bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Equipoise in Sleep Surgery
Authors: Field Clarice J. , Robinson Sam , Mackay Stuart , Harrison James D. , Marshall Nathaniel S. 
Published: April 2011

ObjectiveSurgical approaches for alleviating snoring and/or obstructive sleep apnea (OSA) have been questioned because of a lack of evidence from high‐quality randomized controlled trials (RCTs). An ethical requirement for RCTs is that they must test questions where community equipoise (ie, uncertainty) exists as to the correct treatment. We aimed to measure perceived importance, community equipoise, and willingness to enroll patients in 5 potential trial targets among members of the Australian Society for Otolaryngology Head and Neck Surgery (ASOHNS).Study Design, Setting, and SubjectsAll ASOHNS members were surveyed using a multistage mail, email, Internet, and phone‐based questionnaire.MethodsEquipoise was measured for each of the scenarios using a bidirectional linear scale comparing 2 treatments. Responses were categorized into 1 of 3 groups: (A) preferred treatment 1, (B) completely undecided, and (C) preferred treatment 2. The resulting proportions are called equipoise ratios: A:B:C. Using tick boxes, the authors queried the general clinical importance and willingness to enroll patients for all scenarios.ResultsA total of 167 of 313 surgeons responded (53.4%). Three of the 5 trial scenarios exhibited evidence of community equipoise, but 2 scenarios, radiofrequency ablation plus uvulopalatopharyngoplasty (UPPP) versus UPPP alone and upper‐airway reconstruction versus mandibular advancement splint (MAS), did not have strong support for enrolling patients. Informal feedback indicates one of these may be feasible in a smaller number of specifically trained surgeons.ConclusionWe suggest 2 potential RCT targets: septoplasty and turbinate reduction versus conservative measures for snoring and airway reconstruction versus MAS for OSA, where importance, clinical equipoise, and willingness all exist.
Intratympanic Dexamethasone to Prevent Cisplatin Ototoxicity
Authors: Murphy Denise , Daniel Sam J. 
Published: April 2011

ObjectiveTo determine whether intratympanic administration of dexamethasone reduces ototoxicity from systemic cisplatin.Study DesignProspective animal study.SettingCisplatin chemotherapy induces ototoxicity manifesting as irreversible, sensorineural hearing loss. This is due to damage to the inner ear structures by free radicals. Steroidal anti‐inflammatories have been shown to reduce the formation of free radicals and protect hearing in animal models.Subjects and MethodsPure tone auditory brainstem responses were obtained in 58 female albino guinea pigs before and 3 days after intraperitoneal (IP) cisplatin chemotherapy. Auditory brainstem responses were also taken up to 1 month after a low dose of cisplatin. Part I consisted of a dosing study to determine the optimal ototoxic dose of cisplatin. In part II, auditory brainstem response thresholds were compared after bilateral intratympanic dexamethasone doses to act as controls. For part III, the otoprotection of dexamethasone against cisplatin was tested in separate bilateral and unilateral studies.ResultsIP injection of 12 mg/kg of cisplatin induced significant hearing loss (57.2 ± 4.4 dB, P <. 01) with 0% mortality. Ears treated with intratympanic dexamethasone alone showed no significant threshold changes. Ears that received IP cisplatin and intratympanic dexamethasone showed reduced threshold shifts at 8 kHz when the greatest concentration of dexamethasone was administered.ConclusionModest intratympanic dexamethasone otoprotection of the guinea pig ear was greatest at the highest concentration tested and occurred in a frequency‐dependent manner. Intratympanic dexamethasone presents as a safe, simple, and effective treatment modality to minimize cisplatin ototoxicity without interfering with the chemotherapeutic effects of cisplatin.
Topical Mithramycin‐A Modulates Submucosal Collagen Deposition after Esophageal Burn Injury in Rats
Authors: Davis Paul Lawson , Hardison Scott , Sullivan Christopher A. 
Published: April 2011

ObjectiveTo evaluate efficacy of a drug‐eluting, dissolvable esophageal (DEDE) stent for the prevention of submucosal collagen deposition in a rat model of acute esophageal injury.SettingUniversity laboratory.Study DesignInterventional randomized controlled trial.Subjects and MethodsForty two adult, male, age‐matched Sprague Dawley rats were randomized to undergo either sham esophageal surgery, esophageal burn injury, or esophageal burn injury and placement of a DEDE stent. All animals underwent open gastrotomy under anesthesia. In group 1, a cautery device was inserted through the gastrotomy into the distal esophagus and removed without creating an injury. In group 2, the cautery was placed in the distal esophagus and a circumferential thermal burn injury was created. In group 3, an identical burn injury was created and a DEDE stent was placed at the site of injury and secured. On postoperative day 28, animals were sacrificed, and the distal esophagi were harvested and processed for histology. Submucosal collagen area was quantified histologically and compared across the 3 experimental groups.ResultsAfter the investigators controlled for luminal circumference and multiple measurements, submucosal collagen area was increased in group 2 (burn) compared with group 1 (sham) (P =. 012). Submucosal collagen area was decreased in group 3 (DEDE stent) compared with group 2 (P =. 042). No statistically significant difference in submucosal collagen area was observed between animals in group 1 and group 3 (P =. 800).ConclusionsTopical application of mithramycin‐A via a DEDE stent modulates collagen deposition after acute thermal injury in the rat esophagus.
Stigma and Access to HIV Care among HIV-Infected Women in Kolkata, West Bengal
Authors: Dasgupta Sharoda , Sullivan Patrick S. , Dasgupta Aparajita , Saha Bibhuti , Salazar Laura F. 
Published: April 2011

Objectives: Stigma is an important issue for marginalized HIV-infected populations. We describe stigma among HIV-infected women on antiretroviral therapy and associations with access to clinical care, demographic factors, and structural elements of support. Methods: HIV-infected women attending a government-supported clinic in Kolkata, India, were asked about experiences with stigma. Clinical information was abstracted from medical records. We described factors associated with stigma using ordinal logistic regression. Results: Among 198 women, higher levels of stigma were associated with lower CD4 count upon entry into care (aOR = 0.78; 95% confidence interval [CI]: [0.65, 0.94]), district of residence (aOR = 1.9; CI: [1.0, 3.4]), presence of extended family in the household (aOR = 0.57; CI: [0.32, 1.0]), and employment at the time of the interview (aOR = 0.48; CI: [0.26, 0.90]). Stigma was not associated with having missed scheduled HIV care appointments. Conclusion: Stigma is prevalent among Indian women with HIV, should be further explored, and may be important in considering public health interventions for better access to care.
TIMP-1 deficiency subverts cell-cycle dynamics in murine long-term HSCs
Authors: Rossi Lara , Ergen Aysegul V. , Goodell Margaret A. 
Published: April 2011

AbstractIn addition to the well-recognized role in extracellular matrix remodeling, the tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested to be involved in the regulation of numerous biologic functions, including cell proliferation and survival. We therefore hypothesized that TIMP-1 might be involved in the homeostatic regulation of HSCs, whose biologic behavior is the synthesis of both microenvironmental and intrinsic cues. We found that TIMP-1−/− mice have decreased BM cellularity and, consistent with this finding, TIMP-1−/− HSCs display reduced capability of long-term repopulation. Interestingly, the cell cycle distribution of TIMP-1−/− stem cells appears distorted, with a dysregulation at the level of the G1 phase. TIMP-1−/− HSCs also display increased levels of p57, p21, and p53, suggesting that TIMP-1 could be intrinsically involved in the regulation of HSC cycling dynamics. Of note, TIMP-1−/− HSCs present decreased levels of CD44 glycoprotein, whose expression has been proven to be controlled by p53, the master regulator of the G1/S transition. Our findings establish a role for TIMP-1 in regulating HSC function, suggesting a novel mechanism presiding over stem cell quiescence in the framework of the BM milieu.
Depletion of CD25+ T cells from hematopoietic stem cell grafts increases posttransplantation vaccine-induced immunity to neuroblastoma
Authors: Jing Weiqing , Yan Xiaocai , Hallett William H. D. , Gershan Jill A. , Johnson Bryon D. 
Published: April 2011

AbstractA multifaceted immunotherapeutic strategy that includes hematopoietic stem cell (HSC) transplantation, T-cell adoptive transfer, and tumor vaccination can effectively eliminate established neuroblastoma tumors in mice. In vivo depletion of CD4+ T cells in HSC transplantation recipients results in increased antitumor immunity when adoptively transferred T cells are presensitized, but development of T-cell memory is severely compromised. Because increased percentages of regulatory T (Treg) cells are seen in HSC transplantation recipients, here we hypothesized that the inhibitory effect of CD4+ T cells is primarily because of the presence of expanded Treg cells. Remarkably, adoptive transfer of presensitized CD25-depleted T cells increased tumor vaccine efficacy. The enhanced antitumor effect achieved by ex vivo depletion of CD25+ Treg cells was similar to that achieved by in vivo depletion of all CD4+ T cells. Depletion of CD25+ Treg cells resulted in elevated frequencies of tumor-reactive CD8 and CD4+ T cells and increased CD8-to-Treg cell ratios inside tumor masses. All mice given presensitized CD25-depleted T cells survived a tumor rechallenge, indicating the development of long-term CD8+ T-cell memory to tumor antigens. These observations should aid in the future design of immunotherapeutic approaches that promote the generation of both acute and long-term antitumor immunity.
Variance adjusted weighted UniFrac: a powerful beta diversity measure for comparing communities based on phylogeny
Authors: Chang Qin , Luan Yihui , Sun Fengzhu 
Published: April 2011

Abstract

Background
Beta diversity, which involves the assessment of differences between communities, is an important problem in ecological studies. Many statistical methods have been developed to quantify beta diversity, and among them, UniFrac and weighted-UniFrac (W-UniFrac) are widely used. The W-UniFrac is a weighted sum of branch lengths in a phylogenetic tree of the sequences from the communities. However, W-UniFrac does not consider the variation of the weights under random sampling resulting in less power detecting the differences between communities.

Results
We develop a new statistic termed variance adjusted weighted UniFrac (VAW-UniFrac) to compare two communities based on the phylogenetic relationships of the individuals. The VAW-UniFrac is used to test if the two communities are different. To test the power of VAW-UniFrac, we first ran a series of simulations which revealed that it always outperforms W-UniFrac, as well as UniFrac when the individuals are not uniformly distributed. Next, all three methods were applied to analyze three large 16S rRNA sequence collections, including human skin bacteria, mouse gut microbial communities, microbial communities from hypersaline soil and sediments, and a tropical forest census data. Both simulations and applications to real data show that VAW-UniFrac can satisfactorily measure differences between communities, considering not only the species composition but also abundance information.

Conclusions
VAW-UniFrac can recover biological insights that cannot be revealed by other beta diversity measures, and it provides a novel alternative for comparing communities.
Genetic analyses place most Spanish isolates of Beauveria bassiana in a molecular group with word-wide distribution
Authors: Garrido-Jurado Inmaculada , Márquez Marcela , Ortiz-Urquiza Almudena , Santiago-Álvarez Cándido , Iturriaga Enrique A , Quesada-Moraga Enrique , Monte Enrique , Hermosa Rosa 
Published: April 2011

Abstract

Background
The entomopathogenic anamorphic fungus Beauveria bassiana is currently used as a biocontrol agent (BCA) of insects. Fifty-seven Beauveria bassiana isolates -53 from Spain- were characterized, integrating group I intron insertion patterns at the 3'-end of the nuclear large subunit ribosomal gene (LSU rDNA) and elongation factor 1-alpha (EF1-α) phylogenetic information, in order to assess the genetic structure and diversity of this Spanish collection of B. bassiana.

Results
Group I intron genotype analysis was based on the four highly conserved insertion sites of the LSU (Ec2653, Ec2449, Ec2066, Ec1921). Of the 16 possible combinations/genotypes, only four were detected, two of which were predominant, containing 44 and 9 members out of 57 isolates, respectively. Interestingly, the members of the latter two genotypes showed unique differences in their growth temperatures. In follow, EF1-α phylogeny served to classify most of the strains in the B. bassiana s.s. (sensu stricto) group and separate them into 5 molecular subgroups, all of which contained a group I intron belonging to the IC1 subtype at the Ec1921 position. A number of parameters such as thermal growth or origin (host, geographic location and climatic conditions) were also examined but in general no association could be found.

Conclusion
Most Spanish B. bassiana isolates (77.2%) are grouped into a major phylogenetic subgroup with word-wide distribution. However, high phylogenetic diversity was also detected among Spanish isolates from close geographic zones with low climatic variation. In general, no correlation was observed between the molecular distribution and geographic origin or climatic characteristics where the Spanish B. bassiana isolates were sampled.
Comparison of three tests of homogeneity of odds ratios in multicenter trials with unequal sample sizes within and among centers
Authors: Bagheri Zahra , Ayatollahi Seyyed Mohammad Taghi , Jafari Peyman 
Published: April 2011

Abstract

Background
Mixed effects logistic models have become a popular method for analyzing multicenter clinical trials with binomial data. However, the statistical properties of these models for testing homogeneity of odds ratios under various conditions, such as within-center and among-centers inequality, are still unknown and not yet compared with those of commonly used tests of homogeneity.

Methods
We evaluated the effect of within-center and among-centers inequality on the empirical power and type I error rate of the three homogeneity tests of odds ratios including likelihood ratio (LR) test of a mixed logistic model, DerSimonian-Laird (DL) statistic and Breslow-Day (BD) test by simulation study. Moreover, the impacts of number of centers (K), number of observations in each center and amount of heterogeneity were investigated by simulation.

Results
As compared with the equal sample size design, the power of the three tests of homogeneity will decrease if the same total sample size, which can be allocated equally within one center or among centers, is allocated unequally. The average reduction in the power of these tests was up to 11% and 16% for within-center and among-centers inequality, respectively. Moreover, in this situation, the ranking of the power of the homogeneity tests was BD≥DL≥LR and the power of these tests increased with increasing K.

Conclusions
This study shows that the adverse effect of among-centers inequality on the power of the homogeneity tests was stronger than that of within-center inequality. However, the financial limitations make the use of unequal sample size designs inevitable in multicenter trials. Moreover, although the power of the BD is higher than that of the LR when K≤6, the proposed mixed logistic model is recommended when K≥8 due to its practical advantages.
Engineering of a plasmid-free Escherichia coli strain for improved in vivo biosynthesis of astaxanthin
Authors: Lemuth Karin , Steuer Kristin , Albermann Christoph 
Published: April 2011

Abstract

Background
The xanthophyll astaxanthin is a high-value compound with applications in the nutraceutical, cosmetic, food, and animal feed industries. Besides chemical synthesis and extraction from naturally producing organisms like Haematococcus pluvialis, heterologous biosynthesis in non-carotenogenic microorganisms like Escherichia coli, is a promising alternative for sustainable production of natural astaxanthin. Recent achievements in the metabolic engineering of E. coli strains have led to a significant increase in the productivity of carotenoids like lycopene or β-carotene by increasing the metabolic flux towards the isoprenoid precursors. For the heterologous biosynthesis of astaxanthin in E. coli, however, the conversion of β-carotene to astaxanthin is obviously the most critical step towards an efficient biosynthesis of astaxanthin.

Results
Here we report the construction of the first plasmid-free E. coli strain that produces astaxanthin as the sole carotenoid compound with a yield of 1.4 mg/g cdw (E. coli BW-ASTA). This engineered E. coli strain harbors xanthophyll biosynthetic genes from Pantoea ananatis and Nostoc punctiforme as individual expression cassettes on the chromosome and is based on a β-carotene-producing strain (E. coli BW-CARO) recently developed in our lab. E. coli BW-CARO has an enhanced biosynthesis of the isoprenoid precursor isopentenyl diphosphate (IPP) and produces β-carotene in a concentration of 6.2 mg/g cdw. The expression of crtEBIY along with the β-carotene-ketolase gene crtW148 (NpF4798) and the β-carotene-hydroxylase gene (crtZ) under controlled expression conditions in E. coli BW-ASTA directed the pathway exclusively towards the desired product astaxanthin (1.4 mg/g cdw).

Conclusions
By using the λ-Red recombineering technique, genes encoding for the astaxanthin biosynthesis pathway were stably integrated into the chromosome of E. coli. The expression levels of chromosomal integrated recombinant biosynthetic genes were varied and adjusted to improve the ratios of carotenoids produced by this E. coli strain. The strategy presented, which combines chromosomal integration of biosynthetic genes with the possibility of adjusting expression by using different promoters, might be useful as a general approach for the construction of stable heterologous production strains synthesizing natural products. This is the case especially for heterologous pathways where excessive protein overexpression is a hindrance.
Chalcone-imidazolone conjugates induce apoptosis through DNA damage pathway by affecting telomeres
Authors: Ramaiah M Janaki , Pushpavalli SNCVL , Krishna G Rama , Sarma Pranjal , Mukhopadhyay Debasmita , Kamal Ahmed , Bhadra Utpal , Bhadra Manika Pal 
Published: April 2011

Abstract

Background
Breast cancer is one of the most prevalent cancers in the world and more than one million women are diagnosed leading to 410,000 deaths every year. In our previous studies new chalcone-imidazolone conjugates were prepared and evaluated for their anticancer activity in a panel of 53 human tumor cell lines and the lead compounds identified were 6 and 8. This prompted us to investigate the mechanism of apoptotic event.

Results
Involvement of pro-apoptotic protein (Bax), active caspase-9 and cleavage of retinoblastoma protein was studied. Interestingly, the compounds caused upregulation of p21, check point proteins (Chk1, Chk2) and as well as their phosphorylated forms which are known to regulate the DNA damage pathway. Increased p53BP1 foci by immunolocalisation studies and TRF1 suggested the possible involvement of telomere and associated proteins in the apoptotic event. The telomeric protein such as TRF2 which is an important target for anticancer therapy against human breast cancer was extensively studied along with proteins involved in proper functioning of telomeres.

Conclusions
The apoptotic proteins such as Bax, active caspase-9 and cleaved RB are up-regulated in the compound treated cells revealing the apoptotic nature of the compounds. Down regulation of TRF2 and upregulation of the TRF1 as well as telomerase assay indicated the decrease in telomeric length revealing telomeric dysfunction and thereby controlling the rapid rate of cell proliferation. In summary, chalcone-imidazolone conjugates displayed significant DNA damage activity particularly at telomeres and caused both apoptosis and senescence-like growth arrest which suggested that these compounds have potential activity against breast carcinoma.
Peripheral myelin protein-22 (PMP22) modulates alpha 6 integrin expression in the human endometrium
Authors: Rao Rajiv G , Sudhakar Deepthi , Hogue Claire P , Amici Stephanie , Gordon Lynn K , Braun Jonathan , Notterpek Lucia , Goodglick Lee , Wadehra Madhuri 
Published: April 2011

Abstract

Background
PMP22, a member of the GAS3 family of tetraspan proteins, is associated with a variety of neurological diseases. Previous studies have shown that PMP22 is expressed in proliferative endometrium, but its function within this tissue is poorly understood. In this study, we first characterized the expression of PMP22 in the human menstrual cycle and began to characterize its function in the endometrium.

Methods
Using a combination of immunohistochemistry and quantitative PCR, we characterized the expression of PMP22 in both proliferative and secretory endometrium. Differences in PMP22 expression between proliferative and secretory endometrium were determined using a Mann-Whitney U test. In order to investigate the influence of PMP22 on α6 integrin expression, cells were created that ectopically overexpressed PMP22 or expressed a siRNA to inhibit its expression. These cells were analyzed for changes in integrins and binding to extracellular matrices.

Results
In this study, we show that PMP22 expression is higher in proliferative phase than secretory phase. Functionally, we have begun to characterize the functional significance of this expression. Previous studies have suggested a link between PMP22 and α6 integrin, and therefore we asked whether PMP22 could associate or potentially modulate the expression of α6 integrin. Expression of both PMP22 and α6 integrin were detectable in endometrial epithelial and stromal cells, and we show that both proteins can associate and colocalize with each other. To understand if PMP22 directly altered the expression of a6 integrin, we examined cell lines with modulated levels of the protein. Overexpression of PMP22 was sufficient to increase α6 integrin surface expression with a concominant increase in binding to the extracellular matrix laminin, while a reduction in PMP22 suppressed α6 integrin surface expression.

Conclusion
These findings suggest a physiologic role for PMP22 on the expression of α6 integrin. We predict that this may be important for the maintainence of endometrial integrity and to the disease biology associated with altered levels of α6 integrin expression in the endometrium.