bluuebunny/crossref_metadata_2025_split huggingface dataset:
The AKT inhibitor AZD5363 is selectively active in PI3KCA mutant gastric cancer, and sensitizes a patient-derived gastric cancer xenograft model with PTEN loss to Taxotere
Authors: Li Jing , Davies Barry R , Han Sufang , Zhou Minhua , Bai Yu , Zhang Jingchuan , Xu Yan , Tang Lily , Wang Huiying , Liu Yuan Jie , Yin Xiaolu , Ji Qunsheng , Yu De-Hua 
Published: October 2013

Abstract

Introduction
Activation of the PI3K/AKT pathway is a common phenomenon in cancer due to multiple mechanisms, including mutation of PI3KCA, loss or mutation of PTEN, or over-expression of receptor tyrosine kinases. We recently developed a novel AKT kinase inhibitor, AZD5363, and demonstrated that HGC27, a cell line harboring both PI3KCA mutation and PTEN loss, displayed the greatest sensitivity to this AKT inhibitor in vitro and in vivo.

Case preparation
To further elucidate the correlation between AZD5363 response and genetic alterations in gastric cancer (GC) and identify GC patients with both PI3KCA mutations and PTEN loss, we investigated the effects of pharmacological inhibition of AKT on a panel of 20 GC cell lines and genetic aberrations in tumor samples from a cohort of Chinese GC patients. We demonstrated that GC cells with PI3KCA mutations were selectively sensitive to AZD5363. Disease linkage studies showed that PI3KCA activating mutations or PTEN loss were found in 2.7% (4/150) and 23% (14/61) of Chinese GC patients respectively. To further dissect the role of PI3KCA mutation and PTEN loss in response to AKT inhibition, we tested the antitumor activity of AZD5363 in two patient-derived GC xenograft (PDGCX) models harboring either PI3KCA mutation or PTEN loss. Our data indicated that AZD5363 monotherapy treatment led to a moderate response in the PI3KCA mutant PDGCX model. Whilst monotherapy AZD5363 or Taxotere were ineffective in the PTEN negative PDGCX model, significant anti-tumor activity was observed when AZD5363 was combined with Taxotere.

Conclusion
Our results indicated that PI3KCA mutation is an important determinant of response to AKT inhibition in GC and combination with AZD5363 can overcome innate resistance to Taxotere in a PTEN loss PDGCX model. It is suggested that AKT inhibitor is an attractive option for treatment of a new segment of GC patients with aberrant PI3K/AKT signaling.
A case report of adult lead toxicity following use of Ayurvedic herbal medication
Authors: Breeher Laura , Gerr Fred , Fuortes Laurence 
Published: October 2013

Abstract

Introduction
Ayurvedic medications consist of herbs that may be intentionally combined with metals, such as lead, mercury, iron, and zinc. Ayurvedic practitioners and their patients believe that the toxic properties of the metals are reduced or eliminated during preparation and processing.

Case report
A 69 year old Caucasian male retired professional with a prior history of stroke presented for evaluation of new onset depression, fatigue, generalized weakness, constipation, anorexia, and weight loss. History revealed that his symptoms were temporally related to initiation of an Ayurvedic herbal medication. The patient had been previously admitted to another hospital for these symptoms and was found to have a severe anemia for which no etiology was found. Laboratory tests revealed an elevated blood lead level and a diagnosis of symptomatic lead toxicity was made. The patient was treated with intramuscular, intravenous, and oral chelation therapy to promote lead excretion. Because of complaints of continued poor mental function, neuropsychological tests were administered before and after one of the chelation treatments and showed improvement in measures of attention and other cognitive domains. In addition, the patient was able to discontinue use of antidepressant medication after chelation.

Discussion
A high index of suspicion of metal toxicity is necessary among persons with characteristic symptoms and signs in the absence of occupational exposure. Despite limited evidence for chelation in adults and in those with modest blood lead levels, this patient appeared to benefit from repeated chelation therapy. Both allopathic and alternative medicine practitioners and public health specialists need to be aware of the potential for contamination of and side effects from alternative pharmacologic and herbal therapies.
Using neoadjuvant chemotherapy and replanning intensity-modulated radiotherapy for nasopharyngeal carcinoma with intracranial invasion to protect critical normal tissue
Authors: Niu Xiaoshuang , Chang Xi , Gao Yunsheng , Hu Chaosu , Kong Lin 
Published: October 2013

Abstract

Purpose
To investigate the feasibility of neoadjuvant chemotherapy and replanning intensity-modulated radiotherapy (IMRT) for intracranial invasion nasopharyngeal carcinoma (NPC).

Methods and materials
From June 2007 to January 2012, 32 patients with intracranial invasion NPC treated with TPF (docetaxel 75 mg/m2, cisplatin 75 mg/m2, 5-FU 2500 mg/m2 every 3 weeks for 3 cycles) neoadjuvant chemotherapy, and replanning IMRT with concurrent chemotherapy were retrospectively studied. The first IMRT plan for each patient was generated based on the original planning CT scan acquired before the start of treatment. Because of tumor shrinkage during radiotherapy, modified gross tumor volume of primary tumor (GTV-P) and high risk clinical target volume (CTV-H), and a new plan was generated and used to complete the course of IMRT. The DVHs of IMRT plan with or without replanning were compared.

Results
There weren’t statistically significant differences in the V95, D-mean, D-95, and D-99 to the modified PTVGTV-P and PTVCTV-H with and without replanning IMRT. Replanning reduced the doses to the brain stem, optic nerve, optic chiasm and temporal lobe. Objective responses were 100.0% 3 months after completion of radiotherapy. Acute toxicities were well tolerated, except for the relatively high incidence of neutropenia. The 2-year local control rates and distant-metastasis free survival were 88.2% (95% CI, 72.9% to 100.0%) and 89.6% (95% CI, 75.9% to 100.0%).

Conclusion
Neoadjuvant chemotherapy and replanning IMRT according to tumor shrinkage during the treatment is essential to ensure safe doses to normal tissues, and produces encouraging outcome for intracranial invasion NPC.
Effects of abscisic acid and brassinolide on photosynthetic characteristics of Leymus chinensis from Songnen Plain grassland in Northeast China
Authors: Hu Yong-Jun , Shi Lian-Xuan , Sun Wei , Guo Ji-Xun 
Published: October 2013

Abstract

Background
It has been well demonstrated that plant growth regulators have important functions in multiple physiological processes. ABA and BR play crucial roles in response of crops to stresses. Photosynthetic capacity of Leymus. chinensis treated by various concentrations of ABA and BR in combination was determined. Further more, the mechanisms of ABA and BR treatments and potential for recovery of saline-alkali grasslands were discussed.

Results
Abscisic acid (ABA) and brassinolide (BR) affected leaf gas exchange, growth and biomass of L. chinensis. The application of ABA and BR mixtures, especially that of 0.01 mM ABA and 2 × 10-4 mM BR, increased the net photosynthetic rate, stomatal conductance, water use efficiency, the maximum net photosynthetic rate, light-saturated rate, leaf respiration rate, the maximum RUBP carboxylation rate, the maximum electron transport rate, the maximum triose-phosphate utilization, carboxylation efficiency and the quantum efficiency of PSII and subsequently enhanced density, height and biomass in L. chinensis. We also observed reduction in the light compensation and saturation points following the application of ABA and BR treatments.

Conclusions
We concluded that proper use of plant growth regulators can enhance the plant growth and productivity on the Songnen grassland, which is particularly important for the improvement of saline – alkaline grassland and the yield of grazing lands.
Localization of organic anion transporting polypeptide (Oatp) 1a4 and Oatp1c1 at the rat blood-retinal barrier
Authors: Akanuma Shin-ichi , Hirose Shiro , Tachikawa Masanori , Hosoya Ken-ichi 
Published: October 2013

Abstract

Background
Organic anion transporting polypeptide (Oatp) transporters at the blood–brain barrier (BBB) and the blood-retinal barrier (BRB), which consists of retinal capillary endothelial cells and retinal pigment epithelial cells, are major determinants of the control of anionic drugs into the brain and retina. Although Oatp1a4 (Slco1a4) and Oatp1c1 (Slco1c1) are known to be expressed in the abluminal and luminal membrane of the rat BBB and Oatp1a4 is known to be expressed at the BRB, the expression and localization of Oatp1c1 at the BRB and subcellular localization of Oatp1a4 at the BRB have received little attention. Therefore, the purpose of present study was to determine the cellular and subcellular localization of Oatp1a4 and 1c1 at the BRB.

Methods
We used guinea pig polyclonal antibodies to Oatp1a4 and 1c1 for immunoblot and immunohistochemical analysis to determine their cellular and subcellular distributions in the rat retina. We compared these distributions with those of the glucose transporter 1 (GLUT1/Slc2a1). Whole brain, brain capillary fractions and kidney were used as control.

Results
Oatp1a4 and 1c1 immunoreactivities were detected in the rat retinal capillaries and co-localized with GLUT1, suggesting that both proteins are located on the abluminal and luminal membrane of the retinal capillary endothelial cells. Oatp1a4 and 1c1 immunoreactivities were preferentially detected on the apical and basolateral membrane of rat retinal pigment epithelial cells, respectively, suggesting that Oatp1a4 and 1c1 are localized on the apical membrane and the basolateral membrane of the retinal pigment epithelial cells, respectively.

Conclusion
Oatp1a4 and 1c1 are present at the BRB and contribute to the transcellular transport of amphipathic organic anions across the BRB.
Predictive factors of successful microdissection testicular sperm extraction
Authors: Bernie Aaron M , Ramasamy Ranjith , Schlegel Peter N 
Published: October 2013

Abstract
Azoospermia in men requires microsurgical reconstruction or a procedure for sperm retrieval with assisted reproduction to allow fertility. While the chance of successful retrieval of sperm in men with obstructive azoospermia approaches >90%, the chances of sperm retrieval in men with non-obstructive azoospermia (NOA) are not as high. Conventional procedures such as fine needle aspiration of the testis, testicular biopsy and testicular sperm extraction are successful in 20-45% of men with NOA. With microdissection testicular sperm extraction (micro-TESE), the chance of successful retrieval can be up to 60%. Despite this increased success, the ability to counsel patients preoperatively on their probability of successful sperm retrieval has remained challenging. A combination of variables such as age, serum FSH and inhibin B levels, testicular size, genetic analysis, history of Klinefelter syndrome, history of cryptorchidism or varicocele and histopathology on diagnostic biopsy have provided some insight into the chance of successful sperm retrieval in men with NOA. The goal of this review was to evaluate the preoperative factors that are currently available to predict the outcome for success with micro-TESE.
Comparative evaluation of the effects of treatment with tocilizumab and TNF-α inhibitors on serum hepcidin, anemia response and disease activity in rheumatoid arthritis patients
Authors: Song Soken-Nakazawa J , Iwahashi Mitsuhiro , Tomosugi Naohisa , Uno Kazuko , Yamana Jiro , Yamana Seizou , Isobe Tomoyasu , Ito Hiroki , Kawabata Hiroshi , Yoshizaki Kazuyuki 
Published: October 2013

Abstract
Introduction
Anemia of inflammation (AI) is a common complication of rheumatoid arthritis (RA) and has a negative impact on RA symptoms and quality of life. Upregulation of hepcidin by inflammatory cytokines has been implicated in AI. In this study, we evaluated and compared the effects of IL-6 and TNF-α blocking therapies on anemia, disease activity, and iron-related parameters including serum hepcidin in RA patients.

Methods
Patients (n = 93) were treated with an anti-IL-6 receptor antibody (tocilizumab) or TNF-α inhibitors for 16 weeks. Major disease activity indicators and iron-related parameters including serum hepcidin-25 were monitored before and 2, 4, 8, and 16 weeks after the initiation of treatment. Effects of tocilizumab and infliximab (anti-TNF-α antibody) on cytokine-induced hepcidin expression in hepatoma cells were analyzed by quantitative real-time PCR.

Results
Anemia at base line was present in 66% of patients. Baseline serum hepcidin-25 levels were correlated positively with serum ferritin, C-reactive protein (CRP), vascular endothelial growth factor (VEGF) levels and Disease Activity Score 28 (DAS28). Significant improvements in anemia and disease activity, and reductions in serum hepcidin-25 levels were observed within 2 weeks in both groups, and these effects were more pronounced in the tocilizumab group than in the TNF-α inhibitors group. Serum hepcidin-25 reduction by the TNF-α inhibitor therapy was accompanied by a decrease in serum IL-6, suggesting that the effect of TNF-α on the induction of hepcidin-25 was indirect. In in vitro experiments, stimulation with the cytokine combination of IL-6+TNF-α induced weaker hepcidin expression than did with IL-6 alone, and this induction was completely suppressed by tocilizumab but not by infliximab.

Conclusions
Hepcidin-mediated iron metabolism may contribute to the pathogenesis of RA-related anemia. In our cohort, tocilizumab was more effective than TNF-α inhibitors for improving anemia and normalizing iron metabolism in RA patients by inhibiting hepcidin production.
Arterial hypertension assessed “out-of-office” in a contemporary cohort of rheumatoid arthritis patients free of cardiovascular disease is characterized by high prevalence, low awareness, poor control and increased vascular damage-associated “white coat” phenomenon
Authors: Protogerou Athanase D , Panagiotakos Demosthenis B , Zampeli Evangelia , Argyris Antonis A , Arida Katerina , Konstantonis Giorgos D , Pitsavos Christos , Kitas George D , Sfikakis Petros P 
Published: October 2013

Abstract
Introduction
Rheumatoid arthritis (RA) is associated with a high cardiovascular disease (CVD) risk, whereas arterial hypertension is a major modifiable CVD risk factor with still unclear prevalence in RA disease. We conducted a comprehensive study on hypertension characteristics evaluating for the first time out-of-office blood pressure (BP) in a typical contemporary RA cohort.

Methods
Assessment of office and out-of-office BP (when office systolic/diastolic BP was >129/79) and vascular studies including evaluation of aortic stiffness, carotid hypertrophy/plaques and ankle-brachial index, were performed in 214 consecutive, consenting RA patients free of CVD (aged 58.4 ± 12.3 years, 82% women). As comparators regarding office hypertension measurements, data from 214 subjects (1:1 matched for age and gender with the RA patients) derived from a cohort designed to assess the prevalence of hypertension in the general population were used.

Results
The prevalence of declared known hypertension in the RA population was 44%. Of the remaining RA patients, 2 in every 5 individuals had abnormal office BP (systolic/diastolic >139/89 mmHg), contributing to almost double the prevalence of declared/office hypertension compared to the general matched population (67% vs. 34%). Out-of-office (home or ambulatory 24 hour) BP measurements revealed that: (i) a 54% prevalence of actual hypertension in RA, in other words almost 10% of the patients were unaware of having hypertension and (ii) 29% of the RA patients with known hypertension were not well controlled. Actual hypertension was positively associated with age and body mass index, and inversely with the use of biologic drugs. Overall, almost 1 out of 5 presented the 'white coat’ phenomenon. An intermediately compromised vascular phenotype was evident in this “white coat” subgroup (lying between patients with sustained normotension and sustained hypertension) in terms of aortic stiffness, carotid hypertrophy and ankle-brachial index, even after adjustment for confounders.

Conclusion
Beyond any doubt on the basis of out-of-office evaluation, arterial hypertension in RA has a high prevalence, low awareness and poor control, as well as substantial and vascular damage-associated “white coat” phenomenon. Thus, correct diagnosis and effective treatment of hypertension is of key importance in RA for CVD risk reduction.
Early treatment with IgM-enriched intravenous immunoglobulin does not mitigate critical illness polyneuropathy and/or myopathy in patients with multiple organ failure and SIRS/sepsis: a prospective, randomized, placebo-controlled, double-blinded trial
Authors: Brunner Richard , Rinner Walter , Haberler Christine , Kitzberger Reinhard , Sycha Thomas , Herkner Harald , Warszawska Joanna , Madl Christian , Holzinger Ulrike 
Published: October 2013

Abstract
Introduction
Critical illness polyneuropathy and/or myopathy (CIPNM) is a severe complication of critical illness. Retrospective data suggest that early application of IgM-enriched intravenous immunoglobulin (IVIG) may prevent or mitigate CIPNM. Therefore, the primary objective was to assess the effect of early IgM-enriched IVIG versus placebo to mitigate CIPNM in a prospective setting.

Methods
In this prospective, randomized, double-blinded and placebo-controlled trial, 38 critically ill patients with multiple organ failure (MOF), systemic inflammatory response syndrome (SIRS)/sepsis, and early clinical signs of CIPNM were included. Patients were randomly assigned to be treated either with IgM-enriched IVIG or placebo over a period of three days. CIPNM was measured by the CIPNM severity sum score based on electrophysiological stimulation of the median, ulnar, and tibial nerves on days 0, 4, 7, 14 and on the histological evaluation of muscle biopsies on days 0 and 14 and ranged from 0 (no CIPNM) to 8 (very severe CIPNM).

Results
A total of 38 critically ill patients were included and randomized to receive either IgM-enriched IVIG (n = 19) or placebo (n = 19). Baseline characteristics were similar between the two groups. CIPNM could not be improved by IVIG treatment, represented by similar CIPNM severity sum scores on day 14 (IVIG vs. placebo: 4.8 ± 2.0 vs. 4.5 ± 1.8; P = 0.70). CIPNM severity sum score significantly increased from baseline to day 14 (3.5 ± 1.6 vs. 4.6 ± 1.9; P = 0.002). After an interim analysis the study was terminated early due to futility in reaching the primary endpoint.

Conclusions
Early treatment with IVIG did not mitigate CIPNM in critically ill patients with MOF and SIRS/sepsis.

Trial registration
Clinicaltrials.gov: NCT01867645
Continuous regional arterial infusion for acute pancreatitis: a propensity score analysis using a nationwide administrative database
Authors: Hamada Tsuyoshi , Yasunaga Hideo , Nakai Yousuke , Isayama Hiroyuki , Horiguchi Hiromasa , Matsuda Shinya , Fushimi Kiyohide , Koike Kazuhiko 
Published: October 2013

Abstract
Introduction
Although continuous regional arterial infusion (CRAI) of a protease inhibitor and an antibiotic may be effective in patients with severe acute pancreatitis, CRAI has not yet been validated in large patient populations. We therefore evaluated the effectiveness of CRAI based on data from a national administrative database covering 1,032 Japanese hospitals.

Methods
In-hospital mortality, length of stay and costs were compared in the CRAI and non-CRAI groups, using propensity score analysis to adjust for treatment selection bias.

Results
A total of 17,415 eligible patients with acute pancreatitis were identified between 1 July and 30 September 2011, including 287 (1.6%) patients who underwent CRAI. One-to-one propensity-score matching generated 207 pairs with well-balanced baseline characteristics. In-hospital mortality rates were similar in the CRAI and non-CRAI groups (7.7% vs. 8.7%; odds ratio, 0.88; 95% confidence interval, 0.44–1.78, P = 0.720). CRAI was associated with significantly longer median hospital stay (29 vs. 18 days, P < 0.001), significantly higher median total cost (21,800 vs. 12,600 United States dollars, P < 0.001), and a higher rate of interventions for infectious complications, such as endoscopic/surgical necrosectomy or percutaneous drainage (2.9% vs. 0.5%, P = 0.061).

Conclusions
CRAI was not effective in reducing in-hospital mortality rate in patients with acute pancreatitis, but was associated with longer hospital stay and higher costs. Randomized controlled trials in large numbers of patients are required to further evaluate CRAI for this indication.
A Tris-fused Tetrathiafulvalene Extended with Cyclohexene-1,4-diylidene: A New Positive Electrode Material for Organic Rechargeable Batteries
Authors: Kato Minami , Ogi Daisuke , Yao Masaru , Misaki Yohji 
Published: October 2013

Abstract
Derivatives of tris-fused TTF donors 3 extended with cyclohexene-1,4-diylidene were synthesized. Cyclic voltammetry revealed that the tetrakis(hexylthio)-3 (3c) exhibited three stages of a two-electron redox process to afford the hexacation. The rechargeable battery incorporating tetrakis(methylsulfanyl)-3 (3b) as the positive electrode material exhibited a high cycle performance in spite of utilizing the highest oxidation state of +6.
Applying Activity Based Costing In Tourism Services In Uzbekistan
Authors: Eshtaev Alisher 
Published: October 2013

The paper studied opportunities of applying activity based costing and management (ABCM) at tourism firms in Uzbekistan. The present accounting practice is analyzed and critically studied, the scientific research done to show the advantages and disadvantages of using present methods of accounting, and need to implementation of more responsive and innovative financial settings in today’s dynamic business environment is proven. The methods of Cooper’s 2-stage implementation, Activity-Product-Dependence matrix by Roztocki were used for Planet Tour Co. ABCM is recommended as accurate cost management of products or services in tourism firms in Uzbekistan.
Viewpoints About Potential Stimulation And Possibilities Of Investments On Textile Industry Uzbekistan
Authors: Madjidov Shakhrukh , Khakimov Bekhzod 
Published: October 2013

Uzbek light industry, in particular, the textile sector is one of the strategically important and dynamic sectors of the national economy. Textile industry of Uzbekistan possesses high ranks in the sectors directed to exportation, therefore it contains wide specter of export ranging from thread up to ready­made product (made of stockinet, sewing, silk and carpet cloth). Contemporarily textile industry gains the fifth rank in the gross domestic product contribution and a third of all the workers in the field of industry is occupied in textile. Uzbek light industry still has significant untapped investment potential, all the conditions for the further rapid growth. Necessary to increase the production of goods for the domestic market to meet the growing needs of the population. This requires investment in projects for the production of finished cotton fabrics, blended fabrics, silk fabrics, garments and knitwear for the establishment of mobile industries with mandatory formation in their composition structures, responsible for design, marketing, quick changeovers production with fashion and demand.In the foreseeable future for the light industry remains a key role in the development of industrial production in the country. Experts believe that more needs to be done to develop the significant potential that lies in the light industry of the country.