bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioethanol Production from Fermentable Sugar Juice
Authors: Zabed Hossain , Faruq Golam , Sahu Jaya Narayan , Azirun Mohd Sofian , Hashim Rosli , Nasrulhaq Boyce Amru
Published: March 2014

Bioethanol production from renewable sources to be used in transportation is now an increasing demand worldwide due to continuous depletion of fossil fuels, economic and political crises, and growing concern on environmental safety. Mainly, three types of raw materials, that is, sugar juice, starchy crops, and lignocellulosic materials, are being used for this purpose. This paper will investigate ethanol production from free sugar containing juices obtained from some energy crops such as sugarcane, sugar beet, and sweet sorghum that are the most attractive choice because of their cost-effectiveness and feasibility to use. Three types of fermentation process (batch, fed-batch, and continuous) are employed in ethanol production from these sugar juices. The most common microorganism used in fermentation from its history is the yeast, especially,Saccharomyces cerevisiae, though the bacterial speciesZymomonas mobilisis also potentially used nowadays for this purpose. A number of factors related to the fermentation greatly influences the process and their optimization is the key point for efficient ethanol production from these feedstocks.
BioTCM-SE: A Semantic Search Engine for the Information Retrieval of Modern Biology and Traditional Chinese Medicine
Authors: Chen Xi , Chen Huajun , Bi Xuan , Gu Peiqin , Chen Jiaoyan , Wu Zhaohui
Published: March 2014

Understanding the functional mechanisms of the complex biological system as a whole is drawing more and more attention in global health care management. Traditional Chinese Medicine (TCM), essentially different from Western Medicine (WM), is gaining increasing attention due to its emphasis on individual wellness and natural herbal medicine, which satisfies the goal of integrative medicine. However, with the explosive growth of biomedical data on the Web, biomedical researchers are now confronted with the problem of large-scale data analysis and data query. Besides that, biomedical data also has a wide coverage which usually comes from multiple heterogeneous data sources and has different taxonomies, making it hard to integrate and query the big biomedical data. Embedded with domain knowledge from different disciplines all regarding human biological systems, the heterogeneous data repositories are implicitly connected by human expert knowledge. Traditional search engines cannot provide accurate and comprehensive search results for the semantically associated knowledge since they only support keywords-based searches. In this paper, we present BioTCM-SE, a semantic search engine for the information retrieval of modern biology and TCM, which provides biologists with a comprehensive and accurate associated knowledge query platform to greatly facilitate the implicit knowledge discovery between WM and TCM.
Lung Metastasis after an Eighteen-Years-Long Disease-Free Period since Uterine Leiomyosarcoma Diagnosis
Authors: Guazzaroni M. , Tosti D. , Rascioni M. , Mataloni M. , Citraro D. , Simonetti G.
Published: March 2014

Uterine leiomyosarcoma (ULMS) is an uncommon malignancy that accounts for one-third of uterine sarcomas and represents 1% of all uterine malignancies, with an incidence averaging 0.5–1/100,000/year. The prognosis is poor due to its intrinsic aggressiveness and its characteristic high metastatic potential with reported distant metastatic spread in lung, abdomen, soft tissue, and brain. We present the case of a 67-year-old woman with lung metastasis after eighteen years since uterine leiomyosarcoma diagnosis and its following surgical resection. The diagnosis of pulmonary metastases was obtained by reviewing the histology of the previous uterine tumor: the tumor cells were immunoreactive for CD10, PR, and smooth muscle actin (SMA), but negative for desmin, S100, CD34, CD 117, cytokeratins AE1AE3, CD68R, and ER. To our knowledge, this disease-free interval is the longest among previous reports of pulmonary metastasis of uterine leiomyosarcoma.
Telomere Length in Peripheral Blood Leukocytes and Lung Cancer Risk: A Large Case–Control Study in Caucasians
Authors: Sanchez-Espiridion Beatriz , Chen Meng , Chang Joe Y. , Lu Charles , Chang David W. , Roth Jack A. , Wu Xifeng , Gu Jian
Published: March 2014

Telomere dysfunction is a crucial event in malignant transformation and tumorigenesis. Telomere length in peripheral blood leukocytes has been associated with lung cancer risk, but the relationship has remained controversial. In this study, we investigated whether the association might be confounded by study of different histological subtypes of lung cancer. We measured relative telomere lengths in patients in a large case–control study of lung cancer and performed stratified analyses according to the two major histologic subtypes [adenocarcinoma and squamous cell carcinoma (SCC)]. Notably, patients with adenocarcinoma had longer telomeres than controls, whereas patients with SCC had shorter telomeres compared with controls. Long telomeres were associated with increased risk of adenocarcinoma, with the highest risk associated with female sex, younger age (<60 years), and lighter smoking (<30 pack-years). In contrast, long telomeres were protective against SCC, particularly in male patients. Our results extend the concept that telomere length affects risk of lung cancer in a manner that differs with histologic subtype. Cancer Res; 74(9); 2476–86. ©2014 AACR.
Gastric Cancer: Descriptive Epidemiology, Risk Factors, Screening, and Prevention
Authors: Karimi Parisa , Islami Farhad , Anandasabapathy Sharmila , Freedman Neal D. , Kamangar Farin
Published: March 2014

Less than a century ago, gastric cancer was the most common cancer in the United States and perhaps throughout the world. Despite its worldwide decline in incidence over the past century, gastric cancer remains a major killer across the globe. This article reviews the epidemiology, screening, and prevention of gastric cancer. We first discuss the descriptive epidemiology of gastric cancer, including its incidence, survival, mortality, and trends over time. Next, we characterize the risk factors for gastric cancer, both environmental and genetic. Serologic markers and histological precursor lesions of gastric cancer and early detection of gastric cancer using these markers are reviewed. Finally, we discuss prevention strategies and provide suggestions for further research. Cancer Epidemiol Biomarkers Prev; 23(5); 700–13. ©2014 AACR.
Reversal of Acquired Drug Resistance in FLT3-Mutated Acute Myeloid Leukemia Cells via Distinct Drug Combination Strategies
Authors: Zhang Weiguo , Gao Chen , Konopleva Marina , Chen Ye , Jacamo Rodrigo O. , Borthakur Gautam , Cortes Jorge E. , Ravandi Farhad , Ramachandran Abhijit , Andreeff Michael
Published: March 2014

Purpose: FMS-like tyrosine kinase-3 (FLT3) internal tandem duplication (FLT3-ITD) mutations are common in patients with acute myeloid leukemia (AML). These patients regularly develop resistance to FLT3 inhibitors suggesting that targeted combination drug strategies are needed to enhance AML therapy efficacy.

Experimental Design: Acquired point mutations of FLT3-ITD gene were screened using cDNA-based sequencing approach in vitro sorafenib-resistant cells, which were developed by long-term exposure of Ba/F3-ITD to increasing doses of sorafenib, and in FLT3-ITD mutated AML patients, who developed relapse following sorafenib therapy. Drug effects (e.g., proliferation inhibition, apoptosis induction, and changes in signal transduction protein expression) were assessed in AML cells harboring the point mutations in vitro and in FLT3-ITD–mutated AML patient samples.

Results: We identified several acquired point mutations in the tyrosine kinase domains (TKD) of the FLT3 gene in sorafenib-resistant murine leukemia cell line carrying human FLT3-ITD mutations, which were also detected in two of four sorafenib-resistant patient samples. Engineering these point mutations into Ba/F3-ITD cells generated sublines that demonstrated varying degrees of sorafenib [a type II tyrosine kinase inhibitor (TKI)] resistance. A similar pattern of resistance could be observed by exposing these sublines to the other type II TKIs AC220 and MLN518. However, these sublines retained sensitivity to the type I TKIs PKC412 or crenolanib. The combination of crenolanib with sorafenib demonstrated marked cytotoxic effects in all of the sorafenib-resistant sublines.

Conclusions: These combination strategies could be clinically important in reversing acquired resistance to FLT3 inhibition in AML. Clin Cancer Res; 20(9); 2363–74. ©2014 AACR.
Nullifying the CDKN2AB Locus Promotes Mutant K-ras Lung Tumorigenesis
Authors: Schuster Katja , Venkateswaran Niranjan , Rabellino Andrea , Girard Luc , Peña-Llopis Samuel , Scaglioni Pier Paolo
Published: March 2014

Lung cancer commonly displays a number of recurrent genetic abnormalities, and about 30% of lung adenocarcinomas carry activating mutations in the Kras gene, often concomitantly with inactivation of tumor suppressor genes p16INK4A and p14ARF of the CDKN2AB locus. However, little is known regarding the function of p15INK4B translated from the same locus. To determine the frequency of CDKN2AB loss in human mutant KRAS lung cancer, The Cancer Genome Atlas (TCGA) database was interrogated. Two-hit inactivation of CDKN2A and CDKN2B occurs frequently in patients with mutant KRAS lung adenocarcinoma. Moreover, p15INK4B loss occurs in the presence of biallelic inactivation of p16INK4A and p14ARF, suggesting that p15INK4B loss confers a selective advantage to mutant KRAS lung cancers that are p16INK4A and p14ARF deficient. To determine the significance of CDKN2AB loss in vivo, genetically engineered lung cancer mouse models that express mutant Kras in the respiratory epithelium were utilized. Importantly, complete loss of CDKN2AB strikingly accelerated mutant Kras–driven lung tumorigenesis, leading to loss of differentiation, increased metastatic disease, and decreased overall survival. Primary mutant Kras lung epithelial cells lacking Cdkn2ab had increased clonogenic potential. Furthermore, comparative analysis of mutant Kras;Cdkn2a null with Kras;Cdkn2ab null mice and experiments with mutant KRAS;CDKN2AB–deficient human lung cancer cells indicated that p15INK4B is a critical tumor suppressor. Thus, the loss of CDKN2AB is of biologic significance in mutant KRAS lung tumorigenesis by fostering cellular proliferation, cancer cell differentiation, and metastatic behavior.

Implications: These findings indicate that mutant Kras;Cdkn2ab null mice provide a platform for accurately modeling aggressive lung adenocarcinoma and testing therapeutic modalities. Mol Cancer Res; 12(6); 912–23. ©2014 AACR.
Molecular Profiling of Premalignant Lesions in Lung Squamous Cell Carcinomas Identifies Mechanisms Involved in Stepwise Carcinogenesis
Authors: Ooi Aik T. , Gower Adam C. , Zhang Kelvin X. , Vick Jessica L. , Hong Longsheng , Nagao Brian , Wallace W. Dean , Elashoff David A. , Walser Tonya C. , Dubinett Steven M. , Pellegrini Matteo , Lenburg Marc E. , Spira Avrum , Gomperts Brigitte N.
Published: March 2014

Lung squamous cell carcinoma (SCC) is thought to arise from premalignant lesions in the airway epithelium; therefore, studying these lesions is critical for understanding lung carcinogenesis. Previous microarray and sequencing studies designed to discover early biomarkers and therapeutic targets for lung SCC had limited success identifying key driver events in lung carcinogenesis, mostly due to the cellular heterogeneity of patient samples examined and the interindividual variability associated with difficult to obtain airway premalignant lesions and appropriate normal control samples within the same patient. We performed RNA sequencing on laser-microdissected representative cell populations along the SCC pathologic continuum of patient-matched normal basal cells, premalignant lesions, and tumor cells. We discovered transcriptomic changes and identified genomic pathways altered with initiation and progression of SCC within individual patients. We used immunofluorescent staining to confirm gene expression changes in premalignant lesions and tumor cells, including increased expression of SLC2A1, CEACAM5, and PTBP3 at the protein level and increased activation of MYC via nuclear translocation. Cytoband enrichment analysis revealed coordinated loss and gain of expression in chromosome 3p and 3q regions, respectively, during carcinogenesis. This is the first gene expression profiling study of airway premalignant lesions with patient-matched SCC tumor samples. Our results provide much needed information about the biology of premalignant lesions and the molecular changes that occur during stepwise carcinogenesis of SCC, and it highlights a novel approach for identifying some of the earliest molecular changes associated with initiation and progression of lung carcinogenesis within individual patients. Cancer Prev Res; 7(5); 487–95. ©2014 AACR.
Long-Term Outcomes of 80-Watt KTP and 120-Watt HPS GreenLight Photoselective Vaporization of the Prostate
Authors: Broggi E. , May A. , Giretti G. , Tabchouri N. , Lorphelin H. , Brichart N. , Bruyère F.
Published: March 2014

Objective: Photoselective vaporization of the prostate (PVP) is becoming a surgical treatment alternative of transurethral resection of the prostate for male lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO). We evaluated the outcome and postoperative complications of PVP performed by 80-W KTP and 120-W HPS GreenLight lasers (AMS®) over a 4-year period. Materials and Methods: This is a prospective monocentric study that included all patients who underwent PVP. They had routine follow-up at 1 month, 3 months, 6 months and every year until the fourth postoperative year. Listed data were maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), post-void residual (PVR) volume, prostate-specific antigen (PSA) and prostate volume. We collected the postoperative complications. Results: From September 2005 to May 2008, 77 patients out of a 409 patients cohort underwent surgery and were followed during 4 years. At 4 years mean Qmax increase was 82.5%; mean IPSS, PVR volume, PSA and prostate volume decreases were 79.1, 69.8, 43.8 and 22.9%, respectively. The main side effects observed were storage LUTS. A urinary catheter was replaced after a first withdrawal failure in 10 patients (15.6%) after surgery. Conclusions: PVP showed a sustainable efficacy and an appealing tolerance profile during a 4-year period in patients with LUTS secondary to BPO.
Augmenting Clinical Interpretability of Thiopurine Methyltransferase Laboratory Evaluation
Authors: Demlova Regina , Mrkvicova Martina , Sterba Jaroslav , Bernatikova Hana , Stary Jan , Sukova Martina , Mikuskova Alena , Chocholova Alica , Mladosievicova Beata , Soltysova Andrea , Behulova Darina , Pilatova Katerina , Zdrazilova-Dubska Lenka , Valik Dalibor
Published: March 2014

Objective: Individuals with decreased thiopurine methyltransferase (TPMT) activity are at risk of adverse effects of thiopurine administration whereas its increased activity may inactivate drugs faster. We evaluated genotype-phenotype correlations in patients with suspected hematological malignancies and inflammatory bowel disease from our region based on findings of nonlinear TPMT enzyme kinetics previously unreported. Patients and Methods: The study group comprised 267 individuals. They were screened for the most common variants of low TPMT activity. TPMT activity was measured in erythrocytes using the HPLC rate-blanked method. Results: Thirty-three patients (12.4%) were heterozygous (26 were TPMT*1/*3A, 5 TPMT*1/*2, 2 TPMT *1/*3C) and 1 was a compound heterozygote (*2/*3A). Normal and low normal TPMT activities substantially overlapped in wild-type and heterozygous individuals, whereas high activities were found in 29 wild-type genotyped patients. Extreme and life-threatening toxicity was observed in the compound heterozygote patient. Conclusion: Activity measurement performed at diagnosis provides clinicians with information on immediate pharmacokinetic-related adverse events and/or hypermetabolism, and genotyping may indicate the rate of pharmacodynamic thioguanine nucleotide accumulation due to slower overall thiopurine metabolism.
Altered Bacterial Profiles in Saliva from Adults with Caries Lesions: A Case-Cohort Study
Authors: Belstrøm D. , Fiehn N.-E. , Nielsen C.H. , Holmstrup P. , Kirkby N. , Klepac-Ceraj V. , Paster B.J. , Twetman S.
Published: March 2014

The aim of this study was to learn whether presence of caries in an adult population was associated with a salivary bacterial profile different from that of individuals without untreated caries. Stimulated saliva samples from 621 participants of the Danish Health Examination Survey were analyzed using the Human Oral Microbe Identification Microarray technology. Samples from 174 individuals with dental caries and 447 from a control cohort were compared using frequency and levels of identified bacterial taxa/clusters as endpoints. Differences at taxon/cluster level were analyzed using Mann-Whitney's test with Benjamini-Hochberg correction for multiple comparisons. Principal component analysis was used to visualize bacterial community profiles. A reduced bacterial diversity was observed in samples from subjects with dental caries. Five bacterial taxa (Veillonella parvula, Veillonella atypica, Megasphaera micronuciformis, Fusobacterium periodontium and Achromobacter xylosoxidans) and one bacterial cluster (Leptotrichia sp. clones C3MKM102 and GT018_ot417/462) were less frequently found in the caries group (adjusted p value <0.01) while two bacterial taxa (Solobacterium moorei and Streptococcus salivarius) and three bacterial clusters (Streptococcus parasanguinis I and II and sp. clone BE024_ot057/411/721, Streptococcus parasanguinis I and II and sinensis_ot411/721/767, Streptococcus salivarius and sp. clone FO042_ot067/755) were present at significantly higher levels (adjusted p value <0.01). The principal component analysis displayed a marked difference in the bacterial community profiles between groups. Presence of manifest caries was associated with a reduced diversity and an altered salivary bacterial community profile. Our data support recent theories that ecological stress-induced changes of commensal microbial communities are involved in the shift from oral health to tooth decay.
Costimulation of the Horizontal Semicircular Canal during Skull Vibrations in Superior Canal Dehiscence Syndrome
Authors: Park Joo Hyun , Kim Hyo Jung , Kim Ji-Soo , Koo Ja-Won
Published: March 2014

A sound- and pressure-induced vestibuloocular reflex (VOR) has been described as vertical and torsional in superior canal dehiscence (SCD), and the rotational axes of induced VOR have been assumed to fit with the axis of the affected superior semicircular canal (SC). However, it has been difficult to characterize the pattern of vibration-induced VOR (ViVOR). We aimed to characterize the pattern of ViVOR by comparing the intensity and the axis of ViVOR with several clinical parameters of SCD. Ten symptomatic SCD patients were recruited. SCD size and location were measured on a reformatted image in the plane of the SC. Unilateral vibratory stimulation (100 Hz) was applied to the mastoid surface. ViVOR were recorded using 3D videooculography. The median 3D velocity of ViVOR was measured and the 3D vector trajectory plotted for reference against the axes of the human semicircular canals. A correlation between the magnitude of ViVOR and the size of SCD was evaluated. We also compared the location of SCD with the vertical-to-torsional component ratio of the ViVOR. ViVOR were present in 7 patients; 6 patients showed a substantial horizontal component in the excitatory direction in addition to strong torsional and weak vertical components. The computed rotational axes of ViVOR were located mostly between the axes of the ipsilateral SC and horizontal canal (HC) with a variable deviation to the axis of the ipsilateral posterior canal (PC). The magnitude of ViVOR was not related to the size of the SCD. The vertical-to-torsional component ratio of ViVOR tended to decline as the dehiscence was closer to the common crus. In SCD, mastoid vibration may stimulate the affected-side HC and PC as well as the SC. SCD can be suspected when excitatory horizontal torsional ViVOR direct to the side of the auditory symptoms.
Effects of Deep Repetitive Transcranial Magnetic Stimulation on Brain-Derived Neurotrophic Factor Serum Concentration in Healthy Volunteers
Authors: Gaede Gunnar , Hellweg Rainer , Zimmermann Hanna , Brandt Alexander U. , Dörr Jan , Bellmann-Strobl Judith , Zangen Abraham , Paul Friedemann , Pfueller Caspar F.
Published: March 2014

Objective: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive, safe and efficacious technique for treating various neuropsychiatric disorders, but its underlying mechanisms are poorly understood. A newly developed H-coil allows the stimulation of deeper brain regions. This study is the first to investigate the effects of deep high-frequency rTMS on brain-derived neurotrophic factor (BDNF) serum concentrations in healthy volunteers. We aimed to evaluate the short-term effect of deep rTMS on BDNF serum concentrations. Methods: This was a double-blind, randomized deep high-frequency rTMS study using an H-coil on a cohort of 13 healthy volunteers (NCT01106365). The following stimulation protocols were applied: 18-Hz stimulation of the left dorsolateral prefrontal cortex (PFC), 5-Hz stimulation of the primary motor cortex (MC) and sham stimulation in random order. Blood samples were obtained before, 30 min after and 60 min after each treatment. Results: The BDNF serum concentration decreased significantly after MC and PFC stimulation, but not after sham stimulation. Furthermore, BDNF serum level changes were associated with changes in individual alertness. Conclusion: Although BDNF serum concentrations do not necessarily correlate with BDNF levels in the cerebrospinal fluid or the brain, these results indicate an acute biological effect of deep rTMS on BDNF release, and demonstrate that this change correlates with alertness.
Maternal Serum Placental Growth Factor Isoforms 1 and 2 at 11-13, 20-24 and 30-34 Weeks' Gestation in Late-Onset Pre-Eclampsia and Small for Gestational Age Neonates
Authors: Nucci Marta , Poon Leona C. , Demirdjian Gaiane , Darbouret Bruno , Nicolaides Kypros H.
Published: March 2014

Objective: To compare the maternal serum concentrations of placental growth factor (PlGF)-1 and PlGF-2 in the first, second and third trimesters in normal pregnancies and in those complicated by pre-eclampsia (PE) or the delivery of small for gestational age (SGA) neonates after 37 weeks. Methods: Serum PlGF-1 and PlGF-2 were measured at 11-13, 20-24 and 30-34 weeks' gestation in 50 cases of PE, 99 cases of SGA and 298 controls. The values of PlGF-1 and PlGF-2 at 11-13 weeks were expressed as multiples of the median (MoM) after adjustment for maternal characteristics. The distributions of PlGF-1 and PlGF-2 in cases and controls at 20-24 and 30-34 weeks were converted to MoM of the values at 11-13 weeks and compared. Results: Serum PlGF-1 and PlGF-2 levels were highly correlated and both increased with gestational age. At 30-34 weeks, the median MoM values for PlGF-1 and PlGF-2 in the late PE (4.2 and 4.3) and late SGA (7.2 and 6.0) groups were significantly lower than in the controls (12.8 and 9.9). Combining the two isoforms did not improve the prediction of late PE and late SGA provided by PlGF-1 alone. Conclusions: The performances of serum PlGF-1 and PlGF-2 in the prediction of late PE and late SGA are similar.
Neonatal Peripheral Immune Challenge Activates Microglia and Inhibits Neurogenesis in the Developing Murine Hippocampus
Authors: Smith Peter L.P. , Hagberg Henrik , Naylor Andrew S. , Mallard Carina
Published: March 2014

The early postnatal period represents an important window in rodent hippocampal development with peak hilar neurogenesis and widespread microgliogenesis occurring in the first week of life. Inflammation occurring during this period may negatively influence development, potentially facilitating or increasing susceptibility to later-life pathology. We administered the Gram-negative bacterial coat protein lipopolysaccharide (LPS) systemically at postnatal day 5 (1 mg/kg i.p.) and assessed potential effects on microgliogenesis, inflammation and neurogenesis in the developing hippocampus. LPS administration led to an acute but transient increase in absolute number and density of ionized calcium-binding adaptor molecule 1-immunoreactive microglia, a change attributable to increased proliferation of central nervous system-resident microglia/microglial precursor cells but not infiltration of peripheral monocyte-derived macrophages. qRT-PCR analysis of hippocampal gene expression showed these LPS-mediated changes to be associated with persistent dysregulation of genes associated with both M1 and M2 microglial phenotypes, indicating prolonged alteration in hippocampal inflammatory status. Further, analysis of progenitor cell regulation in the hippocampal subgranular zone revealed a transient inhibition of the neuronal differentiation pathway up to 2 weeks after LPS administration, a change occurring specifically through effects on type 3 neural progenitor cells and independently of altered cell proliferation or survival of newly born cells. Together, our results show that systemic inflammation occurring during the early neonatal period is sufficient to alter inflammatory status and dysregulate the ongoing process of neurogenesis in the developing hippocampal germinal niche.
Fat Mass Gain Predicts Estimated GFR Decline in a Relatively Healthy Korean Population
Authors: Hyun Young Youl , Kim Hyang , Lee Kyu Beck
Published: March 2014

Background: Previous studies have shown that obesity is a risk factor for estimated glomerular filtration rate (eGFR) decline and chronic kidney disease (CKD). However, the relationship between fat mass directly measured by bioimpedance analysis and eGFR is not well known. Methods: We analyzed 21,859 participants without CKD at baseline who underwent two health checkups at a 5-year interval during 2002-2009. Fat mass was measured by Inbody 3.0 (Biospace, Seoul, Korea). eGFR decline was defined as eGFR <60 ml/min/1.73 m2 at second checkup. Logistic regression analysis was used to analyze factors related to eGFR decline. Results: Participants were divided into tertiles according to their fat mass change over 5 years: lower tertile (n = 7,042; <-0.7 kg), middle tertile (n = 7,478; -0.7 to 1.2 kg) and higher tertile (n = 7,339; >1.2 kg). After 5 years, 246 cases of eGFR decline were observed. Multivariate logistic analysis revealed that age (OR 1.03, 95% CI 1.02-1.05, p < 0.001), diabetes mellitus (OR 2.04, 95% CI 1.22-3.40, p = 0.007), baseline eGFR (OR 0.80, 95% CI 0.78-0.83, p < 0.001) and higher tertile of fat mass change (OR 1.58, 95% CI 1.16-2.13, p = 0.003) were associated with eGFR decline after adjustment for sex, hypertension, dyslipidemia, cardiovascular disease, smoking status, body mass index, and high-density lipoprotein cholesterol level. Conclusions: Fat mass gain over 5 years was independently associated with eGFR decline to <60 ml/min/1.73 m2 in a relatively healthy Korean population. This finding suggests that lifestyle changes to prevent fat mass gain could be protective against the development of CKD.
Expression of Eukaryotic Initiation Factor 3f Is Associated with Prognosis in Gastric Carcinomas
Authors: Cheng Yu , Jia Cuimei , Li Guanghua , Li Honglun
Published: March 2014

Background: Eukaryotic initiation factor 3f (eIF3f) expression, which plays an important role in human cancer, is significantly decreased in various types of cancers. The aim of this study was to detect the expression of eIF3f in gastric carcinoma (GC), which until now has not been reported. Methods: Expression of eIF3f was detected by immunohistochemistry in GC tissues and adjacent non-cancerous tissues (ANCT) from 195 patients with stage I-III GC who underwent curative gastrectomy. Clinicopathological results, including survival, were analyzed. Results: Expression rate of eIF3f in GC and ANCT were 44.8 and 81.7% respectively. Low expression of eIF3f was significantly associated with an increased serum level of carcinoma embryonic antigen (p = 0.02), but not with levels of carbohydrate antigen 19-9 (p = 0.29). eIF3f levels were linked to more advanced tumor stages and likelihood of recurrence (all p < 0.05).The Kaplan-Meier survival curves indicated that decreased expression of eIF3f was a significant factor for a poor prognosis for GC patients (p = 0.04). Conclusion: eIF3f may play an important role in recurrence. Its function and potential as a prognostic marker should be further verified in GC.
Kimura's Disease of the Orbit Successfully Treated with Radiotherapy Alone: A Case Report
Authors: Monzen Yoshio , Kiya Katsuzo , Nishisaka Takashi
Published: March 2014

We performed radiotherapy in a 28-year-old patient with Kimura's disease of the orbit. Irradiation with 21.6 Gy was administered to the tumor bed with a single dose of 1.8 Gy in 5 weekly fractions delivered via a high-energy linear accelerator (6-MV X-ray). Complete remission of the tumor and improvements in the neurological findings were achieved. Neither tumor regrowth nor late complications were detected up to 84 months after radiotherapy. Radiotherapy is an effective treatment for Kimura's disease of the orbit.
Gastric Metastasis of Lung Cancer Mimicking an Adrenal Tumor
Authors: Hung Tsung I , Chu Kuang-En , Chou Yenn Hwei , Yang Kuo-Ching
Published: March 2014

Lung cancer is one of the leading causes of cancer deaths worldwide. Metastatic spreads of lung cancer are often found in the adrenal glands, bone, liver, brain and kidneys; the gastrointestinal tract is less commonly involved. However, according to some reports in the literature, the incidence of gastrointestinal metastases, most of them asymptomatic, might be as frequent as 11% in autopsy studies of lung cancer, which suggests that this condition is not as rare as it was previously considered. We report a very rare case of small cell lung cancer with a solitary gastric metastasis mimicking an adrenal tumor which was belatedly diagnosed due to its unusual presentation and treated actively with surgery and chemotherapy, achieving a relatively favorable outcome.
Kussmaul Physiology in Patients With Heart Failure
Authors: Nadir Adnan M. , Beadle Roger , Lim Hoong Sern
Published: March 2014

Background—

A paradoxical inspiratory rise in right atrial pressure (in contrast to the normal fall during inspiration), Kussmaul sign, has been described in congestive heart failure (CHF). However, the clinical and hemodynamic characteristics and clinical outcomes of patients with CHF and Kussmaul physiology have not been studied.

Methods and Results—

This is a single-center study of consecutive ambulant patients with CHF (New York Heart Association class III/IV) referred for assessment for heart transplantation between November 2011 and April 2013. Kussmaul physiology was defined as inspiratory rise in right atrial pressure during right heart catheterization. Clinical, biochemical, echocardiographic, and hemodynamic correlates were studied and outcomes assessed in patients with or without Kussmaul physiology after a mean follow-up of 379±227 days. Ninety ambulant patients (age, 53±12 years; 86% men) with CHF were studied. Kussmaul physiology was demonstrated in 39 (43%) patients, and it was associated with higher pulmonary pressures and lower cardiac index and pulmonary capacitance (all
P
<0.05). Patients with Kussmaul physiology were more likely to be treated with higher doses of diuretics, while higher filling pressures, N-terminal pro–B natriuretic peptide levels, and hyponatremia reflected greater neurohormonal activation. Echocardiography revealed greater left and right ventricular dimensions/volumes, restrictive transmitral filling pattern, and lower left ventricular ejection fraction and lower tricuspid annular plane systolic excursion. Peak oxygen uptake was low and comparable in both groups, but ventilation slope was higher in patients with Kussmaul physiology who also had a higher incidence of post-transplant right ventricular failure and overall mortality (
P
<0.05).

Conclusions—

Kussmaul physiology is common in patients with CHF referred for heart transplantation and is associated with adverse cardiopulmonary hemodynamics. As a result of the latter, Kussmaul physiology is associated with poorer clinical outcomes. Kussmaul physiology may be useful during assessment of right heart function and pulmonary pressures before transplantation.
Cardiac Magnetic Resonance Parameters Predict Transplantation-Free Survival in Patients With Fontan Circulation
Authors: Rathod Rahul H. , Prakash Ashwin , Kim Yuli Y. , Germanakis Ioannis E. , Powell Andrew J. , Gauvreau Kimberlee , Geva Tal
Published: March 2014

Background—

Several clinical risk factors for death and heart transplantation have been identified in patients with Fontan circulation. It is unknown whether cardiac magnetic resonance (CMR) measurements of ventricular size and function are independently associated with these outcomes and further improve risk stratification.

Methods and Results—

Data on patients with Fontan circulation who had a CMR study from January 2002 to January 2011 were retrospectively reviewed. The end point was time to death or listing for heart transplantation after the CMR study. The median age of the 215 patients was 18.3 years (25th, 75th percentiles: 14, 26) with a median age at Fontan of 3.6 years (2.3, 7.1). During a median post-CMR follow-up period of 4.1 years (2.6, 6.2), 24 patients (11%) reached the end point: 20 deaths, 3 transplantations, and 1 transplantation listing. In a multivariable Cox regression model with clinical parameters only, protein-losing enteropathy was associated with death or listing for transplant. A multivariable model, including clinical and CMR parameters, showed that in addition to protein-losing enteropathy, ventricular indexed end-diastolic volume >125 mL/body surface area raised to the 1.3 power was associated with the endpoint. A likelihood-ratio test comparing the 2 models showed that the addition of indexed end-diastolic volume resulted in a significantly improved end point prediction (
P
<0.001)—
C
-index increased from 0.63 to 0.79.

Conclusions—

CMR-derived ventricular indexed end-diastolic volume is an independent predictor of death or transplant in patients late after the Fontan operation and adds incremental value over clinical symptoms alone for risk stratification.
Hospital Quality Improvement Initiative for Patients With Acute Coronary Syndromes in China
Authors: Du Xin , Gao Runlin , Turnbull Fiona , Wu Yangfeng , Rong Ye , Lo Serigne , Billot Laurent , Hao Zhixin , Ranasinghe Isuru , Iedema Rick , Kong Lingzhi , Hu Dayi , Lin Shuguang , Shen Weifeng , Huang Dejia , Yang Yuejing , Ge Junbo , Han Yaling , Lv Shuzheng , Ma Aiqun , Gao Wei , Patel Anushka
Published: March 2014

Background—

Substantial evidence-practice gaps exist in the management of acute coronary syndromes (ACS) in China. Clinical pathways are tools for improving ACS quality of care but have not been rigorously evaluated.

Methods and Results—

Between October 2007 and August 2010, a quality improvement program was conducted in 75 hospitals throughout China with mixed methods evaluation in a cluster randomized, controlled trial. Eligible hospitals were level 2 or level 3 centers routinely admitting >100 patients with ACS per year. Hospitals were assigned immediate implementation of the American Heart Association/American College of Cardiology guideline based clinical pathways or commencement of the intervention 12 months later. Outcomes were several key performance indicators reflecting the management of ACS. The key performance indicators were measured 12 months after commencement in intervention hospitals and compared with baseline data in control hospitals, using data collected from 50 consecutive patients in each hospital. Pathway implementation was associated with an increased proportion of patients discharged on appropriate medical therapy, with nonsignificant improvements or absence of effects on other key performance indicators.

Conclusions—

Among hospitals in China, the use of a clinical pathway for the treatment of ACS compared with usual care improved secondary prevention treatments, but effectiveness was otherwise limited. An accompanying process evaluation identified several health system barriers to more successful implementation.

Clinical Trial Registration—

URL:
http://www.anzctr.org.au/default.aspx
. Unique identifier: ACTRN12609000491268.
System Barriers to the Evidence-Based Care of Acute Coronary Syndrome Patients in China
Authors: Ranasinghe Isuru , Rong Ye , Du Xin , Wang Yangfang , Gao Runlin , Patel Anushka , Wu Yangfeng , Iedema Rick , Hao Zhixin , Hu Dayi , Turnbull Fiona
Published: March 2014

Background—

Organizational and wider health system factors influence the implementation and success of interventions. Clinical Pathways in Acute Coronary Syndromes 2 is a cluster randomized trial of a clinical pathway–based intervention to improve acute coronary syndrome care in hospitals in China. We performed a qualitative evaluation to examine the system-level barriers to implementing clinical pathways in the dynamic healthcare environment of China.

Methods and Results—

A qualitative descriptive analysis of 40 in-depth interviews with health professionals conducted in a sample of 10 hospitals purposively selected to explore barriers to implementation of the intervention. Qualitative data were analyzed using the Framework method. In-depth interviews identified 5 key system-level barriers to effective implementation: (1) leadership support for implementing quality improvement, (2) variation in the capacity of clinical services and quality improvement resources, (3) fears of patient disputes and litigation, (4) healthcare funding constraints and high out-of-pocket expenses, and (5) patient-related factors.

Conclusions—

System-level barriers affect the ability of acute coronary syndrome clinical pathways to change practice. Addressing these barriers in the context of current and planned national health system reform will be critical for future improvements in the management of acute coronary syndromes, and potentially other hospitalized conditions, in China.

Clinical Trial Registration—

URL:
http://www.anzctr.org.au/default.aspx
. Register. Unique identifier: ACTRN12609000491268.
Prohibitin Viral Gene Transfer Protects Hippocampal CA1 Neurons From Ischemia and Ameliorates Postischemic Hippocampal Dysfunction
Authors: Kurinami Hitomi , Shimamura Munehisa , Ma Tao , Qian Liping , Koizumi Kenzo , Park Laibaik , Klann Eric , Manfredi Giovanni , Iadecola Costantino , Zhou Ping
Published: March 2014

Background and Purpose—

Prohibitin is a multi-functional protein involved in numerous cellular activities. Prohibitin overexpression protects neurons from injury in vitro, but it is unclear whether prohibitin can protect selectively vulnerable hippocampal CA1 neurons in a clinically relevant injury model in vivo and, if so, whether the salvaged neurons remain functional.

Methods—

A mouse model of transient forebrain ischemia that mimics the brain damage produced by cardiac arrest in humans was used to test whether prohibitin expression protects CA1 neurons from injury. Prohibitin-expressing viral vector was microinjected in mouse hippocampus to upregulate prohibitin.

Results—

Prohibitin overexpression protected CA1 neurons from transient forebrain ischemia. The protection was associated with dampened postischemic reactive oxygen species generation, reduced mitochondrial cytochrome
c
release, and decreased caspase-3 activation. Importantly, the improvement in CA1 neuronal viability translated into an improvement in hippocampal function: prohibitin expression ameliorated the spatial memory deficit induced by ischemia, assessed by the Y-maze test, and restored postischemic synaptic plasticity assessed by long-term potentiation, indicating that the neurons spared form ischemic damage were functionally competent.

Conclusions—

These data demonstrate that prohibitin overexpression protects highly vulnerable CA1 neurons from ischemic injury in vivo and suggest that the effect is mediated by reduction of postischemic reactive oxygen species generation and preservation of mitochondrial outer membrane integrity that prevents activation of apoptosis. Measures to enhance prohibitin expression could have translational value in ischemic brain injury and, possibly, other forms of brain injury associated with mitochondrial dysfunction.
Prothrombin G20210A Mutation Is Associated With Young-Onset Stroke
Authors: Jiang Baijia , Ryan Kathleen A. , Hamedani Ali , Cheng Yuching , Sparks Mary J. , Koontz Deborah , Bean Christopher J. , Gallagher Margaret , Hooper W. Craig , McArdle Patrick F. , O’Connell Jeffrey R. , Stine O. Colin , Wozniak Marcella A. , Stern Barney J. , Mitchell Braxton D. , Kittner Steven J. , Cole John W.
Published: March 2014

Background and Purpose—

Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in a white case–control population and additionally performed a meta-analysis.

Methods—

From the population-based Genetics of Early Onset Stroke (GEOS) study, we identified 397 individuals of European ancestry aged 15 to 49 years with first-ever ischemic stroke and 426 matched controls. Logistic regression was used to calculate odds ratios (ORs) in the entire population and for subgroups stratified by sex, age, oral contraceptive use, migraine, and smoking status. A meta-analysis of 17 case–control studies (n=2305 cases <55 years) was also performed with and without GEOS data.

Results—

Within GEOS, the association of the prothrombin G20210A mutation with ischemic stroke did not achieve statistical significance (OR=2.5; 95% confidence interval [CI]=0.9–6.5;
P
=0.07). However, among adults aged 15 to 42 years (younger than median age), cases were significantly more likely than controls to have the mutation (OR=5.9; 95% CI=1.2–28.1;
P
=0.03), whereas adults aged 42 to 49 years were not (OR=1.4; 95% CI=0.4–5.1;
P
=0.94). In our meta-analysis, the mutation was associated with significantly increased stroke risk in adults ≤55 years (OR=1.4; 95% CI=1.1–1.9;
P
=0.02), with significance increasing with addition of the GEOS results (OR=1.5; 95% CI=1.1–2.0;
P
=0.005).

Conclusions—

The prothrombin G20210A mutation is associated with ischemic stroke in young adults and may have an even stronger association among those with earlier onset strokes. Our finding of a stronger association in the younger young adult population requires replication.
Market Equilibrium and the Environmental Effects of Tax Adjustments in China's Automobile Industry
Authors: Xiao Junji , Ju Heng
Published: March 2014

This paper explores the effects of consumption-tax and fuel-tax adjustments in the Chinese automobile industry. Applying the model and simulation method of Berry, Levinson, and Pakes (1995), we conduct a comparative static analysis of equilibrium prices and sales, fuel consumption, and social welfare before and after tax adjustments. For the first time, we compare the progressivity of both taxes. Our empirical findings suggest that the fuel tax is effective in decreasing fuel consumption at the expense of social welfare, while the consumption tax does not significantly affect either fuel consumption or social welfare.
Splitting, splitting and splitting again: A brief history of the development of regional government in Indonesia since independence
Authors: Booth Anne
Published: March 2014

The paper reviews the changes in the structure and role of provincial and sub-provincial governments in Indonesia since independence. Particular attention is paid to the process of splitting both provinces and districts (kabupaten and kota) into smaller units. The paper points out that this process has been going on since the 1950s, but has accelerated in the post-Soeharto era. The paper examines why the splitting of government units has occurred in some parts of the Outer Islands to a much greater extent than in Java, and also examines the implications of developments since 1999 for the capacity of local government units to deliver basic services such as health and education.
James C. Scott, The art of not being governed: An anarchist history of upland Southeast Asia.
Authors: Dove Michael R. , Jonsson Hjorleifur , Aung-Thwin Michael
Published: March 2014

In this feature we highlight a recently launched book. We invite specialists in the field to comment on the book, and we invite the author to respond to their comments. In this issue we focus on James C. Scott's, The art of not being governed: An anarchist history of upland Southeast Asia. Those invited to comment on the book are Michael Dove, Hjorleifur Jonsson and Michael Aung-Thwin. James Scott, in keeping with his long-standing practice, has chosen not to react to the reviews. The editor regrets that the author of The art of not being governed, reviewers, and editor have had different expectations of this discussion, but respects the decision of the author. The comments of Michael Dove, Hjorleifur Jonsson, and Michael Aung-Thwin are worth to be published also without a response by James Scott. Registered readers may participate in the debate.
Convective Cells in Altocumulus Observed with a High-Resolution Radar
Authors: Schmidt Jerome M. , Flatau Piotr J. , Yates Robert D.
Published: March 2014

Very-high-resolution Doppler radar observations are used together with aircraft measurements to document the dynamic and thermodynamic structure of a dissipating altocumulus cloud system associated with a deep virga layer. The cloud layer circulation is shown to consist of shallow vertical velocity couplets near cloud top and a series of subkilometer-scale Rayleigh–Bénard-like cells that extend vertically through the depth of the cloud layer. The subcloud layer was observed to contain a number of narrow virga fall streaks that developed below the more dominant Rayleigh–Bénard updraft circulations in the cloud layer. These features were discovered to be associated with kilometer-scale horizontally orientated rotor circulations that formed along the lateral flanks of the streaks collocated downdraft circulation. The Doppler analysis further reveals that a layer mean descent was present throughout both the cloud and subcloud layers. This characteristic of the circulation is analyzed with regard to the diabatic and radiative forcing on horizontal length scales ranging from the Rayleigh–Bénard circulations to the overall cloud layer width. In particular, linear analytical results indicate that a deep and broad mesoscale region of subsidence is quickly established in middle-level cloud layers of finite width when a layer-wide horizontal gradient in the cloud-top radiative cooling rate is present. A conceptual model summarizing the primary observed and inferred circulation features of the altocumulus layer is presented.