bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascularity of primary and metastatic renal cell carcinoma specimens
Authors: Aziz Saadia A , Sznol Joshua , Adeniran Adebowale , Colberg John W , Camp Robert L , Kluger Harriet M 
Published: January 2013

Abstract

Purpose
Anti-angiogenic therapies are among the most commonly used drugs in renal cell carcinoma. Tumor vascularity, defined by microvessel area, may be associated with response to these drugs. Clinical studies suggest that metastatic sites are more responsive than primary tumors. Our purpose was to characterize microvessel area (MVA) in matched primary and metastatic samples and in samples of different histologies.

Methods
We employed a method of automated, quantitative analysis of in situ tumor components to identify the area of CD-34 staining endothelial cells within renal cell carcinoma tumors. MVA was assessed in corresponding primary and metastatic samples from 34 patients, as well as in 334 primary nephrectomy specimens with variable histologies.

Results
MVA measurements from different parts of the same tumor correlated well (R = 0.75), indicating that MVA was fairly uniform within a tumor. While MVA was slightly higher in primary tumors than corresponding metastatic sites, the difference was not statistically significant (P = 0.1). MVA in paired primary and metastatic samples correlated moderately well (R = 0.36). MVA was higher in clear cell than papillary histology and oncocytomas (P < 0.0001 and P = 0.018, respectively).

Conclusions
Lack of significant differences MVA in matched primary and metastatic samples suggests that both types of tumors should respond to anti-angiogenic drugs. This should be confirmed on additional cohorts. Given the small cohort, future predictive biomarker studies entailing MVA measurements should include specimens from both sites. Clear cell carcinomas are more vascular than other histologic subtypes, which may explain the higher response rates to anti-angiogenic therapies in clear cell tumors.
A do-it-yourself protocol for simple transcription activator-like effector assembly
Authors: Uhde-Stone Claudia , Gor Nilang , Chin Tiffany , Huang Joseph , Lu Biao 
Published: January 2013

Abstract

Background
TALEs (transcription activator-like effectors) are powerful molecules that have broad applications in genetic and epigenetic manipulations. The simple design of TALEs, coupled with high binding predictability and specificity, is bringing genome engineering power to the standard molecular laboratory. Currently, however, custom TALE assembly is either costly or limited to few research centers, due to complicated assembly protocols, long set-up time and specific training requirements.

Results
We streamlined a Golden Gate-based method for custom TALE assembly. First, by providing ready-made, quality-controlled monomers, we eliminated the procedures for error-prone and time-consuming set-up. Second, we optimized the protocol toward a fast, two-day assembly of custom TALEs, based on four thermocycling reactions. Third, we increased the versatility for diverse downstream applications by providing series of vector sets to generate both TALENs (TALE nucleases) and TALE-TFs (TALE-transcription factors) under the control of different promoters. Finally, we validated our system by assembling a number of TALENs and TALE-TFs with DNA sequencing confirmation. We further demonstrated that an assembled TALE-TF was able to transactivate a luciferase reporter gene and a TALEN pair was able to cut its target.

Conclusions
We established and validated a do-it-yourself system that enables individual researchers to assemble TALENs and TALE-TFs within 2 days. The simplified TALE assembly combined with multiple choices of vectors will facilitate the broad use of TALE technology.
Raman study on zinc-blende single InAs nanowire grown on Si (111) substrate
Authors: Li Tianfeng , Gao Lizhen , Lei Wen , Guo Lijun , Yang Tao , Chen Yonghai , Wang Zhanguo 
Published: January 2013

Abstract
We report polarized Raman scattering studies on single InAs nanowires (NWs). The NWs were grown by metalorganic chemical vapor deposition on Si (111) substrates without external catalyst and showed a zinc-blende crystal structure. The single NWs were studied for different polarization excitation of the incident laser beam relative to the NW axis. The transverse optical (TO) mode exhibits maximum intensity when both the incident and analyzed light polarizations are parallel to the NW axis. The TO mode of InAs NWs is found to act like a nearly perfect dipole antenna, which can be attributed to the one-dimensional NW geometry and Raman selection rules.
Mechanisms of action of naturally occurring antibodies against β-amyloid on microglia
Authors: Gold Maike , Mengel David , Röskam Stephan , Dodel Richard , Bach Jan-Philipp 
Published: January 2013

Abstract

Background
Naturally occurring autoantibodies against amyloid-β (nAbs-Aβ) have been shown to exert beneficial effects on transgenic Alzheimer’s disease (AD) animals in vivo and on primary neurons in vitro. Not much is known about their effect on microglial cells. Our aim was to investigate the effect of nAbs-Aβ on amyloid-β (Aβ)-treated microglial cells in vitro with respect to cell viability, stress pathways, cytokine production and phagocytotic abilities and whether these effects can be conveyed to neurons.

Methods
Primary microglial cells isolated from Swiss Webster mouse mesencephalons on embryonic day 13.5 were pretreated with nAbs-Aβ and then treated with Aβ oligomers. After 3 hours, phagocytosis as well as western blot analysis were evaluated to measure the amount of phagocytized Aβ. Cell viability was analyzed using an MTT assay 24 hours after treatment. Pro-inflammatory cytokines in the supernatants were analyzed with ELISAs and then we treated primary neuronal cells with these conditioned microglia supernatants. Twenty-four hours later we did a MTT assay of the treated neurons. We further investigated the effect of a single nAbs-Aβ administration on Tg2576 mice in vivo.

Results
Upon co-administration of Aβ and nAbs-Aβ no change in microglia viability was observed. However, there was an increase in phosphorylated p38 protein level, an increase in the pro-inflammatory cytokines TNF-α and IL-6 and an increase in Aβ uptake by microglial cells. Treatment of primary neurons with conditioned microglia medium led to a 10% improvement in cell viability when nAbs-Aβ were co-administered compared to Aβ-treated cells alone. We were unable to detect changes in cytokine production in brain lysates of Tg2576 mice.

Conclusions
We provide evidence on the mechanism of action of nAbs-Aβ on microglia in vitro. Interestingly, our in vivo data indicate that nAbs-Aβ administration should be considered as a therapeutic strategy in AD, since there is no inflammatory reaction.
Preferences for mode of delivery in nulliparous Argentinean women: a qualitative study
Authors: Liu Nancy H , Mazzoni Agustina , Zamberlin Nina , Colomar Mercedes , Chang Olivia H , Arnaud Lila , Althabe Fernando , Belizán José M 
Published: January 2013

Abstract

Background
Over the last three decades, cesarean section (CS) rates have been rising around the world despite no associated improvement in maternal and perinatal mortality and morbidity. The role of women’s preferences for mode of delivery in contributing to the high CS rate remains controversial; however these preferences are difficult to assess, as they are influenced by culture, knowledge of risk and benefits, and personal and social factors. In this qualitative study, our objective was to understand women’s preferences and motivational factors for mode of delivery. This information will inform the development and design of an assessment aimed at understanding the role of the women’s preferences for mode of delivery.

Methods
We conducted 4 focus group discussions (FGDs) and 12 in-depth interviews with pregnant women in Buenos Aires, Argentina in 4 large non-public and public hospitals. Our sample included 29 nulliparous pregnant women aged 18–35 years old, with single pregnancies over 32 weeks of gestational age, without pregnancies resulting from assisted fertility, without known pre-existing medical illness or diseases diagnosed during pregnancy, without an indication of elective cesarean section, and who are not health professionals. FGDs and interviews followed a pre-designed guide based on the health belief model and social cognitive theory of health decisions and behaviors.

Results
Most of the women preferred vaginal delivery (VD) due to cultural, personal, and social factors. VD was viewed as normal, healthy, and a natural rite of passage from womanhood to motherhood. Pain associated with vaginal delivery was viewed positively. In contrast, women viewed CS as a medical decision and often deferred decisions to medical staff in the presence of medical indication.

Conclusions
These findings converge with quantitative and qualitative studies showing that women prefer towards VD for various cultural, personal and social reasons. Actual CS rates appear to diverge from women’s preferences and reasons are discussed.
Right ventricular function impaired in children and adolescents with severe idiopathic scoliosis
Authors: Li Shujuan , Yang Junlin , Li Yunquan , Zhu Ling , Lin Yuese , Li Xuandi , Huang Zifang , Wang Huishen 
Published: January 2013

Abstract

Background
Although it is speculated that scoliosis may induce cardiac dysfunction, there is no report about evaluation of cardiac function, especially right cardiac function in patients with scoliosis. Therefore, we evaluated right ventricular function in idiopathic scoliotic patients with mild to severe curves and compared them with healthy children and adolescents matched in age, then explored relationship between scoliosis and right ventricular function.

Methods
Thirty-seven patients diagnosed with idiopathic scoliosis with a mean age of 16y/o (range, 8-25y/o) and an average spine curve of 77.5°Cobb (range, 30-157°) were studied by echocardiography. TAD was obtained using M-mode echocardiography. Similar examination was performed in a control group of 17 healthy individuals in matched-age. According to the different curve degree, all patients were divided into 3 groups (mild, moderate and severe). Comparison was done among the groups and the relationship between TAD and spine curve of Cobb was analyzed.

Results
Patients with severe scoliosis showed depressed TAD. There was good correlation between TAD and spine curve of Cobb.

Conclusions
Patients with severe scoliosis showed a significant lower right ventricular systolic function.
Malignant atrophic papulosis (Köhlmeier-Degos disease) - A review
Authors: Theodoridis Athanasios , Makrantonaki Evgenia , Zouboulis Christos C 
Published: January 2013

Abstract

Definition of the disease
Malignant atrophic papulosis (MAP), described independently by Köhlmeier and Degos et al., is a rare, chronic, thrombo-obliterative vasculopathy characterized by papular skin lesions with central porcelain-white atrophy and surrounding teleangiectatic rim.

Epidemiology
Less than 200 cases have been described in the literature. The first manifestation of MAP usually occurs between the 20th and 50th year of life.

Clinical description
The cutaneous clinical picture is almost pathognomonic. The histology is not consistent but in most cases it shows a wedge-shaped connective tissue necrosis in the deep corium due to a thrombotic occlusion of the small arteries. In the systemic variant, manifestations mostly occur at the intestine and central nervous system.

Etiology
The etiopathogenesis of the disease remains unknown, a genetic predisposition may occur. Vasculitis, coagulopathy or primary dysfunction of the endothelial cells have been implicated.

Diagnostic methods
Diagnosis is only based on the characteristic skin lesions.

Differrential diagnosis
It depends on the clinical presentation of MAP, but systemic lupus erythematosus and other connective tissue diseases need to be considered.

Management
No effective treatment exists for the systemic manifestations, while compounds that facilitate blood perfusion have achieved a partial regression of the skin lesions in single cases.

Prognosis
An apparently idiopathic, monosymptomatic, cutaneous, benign variant and a progressive, visceral one with approx. 50% lethality within 2–3 years have been reported. Systemic manifestations can develop years after the occurrence of skin lesions leading to bowel perforation and peritonitis, thrombosis of the cerebral arteries or massive intracerebral hemorrhage, meningitis, encephalitis, radiculopathy, myelitis.
Compounds that correct F508del-CFTR trafficking can also correct other protein trafficking diseases: an in vitro study using cell lines
Authors: Sampson Heidi M , Lam Hung , Chen Pei-Chun , Zhang Donglei , Mottillo Cristina , Mirza Myriam , Qasim Karim , Shrier Alvin , Shyng Show-Ling , Hanrahan John W , Thomas David Y 
Published: January 2013

Abstract

Background
Many genetic diseases are due to defects in protein trafficking where the mutant protein is recognized by the quality control systems, retained in the endoplasmic reticulum (ER), and degraded by the proteasome. In many cases, the mutant protein retains function if it can be trafficked to its proper cellular location. We have identified structurally diverse correctors that restore the trafficking and function of the most common mutation causing cystic fibrosis, F508del-CFTR. Most of these correctors do not act directly as ligands of CFTR, but indirectly on other pathways to promote folding and correction. We hypothesize that these proteostasis regulators may also correct other protein trafficking diseases.

Methods
To test our hypothesis, we used stable cell lines or transient transfection to express 2 well-studied trafficking disease mutations in each of 3 different proteins: the arginine-vasopressin receptor 2 (AVPR2, also known as V2R), the human ether-a-go-go-related gene (KCNH2, also known as hERG), and finally the sulfonylurea receptor 1 (ABCC8, also known as SUR1). We treated cells expressing these mutant proteins with 9 structurally diverse F508del-CFTR correctors that function through different cellular mechanisms and assessed whether correction occurred via immunoblotting and functional assays. Results were deemed significantly different from controls by a one-way ANOVA (p < 0.05).

Results
Here we show that F508del-CFTR correctors RDR1, KM60 and KM57 also correct some mutant alleles of other protein trafficking diseases. We also show that one corrector, the cardiac glycoside ouabain, was found to alter the glycosylation of all mutant alleles tested.

Conclusions
Correctors of F508del-CFTR trafficking might have broader applications to other protein trafficking diseases.
Effect of hypobaric storage on quality, antioxidant enzyme and antioxidant capability of the Chinese bayberry fruits
Authors: Chen Hangjun , Yang Hailong , Gao Haiyan , Long Jie , Tao Fei , Fang Xiangjun , Jiang Yueming 
Published: January 2013

Abstract

Background
The Chinese bayberry (Myrica rubra Sieb. and Zucc.) is a subtropical fruit native to China, with unique flavor, sweet and sour taste, and high nutrition and health values. The fruit is highly perishable and susceptible to mechanical injury, physiological deterioration and fungal decay once harvested. This study was to investigate the effect of hypobaric storage on the quality of Chinese bayberry fruit and then develop storage technology to prolong the supply of the fruit.

Results
The fruit stored under hypobaric conditions exhibited lower decay, higher titratable acidity and total phenolics compared with those stored under normal atmospheric conditions. Hypobaric storage significantly reduced malonaldehyde accumulation, respiratory rate and maintained high catalase and peroxidase activities of Chinese bayberry fruit. Ferric reducing antioxidant power was also higher in the fruit stored under hypobaric condition than those under normal atmospheric conditions.

Conclusion
Hypobaric storage improved the metabolism, antioxidant system and postharvest quality of Chinese bayberry fruit and provided an effective alternative method to prolong the storage life of this fruit.
Development and validation of ultra-performance liquid chromatographic method with tandem mass spectrometry for determination of lenalidomide in rabbit and human plasma
Authors: Iqbal Muzaffar , Wani Tanveer A , Khalil Nasr Y , Darwish Ibrahim A 
Published: January 2013

AbstractBackgroundLenalidomide (LND) is a potent novel thalidomide analog which demonstrated remarkable clinical activity in treatment of multiple myeloma disease via a multiple-pathways mechanism. Validated sensitive method with high throughput is required for the determination of lenalidomide for pharmacokinetics and toxicokinetic studies. Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is a preeminent analytical tool for rapid biomedical analysis.ResultsA simple, highly sensitive UPLC-MS/MS method was developed and validated for the determination of LND in rabbit and human plasma. After a simple protein precipitation using methanol, LND and carbamazepine (IS) were separated on Acquity UPLC BEH™ C18column (50 × 2.1 mm, i.d. 1.7 μm, Waters, USA) using a mobile phase consisted of acetonitrile:water:formic acid (65:35:0.1%, v/v/v) pumped at a flow rate of 0.2 mL/min. LND and IS were eluted at 0.71 and 1.92 min, respectively. The mass spectrometric determination was carried out using an electrospray interface operated in the positive mode with multiple reaction monitoring (MRM) mode. The precursor to product ion transitions ofm/z260.1 > 149.0 andm/z237.0 > 179.0 were used to quantify LND and IS, respectively. The method was linear in the concentration range of 0.23–1000 ng/mL with a limit of quantitation of 0.23 ng/mL. All the validation parameters were in the ranges acceptable by the guidelines of analytical method validation.ConclusionThe proposed UPLC-MS/MS method is simple, rapid and highly sensitive, and hence it could be reliable for pharmacokinetic and toxicokinetic study in both animals and humans.
Primary intestinal lymphangiectasia diagnosed by double-balloon enteroscopy and treated by medium-chain triglycerides: a case report
Authors: Lai Yu , Yu Tao , Qiao Xiao-yu , Zhao Li-na , Chen Qi-kui 
Published: January 2013

Abstract

Introduction
Primary intestinal lymphangiectasia is a disorder characterized by exudative enteropathy resulting from morphologic abnormalities of the intestinal lymphatics. Intestinal lymphangiectasia can be primary or secondary, so the diagnosis of primary intestinal lymphangiectasia must first exclude the possibility of secondary intestinal lymphangiectasia. A double-balloon enteroscopy and biopsy, as well as the pathology can be used to confirm the diagnosis of intestinal lymphangiectasia. A polymeric diet containing medium-chain triglycerides and total parenteral nutrition may be a useful therapy.

Case presentation
A 17-year-old girl of Mongoloid ethnicity was admitted to our hospital with a history of diarrhea and edema. She was diagnosed with protein-losing enteropathy caused by intestinal lymphangiectasia. This was confirmed by a double-balloon enteroscopy and multi-dot biopsy. After treatment with total parenteral nutrition in hospital, which was followed by a low-fat and medium-chain triglyceride diet at home, she was totally relieved of her symptoms.

Conclusion
Intestinal lymphangiectasia can be diagnosed with a double-balloon enteroscopy and multi-dot biopsy, as well as the pathology of small intestinal tissue showing edema of the submucosa and lymphangiectasia. Because intestinal lymphangiectasia can be primary or secondary, the diagnosis of primary intestinal lymphangiectasia must first exclude the possibility of secondary intestinal lymphangiectasia. A positive clinical response to the special diet therapy, namely a low-fat and medium-chain triglyceride diet, can further confirm the diagnosis of primary intestinal lymphangiectasia.
Enhanced ranking of PknB Inhibitors using data fusion methods
Authors: Seal Abhik , Yogeeswari Perumal , Sriram Dharmaranjan , Consortium OSDD , Wild David J 
Published: January 2013

Abstract

Background
Mycobacterium tuberculosis encodes 11 putative serine-threonine proteins Kinases (STPK) which regulates transcription, cell development and interaction with the host cells. From the 11 STPKs three kinases namely PknA, PknB and PknG have been related to the mycobacterial growth. From previous studies it has been observed that PknB is essential for mycobacterial growth and expressed during log phase of the growth and phosphorylates substrates involved in peptidoglycan biosynthesis. In recent years many high affinity inhibitors are reported for PknB. Previously implementation of data fusion has shown effective enrichment of active compounds in both structure and ligand based approaches .In this study we have used three types of data fusion ranking algorithms on the PknB dataset namely, sum rank, sum score and reciprocal rank. We have identified reciprocal rank algorithm is capable enough to select compounds earlier in a virtual screening process. We have also screened the Asinex database with reciprocal rank algorithm to identify possible inhibitors for PknB.

Results
In our work we have used both structure-based and ligand-based approaches for virtual screening, and have combined their results using a variety of data fusion methods. We found that data fusion increases the chance of actives being ranked highly. Specifically, we found that the ranking of Pharmacophore search, ROCS and Glide XP fused with a reciprocal ranking algorithm not only outperforms structure and ligand based approaches but also capable of ranking actives better than the other two data fusion methods using the BEDROC, robust initial enhancement (RIE) and AUC metrics. These fused results were used to identify 45 candidate compounds for further experimental validation.

Conclusion
We show that very different structure and ligand based methods for predicting drug-target interactions can be combined effectively using data fusion, outperforming any single method in ranking of actives. Such fused results show promise for a coherent selection of candidates for biological screening.