bluuebunny/crossref_metadata_2025 huggingface dataset:
Case report of exocrine pancreatic insufficiency in two palliative care patients
Authors: Stockley Amelia J
Published: April 2014

Background:

This case report describes two patients with advanced disease who were found to have exocrine pancreatic insufficiency. There have been no prior case reports of exocrine pancreatic insufficiency in patients with advanced malignant disease in the palliative care setting. The instigation of diagnostic tests for exocrine pancreatic insufficiency might be delayed or omitted in light of the plausible explanations for symptoms of gastrointestinal disturbance in patients with progressive life-limiting illness, making clinical vigilance about this condition important, since the identification and treatment of exocrine pancreatic insufficiency could improve quality of life.

Case presentation:

Both patients were admitted to the hospice with symptoms of gastrointestinal upset and weight loss. Once medications and dietary manipulation had failed to improve symptoms significantly, more detailed investigations resulted in diagnoses of exocrine pancreatic insufficiency.

Case management:

Pancreatic enzyme replacement therapy was commenced.

Case outcome:

Improvement in symptoms for both patients facilitated nursing care in the final stages of life.

Conclusions:

Identification of exocrine pancreatic insufficiency and the instigation of pancreatic enzyme replacement therapy can, even in the late stages of illness, contribute significantly to symptom control of gastrointestinal disturbance and may allow patients to be cared for in their preferred environment.
Alleviation of Retching and Feeding Intolerance After Fundoplication
Authors: Cook Robin C. , Blinman Thane A.
Published: April 2014

Background: Although surgical intervention for gastroesophageal reflux disease (GERD) in children offers the strongest control of GERD, these results are tempered by postoperative problems such as retching, bloat, dysphagia, dumping syndrome, and postprandial hypoglycemia. We created a specialty clinic and an algorithmic approach to ameliorating these problems. Here, we present our experience with the first 60 patients. Methods: Patients referred to the clinic for feeding problems after fundoplication were tracked as part of quality improvement monitoring. Patients were treated according to a heuristic algorithm intended to reduce iatrogenic causes of feeding intolerance and to identify medical and mechanical contributors to retching. These etiological factors were tracked, along with patient responses. Results: Of the 60 initial patients, 92% completed ≥4 visits. A heuristic algorithm produced near‐complete or complete resolution in 97.5% of those patients. In most patients, multiple causes contributed to retching and were commonly iatrogenic (eg, very large boluses, overfeeding, polypharmacy). Surgical failure was a relatively uncommon contributor to intolerance. Conclusions: Successful results after antireflux surgery depend both on surgical technique and on strategic postoperative feeding. The finding that there are multiple contributors to feeding problems supports a threshold hypothesis for retching and lends credibility to the maxim “retching is rarely reflux.” Heuristics that respect surgical constraints on gastric performance, physiological scaling, and the whole patient yield improved growth and tolerance even in complex patients.
A broad-spectrum subsistence economy in Neolithic Inner Mongolia, China: Evidence from grinding stones
Authors: Liu Li , Kealhofer Lisa , Chen Xingcan , Ji Ping
Published: April 2014

Recent archaeological and archaeobotanical data suggest a very long tradition for the broad-spectrum subsistence economy in North China. It can be traced back at least to the Upper Paleolithic, in the last glacial maximum, and it continued into the early Neolithic period. Subsistence strategies also show great regional variation, suggesting a complex mosaic of adaptations in the transition to agriculture. The research reported here focuses on the plant-derived subsistence economy of the earliest Neolithic communities in the Daihai Lake area, Inner Mongolia, where the ecosystem was sensitive to climatic fluctuations. Neolithic groups likely migrated to the region as part of population expansion from the Central Plain. Previous scholars have suggested that this expansion was due to a search for agricultural land for millet farming. By examining residue remains and usewear patterns on sandstone grinding stone tools unearthed from the Shihushan I and Shihushan II sites, dating to the mid-5th millennium bc, we show that the earliest Neolithic settlers in Daihai appear to have enjoyed a way of life making use, and possibly management, of a wide range of plants, including various underground storage organs (tubers, roots, rhizomes, and bulbs), nuts, and wild grasses, while engaged in a limited level of millet production. This study adds to a growing literature that questions the economic significance of early cereal crops in subsistence system, suggesting that it is important to understand the role of roots and tubers in the development of early agriculture in Neolithic North China.
The transition movement and food sovereignty: From local resilience to global engagement in food system transformation
Authors: Sage Colin
Published: April 2014

The emergence of grassroots social movements variously preoccupied with a range of external threats, such as diminishing supplies of fossil energy or climate change, has led to increased interest in the production of local food. Drawing upon the notion of cognitive praxis, this article utilises transition as a trajectory guided by an overarching cosmology that brings together a broad social movement seeking a more resilient future. This ‘grand narrative’ is reinforced by ‘transition movement intellectuals’ who serve to shape an agenda of local preparedness in the face of uncertainty, rather than structural analysis of the global system. In this context, growing and producing food offers important multi-functional synergies by reconnecting people to place and its ecological endowments and serves to provide a vital element in civic mobilisation. Yet, local food could also become a means to build international solidarity in defence of food sovereignty and establish a global coalition opposed to the corporate agri-food agenda of biotechnologies, land grabbing and nutritional impoverishment.
The intestinal microbiome of fish under starvation
Authors: Xia Jun Hong , Lin Grace , Fu Gui Hong , Wan Zi Yi , Lee May , Wang Le , Liu Xiao Jun , Yue Gen Hua
Published: April 2014

Background

Starvation not only affects the nutritional and health status of the animals, but also the microbial composition in the host’s intestine. Next-generation sequencing provides a unique opportunity to explore gut microbial communities and their interactions with hosts. However, studies on gut microbiomes have been conducted predominantly in humans and land animals. Not much is known on gut microbiomes of aquatic animals and their changes under changing environmental conditions. To address this shortcoming, we determined the microbial gene catalogue, and investigated changes in the microbial composition and host-microbe interactions in the intestine of Asian seabass in response to starvation.

Results

We found 33 phyla, 66 classes, 130 orders and 278 families in the intestinal microbiome. Proteobacteria (48.8%), Firmicutes (15.3%) and Bacteroidetes (8.2%) were the three most abundant bacteria taxa. Comparative analyses of the microbiome revealed shifts in bacteria communities, with dramatic enrichment of Bacteroidetes, but significant depletion of Betaproteobacteria in starved intestines. In addition, significant differences in clusters of orthologous groups (COG) functional categories and orthologous groups were observed. Genes related to antibiotic activity in the microbiome were significantly enriched in response to starvation, and host genes related to the immune response were generally up-regulated.

Conclusions

This study provides the first insights into the fish intestinal microbiome and its changes under starvation. Further detailed study on interactions between intestinal microbiomes and hosts under dynamic conditions will shed new light on how the hosts and microbes respond to the changing environment.
Deregulated expression of circadian clock genes in gastric cancer
Authors: Hu Ming-Luen , Yeh Kun-Tu , Lin Pai-Mei , Hsu Cheng-Ming , Hsiao Hui-Hua , Liu Yi-Chang , Lin Hugo You-Hsien , Lin Sheng-Fung , Yang Ming-Yu
Published: April 2014

Background

Gastric cancer (GC), an aggressive malignant tumor of the alimentary tract, is a leading cause of cancer-related death. Circadian rhythm exhibits a 24-hour variation in physiological processes and behavior, such as hormone levels, metabolism, gene expression, sleep and wakefulness, and appetite. Disruption of circadian rhythm has been associated with various cancers, including chronic myeloid leukemia, head and neck squamous cell carcinoma, hepatocellular carcinoma, endometrial carcinoma, and breast cancer. However, the expression of circadian clock genes in GC remains unexplored.

Methods

In this study, the expression profiles of eight circadian clock genes (PER1, PER2, PER3, CRY1, CRY2, CKIϵ, CLOCK, and BMAL1) of cancerous and noncancerous tissues from 29 GC patients were investigated using real-time quantitative reverse-transcriptase polymerase chain reaction and validated through immunohistochemical analysis.

Results

We found that PER2 was significantly up-regulated in cancer tissues (p < 0.005). Up-regulated CRY1 expression was significantly correlated with more advanced stages (stage III and IV) (p < 0.05).

Conclusions

Our results suggest deregulated expressions of circadian clock genes exist in GC and circadian rhythm disturbance may be associated with the development of GC.
The impact of HBV or HCV infection in a cohort of HIV-infected pregnant women receiving a nevirapine-based antiretroviral regimen in Malawi
Authors: Andreotti Mauro , Pirillo Maria Franca , Liotta Giuseppe , Jere Haswell , Maulidi Martin , Sagno Jean-Baptiste , Luhanga Richard , Amici Roberta , Mancini Maria Grazia , Gennaro Elisabetta , Marazzi Maria Cristina , Vella Stefano , Giuliano Marina , Palombi Leonardo , Mancinelli Sandro
Published: April 2014

Background

Coinfection with the hepatitis viruses is common in the HIV population in sub-Saharan Africa. The aim of this study was to assess, in a cohort of HIV-infected pregnant women receiving antiretroviral drugs (ARVs), the prevalence of HBV and HCV infections and to determine the impact of these infections on the occurrence of liver toxicity and on the viro-immunological response.

Methods

Women were screened for HBsAg and HCV-RNA before starting, at week 25 of gestational age, an antiretroviral regimen consisting of lamivudine and nevirapine plus either stavudine or zidovudine. Women with CD4+ < 350/mm3 continued ARVs indefinitely, while the other women interrupted treatment 6 months postpartum (end of breastfeeding period). Both groups were followed for 2 years after delivery. Liver function was monitored by alanine aminotransferase (ALT) measurement. The Cox proportional hazards model was used to identify factors associated with the emergence of liver toxicity.

Results

A total of 28 women out of the 309 enrolled in the study (9.1%) were coinfected with HBV (n. 27), or HCV (n. 1). During follow-up 125 women (40.4%) developed a grade ≥ 1 ALT elevation, 28 (9.1%) a grade ≥ 2 and 6 (1.9%) an elevation defining grade 3 toxicity. In a multivariate model including age, baseline CD4+ count and hemoglobin level, the presence of either HBV or HCV infection was significantly associated with the development of an ALT increase of any grade (P = 0.035). Moderate or severe liver laboratory toxicity (grade ≥ 2) was more frequent among women with baseline CD4+ > 250/mm3 (P = 0.030). In HBV-infected women a baseline HBV-DNA level above 10,000 IU/ml was significantly associated to the development of liver toxicity of grade ≥ 1 (P = 0.040). Coinfections had no impact on the immunological and virological response to antiretroviral drugs up to 2 years after delivery.

Conclusions

In this cohort of nevirapine-treated women the presence of HBV or HCV was associated only to the development of mild liver toxicity, while the occurrence of moderate or severe hepatoxicity was correlated to a baseline CD4+ count > 250/mm3. No statistically significant effect of the coinfections was observed on the efficacy of antiretroviral therapy.
p21 and CD166 as predictive markers of poor response and outcome after fluorouracil-based chemoradiotherapy for the patients with rectal cancer
Authors: Sim Sung Hoon , Kang Mi-Hyun , Kim Yu Jung , Lee Keun-Wook , Kim Duck-Woo , Kang Sung-Bum , Eom Keun-Yong , Kim Jae-Sung , Lee Hye Seung , Kim Jee Hyun
Published: April 2014

Background

Pre-operative chemoradiotherapy (CRT) is the standard treatment in clinical stage T3/4 or node positive rectal cancer. However, there are no established biomarkers that can predict the pathological response and clinical outcome to CRT.

Methods

Immunohistochemical staining was performed in tissue arrays constructed from core tissue specimens taken before treatment and from operative specimens from 112 patients who received 5-FU based pre-operative CRT and surgery. Expression of Ki67, TS, BAX, EpCAM, p53, p21, EGFR, CD44, CD133, CD166, HIF1α and ALDH1 were assessed and correlated with tumor regression grades and disease free survival.

Results

Of the 112 patients (M/F 74/38, median age: 62), 20 (17.9%) patients achieved pathologic complete remission (pCR). In analyzing the associations between marker expressions and tumor regression grades, high p21 expression at the pretreatment biopsy was significantly associated with non-pCR (p = 0.022) and poor disease free survival (median DFS - low vs high p21: 75.8 vs 58.1 months, p = 0.002). In the multivariate analysis, high p21 expression level at the pre-treatment biopsy was significantly associated with poor DFS (p = 0.001, HR 6.14; 95% CI 2.03, 18.55). High CD166 expression level at the pretreatment biopsy was also associated with poor DFS (p = 0.003; HR 5.61; 95% CI 1.81, 17.35).

Conclusion

These show high p21 and CD166 expression at the pretreatment biopsy were associated with tumor regression and poor prognosis in patients treated with 5-FU based CRT. Larger, prospective and functional studies are warranted to determine the role of p21 and CD166 as predictive biomarker of response to CRT.
Effects of honey supplementation combined with different jumping exercise intensities on bone mass, serum bone metabolism markers and gonadotropins in female rats
Authors: Mosavat Maryam , Ooi Foong Kiew , Mohamed Mahaneem
Published: April 2014

Background

The effects of high and low jumping exercise intensities combined with honey on bone and gonadotrophins were investigated in eighty four 9 week-old female rats.

Methods

The experimental groups were 20 or 80 jumps per day combined with or without honey supplementation (HJ20, HJ80, J20 and J80), honey supplementation (H), sedentary without supplementation control (C), and baseline control (C0) groups.

Results

Study results showed that HJ80 elicited greatest beneficial effects on tibial and femoral mass, serum total calcium and alkaline phosphatase concentrations. There were significantly (p < 0.05) lower levels of serum follicle stimulating hormone concentrations in H, J20, J80 compared to C, with exception of HJ20 and HJ80. Serum luteinizing hormone concentrations were significantly (p < 0.05) greater in HJ20, HJ80 and J20 compared to J80.

Conclusions

It appears that high intensity jumping exercise combined with honey supplementation resulted more discernable effects on bone. Meanwhile, honey may protect against the adverse effects induced by jumping exercise on gonadotropins in female rats.
IMPACT - Integrative Medicine PrimAry Care Trial: protocol for a comparative effectiveness study of the clinical and cost outcomes of an integrative primary care clinic model
Authors: Herman Patricia M , Dodds Sally E , Logue Melanie D , Abraham Ivo , Rehfeld Rick A , Grizzle Amy J , Urbine Terry F , Horwitz Randy , Crocker Robert L , Maizes Victoria H
Published: April 2014

Background

Integrative medicine (IM) is a patient-centered, healing-oriented clinical paradigm that explicitly includes all appropriate therapeutic approaches whether they originate in conventional or complementary medicine (CM). While there is some evidence for the clinical and cost-effectiveness of IM practice models, the existing evidence base for IM depends largely on studies of individual CM therapies. This may in part be due to the methodological challenges inherent in evaluating a complex intervention (i.e., many interacting components applied flexibly and with tailoring) such as IM.

Methods/Design

This study will use a combination of observational quantitative and qualitative methods to rigorously measure the health and healthcare utilization outcomes of the University of Arizona Integrative Health Center (UAIHC), an IM adult primary care clinic in Phoenix, Arizona. There are four groups of study participants. The primary group consists of clinic patients for whom clinical and cost outcomes will be tracked indicating the impact of the UAIHC clinic (n = 500). In addition to comparing outcomes pre/post clinic enrollment, where possible, these outcomes will be compared to those of two matched control groups, and for some self-report measures, to regional and national data. The second and third study groups consist of clinic patients (n = 180) and clinic personnel (n = 15-20) from whom fidelity data (i.e., data indicating the extent to which the IM practice model was implemented as planned) will be collected. These data will be analyzed to determine the exact nature of the intervention as implemented and to provide covariates to the outcomes analyses as the clinic evolves. The fourth group is made up of patients (n = 8) whose path through the clinic will be studied in detail using qualitative (periodic semi-structured interviews) methods. These data will be used to develop hypotheses regarding how the clinic works.

Discussion

The US health care system needs new models of care that are more patient-centered and empower patients to make positive lifestyle changes. These models have the potential to reduce the burden of chronic disease, lower the cost of healthcare, and offer a sustainable financial paradigm for our nation. This protocol has been designed to test whether the UAIHC can achieve this potential.

Trial registration

Clinical Trials.gov NCT01785485.
Relative efficiency and productivity: a preliminary exploration of public hospitals in Beijing, China
Authors: Li Hao , Dong Siping , Liu Tingfang
Published: April 2014

Background

Third-grade hospitals in Beijing have been rapidly developing in capacity and scale for many years. These hospitals receive a large number of patients, and ensuring their efficient operation is crucial in meeting people’s healthcare needs. In this context, a study of their relative efficiency and productivity would be helpful to identify the driving factors and further improve their performance.

Methods

After a review of literature, the current numbers of open beds and employees were selected as input variables. The number of outpatient and emergency visits and the number of discharged patients were selected as output variables. A total of 12 third-grade Class A general public hospitals in Beijing were selected for a preliminary study. The panel data from 2006–2009 were collected by the National Institute of Hospital Administration, Ministry of Health of P.R. China. Descriptive analysis and data envelopment analysis were used to analyze the data using Stata 10.0 and DEAP(V2.1) software.

Results

In the 2006–2009 period, descriptive results show that sample hospitals continuously expanded their capacity and scale, with growth rate of total revenue being the highest among all variables. The DEA results show that the average annual growth rate of productivity was 26.7%, and the rates were 47.3%, 21.3% and 13.8% respectively for two consecutive years. The average annual growth rate of technological change was 28.3%, and the rates were 49.4%, 21.5% and 16.4% respectively for two consecutive years. The average annual growth rate of technical efficiency change was -1.3%, and the rates were -1.4%, -0.02% and -2.2% respectively for two consecutive years.

Conclusions

The sample hospitals in Beijing experienced substantial productivity growth, but annual growth rates were declining. Substantial technological change was the main contributor to the growth. Although some hospitals exhibited improvements in technical efficiency, there was a slight decline in general. To improve overall efficiency and productivity, both government and hospitals need to further drive positive technological change, technical change, and allocative efficiency of public hospitals. More empirical studies are needed to include more hospitals of all three grades at a larger scale.
Slit2N and Robo4 regulate lymphangiogenesis through the VEGF-C/VEGFR-3 pathway
Authors: Yu Jinlong , Zhang Xuefeng , Kuzontkoski Paula M , Jiang Shuxian , Zhu Weiquan , Li Dean Y , Groopman Jerome E
Published: April 2014

Background

Signaling through vascular endothelial growth factor C (VEGF–C) and VEGF receptor 3 (VEGFR-3) plays a central role in lymphangiogenesis and the metastasis of several cancers via the lymphatics. Recently, the Slit2/Robo4 pathway has been recognized as a modulator of vascular permeability and integrity. Signaling via the Robo receptor inhibits VEGF-mediated effects; however, its effects on lymphatic endothelial cell function have not been well characterized.

Results

We found that pretreatment with Slit2N, an active fragment of Slit2, inhibited VEGF-C-mediated lung-derived lymphatic endothelial cell (L-LEC) proliferation, migration, and in vitro tube formation. Slit2N induced the internalization of VEGFR-3, which blocked its activation, and inhibited the activation of the PI3K/Akt pathway by VEGF-C in L-LECs. Moreover, we found that inhibition of VEGF-C-induced effects by Slit2N was Robo4-dependent.

Conclusion

These results indicate that Slit2N/Robo4 modulates several key cellular functions, which contribute to lymphangiogenesis, and identify this ligand-receptor pair as a potential therapeutic target to inhibit lymphatic metastasis of VEGF-C-overexpressing cancers and manage lymphatic dysfunctions characterized by VEGF-C/VEGFR-3 activation.
Preparation of uniform magnetic recoverable catalyst microspheres with hierarchically mesoporous structure by using porous polymer microsphere template
Authors: Ren Lianbing , Teng Chao , Zhu Lili , He Jie , Wang You , Zuo Xinbing , Hong Mei , Wang Yong , Jiang Biwang , Zhao Jing
Published: April 2014

Merging nanoparticles with different functions into a single microsphere can exhibit profound impact on various applications. However, retaining the unique properties of each component after integration has proven to be a significant challenge. Our previous research demonstrated a facile method to incorporate magnetic nanoparticles into porous silica microspheres. Here, we report the fabrication of porous silica microspheres embedded with magnetic and gold nanoparticles as magnetic recoverable catalysts. The as-prepared multifunctional composite microspheres exhibit excellent magnetic and catalytic properties and a well-defined structure such as uniform size, high surface area, and large pore volume. As a result, the very little composite microspheres show high performance in catalytic reduction of 4-nitrophenol, special convenient magnetic separability, long life, and good reusability. The unique nanostructure makes the microspheres a novel stable and highly efficient catalyst system for various catalytic industry processes.

PACS: 61.46.-w; 75.75.-c; 81.07.-b
Predicting gene ontology annotations of orphan GWAS genes using protein-protein interactions
Authors: Kuppuswamy Usha , Ananthasubramanian Seshan , Wang Yanli , Balakrishnan Narayanaswamy , Ganapathiraju Madhavi K
Published: April 2014

Background

The number of genome-wide association studies (GWAS) has increased rapidly in the past couple of years, resulting in the identification of genes associated with different diseases. The next step in translating these findings into biomedically useful information is to find out the mechanism of the action of these genes. However, GWAS studies often implicate genes whose functions are currently unknown; for example, MYEOV, ANKLE1, TMEM45B and ORAOV1 are found to be associated with breast cancer, but their molecular function is unknown.

Results

We carried out Bayesian inference of Gene Ontology (GO) term annotations of genes by employing the directed acyclic graph structure of GO and the network of protein-protein interactions (PPIs). The approach is designed based on the fact that two proteins that interact biophysically would be in physical proximity of each other, would possess complementary molecular function, and play role in related biological processes. Predicted GO terms were ranked according to their relative association scores and the approach was evaluated quantitatively by plotting the precision versus recall values and F-scores (the harmonic mean of precision and recall) versus varying thresholds. Precisions of ~58% and ~ 40% for localization and functions respectively of proteins were determined at a threshold of ~30 (top 30 GO terms in the ranked list). Comparison with function prediction based on semantic similarity among nodes in an ontology and incorporation of those similarities in a k-nearest neighbor classifier confirmed that our results compared favorably.

Conclusions

This approach was applied to predict the cellular component and molecular function GO terms of all human proteins that have interacting partners possessing at least one known GO annotation. The list of predictions is available at http://severus.dbmi.pitt.edu/engo/GOPRED.html. We present the algorithm, evaluations and the results of the computational predictions, especially for genes identified in GWAS studies to be associated with diseases, which are of translational interest.
Video-assisted thoracic bronchial sleeve lobectomy with bronchoplasty for treatment of lung cancer confined to a single lung lobe: a case series of Chinese patients
Authors: Yu Daping , Han Yi , Zhou Shijie , Song Xiaoyun , Li Yunsong , Xiao Ning , Liu Zhidong
Published: April 2014

Background

The outcomes of video-assisted thoracic bronchial sleeve lobectomy (VABSL), a minimally invasive video-assisted thoracoscopic (VATS) lobectomy, are mostly unknown in Chinese patients.

Objectives

To investigate operative and postoperative outcomes of VABSL in a cases series of Chinese patients with lung cancer.

Methods

Retrospective study of 9 patients (male:female 8:1; mean age 59.4 ± 17.6 years, ranging 21–79 years) diagnosed with lung cancer of a single lobe, treated with VABSL between March 2009 and November 2011, and followed up for at least 2 months (mean follow-up: 14.17 ± 12.91 months). Operative outcomes (tumor size, operation time, estimated blood loss and blood transfusion), postoperative outcomes (intensive care unit [ICU] stay, hospitalization length and pathological tumor stage), death, tumor recurrence and safety were assessed.

Results

Patients were diagnosed with carcinoid cancer (11.1%), squamous carcinoma (66.7%) or small cell carcinoma (22.2%), affecting the right (77.8%) or left (22.2%) lung lobes in the upper (55.6%), middle (11.1%) or lower (33.3%) regions. TNM stages were T2 (88.9%) or T3 (11.1%); N0 (66.7%), N1 (11.1%) or N2 (22.2%); and M0 (100%). No patient required conversion to thoracotomy. Mean tumor size, operation time and blood loss were 2.50 ± 0.75 cm, 203 ± 20 min and 390 ± 206 ml, respectively. Patients were treated in the ICU for 18.7 ± 0.7 hours, and overall hospitalization duration was 20.8 ± 2.0 days. No deaths, recurrences or severe complications were reported.

Conclusions

VABSL surgery is safe and effective for treatment of lung cancer by experienced physicians, warranting wider implementation of VABSL and VATS training in China.
Canadian Journal of Kidney Health and Disease: A Unique Launch of a Unique Journal
Authors: Levin Adeera , Clase Catherine M , Sood Manish M , Dicks Elizabeth , Fortin Marie-Chantal , Hartwig Sunny , Holden Rachel , Lafrance Jean-Philippe , Molzahn Anita , Rosenblum Norman , Samuel Susan , Soroka Steven
Published: April 2014

Usually inaugural editorials are written by the Editor-in-Chief to describe the scope and vision for the journal to potential authors and readers. This editorial is written by the Editor-in-Chief, the Deputy Editors and the Associate Editors collaboratively as a clear signal that this is a unique and different journal. We will build this journal on a set of principles which are fundamental to improving the outcomes of patients with kidney disease. To that end, we aim to be supportive, to collaborate, to integrate multiple perspectives and to be open to possibilities.
Patient-derived xenografts of triple-negative breast cancer reproduce molecular features of patient tumors and respond to mTOR inhibition
Authors: Zhang Haiyu , Cohen Adam L , Krishnakumar Sujatha , Wapnir Irene L , Veeriah Selvaraju , Deng Glenn , Coram Marc A , Piskun Caroline M , Longacre Teri A , Herrler Michael , Frimannsson Daniel O , Telli Melinda L , Dirbas Frederick M , Matin AC , Dairkee Shanaz H , Larijani Banafshe , Glinsky Gennadi V , Bild Andrea H , Jeffrey Stefanie S
Published: April 2014

Introduction

Triple-negative breast cancer (TNBC) is aggressive and lacks targeted therapies. Phosphatidylinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways are frequently activated in TNBC patient tumors at the genome, gene expression and protein levels, and mTOR inhibitors have been shown to inhibit growth in TNBC cell lines. We describe a panel of patient-derived xenografts representing multiple TNBC subtypes and use them to test preclinical drug efficacy of two mTOR inhibitors, sirolimus (rapamycin) and temsirolimus (CCI-779).

Methods

We generated a panel of seven patient-derived orthotopic xenografts from six primary TNBC tumors and one metastasis. Patient tumors and corresponding xenografts were compared by histology, immunohistochemistry, array comparative genomic hybridization (aCGH) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) sequencing; TNBC subtypes were determined. Using a previously published logistic regression approach, we generated a rapamycin response signature from Connectivity Map gene expression data and used it to predict rapamycin sensitivity in 1,401 human breast cancers of different intrinsic subtypes, prompting in vivo testing of mTOR inhibitors and doxorubicin in our TNBC xenografts.

Results

Patient-derived xenografts recapitulated histology, biomarker expression and global genomic features of patient tumors. Two primary tumors had PIK3CA coding mutations, and five of six primary tumors showed flanking intron single nucleotide polymorphisms (SNPs) with conservation of sequence variations between primary tumors and xenografts, even on subsequent xenograft passages. Gene expression profiling showed that our models represent at least four of six TNBC subtypes. The rapamycin response signature predicted sensitivity for 94% of basal-like breast cancers in a large dataset. Drug testing of mTOR inhibitors in our xenografts showed 77 to 99% growth inhibition, significantly more than doxorubicin; protein phosphorylation studies indicated constitutive activation of the mTOR pathway that decreased with treatment. However, no tumor was completely eradicated.

Conclusions

A panel of patient-derived xenograft models covering a spectrum of TNBC subtypes was generated that histologically and genomically matched original patient tumors. Consistent with in silico predictions, mTOR inhibitor testing in our TNBC xenografts showed significant tumor growth inhibition in all, suggesting that mTOR inhibitors can be effective in TNBC, but will require use with additional therapies, warranting investigation of optimal drug combinations.
President's Page
Authors: Abdelmoaty Samir
Published: April 2014

In 1951, SEG established a committee on safety to further the cause of accident prevention in the geophysical industry (Sorge, 1952). This became known as the SEG Safety Committee and its work is further evidenced by Safety Committee annual reports for 1973, 1974, 1977, and 1979 that can be found in the archives of Geophysics. At the SPE International Conference on Health, Safety, and Environment in March of this year, Threadgold (2014) mentioned that this SEG committee was officially dissolved in 1985, a fact recorded in the SEG Board minutes. Its last known annual safety report was issued for 1982 (Proubasta, 1987).
Foundation News
Authors: Blythe Natalie
Published: April 2014

The power of engaging donors, both on a volunteer and philanthropic level, can produce remarkable, impactful results. Recently, ExxonMobil Exploration Corporation demonstrated this power by making a $1 million investment in one of SEG's flagship programs, the SEG/ExxonMobil Student Education Program (SEP). Along with its generous philanthropic support, ExxonMobil Exploration provides volunteer professional staff to assist in the training of some of the world's top young geophysics students. The SEP has become a global hit, attracting student applicants from many of SEG's 301 worldwide student chapters. The result is a collection of some of the top geophysics students working together to learn from industry experts and develop answers to challenging industry issues.
Outstanding reviewers
Authors: Slob Evert
Published: April 2014

The term of the 2013–2015 Geophysics Editorial Board is well on its way. My team of editors works with reviewers and authors to continue the tradition of a fair, professional, and timely review process. With the peer-review process, we strive for high-quality published papers. The authors, reviewers, and editors are all crucially important for keeping Geophysics at the top of the applied geophysics journals. Authors and editors are visible in publications and the editorial board information pages, while reviewers are not often visible. I am happy to recognize some of our excellent reviewers here. These nominated reviewers are recognized as candidates for the Reviewer of the Year award.
Use the SEG Web site today to prepare for SEG Denver 2014 in October
Authors: Posey Chris
Published: April 2014

By the time this issue of The Leading Edge reaches your desk, Online Abstract Submission for SEG Denver 2014 will have come and gone. Nevertheless, the SEG Web site will remain a key productivity tool for you as you prepare to attend SEG's 84th Annual Meeting and International Exposition in Denver, Colorado, this coming October.
Professional Development
Authors: Blythe Natalie
Published: April 2014

With more than 33,000 members around the world, SEG continues to evolve and change to meet the growing demand of its global membership. One of the facets that SEG constantly strengthens is its online educational offerings. With more than two-thirds of members living outside of the United States — and many with limited access to classroom education — SEG strives to provide to its members high-quality online education regardless of where they live and work. One of these areas of focus is providing online courses through the International Human Resources Development Corporation (IHRDC), the worldwide leader in training and competency development for the oil and gas industry.
Epistemic Uncertainty for NGA-West2 Models
Authors: Atik Linda Al , Youngs Robert R.
Published: April 2014

The development of the NGA-West2 ground motion prediction equations (GMPEs) is a collaborative effort with many interactions and exchange of ideas among the developers. The NGA-West2 developers indicate that additional epistemic uncertainty needs to be incorporated into the median ground motion estimation from each of the five NGA-West2 GMPEs in order to more fully represent an appropriate level of epistemic uncertainty. A proposed minimum additional epistemic uncertainty is evaluated based on statistical estimates of the uncertainty in the median predictions of each GMPE. The proposed additional epistemic uncertainty model is distance-independent but depends on magnitude, style of faulting (SOF), and spectral period. The epistemic uncertainty in the median predictions from each GMPE is then modeled using a three-point discrete approximation to a normal distribution.
Genetic Control of Ductal Morphology, Estrogen-Induced Ductal Growth, and Gene Expression in Female Mouse Mammary Gland
Authors: Wall Emma H. , Case Laure K. , Hewitt Sylvia C. , Nguyen-Vu Trang , Candelaria Nicholes R. , Teuscher Cory , Lin Chin-Yo
Published: April 2014

The uterotropic response of the uterus to 17β-estradiol (E2) is genetically controlled, with marked variation observed depending on the mouse strain studied. Previous genetic studies from our laboratory using inbred mice that are high (C57BL6/J; B6) or low (C3H/HeJ; C3H) responders to E2 led to the identification of quantitative trait loci (QTL) associated with phenotypic variation in uterine growth and leukocyte infiltration. Like the uterus, phenotypic variation in the responsiveness of the mammary gland to E2 during both normal and pathologic conditions has been reported. In the current experiment, we utilized an E2-specific model of mammary ductal growth combined with a microarray approach to determine the degree to which genotype influences the responsiveness of the mammary gland to E2, including the associated transcriptional programs, in B6 and C3H mice. Our results reveal that E2-induced mammary ductal growth and ductal morphology are genetically controlled. In addition, we observed a paradoxical effect of mammary ductal growth in response to E2 compared with what has been reported for the uterus; B6 is a high responder for the uterus and was a low responder for mammary ductal growth, whereas the reverse was observed for C3H. In contrast, B6 was a high responder for mammary ductal side branching. The B6 phenotype was associated with increased mammary epithelial cell proliferation and apoptosis, and a distinct E2-induced transcriptional program. These findings lay the groundwork for future experiments designed to investigate the genes and mechanisms underlying phenotypic variation in tissue-specific sensitivity to systemic and environmental estrogens during various physiological and disease states.
GH Administration Rescues Fatty Liver Regeneration Impairment by Restoring GH/EGFR Pathway Deficiency
Authors: Collin de l’Hortet A. , Zerrad-Saadi A. , Prip-Buus C. , Fauveau V. , Helmy N. , Ziol M. , Vons C. , Billot K. , Baud V. , Gilgenkrantz Hélène , Guidotti Jacques-Emmanuel
Published: April 2014

GH pathway has been shown to play a major role in liver regeneration through the control of epidermal growth factor receptor (EGFR) activation. This pathway is down-regulated in nonalcoholic fatty liver disease. Because regeneration is known to be impaired in fatty livers, we wondered whether a deregulation of the GH/EGFR pathway could explain this deficiency. Hepatic EGFR expression and triglyceride levels were quantified in liver biopsies of 32 obese patients with different degrees of steatosis. We showed a significant inverse correlation between liver EGFR expression and the level of hepatic steatosis. GH/EGFR down-regulation was also demonstrated in 2 steatosis mouse models, a genetic (ob/ob) and a methionine and choline-deficient diet mouse model, in correlation with liver regeneration defect. ob/ob mice exhibited a more severe liver regeneration defect after partial hepatectomy (PH) than methionine and choline-deficient diet-fed mice, a difference that could be explained by a decrease in signal transducer and activator of transcription 3 phosphorylation 32 hours after PH. Having checked that GH deficiency accounted for the GH signaling pathway down-regulation in the liver of ob/ob mice, we showed that GH administration in these mice led to a partial rescue in hepatocyte proliferation after PH associated with a concomitant restoration of liver EGFR expression and signal transducer and activator of trnascription 3 activation. In conclusion, we propose that the GH/EGFR pathway down-regulation is a general mechanism responsible for liver regeneration deficiency associated with steatosis, which could be partially rescued by GH administration.
Minireview: Pathophysiological Roles of the TR4 Nuclear Receptor: Lessons Learned From Mice Lacking TR4
Authors: Lin Shin-Jen , Zhang Yanqing , Liu Ning-Chun , Yang Dong-Rong , Li Gonghui , Chang Chawnshang
Published: April 2014

Testicular nuclear receptor 4 (TR4), also known as NR2C2, belongs to the nuclear receptor superfamily and shares high homology with the testicular nuclear receptor 2. The natural ligands of TR4 remained unclear until the recent discoveries of several energy/lipid sensors including the polyunsaturated fatty acid metabolites, 13-hydroxyoctadecadienoic acid and 15-hydroxyeicosatetraenoic acid, and their synthetic ligands, thiazolidinediones, used for treatment of diabetes. TR4 is widely expressed throughout the body and particularly concentrated in the testis, prostate, cerebellum, and hippocampus. It has been shown to play important roles in cerebellar development, forebrain myelination, folliculogenesis, gluconeogenesis, lipogenesis, muscle development, bone development, and prostate cancer progression. Here we provide a comprehensive summary of TR4 signaling including its upstream ligands/activators/suppressors, transcriptional coactivators/repressors, downstream targets, and their in vivo functions with potential impacts on TR4-related diseases. Importantly, TR4 shares similar ligands/activators with another key nuclear receptor, peroxisome proliferator-activated receptor γ, which raised several interesting questions about how these 2 nuclear receptors may collaborate with or counteract each other's function in their related diseases. Clear dissection of such molecular mechanisms and their differential roles in various diseases may help researchers to design new potential drugs with better efficacy and fewer side effects to battle TR4 and peroxisome proliferator-activated receptor γ involved diseases.
A Heterometallic Protocol for Turn-on Fluorescence. Synthesis, Structure, and Luminescence Behavior of a Diruthenium(III)–Magnesium(II) Complex Decorated with Four Pyrenecarboxylates
Authors: Ikegami Atsushi , Abe Masaaki , Hisaeda Yoshio
Published: April 2014

A new heterometallic diruthenium(III)–magnesium(II) complex functionalized with four pyrenecarboxylate fluorophores 1 has been synthesized and structurally characterized. Fluorescence from the pyrene moieties in 1 was nearly completely quenched in CH2Cl2 (>98%), but turn-on fluorescence was successfully observed after regioselective substitution of the carboxylates bridging the heterometallic Ru(III)···Mg(II) sites.
Underwater Superoleophobicity of TiO2 Nanotube Arrays
Authors: Nishimoto Shunsuke , Sawai Yusuke , Kameshima Yoshikazu , Miyake Michihiro
Published: April 2014

TiO2 nanotube arrays prepared by the anodization of Ti plate exhibited underwater superoleophobicity. The surface almost completely repelled the oil droplet in water, even after storage in dark for one week under ambient conditions. The TiO2 nanotube arrays fabricated on a Ti mesh were found to be useful as oil–water-separation filters.
Cobalt-catalyzed Reductive Carboxylation on α,β-Unsaturated Nitriles with Carbon Dioxide
Authors: Hayashi Chika , Hayashi Takuo , Kikuchi Satoshi , Yamada Tohru
Published: April 2014

The reductive carboxylation of α,β-unsaturated carbonyl compounds with carbon dioxide was studied. After the screening of various transition-metal complex catalysts and reducing agents, it was found that the combination of bis(acetylacetonato)cobalt(II) and diethylzinc could effectively afford the corresponding α-carboxylate in high yield from α,β-unsaturated nitriles. The product was obtained after esterification by trimethylsilyldiazomethane. The highly selective carboxylation was observed at the α-position in the present study.
Optical Changes in the Fatty Liver—First Results of a near Infrared Spectroscopy Study in a Small Animal Model
Authors: Kaschowitz Tobias , Kroker Anne , Plettenberg Holger Kurt Walter , Wei Weiwei , Dahmen Uta
Published: April 2014

In this experimental study we investigated the potential of near infrared (NIR) spectroscopy to support intra-operative assessment of the fat content of the liver, as needed in the context of liver transplantation. Rats with hepatic steatosis of different severities were subjected to the intra-operative assessment using a medical device to record NIR spectra. We observed that the changes in the optical properties of the liver, at 1210 nm using the second derivative, corresponded to the severity of hepatic steatosis as assessed by histology. Further studies have to be undertaken to validate the results, to add more parameters, and to further develop the technology for easy and safe use in the clinic.
Sleeping on Mt Kilimanjaro—The Influence of Hypobaric Hypoxia on Brain Perfusion and Cerebral Tissue Oxygenation
Authors: Stein Peter , Lampe Anne , Pape Andreas , Zacharowski Kai , Hudek Robert , Weber Christian Friedrich
Published: April 2014

The hypobaric hypoxia encountered at high altitudes poses great challenges to the human body when adapting to these environmental conditions. Prior to full acclimatisation, a Cheyne–Stokes-like breathing pattern is commonly observed during sleep in altitude above 2500 m. We investigated the consequences of this hyperventilation and hypoventilation or apnoea on cerebral blood perfusion and tissue oxygenation during states of reduced consciousness. Perfusion and oxygen saturation of the cerebral tissue of healthy climbers were monitored with near infrared spectroscopy at night-time over the course of a six-day ascent to the summit of Mt Kilimanjaro in Tanzania. All climbers ( n = 6) experienced cyclic changes in oxygenated haemoglobin and total haemoglobin with no significant alteration of the deoxygenated haemoglobin. This is the typical pattern for periodic hypocapnic arteriolar vasoconstriction with following hypoxic vasodilation in response to blood gas changes found in Cheyne–Stokes breathing. The percentage of periodic vasoactivity increased at higher altitudes and decreased on subsequent nights at the same altitude, suggesting initial maladaptation. Conversely, cycle length decreased at greater heights and increased on subsequent nights at the same level of altitude. Periodic breathing during sleep at high altitude results in periodic changes in brain perfusion without any significant drop in tissue oxygenation. Furthermore, the results of the present investigation indicate a vasomotoric component in the pathogenesis of altitude induced headache.