bluuebunny/crossref_metadata_2025_split huggingface dataset:
Centrosomal and mitotic abnormalities in cell lines derived from papillary thyroid cancer harboring specific gene alterations
Authors: Maric Irena , Viaggi Silvia , Caria Paola , Frau Daniela V , Degan Paolo , Vanni Roberta 
Published: December 2011

Abstract

Background
Differentiated thyroid carcinoma offers a good model to investigate the possible correlation between specific gene mutations and chromosome instability. Papillary thyroid neoplasms are characterized by different mutually exclusive genetic alterations, some of which are associated with aneuploidy and aggressive phenotype.

Results
We investigated the centrosome status and mitotic abnormalities in three thyroid carcinoma-derived cell lines, each maintaining the specific, biologically relevant gene alteration harbored by the parental tumors: RET/PTC1 rearrangement in TPC1; heterozygous and homozygous BRAF

V600E
mutation in K1 and in B-CPAP, respectively. B-CPAP cells showed a statistically significant (P < 0.01) higher frequency of abnormal mitotic figures compared to TPC1 and K1 cells.

Conclusions
Our data indicate that RET/PTC1 oncogenic activity is not related to mitotic chromosome impairment and missegregation whereas, based on the consistent difference in types/frequencies of centrosome and spindle abnormalities observed between K1 and B-CPAP cells, the hetero/homozygous allelic status of BRAF

V600E
mutation seems to be not irrelevant in respect to chromosomal instability development.
Comparison of RNA extraction methods from biofilm samples of Staphylococcus epidermidis
Authors: França Angela , Melo Luís DR , Cerca Nuno 
Published: December 2011

Abstract

Background
Microbial biofilms are communities of bacteria adhered to a surface and surrounded by an extracellular polymeric matrix. Biofilms have been associated with increased antibiotic resistance and tolerance to the immune system. Staphylococcus epidermidis is the major bacterial species found in biofilm-related infections on indwelling medical devices. Obtaining high quality mRNA from biofilms is crucial to validate the transcriptional measurements associated with the switching to the biofilm mode of growth. Therefore, we selected three commercially available RNA extraction kits with distinct characteristics, including those using silica membrane or organic extraction methods, and enzymatic or mechanical cell lysis, and evaluated the RNA quality obtained from two distinct S. epidermidis bacterial biofilms.

Results
RNA extracted using the different kits was evaluated for quantity, purity, integrity, and functionally. All kits were able to extract intact and functional total RNA from the biofilms generated from each S. epidermidis strain. The results demonstrated that the kit based on mechanical lysis and organic extraction (FastRNA® Pro Blue) was the only one that was able to isolate pure and large quantities of RNA. Normalized expression of the icaA virulence gene showed that RNA extracted with PureLink™ had a significant lower concentration of icaA mRNA transcripts than the other kits tested.

Conclusions
When working with complex samples, such as biofilms, that contain a high content extracellular polysaccharide and proteins, special care should be taken when selecting the appropriate RNA extraction system, in order to obtain accurate, reproducible, and biologically significant results. Among the RNA extraction kits tested, FastRNA® Pro Blue was the best option for both S. epidermidis biofilms used.
What works to meet the sexual and reproductive health needs of women living with HIV/AIDS
Authors: Gay Jill , Hardee Karen , Croce‐Galis Melanie , Hall Carolina 
Published: December 2011

It is critical to include a sexual and reproductive health lens in HIV programming as most HIV transmission occurs through sexual intercourse. As global attention is focusing on the sexual and reproductive health needs of women living with HIV, identifying which interventions work becomes vitally important. What evidence exists to support sexual and reproductive health programming related to HIV programmes?This article reviews the evidence of what works to meet the sexual and reproductive health needs of women living with HIV in developing countries and includes 35 studies and evaluations of eight general interventions using various methods of implementation science from 15 countries. Data are primarily from 2000‐2009. Searches to identify effective evaluations used SCOPUS, Popline, Medline, websites and consultations with experts. Evidence was ranked using the Gray Scale.A range of successful and promising interventions to improve the sexual and reproductive health and rights of women living with HIV include: providing contraceptives and family planning counselling as part of HIV services; ensuring early postpartum visits providing family planning and HIV information and services; providing youth‐friendly services; supporting information and skills building; supporting disclosure; providing cervical cancer screening; and promoting condom use for dual protection against pregnancy and HIV. Provision of antiretrovirals can also increase protective behaviours, including condom use.While many gaps in programming and research remain, much can be done now to operationalize evidence‐based effective interventions to meet the sexual and reproductive health needs of women living with HIV.
Disturbances of the hypothalamic-pituitary-adrenal axis and plasma electrolytes during experimental sepsis
Authors: Flierl Michael A , Rittirsch Daniel , Weckbach Sebastian , Huber-Lang Markus , Ipaktchi Kyros , Ward Peter A , Stahel Philip F 
Published: December 2011

Abstract

Background
Sepsis continues to be a poorly understood syndrome with a high mortality rate. While we are beginning to decipher the intricate interplay of the inflammatory response during sepsis, the precise regulation of the hypothalamic-pituitary-adrenal (HPA) axis and its impact on electrolyte homeostasis during sepsis remains incompletely understood.

Methods
Sepsis was induced in adult male Sprague-Dawley rats by cecal ligation and puncture (CLP). Plasma samples were obtained as a function of time (6-48 hrs) after CLP and compared with healthy animals (neg ctrl). Samples were analyzed for adrenocorticotropin (ACTH), corticosterone, and aldosterone levels, as well as concentrations of sodium (Na+), potassium (K+), chloride (Cl-), and magnesium (Mg2+).

Results
ACTH levels were found to be significantly reduced 6-24 hrs after CLP in comparison to baseline levels and displayed gradual recovery during the later course (24-48 hrs) of sepsis. Plasma corticosterone concentrations exhibited a bell-shaped response, peaking between 6 and 12 hrs followed by rapid decline and concentrations below negative control levels 48 hrs after injury. Aldosterone levels in septic animals were continuously elevated between 6 and 48 hrs. Whereas plasma Na+ levels were found to be persistently elevated following CLP, levels of K+, Cl- and Mg2+ were significantly reduced as a function of time and gradually recovered during the later course of sepsis.

Conclusions
CLP-induced sepsis resulted in dynamic changes of ACTH, corticosterone, and aldosterone levels. In addition, electrolyte levels showed significant disturbances after CLP. These electrolyte perturbations might be evoked by a downstream effect or a dysfunctional HPA-axis response during sepsis and contribute to severe complications during sepsis.
MicroRNAs and their isomiRs function cooperatively to target common biological pathways
Authors: Cloonan Nicole , Wani Shivangi , Xu Qinying , Gu Jian , Lea Kristi , Heater Sheila , Barbacioru Catalin , Steptoe Anita L , Martin Hilary C , Nourbakhsh Ehsan , Krishnan Keerthana , Gardiner Brooke , Wang Xiaohui , Nones Katia , Steen Jason A , Matigian Nicholas A , Wood David L , Kassahn Karin S , Waddell Nic , Shepherd Jill , Lee Clarence , Ichikawa Jeff , McKernan Kevin , Bramlett Kelli , Kuersten Scott , Grimmond Sean M 
Published: December 2011

Abstract
Background
Variants of microRNAs (miRNAs), called isomiRs, are commonly reported in deep-sequencing studies; however, the functional significance of these variants remains controversial. Observational studies show that isomiR patterns are non-random, hinting that these molecules could be regulated and therefore functional, although no conclusive biological role has been demonstrated for these molecules.

Results
To assess the biological relevance of isomiRs, we have performed ultra-deep miRNA-seq on ten adult human tissues, and created an analysis pipeline called miRNA-MATE to align, annotate, and analyze miRNAs and their isomiRs. We find that isomiRs share sequence and expression characteristics with canonical miRNAs, and are generally strongly correlated with canonical miRNA expression. A large proportion of isomiRs potentially derive from AGO2 cleavage independent of Dicer. We isolated polyribosome-associated mRNA, captured the mRNA-bound miRNAs, and found that isomiRs and canonical miRNAs are equally associated with translational machinery. Finally, we transfected cells with biotinylated RNA duplexes encoding isomiRs or their canonical counterparts and directly assayed their mRNA targets. These studies allow us to experimentally determine genome-wide mRNA targets, and these experiments showed substantial overlap in functional mRNA networks suppressed by both canonical miRNAs and their isomiRs.

Conclusions
Together, these results find isomiRs to be biologically relevant and functionally cooperative partners of canonical miRNAs that act coordinately to target pathways of functionally related genes. This work exposes the complexity of the miRNA-transcriptome, and helps explain a major miRNA paradox: how specific regulation of biological processes can occur when the specificity of miRNA targeting is mediated by only 6 to 11 nucleotides.
The RANKL Distal Control Region Is Required for the Increase in RANKL Expression, But Not the Bone Loss, Associated with Hyperparathyroidism or Lactation in Adult Mice
Authors: Onal Melda , Galli Carlo , Fu Qiang , Xiong Jinhu , Weinstein Robert S. , Manolagas Stavros C. , O'Brien Charles A. 
Published: December 2011

Abstract
Osteoclast-mediated bone resorption plays an essential role in calcium homeostasis and lactation. The cytokine receptor activator of nuclear factor κB ligand (RANKL) is one of a number of factors that controls the production, survival, and activity of osteoclasts. Calciotropic hormones, such as PTH, control RANKL transcription in part via an enhancer known as the distal control region (DCR), and mice lacking this enhancer have fewer osteoclasts under normal physiological conditions. Here, we have addressed the role of the DCR in situations in which activation of the PTH receptor is thought to stimulate bone resorption via elevation of RANKL expression. Dietary calcium deficiency stimulated RANKL expression in the bone of young (1 month old) wild-type, but not DCR knockout (KO), mice. Consistent with this, the cancellous bone loss and the increase in osteoclasts caused by dietary calcium deficiency were blunted in young KO mice. DCR deletion also prevented the increase in RANKL expression caused by dietary calcium deficiency in 6-month-old mice. However, the diet-induced bone loss was similar in wild-type and KO mice at this age. The increase in RANKL expression caused by lactation was also blunted in DCR KO mice, but lactation-induced bone loss was similar in both genotypes. These results demonstrate that, even though the DCR is required for the increase in RANKL expression associated with hyperparathyroidism or lactation, this increase is not required for the bone loss caused by these conditions in adult mice, suggesting that changes in other factors, such as osteoprotegerin or estrogen levels, play a dominant role.
Ambident Reactivity of Chloro(dialkylamino)(diphenylphosphinoyl)methanes
Authors: Morgalyuk Vasilii Petrovich , Strelkova Tat’yana Vladimirovna , Nifant’ev Eduard Eugenievich 
Published: December 2011

Abstract
The chemical properties of chloro(dialkylamino)(diphenylphosphinoyl)methanes have been studied using the simplest compound of this series, chloro(dimethylamino)(diphenylphosphinoyl)methane, as an example. Chloro(dimethylamino)(diphenylphosphinoyl)methane shows ambident reactivity when reacting with electrophiles and nucleophiles depending on coreactant nature, it behaves as either electrophilic substrate or phosphorus nucleophile. This fact can be explained by its dissociation in solutions with both C–Cl bond cleavage to give (dimethylamino)(diphenylphosphinoyl)methyl cation and Cl− anion and C–P bond cleavage to form chloro(dimethylamino)methyl cation and diphenylphosphinite anion. The capability of chloro(dimethylamino)(diphenylphosphinoyl)methane to produce spontaneously Ph2PO–anion allows us to recommend application in organic and organophosphorus synthesis as a synthetic equivalent (synthon) of diphenylphosphinite anion.
Oral Adverse Events Associated with Tyrosine Kinase and Mammalian Target of Rapamycin Inhibitors in Renal Cell Carcinoma: A Structured Literature Review
Authors: Boers-Doets Christine B. , Epstein Joel B. , Raber-Durlacher Judith E. , Ouwerkerk Jan , Logan Richard M. , Brakenhoff Jan A. , Lacouture Mario E. , Gelderblom Hans 
Published: December 2011

Abstract

Learning Objectives
After completing this course, the reader will be able to: Describe the oral manifestations that can appear with TKI/mTORI.Describe the limitations of the current oral assessment tools in assessing these novel presentations and list items needed to assess the presentations properly.
This article is available for continuing medical education credit at CME.TheOncologist.com

Background.
Oral adverse events (OAEs) associated with multitargeted tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors (mTORIs) are underestimated but frequent and novel presentations of mucosal manifestations. Because optimal antitumor activity requires maintaining the optimal dose, it is essential to avoid unintended treatment delays or interruptions.

Methods.
We review the reported prevalence and appearance of OAEs with TKIs and mTORIs and the current oral assessment tools commonly used in clinical trials. We discuss the correlations between OAEs and hand–foot skin reaction (HFSR) and rash.

Results.
The reported prevalence of oral mucositis/stomatitis of any grade is 4% for pazopanib, 28% for sorafenib, 38% for sunitinib, 41% for temsirolimus, and 44% for everolimus. Oral lesions associated with these agents have been reported to more closely resemble aphthous stomatitis than OM caused by conventional agents. In addition, these agents may result in symptoms such as oral mucosal pain, dysgeusia, and dysphagia, in the absence of clinical lesions. Because of these factors, OAEs secondary to targeted agents may be underreported. In addition, a correlation between OAEs and HFSR was identified.

Conclusions.
OAEs caused by TKIs and mTORIs may represent dose-limiting toxicities, especially considering the fact that even low grades of OAEs may be troubling to the patient. We discuss how these novel AEs can be assessed because current mucositis assessment tools have limitations. Prospective studies investigating the pathogenesis, risk factors, and management of OAEs are needed in order to minimize the impact on patient's health-related quality of life.
Hepatic differentiation from human mesenchymal stem cells on a novel nanofiber scaffold
Authors: Ghaedi Mahboobe , Soleimani Masoud , Shabani Iman , Duan Yuyou , Lotfi Abbas 
Published: December 2011

AbstractThe emerging fields of tissue engineering and biomaterials have begun to provide potential treatment options for liver failure. The goal of the present study is to investigate the ability of a poly L-lactic acid (PLLA) nanofiber scaffold to support and enhance hepatic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs). A scaffold composed of poly L-lactic acid and collagen was fabricated by the electrospinning technique. After characterizing isolated hMSCs, they were seeded onto PLLA nanofiber scaffolds and induced to differentiate into a hepatocyte lineage. The mRNA levels and protein expression of several important hepatic genes were determined using RT-PCR, immunocytochemistry and ELISA. Flow cytometry revealed that the isolated bone marrow-derived stem cells were positive for hMSC-specific markers CD73, CD44, CD105 and CD166 and negative for hematopoietic markers CD34 and CD45. The differentiation of these stem cells into adipocytes and osteoblasts demonstrated their multipotency. Scanning electron microscopy showed adherence of cells in the nanofiber scaffold during differentiation towards hepatocytes. Our results showed that expression levels of liver-specific markers such as albumin, α-fetoprotein, and cytokeratins 8 and 18 were higher in differentiated cells on the nanofibers than when cultured on plates. Importantly, liver functioning serum proteins, albumin and α-1 antitrypsin were secreted into the culture medium at higher levels by the differentiated cells on the nanofibers than on the plates, demonstrating that our nanofibrous scaffolds promoted and enhanced hepatic differentiation under our culture conditions. Our results show that the engineered PLLA nanofibrous scaffold is a conducive matrix for the differentiation of MSCs into functional hepatocyte-like cells. This represents the first step for the use of this nanofibrous scaffold for culture and differentiation of stem cells that may be employed for tissue engineering and cell-based therapy applications.
Connectedness of the sets of weak efficient solutions for generalized vector equilibrium problems
Authors: Liu Qing-You , Long Xian-Jun , Huang Nan-jing 
Published: December 2011

Abstract
In this paper, a generalized vector equilibrium problem is introduced and studied. A scalar characterization of weak efficient solutions for the generalized vector equilibrium problem is obtained. By using the scalarization result, the existence of the weak efficient solutions and the connectedness of the set of weak efficient solutions for the generalized vector equilibrium problem are proved in locally convex spaces.
Transcranial magnetic resonance imaging–guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain
Authors: Jeanmonod Daniel , Werner Beat , Morel Anne , Michels Lars , Zadicario Eyal , Schiff Gilat , Martin Ernst 
Published: December 2011

Object
Recent technological developments open the field of therapeutic application of focused ultrasound to the brain through the intact cranium. The goal of this study was to apply the new transcranial magnetic resonance imaging–guided focused ultrasound (tcMRgFUS) technology to perform noninvasive central lateral thalamotomies (CLTs) as a treatment for chronic neuropathic pain.

Methods
In 12 patients suffering from chronic therapy-resistant neuropathic pain, tcMRgFUS CLT was proposed. In 11 patients, precisely localized thermal ablations of 3–4 mm in diameter were produced in the posterior part of the central lateral thalamic nucleus at peak temperatures between 51°C and 64°C with the aid of real-time patient monitoring and MR imaging and MR thermometry guidance. The treated neuropathic pain syndromes had peripheral (5 patients) or central (6 patients) origins and covered all body parts (face, arm, leg, trunk, and hemibody).

Results
Patients experienced mean pain relief of 49% at the 3-month follow-up (9 patients) and 57% at the 1-year follow-up (8 patients). Mean improvement according to the visual analog scale amounted to 42% at 3 months and 41% at 1 year. Six patients experienced immediate and persisting somatosensory improvements. Somatosensory and vestibular clinical manifestations were always observed during sonication time because of ultrasound-based neuronal activation and/or initial therapeutic effects. Quantitative electroencephalography (EEG) showed a significant reduction in EEG spectral overactivities. Thermal ablation sites showed sharply delineated ellipsoidal thermolesions surrounded by short-lived vasogenic edema. Lesion reconstructions (18 lesions in 9 patients) demonstrated targeting precision within a millimeter for all 3 coordinates. There was 1 complication, a bleed in the target with ischemia in the motor thalamus, which led to the introduction of 2 safety measures, that is, the detection of a potential cavitation by a cavitation detector and the maintenance of sonication temperatures below 60°C.

Conclusions
The authors assert that tcMRgFUS represents a noninvasive, precise, and radiation-free neurosurgical technique for the treatment of neuropathic pain. The procedure avoids mechanical brain tissue shift and eliminates the risk of infection. The possibility of applying sonication thermal spots free from trajectory restrictions should allow one to optimize target coverage. The real-time continuous MR imaging and MR thermometry monitoring of targeting accuracy and thermal effects are major factors in optimizing precision, safety, and efficacy in an outpatient context.
Gross and microscopic study of the filum terminale: does the filum contain functional neural elements?
Authors: Gaddam Samson Sujit Kumar , Santhi Vissa , Babu Srinivasa , Chacko Geeta , Baddukonda Ramakrishna Appala , Rajshekhar Vedantam 
Published: December 2011

Object
The filum terminale (FT) is considered a fibrous structure that extends from conus medullaris of the spinal cord to coccyx. Based on previous studies and from their own experience with intraoperative electrophysiological monitoring of the sacral nervous system, the authors postulate that the FT contains functional neural elements in some individuals.

Methods
The FT was dissected from 13 fresh stillborn cadavers (7 male, 6 female; mean gestational age 36 weeks and 1 day). The gross anatomical features were recorded, and connections between the FT and the nerve roots of the cauda equina were noted. These connections, when present, were sectioned for histological studies. The fila (both interna and externa) were also sectioned for histological and immunohistochemical studies. In addition, FT specimens were obtained from 5 patients undergoing sectioning of the FT in an untethering surgical procedure.

Results
There were 5 gross connections between the FT and nerve roots demonstrating nerve fibers that were positive for S100. The FT showed islands of cells that were positive for GFAP in 10 cases, synaptophysin in 3 cases, S100 in 11 cases, and nestin in 2 cases. The nerve fibers in the FT were myelinated in 2 cases. The conus ended at the L-1 or L-2 vertebral level in all 13 specimens. The dural sac terminated at the S-2 vertebral level in most of the specimens. The 5 FT specimens that were obtained from patients revealed nerve bundles that were positive for S100 in 4 cases and cells that were positive for GFAP in 3 cases.

Conclusions
There are gross anatomical connections between the FT and nerve roots that contain nerve fibers. Apart from fibrous stroma, the FT may contain nerve bundles and cells that stain positive for GFAP, synaptophysin, S100, and nestin. These microscopic findings and previous intraoperative electrophysiological studies suggest a probable functional role for the FT in some individuals. At birth, the conus ends at a higher vertebral level (lower L-1 or upper L-2) than L-3.