bluuebunny/crossref_metadata_2025 huggingface dataset:
Two patients treated with pegylated interferon/ribavirin/telaprevir triple therapy for recurrent hepatitis C after living donor liver transplantation
Authors: Kawaoka Tomokazu , Takahashi Shoichi , Tatsukawa Yumiko , Hiramatsu Akira , Hiraga Nobuhiko , Miki Daiki , Tsuge Masataka , Imamura Michio , Kawakami Yoshiiku , Aikata Hiroshi , Ochi Hidenori , Ishiyama Kouhei , Ide Kentaro , Tashiro Hirotaka , Ohdan Hideki , Chayama Kazuaki
Published: January 2014

It is difficult to use protease inhibitors in patients with recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) due to interaction with immunosuppressive drugs. We report our experience with two patients treated with telaprevir (TVR) combined with pegylated interferon/ribavirin (PEG IFN/RBV) for recurrent HCV genotype 1 infection after LT. The first was a 63‐year‐old man with HCV‐related liver cirrhosis, who failed to respond to IFN‐β plus RBV after LT. Treatment was switched to PEG IFN‐α‐2b plus RBV and TVR was started. The donor had TT genotype of interleukin (IL)‐28 single nucleotide polymorphisms (SNP) (rs8099917). The recipient had TT genotype of IL‐28 SNP (rs8099917). Completion of 12‐week triple therapy was followed by PEG IFN‐α‐2b plus RBV for 36 weeks. Finally, he had sustained viral response. The second was a 70‐year‐old woman with HCV‐related liver cirrhosis and hepatocellular carcinoma. She failed to respond to PEG IFN‐α‐2b plus RBV after LT, and was subsequently switched to PEG IFN‐α‐2b/RBV/TVR. Genotype analysis showed TG genotype of IL‐28 SNP for the donor, and TT genotype of IL‐28 SNP for the recipient. Serum HCV RNA titer decreased below the detection limit at 5 weeks. However, triple therapy was withdrawn at 11 weeks due to general fatigue, which resulted in HCV RNA rebound 4 weeks later. Both patients were treated with cyclosporin, starting with a small dose to avoid interactions with TVR. TVR is a potentially suitable agent for LT recipients who do not respond to PEG IFN‐α‐2b plus RBV after LT.
Clear cell papillary renal cell carcinoma is an indolent and low‐grade neoplasm with overexpression of cyclin‐D1
Authors: Leroy Xavier , Camparo Philippe , Gnemmi Viviane , Aubert Sebastien , Flamand Vincent , Roupret Morgan , Fantoni Jean‐Christophe , Comperat Eva
Published: January 2014

Aims

Several entities have been individualized recently within the family of renal neoplasms with papillary features. Clear cell papillary renal cell carcinoma (CCPRCC) was first described in patients with end‐stage renal disease, but is also observed in patients with normal renal function. The objective of this study was to document the clinicopathological and immunohistochemical characteristics of CCPRCC, with a special emphasis on cyclin D1 expression.

Methods and results

The patients were 25 men and 17 women, mean age 60.7 years. Seventeen patients had a chronic renal disease. All tumours were stage pT1, with a mean diameter of 2 cm. Six tumours were multifocal. Tumours cells were mainly cuboidal, with clear cytoplasm and low‐grade nuclei apically aligned. In all cases, Fuhrman nuclear grade was one or two. No necrosis or vascular invasion was seen. During follow‐up (10–72 months), no metastasis or death related to the disease was observed. Immunohistochemistry showed strong and diffuse cytokeratin 7 immunoreactivity in all cases, but no labelling for AMACR or TFE3. There was diffuse nuclear cyclin D1 immunoreactivity in 83% of cases.

Conclusion

CCPRCC is now a well‐characterized entity. This tumour is an indolent and very low‐grade neoplasm. Here we report the first study, to our knowledge, demonstrating the overexpression of cyclin D1 immunostaining by this tumour.
Uroplakin II outperforms uroplakin III in diagnostically challenging settings
Authors: Smith Steven C , Mohanty Sambit K , Kunju Lakshmi P , Chang Elena , Chung Fai , Carvalho Jason C , Paner Gladel P , Hansel Donna E , Luthringer Daniel J , de Peralta‐Ventrurina Mariza N , Amin Mahul B
Published: January 2014

Aims

We performed a head‐to‐head comparison of an antibody against uroplakin III (UP3) and a new uroplakin II (UP2) antibody that remains untested in diagnostically challenging settings.

Methods and results

We immunostained high‐grade bladder neck carcinomas (n = 35), high‐grade upper tract urothelial carcinomas (UC) and renal carcinomas (n = 85), metastases of UC (n = 30) and a multicancer tissue microarray (n = 88) for UP3 and UP2, and scored staining intensity and proportion. UP3 showed membranous plaque‐like expression, while UP2 staining showed both membranous and cytoplasmic positivity. Significantly greater intensity (P = 0.003) and proportion (P = 0.03) of staining was noted for UP2 among bladder neck lesions, with UP2 staining showing greater sensitivity (63% versus 19%) and similar specificity (95% versus 100%) for UC over prostate carcinoma (P = 0.02). Among upper tract lesions, UP2 staining showed greater intensity and proportion than UP3 (both P < 0.001), including improved sensitivity (68% versus 23%) and equal specificity (both 100%) for UC (P = 0.006). Among UC metastases, UP2 staining showed greater intensity and proportion (both P < 0.001) with higher sensitivity (73% versus 37%, respectively, P = 0.001). Of 88 additional cases tested, no non‐urothelial cases stained for either UP.

Conclusions

The UP2 antibody outperforms the UP3 antibody, including in diagnostically challenging settings, and is a useful addition to the armamentarium of biomarkers for UC.
Epidemiological and clinical data of hospitalizations associated with respiratory syncytial virus infection in children under 5 years of age in Spain: FIVE multicenter study
Authors: Moreno‐Perez David , Calvo Cristina ,   Five Study Group
Published: January 2014

Background

Respiratory syncytial virus (RSV) is an important pathogen in lower respiratory tract infections (LRTI) in infants, but there are limited data concerning patients with underlying conditions and children older than 2 years of age.

Methods

We have designed a prospective observational multicenter national study performed in 26 Spanish hospitals (December 2011–March 2012). Investigational cases were defined as children with underlying chronic diseases and were compared with a group of previously healthy children (proportion 1:2). Clinical data were compared between the groups.

Results

A total of 1763 children hospitalized due to RSV infection during the inclusion period were analyzed. Of them, 225 cases and 460 healthy children were enrolled in the study. Underlying diseases observed were respiratory (64%), cardiovascular (25%), and neurologic (12%), as well as chromosomal abnormalities (7·5%), immunodeficiencies (6·7%), and inborn errors of metabolism (3·5%). Cases were statistically older than previously healthy children (average age: 16·3 versus 5·5 months). Cases experienced hypoxemia more frequently (P < 0·001), but patients with respiratory diseases required oxygen therapy more often (OR: 2·99; 95% CI: 1·03–8·65). Mechanical ventilation was used more in patients with cardiac diseases (OR: 3·0; 95% CI: 1·07–8·44) and in those with inborn errors of metabolism (OR: 12·27; 95% CI: 2·11–71·47). This subgroup showed a higher risk of admission to the PICU (OR: 6·7, 95% CI: 1·18–38·04). Diagnosis of pneumonia was more frequently found in cases (18·2% versus 9·3%; P < 0·01).

Conclusions

A significant percentage of children with RSV infection have underlying diseases and the illness severity is higher than in healthy children.
Trachycarpus ravenii sp. nov. (Arecaceae, Corypheae) from central Laos
Authors: Averyanov Leonid V. , Nguyen Khang Sinh , Nguyen Tien Hiep , Pham The Van , Lorphengsy Shengvilai
Published: January 2014

A new species Trachycarpus ravenii discovered in Kasi district, Vientiane province of central Laos is described and illustrated. Morphologically, it is closest to T. oreophilus and T. princeps, but differs by having a shorter stem of mature plants; glabrous, dull green petiole; almost circular leaf blade, waxy bluish–white abaxially; narrow leaf segments with narrow free lobes densely adpressed to each other, as well as in oblique‐round apices of median leaf segments.
Intermittent Atrial Tachycardia Promotes Repolarization Alternans and Conduction Slowing During Rapid Rates, and Increases Susceptibility to Atrial Fibrillation in a Free‐Behaving Sheep Model
Authors: MONIGATTI‐TENKORANG JOANNA , JOUSSET FLORIAN , PASCALE PATRIZIO , VESIN JEAN‐MARC , RUCHAT PATRICK , FROMER MARTIN , NARAYAN SANJIV M. , PRUVOT ETIENNE
Published: January 2014

Repolarization Alternans and Atrial Remodeling

Introduction

Paroxysmal atrial fibrillation (AF) may be triggered by intermittent atrial tachycardia, and ultimately lead to persistent AF. However, the mechanisms by which intermittent atrial tachycardia promotes sustained AF are not well understood.

Methods and Results

Eight sheep were chronically implanted with 2 pacemakers for the recording of broadband right atrial unipolar electrograms, and for the delivery of electrophysiological stimulation protocols and intermittent right atrial tachycardia. Right atrial kinetics of activation recovery interval (ARI) as a surrogate for action potential duration, of conduction time and velocity, and of repolarization alternans were analyzed at incremental pacing rates during the remodeling process induced by weeks of intermittent atrial tachycardia until the development of sustained AF.

Intermittent atrial tachycardia decreased ARI and blunted its rate adaptation, facilitated atrial capture, and slowed conduction at high rates, and increased susceptibility to pacing‐induced AF. In spite of blunted ARI rate adaptation, right atrial repolarization alternans was maintained during remodeling, and further increased in magnitude just before rapid pacing‐induced AF.

Conclusion

This study suggests that weeks of intermittent right atrial tachycardia result in a gradual electrical remodeling favorable for wavebreaks and reentry that may facilitate fibrillation.
Comparison of Left Atrial Area Marked Ablated in Electroanatomical Maps with Scar in MRI
Authors: PARMAR BHRIGU R. , JARRETT TYLER R. , BURGON NATHAN S. , KHOLMOVSKI EUGENE G. , AKOUM NAZEM W. , HU NAN , MACLEOD ROB S. , MARROUCHE NASSIR F. , RANJAN RAVI
Published: January 2014

Electroanatomic Map Overestimates the Ablated Area

Background

Three‐dimensional electroanatomic mapping (EAM) is routinely used to mark ablated areas during radiofrequency ablation. We hypothesized that, in atrial fibrillation (AF) ablation, EAM overestimates scar formation in the left atrium (LA) when compared to the scar seen on late‐gadolinium enhancement magnetic resonance imaging (LGE‐MRI).

Methods and Results

Of the 235 patients who underwent initial ablation for AF at our institution between August 2011 and December 2012, we retrospectively identified 70 patients who had preprocedural magnetic resonance angiography merged with LA anatomy in EAM software and had a 3‐month postablation LGE‐MRI for assessment of scar. Ablated area was marked intraprocedurally using EAM software and quantified retrospectively. Scarred area was quantified in 3‐month postablation LGE‐MRI. The mean ablated area in EAM was 30.5 ± 7.5% of the LA endocardial surface and the mean scarred area in LGE‐MRI was 13.9 ± 5.9% (P < 0.001). This significant difference in the ablated area marked in the EAM and scar area in the LGE‐MRI was present for each of the 3 independent operators. Complete pulmonary vein (PV) encirclement representing electrical isolation was observed in 87.8% of the PVs in EAM as compared to only 37.4% in LGE‐MRI (P < 0.001).

Conclusions

In AF ablation, EAM significantly overestimates the resultant scar as assessed with a follow‐up LGE‐MRI.
Spawning activity of the Australian lungfish Neoceratodus forsteri in an impoundment
Authors: Roberts D. T. , Mallett S. , Krück N. C. , Loh W. , Tibbetts I.
Published: January 2014

This study assessed the spawning activity of the threatened Australian lungfish Neoceratodus forsteri by measuring egg densities within the artificial habitat of a large impoundment (Lake Wivenhoe, Australia). Eggs were sampled (August to November 2009) from multiple locations across the impoundment, but occurred at highest densities in water shallower than 40 cm along shorelines with a dense cover of submerged terrestrial vegetation. The numbers of eggs declined over the study period and all samples were dominated by early developmental stages and high proportions of unviable eggs. The quality of the littoral spawning habitats declined over the study as flooded terrestrial grasses decomposed and filamentous algae coverage increased. Water temperatures at the spawning site exhibited extreme variations, ranging over 20·4° C in water shallower than 5 cm. Dissolved oxygen concentrations regularly declined to <1 mg l−1 at 40 and 80 cm water depth. Spawning habitats utilised by N. forsteri within impoundments expose embryos to increased risk of desiccation or excessive submergence through water‐level variations, and extremes in temperature and dissolved oxygen concentration that present numerous challenges for successful spawning and recruitment of N. forsteri in large impoundment environments.
Shake and stew: a non‐destructive PCR‐ready DNA isolation method from a single preserved fish larva
Authors: Alvarado Bremer J. R. , Smith B. L. , Moulton D. L. , Lu C.‐P. , Cornic M.
Published: January 2014

A rapid non‐destructive alternative to isolate DNA from an individual fish larva is presented, based on the suspension of epithelial cells through vortex forces, and the release of DNA in a heated alkaline solution. DNA from >6056 fish larvae isolated using this protocol has yielded a high PCR amplification success rate (>93%), suggesting its applicability to other taxonomic groups or sources when tissue amount is the limiting factor.
Restarting the Cycle: Incidence and Predictors of First Acute Care Use After Nursing Home Discharge
Authors: Toles Mark , Anderson Ruth A. , Massing Mark , Naylor Mary D. , Jackson Eric , Peacock‐Hinton Sharon , Colón‐Emeric Cathleen
Published: January 2014

Objectives

To describe the time to first acute care use (e.g., emergency department (ED) use without hospitalization or rehospitalization) for older adults discharged to home after receiving postacute care in skilled nursing facilities (SNFs); to identify predictors of first acute care use.

Design

Retrospective cohort study using administrative claims data.

Setting

SNFs providing postacute care for patients in North and South Carolina (N = 1,474).

Participants

A cohort of Medicare beneficiaries aged 65 and older (N = 55,980) who were hospitalized and then transferred to a SNF for postacute care and subsequently discharged home (January 1, 2010, to August 31, 2011).

Measurements

Medicare institutional claims data (Parts A and B) and Medicare enrollment data were used; facility‐level variables were obtained from CMS Nursing Home Compare. Survival from SNF discharge to first acute care use was explored. Cox proportional hazards regression models were used to describe individual‐, home care–, and nursing facility–level predictors.

Results

After discharge from SNF to home, 22.1% of older adults had an episode of acute care use within 30 days, including 7.2% with an ED visit without hospitalization and 14.8% with a rehospitalization; 37.5% of older adults had their first acute care use within 90 days. Male sex, dual eligibility status, higher Charlson comorbidity score, certain primary diagnoses at index hospitalization (neoplasms and respiratory disease), and care in SNFs with for‐profit ownership or fewer licensed practical nurses hours per patient‐day were associated with greater likelihood of acute care use.

Conclusion

Medicare beneficiaries have a high use of acute care services after discharge from SNFs, and several factors associated with acute care use are potentially modifiable. Findings suggest the need for interventions to support beneficiaries as they transition from SNFs to home.
Anticholinergic Activity in Cerebrospinal Fluid and Serum in Individuals with Hip Fracture with and without Delirium
Authors: Watne Leiv Otto , Hall Roanna J. , Molden Espen , Ræder Johan , Frihagen Frede , MacLullich Alasdair M. J. , Juliebø Vibeke , Nyman Armika , Meagher David , Wyller Torgeir B.
Published: January 2014

Objectives

To examine whether anticholinergic activity (AA) in cerebrospinal fluid (CSF) and serum is associated with risk of delirium in individuals with hip fracture.

Design

Prospective cohort study.

Setting

Two university hospitals in Oslo, Norway, and Edinburgh, UK.

Participants

Individuals admitted with acute hip fracture (N = 151).

Measurements

Participants were assessed daily for delirium using the Confusion Assessment Method (preoperatively and postoperative days 1–5 (all) or until discharge (participants with delirium)). Prefracture cognitive function was assessed using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Serum was collected preoperatively and CSF at the onset of spinal anesthesia. AA in serum (SAA) and CSF samples was determined according to a muscarinic radio receptor bioassay. The association between AA measures and delirium was evaluated using logistic multivariate analyses.

Results

Fifty‐two (54%) of the participants in Oslo and 20 (39%) in Edinburgh developed delirium. There was no statistically significant difference in AA between participants with and without delirium in Oslo (serum: 7.02 vs 6.08 pmol/mL, P = .54; CSF: 0.39 vs 0.48 pmol/mL, P = .26) or in Edinburgh (serum: 1.35 vs 1.62 pmol/mL, P = .76; CSF: 0.36 vs 0.31 pmol/mL, P = .93). Nor was there any difference in SAA (Oslo, P = .74; Edinburgh, P = .51) or CSF AA (Oslo, P = .21; Edinburgh, P = .93) when participants were subdivided into prevalent, incident, subsyndromal, and never delirium. Stratifying participants according to prefracture cognitive status (IQCODE) gave the same results.

Conclusion

This is the first study of AA in CSF of individuals with and without delirium. The study does not support the hypothesis that central (CSF) or peripheral (serum) AA is an important mechanism of delirium in individuals with hip fracture.
Demographic Characteristics and Healthcare Use of Centenarians: A Population‐Based Cohort Study
Authors: Rochon Paula A. , Gruneir Andrea , Wu Wei , Gill Sudeep S. , Bronskill Susan E. , Seitz Dallas P. , Bell Chaim M. , Fischer Hadas D. , Stephenson Anne L. , Wang Xuesong , Gershon Andrea S. , Anderson Geoffrey M.
Published: January 2014

Objectives

To better understand how centenarians use the healthcare system as an important step toward improving their service delivery.

Design

Population‐based retrospective cohort study using linked health administrative data.

Setting

Ontario—Canada's largest province.

Participants

All individuals living in Ontario aged 65 and older on April 1 of each year between 1995 and 2010 were identified and divided into three age groups (65–84, 85–99, ≥100). A detailed description was obtained on 1,842 centenarians who were alive on April 1, 2010.

Measurements

Sociodemographic characteristics and use of health services.

Results

The number of centenarians increased from 1,069 in 1995 to 1,842 in 2010 (72.3%); 6.7% were aged 105 and older. Over the same period, the number of individuals aged 85 to 99 grew from 119,955 to 227,703 (89.8%). Women represented 85.3% of all centenarians and 89.4% of those aged 105 and older. Almost half of centenarians lived in the community (20.0% independently, 25.3% with publicly funded home care). Preventive drug therapies (bisphosphonates and statins) were frequently dispensed. In the preceding year, 18.2% were hospitalized and 26.6% were seen in an emergency department. More than 95% saw a primary care provider, and 5.3% saw a geriatrician.

Conclusion

The number of centenarians in Ontario increased by more than 70% over the last 15 years, with even greater growth among older people who could soon become centenarians. Almost half of centenarians live in the community, most are women, and almost all receive care from a primary care physician.
Sulforaphane enhances proteasomal and autophagic activities in mice and is a potential therapeutic reagent for Huntington's disease
Authors: Liu Yanying , Hettinger Casey L. , Zhang Dong , Rezvani Khosrow , Wang Xuejun , Wang Hongmin
Published: January 2014

The ubiquitin proteasome system (UPS) is impaired in Huntington's disease, a devastating neurodegenerative disorder. Sulforaphane, a naturally occurring compound, has been shown to stimulate UPS activity in cell cultures. To test whether sulforaphane enhances UPS function in vivo, we treated UPS function reporter mice ubiquitously expressing the green fluorescence protein (GFP) fused to a constitutive degradation signal that promotes its rapid degradation in the conditions of a healthy UPS. The modified GFP is termed GFP UPS reporter (GFPu). We found that both GFPu and ubiquitinated protein levels were significantly reduced and the three peptidase activities of the proteasome were increased in the brain and peripheral tissues of the mice. Interestingly, sulforaphane treatment also enhanced autophagy activity in the brain and the liver. To further examine whether sulforaphane promotes mutant huntingtin (mHtt) degradation, we treated Huntington's disease cells with sulforaphane and found that sulforaphane not only enhanced mHtt degradation but also reduced mHtt cytotoxicity. Sulforaphane‐mediated mHtt degradation was mainly through the UPS pathway as the presence of a proteasome inhibitor abolished this effect. Taken together, these data indicate that sulforaphane activates protein degradation machineries in both the brain and peripheral tissues and may be a therapeutic reagent for Huntington's disease and other intractable disorders.

image

Accumulation of mutant huntingtin (mHtt) protein causes Huntington's disease (HD). Sulforaphane (SFN), a naturally occurring compound, increased proteasome and autophagy activities in vivo and enhanced mHtt turnover and cell survival in HD cell models. SFN‐mediated mHtt degradation is mainly through the proteasome pathway. These data suggest that SFN can be a therapeutic reagent for treating HD and other intractable disorders.
Rent‐Based Exploitation: Top, Bottom and Horizontal
Authors: Izyumov Alexei , Vahaly John
Published: January 2014

In this essay we argue that current emphasis on economic rents captured by the wealthy produces an incomplete representation of exploitative incomes and propose to expand the analysis by including in it economic rents accruing to segments of the poor and the working population.
Taxes, tax administrative burdens and new firm formation
Authors: Braunerhjelm Pontus , Eklund Johan E.
Published: January 2014

This paper examines the tax administrative burden and its effect on new firm formation. It is well recognized that entrepreneurship and new firm formation are critical factors in determining economic growth and development. New firm entry into the marketplace enhances welfare in two distinct ways: 1) by promoting innovation, productivity and economic growth and 2) by increasing competition, which lowers prices and expands output. It is also well documented that barriers to entry reduce the likelihood that new firms will enter various sectors. We argue that the burden imposed by tax codes and tax compliance constitutes a barrier to entry that has been neglected in the previous literature. We use data from the World Bank to measure the administrative burden that the complexity of tax policy imposes on new firms. Additionally, we use a measure of new firm formation – entry density. Our data cover 118 countries over a period of six years. We find that the entry rate is significantly reduced by the tax administrative burden and that this effect is unrelated to general taxes on corporate profits and is robust to the inclusion of several important control variables.
Clinical and metabolic factors associated with development and regression of nonalcoholic fatty liver disease in nonobese subjects
Authors: Kim Nam Hoon , Kim Joo Hyung , Kim Yoon Jung , Yoo Hye Jin , Kim Hee Young , Seo Ji A , Kim Nan Hee , Choi Kyung Mook , Baik Sei Hyun , Choi Dong Seop , Kim Sin Gon
Published: January 2014

Background & Aims

The course of NAFLD (nonalcoholic fatty liver disease) and associated factors in nonobese subjects are not well established. We investigated contributing factors for the development and regression of NAFLD in nonobese Koreans, and whether they would differ from those of obese subjects.

Methods

Two thousand three hundred and seven adults aged over 18 years participated in this longitudinal observational study. The mean duration of follow‐up was 28.7 (±13.2) months. The participants were divided into two groups according to the baseline BMI (nonobese group: BMI <25 kg/m2, obese group: BMI ≥25 kg/m2). The presence or absence of NAFLD was assessed by abdominal ultrasonography.

Results

Body weight change was independently associated with both the development and regression of NAFLD in nonobese subjects as well as obese subjects. Among the subjects who developed NAFLD, the amount of weight change was higher in nonobese subjects compared to obese subjects (1.6 ± 3.9% vs 0.6 ± 4.2%, P = 0.022); and among those who showed regression of NAFLD, the amount of weight change was lower in nonobese subjects (−1.9 ± 4.0% vs −5.0 ± 4.6%, P < 0.001). Among all the components of metabolic syndrome, only high triglyceride levels (>150 mg/dl) at the baseline were significantly associated with both the development and regression of NAFLD in nonobese subjects (ORs, 1.54 (1.10–2.14), and 0.60 (0.38–0.96) respectively).

Conclusion

Body weight change and baseline triglyceride levels were strong indicators for the development and regression of NAFLD in a nonobese population.
The p53 mutation spectrum in hepatocellular carcinoma from Guangxi, China : role of chronic hepatitis B virus infection and aflatoxin B1 exposure
Authors: Qi Lu‐Nan , Bai Tao , Chen Zu‐Shun , Wu Fei‐Xiang , Chen Yuan‐Yuan , De Xiang Bang‐ , Peng Tao , Han Ze‐Guang , Li Le‐Qun
Published: January 2014

Background & Aims

p53 is one of the most frequently mutated human tumour suppressor genes. Chronic infection with hepatitis B virus (HBV) and exposure to aflatoxin B1 (AFB1) induces p53 mutations in hepatocellular carcinoma (HCC) tissue. The aims of present study are to investigate the p53 mutation spectrum in HBV‐ and AFB1‐related hepatocarcinogenesis in patients with hepatocellular carcinoma (HCC) in Guangxi, China.

Methods

Tumour and adjacent liver tissue were collected from 397 HCC patients who were subdivided into HBV(+)/AFB1(+), HBV(+)/AFB1(−), HBV(−)/AFB1(+) and HBV(−)/AFB1(−) four groups. All 11 exons of the p53 gene were PCR‐amplified and sequenced. Immunohistochemistry was used to evaluate the effect of mutations on the expression of p53 protein.

Results and Conclusions

P53 mutations were detected in 223 HCC samples, 13 adjacent liver tissue samples and only 1 of 68 normal liver tissue samples. The mutation sites concentrated at exon 4, 5, 6, 7, 8, 9 and no mutation was detected in exon 1, 2, 3, 10 and 11. The most frequently occurring mutation was in codon 249 (R249S) in exon 7. Patients in the HBV(+)/AFB1(+) and HBV(−)/AFB1(+) groups had significantly higher mutation rates compared with patients in the HBV(+)/AFB1(−) and HBV(−)/AFB1(−) groups. P53 mutation status and HBV/AFB1 status were independent predictors of tumour recurrence after surgery. Immunohistochemical analysis revealed that p53 gene mutations were correlated with the p53 expression. In Guangxi area, the significant association between AFB1‐induced p53 mutations and the expression of p53 protein suggest an important role for p53 mutations in carcinogenesis of HCC.
Female mating preferences and offspring survival: testing hypotheses on the genetic basis of mate choice in a wild lekking bird
Authors: Sardell Rebecca J. , Kempenaers Bart , DuVal Emily H.
Published: January 2014

Indirect benefits of mate choice result from increased offspring genetic quality and may be important drivers of female behaviour. ‘Good‐genes‐for‐viability’ models predict that females prefer mates of high additive genetic value, such that offspring survival should correlate with male attractiveness. Mate choice may also vary with genetic diversity (e.g. heterozygosity) or compatibility (e.g. relatedness), where the female's genotype influences choice. The relative importance of these nonexclusive hypotheses remains unclear. Leks offer an excellent opportunity to test their predictions, because lekking males provide no material benefits and choice is relatively unconstrained by social limitations. Using 12 years of data on lekking lance‐tailed manakins, Chiroxiphia lanceolata, we tested whether offspring survival correlated with patterns of mate choice. Offspring recruitment weakly increased with father attractiveness (measured as reproductive success, RS), suggesting attractive males provide, if anything, only minor benefits via offspring viability. Both male RS and offspring survival until fledging increased with male heterozygosity. However, despite parent–offspring correlation in heterozygosity, offspring survival was unrelated to its own or maternal heterozygosity or to parental relatedness, suggesting survival was not enhanced by heterozygosity per se. Instead, offspring survival benefits may reflect inheritance of specific alleles or nongenetic effects. Although inbreeding depression in male RS should select for inbreeding avoidance, mates were not less related than expected under random mating. Although mate heterozygosity and relatedness were correlated, selection on mate choice for heterozygosity appeared stronger than that for relatedness and may be the primary mechanism maintaining genetic variation in this system despite directional sexual selection.
Genomic evaluation of oxalate‐degrading transgenic soybean in response to Sclerotinia sclerotiorum infection
Authors: Calla Bernarda , Blahut‐Beatty Laureen , Koziol Lisa , Zhang Yunfang , Neece David J. , Carbajulca Doris , Garcia Alexandre , Simmonds Daina H. , Clough Steven J.
Published: January 2014

Oxalate oxidases (OxO) catalyse the degradation of oxalic acid (OA). Highly resistant transgenic soybean carrying an OxO gene and its susceptible parent soybean line, AC Colibri, were tested for genome‐wide gene expression in response to the necrotrophic, OA‐producing pathogen Sclerotinia sclerotiorum using soybean cDNA microarrays. The genes with changed expression at statistically significant levels (overall F‐test P‐value cut‐off of 0.0001) were classified into functional categories and pathways, and were analysed to evaluate the differences in transcriptome profiles. Although many genes and pathways were found to be similarly activated or repressed in both genotypes after inoculation with S. sclerotiorum, the OxO genotype displayed a measurably faster induction of basal defence responses, as observed by the differential changes in defence‐related and secondary metabolite genes compared with its susceptible parent AC Colibri. In addition, the experiment presented provides data on several other transcripts that support the hypothesis that S. sclerotiorum at least partially elicits the hypersensitive response, induces lignin synthesis (cinnamoyl CoA reductase) and elicits as yet unstudied signalling pathways (G‐protein‐coupled receptor and related). Of the nine genes showing the most extreme opposite directions of expression between genotypes, eight were related to photosynthesis and/or oxidation, highlighting the importance of redox in the control of this pathogen.
Optimization of virus‐induced gene silencing in Catharanthus roseus
Authors: Sung Y.‐C. , Lin C.‐P. , Chen J.‐C.
Published: January 2014

Catharanthus roseus (periwinkle) contains abundant alkaloids and is the only commercial source of two cancer drugs, vinblastine and vincristine. The plant is also used as an experimental host for phytoplasmas because it can be infected by most phytoplasmas and shows distinctive symptoms. Abundant gene sequences for periwinkle have become available through high‐throughput transcriptome sequencing, so periwinkle has become an ideal model for studies of alkaloid metabolism and plant–phytoplasma interactions. Tobacco rattle virus (TRV)‐based virus‐induced gene silencing (VIGS) for functional genomics studies has been established, but the duration of the system was too short for plant–phytoplasma interaction studies. To improve the system, several factors were analysed, including culture temperature, plant age, leaf age, organ preferences and virus distribution, for their effects on VIGS efficacy. A new agroinfiltration method was also used for inoculating entire seedlings. High temperature (30°C) strongly inhibited VIGS, but low temperature (16°C) inhibited plant growth. VIGS efficacy was reduced in old leaves but was not affected by plant age. VIGS occurred in all examined organs, including roots, stems, leaves and flowers, but was most effective in leaves and flowers. The TRV‐based system required the existence of TRV2 to maintain gene silencing, so TRV2 concentration may be used as an indicator of successful gene silencing. The optimized VIGS system was useful for studies of plant–phytoplasma interactions and conferred gene silencing for more than 6 months.
The Lymphoid Chemokine CCL21 Enhances the Cytotoxic T Lymphocyte‐Inducing Functions of Dendritic Cells
Authors: Hong C. Y. , Lee H.‐J. , Kim H.‐J. , Lee J.‐J
Published: January 2014

The potential use of lymphoid chemokines to generate a dendritic cell (DC) cancer vaccine is not yet clear. We investigated the effect of lymphoid chemokines on DC function and on the production of effective cytotoxic T lymphocytes (CTLs) for application of cancer vaccine using monocyte‐derived mature DCs (mDCs) prestimulated with lymphoid chemokines. mDCs exposed to a secondary lymphoid organ chemokine (SLC/CCL21) dramatically induced CTL response by increasing cytolytic activity without any significant alterations on expression of cell surface markers (e.g. CD80, CD83, CD86 and CCR7) or on the production of cytokines (e.g. IL‐12p70, IL‐10 and IL‐23). Interestingly, mDCs prestimulated with CCL21 showed higher levels of CXCL10 (IP‐10) production, but not the production of CCL22, compared with untreated mDCs. IP‐10 treatment during CTL generation with DCs dramatically enhanced tumour‐specific CTL response compared with untreated CTLs, and these enhanced CTL‐inducing functions of CCL21‐treated DCs were inhibited by anti‐IP‐10 treatment. Taken together, our data suggested an important role of the lymphoid‐endothelium‐associated chemokine, CCL21, on DCs in the induction of CTL responses.
IL‐17 and Glutamate Excitotoxicity in the Pathogenesis of Multiple Sclerosis
Authors: Kostic M. , Dzopalic T. , Zivanovic S. , Zivkovic N. , Cvetanovic A. , Stojanovic I. , Vojinovic S. , Marjanovic G. , Savic V. , Colic M.
Published: January 2014

Immunoinflammatory‐mediated demyelination, the main pathological feature of multiple sclerosis (MS), is regularly accompanied by neurodegenerative processes, mostly in the form of axonal degeneration, which could be initiated by glutamate excitotoxicity. In the current study, the relationship between Th17‐mediated inflammatory and excitotoxic events was investigated during an active phase of MS. Cerebrospinal fluid (CSF) of patients with MS and control subjects was collected, and IL‐17A and glutamate levels were determined. IL‐17A level was significantly higher in patients with MS; whereas no statistically significant changes in glutamate concentrations were found. There was a direct correlation between IL‐17A and glutamate levels; IL‐17A levels were also associated with the neutrophil expansion in CSF and blood–brain barrier disruption. However, IL‐17A level and the number of neutrophils tended to fall with disease duration. The results suggest that Th17 cells might enhance and use glutamate excitotoxicity as an effector mechanism in the MS pathogenesis. Furthermore, Th17 immune response, as well as neutrophils, could be more important for MS onset rather than further disease development and progression, what could explain why some MS clinical trials, targeting Th17 cells in the later stage of the disease, failed to provide any clinical benefit.
Quinoline‐3‐Carboxamides Modulate Primary T Cell‐Dependent B Cell Responses but do not Inhibit Functional Immunity
Authors: Källberg E. , Ivars F. , Leanderson T.
Published: January 2014

The effect of a quinoline‐3‐carboxamide on the T cell‐dependent B cell response was investigated in C57BL/6 mice after NP‐CGG immunization. The primary serum response to the hapten was slightly inhibited by treatment with a quinoline‐3‐carboxamide. This inhibition was paralleled by reduced numbers of germinal centre (GC) B cells and follicular T cells in the spleen up to 21 days after immunization. Also, both the number of GCs formed and their size were reduced by quinoline‐3‐carboxamide treatment. In contrast to the observation in the primary immune response, there was no inhibitory effect on the secondary immune response. These data could help to explain how quinoline‐3‐carboxamides can modulate immune function in autoimmune diseases without being immunosuppressive.
The Role of T cell Immunoglobulin and Mucin Domain‐3 in Immune Thrombocytopenia
Authors: Zhang X.‐M. , Shan N.‐N.
Published: January 2014

T cell immunoglobulin and mucin domain‐3 (TIM‐3), originally identified as a T helper (Th) 1‐specific type I membrane protein, plays a vital role in Th1 immunity and tolerance induction through interaction with its ligand, galectin‐9. The binding of TIM‐3 by galectin‐9 serves to downregulate Th1 responses. Moreover, the regulatory function of TIM‐3 has been extended to other cells, such as Th17 cells, CD4+CD25+ regulatory T cells (Tregs), CD8+ T cells and certain innate immune cells. Previous studies have acknowledged that the TIM‐3 pathway is involved in the pathogenesis of several human autoimmune diseases, such as systemic lupus erythematous, rheumatoid arthritis and aplastic anaemia. Moreover, genetic data suggest a role for TIM‐3 in human autoimmune diseases. However, in immune thrombocytopenia (ITP), a common Th1‐ and possibly Th17‐biased autoimmune disorder, the role of TIM‐3 has not been explored. Recently, our data have demonstrated that TIM‐3 expression is reduced in ITP patients, and we have found a potential link between ITP and the TIM‐3 pathway. In this article, we discuss and speculate on the role of the TIM‐3 pathway in ITP.
Fates of Setaria faberi and Abutilon theophrasti seeds in three crop rotation systems
Authors: Liebman M , Miller Z J , Williams C L , Westerman P R , Dixon P M , Heggenstaller A , Davis A S , Menalled F D , Sundberg D N
Published: January 2014

Weed seeds in and on the soil are the primary cause of weed infestations in arable fields. Previous studies have documented reductions in weed seedbanks due to cropping system diversification through extended rotation sequences, but the impacts of different rotation systems on additions to and losses from weed seedbanks remain poorly understood. We conducted an experiment in Iowa, USA, to determine the fates of Setaria faberi and Abutilon theophrasti seeds in 2‐, 3‐ and 4‐year crop rotation systems when seed additions to the soil seedbank were restricted to a single pulse at the initiation of the study. Over the course of the experiment, seedlings were removed as they emerged and prevented from producing new seeds. After 41 months, seed population densities dropped >85% for S. faberi and >65% for A. theophrasti, but differences between rotation systems in the magnitude of seedbank reductions were not detected. Most of the reductions in seedbank densities took place from autumn through early spring in the first 5 months following seed deposition, before seedling emergence occurred, suggesting that seed predation and/or seed decay was important. For S. faberi, total cumulative seedling emergence and total seed mortality did not differ between rotation systems. In contrast, for A. theophrasti, seedling emergence was 71% lower and seed mortality was 83% greater in the 3‐ and 4‐year rotation systems than in the 2‐year system. Results of this study indicate that for certain weed species, such as A. theophrasti, crop rotation systems can strongly affect life‐history processes associated with soil seedbanks.
Experimental Validation of Finite Element Analysis of Human Vertebral Collapse Under Large Compressive Strains
Authors: Hosseini Hadi S. , Clouthier Allison L. , Zysset Philippe K.
Published: January 2014

Osteoporosis-related vertebral fractures represent a major health problem in elderly populations. Such fractures can often only be diagnosed after a substantial deformation history of the vertebral body. Therefore, it remains a challenge for clinicians to distinguish between stable and progressive potentially harmful fractures. Accordingly, novel criteria for selection of the appropriate conservative or surgical treatment are urgently needed. Computer tomography-based finite element analysis is an increasingly accepted method to predict the quasi-static vertebral strength and to follow up this small strain property longitudinally in time. A recent development in constitutive modeling allows us to simulate strain localization and densification in trabecular bone under large compressive strains without mesh dependence. The aim of this work was to validate this recently developed constitutive model of trabecular bone for the prediction of strain localization and densification in the human vertebral body subjected to large compressive deformation. A custom-made stepwise loading device mounted in a high resolution peripheral computer tomography system was used to describe the progressive collapse of 13 human vertebrae under axial compression. Continuum finite element analyses of the 13 compression tests were realized and the zones of high volumetric strain were compared with the experiments. A fair qualitative correspondence of the strain localization zone between the experiment and finite element analysis was achieved in 9 out of 13 tests and significant correlations of the volumetric strains were obtained throughout the range of applied axial compression. Interestingly, the stepwise propagating localization zones in trabecular bone converged to the buckling locations in the cortical shell. While the adopted continuum finite element approach still suffers from several limitations, these encouraging preliminary results towardsthe prediction of extended vertebral collapse may help in assessing fracture stability in future work.
Effect of plasma treatment of resistive layer on a Cu/SiOx/Pt memory device
Authors: Liu Chih-Yi , Tsai Yueh-Ying , Lai Chun-Hung
Published: January 2014

In this paper, a 20-nm SiOx thin film was deposited on a Pt/Ti/SiO2/Si substrate using radio-frequency magnetron sputtering. A Cu top electrode was deposited to form a Cu/SiOx/Pt device. The device was reversibly switched between a low-resistance state and a high-resistance state using DC voltage sweeping. Because of its bipolar switching behavior and the device structure, the switching mechanism can be explained by the formation and rupture of Cu filaments within the SiOx layer. An Argon (Ar) plasma treatment was used to modify the SiOx layer, which stabilized the resistive switching and, thus, improved the switching dispersion. The Ar plasma treatment caused ion bombardment, which increased the Cu diffusion coefficient within the SiOx layer, thus decreasing the operating voltage. In addition, various level of bombardment within the SiOx film caused partial damage of the SiOx film, which influenced the switching dispersion. The Ar-treated device in the 20-s plasma treatment demonstrated favorable memory properties, including a long retention time, nondestructive readout, and high resistance ratio, indicating that it could be viably applied in next-generation nonvolatile memory devices.
Leading U.S. X-ray Source Goes After Bigger Upgrade
Authors: Cho Adrian
Published: January 2014

U.S. physicists want to completely rebuild the particle accelerator that drives the Advanced Photon Source, a more radical—and disruptive—upgrade than originally planned.
Google Scholar Wins Raves—But Can It Be Trusted?
Authors: Bohannon John
Published: January 2014

Scientists have embraced the free academic search service Google Scholar. But its citation metric can be gamed.
Draft Genome Sequence of the Alga-Aggregating Bacterium
Bacillus
sp. Strain RP1137
Authors: Powell Ryan J. , Bachvaroff Tsvetan R. , Hill Russell T.
Published: January 2014

Bacillus
sp. strain RP1137 is a bacterium that is able to rapidly and efficiently aggregate biofuel-producing microalgae. By 16S rRNA gene sequencing, it was found to be related to the industrially important
Bacillus megaterium
. Here, we report the draft genome sequence of
Bacillus
sp. strain RP1137.
Association of early adult modifiable cardiovascular risk factors with left atrial size over a 20-year follow-up period: the CARDIA study
Authors: Armstrong Anderson C , Gidding Samuel S , Colangelo Laura A , Kishi Satoru , Liu Kiang , Sidney Stephen , Konety Suma , Lewis Cora E , Correia Luís C L , Lima Joao A C
Published: January 2014

Objectives

We investigate how early adult and 20-year changes in modifiable cardiovascular risk factors (MRF) predict left atrial dimension (LAD) at age 43–55 years.

Methods

The Coronary Artery Risk Development in Young Adults (CARDIA) study enrolled black and white adults (1985–1986). We included 2903 participants with echocardiography and MRF assessment in follow-up years 5 and 25. At years 5 and 25, LAD was assessed by M-mode echocardiography, then indexed to body surface area (BSA) or height. Blood pressure (BP), body mass index (BMI), heart rate (HR), smoking, alcohol use, diabetes and physical activity were defined as MRF. Associations of MRF with LAD were assessed using multivariable regression adjusted for age, ethnicity, gender and year-5 left atrial (LA) size.

Results

The participants were 30±4 years; 55% white; 44% men. LAD and LAD/height were modest but significantly higher over the follow-up period, but LAD/BSA decreased slightly. Increased baseline and 20-year changes in BP were related to enlargement of LAD and indices. Higher baseline and changes in BMI were also related to higher LAD and LAD/height, but the opposite direction was found for LAD/BSA. Increase in baseline HR was related to lower LAD but not LAD indices, when only baseline covariates were included in the model. However, baseline and 20-year changes in HR were significantly associated to LA size.

Conclusions

In a biracial cohort of young adults, the most robust predictors for LA enlargement over a 20-year follow-up period were higher BP and BMI. However, an inverse direction was found for the relationship between BMI and LAD/BSA. HR showed an inverse relation to LA size.