively insensitive to chemotherapy and radiation therapy. We recently identified GGTI compounds that are designed to block geranylgeranylation and membrane association of signaling proteins including the Rho family G-proteins. One of the GGTIs is P61A6 which inhibits proliferation of human cancer cells, causes cell cycle effects with G1 accumulation and exhibits tumor-suppressing effects with human pancreatic cancer xenografts. In this paper, we investigated effects of P61A6 on non-small cell lung cancer (NSCLC) cells in vitro and in vivo.

Methods
Three non-small cell lung cancer cell lines were used to test the ability of P61A6 to inhibit cell proliferation. Further characterization involved analyses of geranylgeranylation, membrane association and activation of RhoA, and anchorage-dependent and –independent growth, as well as cell cycle effects and examination of cell cycle regulators. We also generated stable cells expressing RhoA-F, which bypasses the geranylgeranylation requirement of wild type RhoA, and examined whether the proliferation inhibition by P61A6 is suppressed in these cells. Tumor xenografts of NSCLC cells growing in nude mice were also used to test P61A6’s tumor-suppressing ability.

Results
P61A6 was shown to inhibit proliferation of NSCLC lines H358, H23 and H1507. Detailed analysis of P61A6 effects on H358 cells showed that P61A6 inhibited geranylgeranylation, membrane association of RhoA and caused G1 accumulation associated with decreased cyclin D1/2. The effects of P61A6 to inhibit proliferation could mainly be ascribed to RhoA, as expression of the RhoA-F geranylgeranylation bypass mutant rendered the cells resistant to inhibition by P61A6. We also found that P61A6 treatment of H358 tumor xenografts growing in nude mice reduced their growth as well as the membrane association of RhoA in the tumors.

Conclusion
Thus, P61A6 inhibits proliferation of NSCLC cells and causes G1 accumulation associated with decreased cyclin D1/2. The result with the RhoA-F mutant suggests that the effect of P61A6 to inhibit proliferation is mainly through the inhibition of RhoA. P61A6 also shows efficacy to inhibit growth of xenograft tumor.
Sexually transmitted infections among HIV-infected women in Thailand
Authors: Asavapiriyanont Suvanna , Lolekha Rangsima , Roongpisuthipong Anuvat , Wiratchai Amornpan , Kaoiean Surasak , Suksripanich Orapin , Chalermchockcharoenkit Amphan , Ausavapipit Jaruensook , Srifeungfung Somporn , Pattanasin Sarika , Katz Kenneth A 
Published: April 2013

AbstractBackgroundData on sexually transmitted infections (STI) prevalence among HIV-infected women in Thailand are limited. We studied, among HIV-infected women, prevalence of STI symptoms and signs; prevalence and correlates of having any STI; prevalence and correlates ofChlamydia trachomatis(CT) orNeisseria gonorrhoeae(GC) among women without CT and/or GC symptoms or signs; and number of women without CT and/or GC symptoms or signs needed to screen (NNS) to detect one woman with CT and/or GC overall, among pregnant women, and among women ≤25 years.MethodsDuring October 2004–September 2006, HIV-infected women at 3 obstetrics and gynecology clinics were asked about sexual behaviors and STI symptoms, physically examined, and screened for chlamydia, gonorrhea, trichomoniasis, and syphilis. Multivariate logistic regression was used to identify correlates of infections. NNS was calculated using standard methods.ResultsAmong 1,124 women, 526 (47.0%) had STI symptoms or signs, 469 (41.7%) had CT and/or GC symptoms or signs, and 133 (11.8%) had an STI. Correlates of having an STI included pregnancy and having STI signs. Among 469 women and 655 women with vs. without CT and/or GC symptoms or signs, respectively, 43 (9.2%) vs. 31 (4.7%), 2 (0.4%) vs. 9 (1.4%), and 45 (9.6%) vs. 38 (5.8%) had CT, GC, or “CT or GC”, respectively; correlates included receiving care at university hospitals and having sex with a casual partner within 3 months. NNS for women overall and women ≤25 years old were 18 (95% CI, 13-25) and 11 (95% CI, 6-23), respectively; and for pregnant and non-pregnant women, 8 (95% CI, 4-24) and 19 (95% CI, 14-27), respectively.ConclusionsSTI prevalence among HIV-infected women, including CT and GC among those without symptoms or signs, was substantial. Screening for CT and GC, particularly for pregnant women, should be considered.
Artemisinin-based combination therapy availability and use in the private sector of five AMFm phase 1 countries
Authors: Davis Ben , Ladner Joel , Sams Kelley , Tekinturhan Ebru , de Korte Donald , Saba Joseph 
Published: April 2013

Abstract

Background
In 2009, the Global Fund to Fight AIDS, Tuberculosis and Malaria established the Affordable Medicines Facility-malaria (AMFm) in order to increase access to quality-assured artemisinin combination therapy (QAACT). AMFm Phase 1, which includes nine pilot programmes in eight countries, was launched in 2009. The objective of this study was to assess anti-malarial stock and purchase patterns at private outlets in five AMFm Phase 1 countries in regard to three of the core AMFm goals: increase the affordability of QAACT, increase the availability of QAACT, and crowd out artemisinin monotherapies and other substandard therapies.

Methods
The study was conducted between April and May 2012 and included interviews with personnel in 598 private pharmaceutical outlets in Ghana, Kenya, Nigeria, Tanzania, and Uganda. Questionnaires were administered at private retail outlets and the data were analyzed to assess within- and between-country differences in QAACT price, availability, and popularity.

Results
AMFm medications were less expensive than their non-AMFm counterparts, yet prices for both types were above country-specific suggested retail prices. Market penetration of AMFm QAACT in both urban and rural areas was high, although stock-outs of both AMFm and non-AMFm products were more common in rural compared with urban outlets in Ghana and Kenya (p = 0.0013). Government recommendation was the most significant factor influencing anti-malarial stock choices in urban (41.5%) and rural (31.9%) outlets. The three top-selling anti-malarials reported for both urban and rural areas in each country were, with the exception of rural Uganda and urban Nigeria, combination therapies.

Conclusions
Results from this study indicate that the AMFm has not fully achieved its affordability and crowd-out objectives. Still, the final purchase price of AMFm QAACT was substantially lower than non-AMFm equivalents. Moreover, for both urban and rural areas, AMFm QAACT availability was found to be high, and the various forms of QAACT were the best-selling products among all anti-malarials. These findings suggest a continued need for initiatives like the AMFm that improve the affordability and accessibility of QAACT. Similar programmes may be especially effective if employed in combination with rapid diagnostic testing to ensure the appropriate use of these products.
Clinicopathologic characteristics at diagnosis and the survival of patients with medullary breast carcinoma in China: a comparison with infiltrating ductal carcinoma-not otherwise specified
Authors: Cao A-Yong , He Min , Huang Liang , Shao Zhi-Ming , Di Gen-Hong 
Published: April 2013

Abstract

Background
Few studies have addressed the biological features of medullary breast carcinoma (MBC) in the context of clinical outcomes. We sought to compare the baseline demographics, standard pathologic factors and long-term clinical outcomes between MBC and infiltrating ductal carcinoma-not otherwise specified (IDC-NOS) using a large database.

Methods
A total of 2,202 cases with pure IDC-NOS and 188 cases with typical MBC meeting the inclusion criteria were identified. The clinical and biological features, the overall survival (OS) and recurrence/metastasis-free survival (RFS) were compared for both groups.

Results
There were a higher proportion of patients diagnosed prior to 40 years of age in the MBC group compared to the IDC-NOS group. MBC cases demonstrated less aggressive tumor features such as lower tumor stage, smaller tumor size and a lower proportion of nodal involvement than IDC-NOS; however, immunohistochemical staining revealed that MBC displayed the triple-negative phenotype more often than IDC-NOS cases (40.4% versus 26.2%; P <0.001). Although the clinical behavior of MBC was not commensurate with its pathologic features, women diagnosed with MBC had a lower frequency of recurrence/metastasis (P = 0.032) and death (P = 0.042) than those with IDC-NOS, and the 10-year OS and RFS were significantly higher for MBC (91% and 74%) compared to IDC-NOS (81% and 64%). Moreover, multivariate analysis revealed that TNM stage was a statistically significant factor for survival.

Conclusions
MBC in Chinese women demonstrated less aggressive behavior and better prognosis than IDC-NOS. This favorable outcome was maintained after 10 years.
Alterations of Gab2 signalling complexes in imatinib and dasatinib treated chronic myeloid leukaemia cells
Authors: Halbach Sebastian , Rigbolt Kristoffer TG , Wöhrle Franziska U , Diedrich Britta , Gretzmeier Christine , Brummer Tilman , Dengjel Jörn 
Published: April 2013

Abstract

Background
The Gab2 docking protein acts as an important signal amplifier downstream of various growth factor receptors and Bcr-Abl, the driver of chronic myeloid leukaemia (CML). Despite the success of Bcr-Abl tyrosine kinase inhibitors (TKI) in the therapy of CML, TKI-resistance remains an unsolved problem in the clinic. We have recently shown that Gab2 signalling counteracts the efficacy of four distinct Bcr-Abl inhibitors. In the course of that project, we noticed that two clinically relevant drugs, imatinib and dasatinib, provoke distinct alterations in the electrophoretic mobility of Gab2, its signalling output and protein interactions. As the signalling potential of the docking protein is highly modulated by its phosphorylation status, we set out to obtain more insights into the impact of TKIs on Gab2 phosphorylation.

Findings
Using stable isotope labelling by amino acids in cell culture (SILAC)-based quantitative mass spectrometry (MS), we show now that imatinib and dasatinib provoke distinct effects on the phosphorylation status and interactome of Gab2. This study identifies several new phosphorylation sites on Gab2 and confirms many sites previously known from other experimental systems. At equimolar concentrations, dasatinib is more effective in preventing Gab2 tyrosine and serine/threonine phosphorylation than imatinib. It also affects the phosphorylation status of more residues than imatinib. In addition, we also identify novel components of the Gab2 signalling complex, such as casein kinases, stathmins and PIP1 as well as known interaction partners whose association with Gab2 is disrupted by imatinib and/or dasatinib.

Conclusions
By using MS-based proteomics, we have identified new and confirmed known phosphorylation sites and interaction partners of Gab2, which may play an important role in the regulation of this docking protein. Given the growing importance of Gab2 in several tumour entities we expect that our results will help to understand the complex regulation of Gab2 and how this docking protein can contribute to malignancy.
Effects of age on noninvasive assessments of vascular function in nonhuman primates: implications for translational drug discovery
Authors: Knight Delvin R , Smith Andrew H , Schroeder Richard L , Huang Chunli , Beebe David A , Sokolowski Sharon A , Wang Miao 
Published: April 2013

Abstract

Background
Endothelium-dependent flow mediated dilation (FMD) and pulse-wave velocity (PWV), are used as measures of vascular health and predictors of cardiovascular risk in clinical studies, and both are age-dependent. Numbers of circulating endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) are also associated with cardiovascular risk, but independent of age in humans. The use of these measurements for pre-clinical assessment of drug cardiovascular safety and efficacy in non-human primates (NHPs) may promote the translation of drug-induced effects on vascular function to clinic outcomes. However, in NHPs, the age effects on the non-invasive measurements of FMD and PWV and the relationship of EMPs/EPCs with FMD are unknown.

Methods
A non-invasive, clinically-relevant approach to assess FMD and PWV was used to examine their relationship with age and with EMPs/EPCs in NHPs. The effects on FMD of nicotine and rosiglitazone were evaluated in senescent primates in an effort to validate our FMD method for pre-clinical assessment of vascular function.

Results
FMD and PWV methods were established in a colony (n = 25) of metabolically healthy, cynomolgus monkeys ranging in age from 6 to 26 years. FMD, defined as the percent change, at 1 min of cuff release, from baseline vascular diameter (0.15 ± 0.03 cm), had a strong, negative correlation with age (r = -0.892, p < 0.0001), ranging from 6% to 33%. PWV positively correlated with age (r = 0.622, p < 0.002) in the same healthy monkeys. Nicotine and rosiglitazone, were evaluated in subsets of senescent primates (mean age 16.3 ± 1.5[SEM] years). Rosiglitazone significantly improved FMD (21.0 ± 1.6% vs. vehicle 16.3 ± 1.6%, p < 0.01) without changing baseline diameters, and coincided with a significant increase in circulating numbers of endothelial progenitor cells (CD45-CD31 + CD34 + VEGFR2+ 7.1 ± 1.3 vs. 4.8 ± 1.1 counts/μl) and a decrease in endothelial microparticles (CD45-CD42a-CD54+ 26.7 ± 11.1 vs. 62.2 ± 9.8 counts/μl)(p < 0.05). Conversely, FMD was significantly reduced with nicotine (8.7 ± 1.4% vs. vehicle 20.1 ± 2.2%, p < 0.05).

Conclusions
Adult NHPs demonstrate the characteristic linear relationship between age and vascular function using the non-invasive clinically-related measurements of FMD and PWV. However, numbers of circulating EMPs and EPCs did not correlate with age. Endothelial function assessed with FMD, together with EMPs/EPCs assessment, may serve as a novel approach for translational research and therapeutic discovery. Age should be considered in the study design or data analyses when FMD or PWV is used in NHPs.
Study of nanostructure growth with nanoscale apex induced by femtosecond laser irradiation at megahertz repetition rate
Authors: Patel Nikunj B , Tan Bo , Venkatakrishnan Krishnan 
Published: April 2013

Abstract
Leaf-like nanostructures with nanoscale apex are induced on dielectric target surfaces by high-repetition-rate femtosecond laser irradiation in ambient conditions. We have recently developed this unique technique to grow leaf-like nanostructures with such interesting geometry without the use of any catalyst. It was found to be possible only in the presence of background nitrogen gas flow. In this synthesis method, the target serves as the source for building material as well as the substrate upon which these nanostructures can grow. In our investigation, it was found that there are three possible kinds of nanotips that can grow on target surfaces. In this report, we have presented the study of the growth mechanisms of such leaf-like nanostructures under various conditions such as different laser pulse widths, pulse repetition rates, dwell times, and laser polarizations. We observed a clear transformation in the kind of nanotips that grew for the given laser conditions.
Infant gut microbiota and the hygiene hypothesis of allergic disease: impact of household pets and siblings on microbiota composition and diversity
Authors: Azad Meghan B , Konya Theodore , Maughan Heather , Guttman David S , Field Catherine J , Sears Malcolm R , Becker Allan B , Scott James A , Kozyrskyj Anita L ,   CHILD Study Investigators
Published: April 2013

Abstract

Background
Multiple studies have demonstrated that early-life exposure to pets or siblings affords protection against allergic disease; these associations are commonly attributed to the “hygiene hypothesis”. Recently, low diversity of the infant gut microbiota has also been linked to allergic disease. In this study, we characterize the infant gut microbiota in relation to pets and siblings.

Methods
The study population comprised a small sub-sample of 24 healthy, full term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mothers reported on household pets and siblings. Fecal samples were collected at 4 months of age, and microbiota composition was characterized by high-throughput signature gene sequencing.

Results
Microbiota richness and diversity tended to be increased in infants living with pets, whereas these measures were decreased in infants with older siblings. Infants living with pets exhibited under-representation of Bifidobacteriaceae and over-representation of Peptostreptococcaceae; infants with older siblings exhibited under-representation of Peptostreptococcaceae.

Conclusions
This study provides new evidence that exposure to pets and siblings may influence the early development of the gut microbiota, with potential implications for allergic disease. These two traditionally protective “hygiene hypothesis” factors appear to differentially impact gut microbiota composition and diversity, calling into question the clinical significance of these measures. Further research is required to confirm and expand these findings.
A juvenile case of conjunctival atypical nevus
Authors: Colarossi Cristina , Milazzo Mario , Paglierani Milena , Massi Daniela , Memeo Lorenzo , Canzonieri Vincenzo 
Published: April 2013

Abstract

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2973228795724608

Melanocytic nevi are the most common tumors of the conjunctiva, accounting for 28% of all neoplastic lesions. These tumors, despite their benign behavior, share some atypical histological features with nevi found in other anatomic sites like the genital and acral regions, globally designated as nevi with site-related atypia. Moreover, in children and adolescents, rapidly growing conjunctival nevi show sometimes worrisome histological patterns in association with a prominent inflammatory infiltrate that may lead to diagnostic problems. In this paper we describe a juvenile compound nevus characterized by marked melanocytic atypia and severe inflammation, which can be considered a rare case of juvenile conjunctival atypical nevus. The final diagnosis relied on morphological and immunohistochemical characterization of the large epithelioid melanocytic cells, and on the results of FISH analysis.
Clinical validation of the gastrointestinal NET grading system: Ki67 index criteria of the WHO 2010 classification is appropriate to predict metastasis or recurrence
Authors: Yamaguchi Takeshi , Fujimori Takahiro , Tomita Shigeki , Ichikawa Kazuhito , Mitomi Hiroyuki , Ohno Kazuya , Shida Yosuke , Kato Hiroyuki 
Published: April 2013

Abstract

Background
In the WHO 2010 classification, the neuroendocrine tumors (NETs) are subdivided by their mitotic index or Ki67 index into either G1 or G2 NETs. Tumors with a Ki67 index of <2% are classified as G1 and those with 3—20% are classified as G2. However, the assessment of tumors with Ki67 index of greater than 2% and less than or equal to 3% is still unclear. To resolve the problem, we validated the Ki67 index criteria of gastrointestinal NETs of the WHO 2010 classification.

Methods
The medical records of 45 patients who were pathologically diagnosed as having NET G1/G2 of the gastrointestinal tract were analyzed retrospectively. According to the WHO 2010 classification, Ki67 index were calculated. Computer-assisted cytometrical analysis of Ki67 immunoreactivity was performed using the WinRooF image processing software. Receiver operating characteristic (ROC) curves were generated to determine the best discriminating Ki67 index. To clarify the assessment of tumors with Ki67 index between 2—3%, the calculated cutoff of Ki67 index was evaluated using Fisher’s exact test.

Results
ROC curve analysis confirmed that 2.8% was the best Ki67 index cutoff value for predicting metastasis or recurrence. The sensitivity of the new Ki67 index cutoff was 42.9%, and the specificity was 86.8%.

Conclusions
Division of NETs into G1/G2 based on Ki67 index of 3% was appropriate to predict metastases or recurrences. The WHO grading system may be the most useful classification to predict metastases or recurrences.

Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1553036118943799