bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carnitine Palmitoyltransferase-1b Deficiency Aggravates Pressure Overload–Induced Cardiac Hypertrophy Caused by Lipotoxicity
Authors: He Lan , Kim Teayoun , Long Qinqiang , Liu Jian , Wang Peiyong , Zhou Yiqun , Ding Yishu , Prasain Jeevan , Wood Philip A. , Yang Qinglin 
Published: August 2012

Background—
Carnitine palmitoyltransferase-1 (CPT1) is a rate-limiting step of mitochondrial β-oxidation by controlling the mitochondrial uptake of long-chain acyl-CoAs. The muscle isoform, CPT1b, is the predominant isoform expressed in the heart. It has been suggested that inhibiting CPT1 activity by specific CPT1 inhibitors exerts protective effects against cardiac hypertrophy and heart failure. However, clinical and animal studies have shown mixed results, thereby creating concerns about the safety of this class of drugs. Preclinical studies using genetically modified animal models should provide a better understanding of targeting CPT1 to evaluate it as a safe and effective therapeutic approach.

Methods and Results—

Heterozygous CPT1b knockout (CPT1b
+/−
) mice were subjected to transverse aorta constriction–induced pressure overload. These mice showed overtly normal cardiac structure/function under the basal condition. Under a severe pressure-overload condition induced by 2 weeks of transverse aorta constriction, CPT1b
+/−
mice were susceptible to premature death with congestive heart failure. Under a milder pressure-overload condition, CPT1b
+/−
mice exhibited exacerbated cardiac hypertrophy and remodeling compared with wild-type littermates. There were more pronounced impairments of cardiac contraction with greater eccentric cardiac hypertrophy in CPT1b
+/−
mice than in control mice. Moreover, the CPT1b
+/−
heart exhibited exacerbated mitochondrial abnormalities and myocardial lipid accumulation with elevated triglycerides and ceramide content, leading to greater cardiomyocyte apoptosis.

Conclusions—
CPT1b deficiency can cause lipotoxicity in the heart under pathological stress, leading to exacerbation of cardiac pathology. Therefore, caution should be exercised in the clinical use of CPT1 inhibitors.
Right Ventricular Structure Is Associated With the Risk of Heart Failure and Cardiovascular Death
Authors: Kawut Steven M. , Barr R. Graham , Lima João A.C. , Praestgaard Amy , Johnson W. Craig , Chahal Harjit , Ogunyankin Kofo O. , Bristow Michael R. , Kizer Jorge R. , Tandri Harikrishna , Bluemke David A. 
Published: August 2012

Background—
Changes in right ventricular (RV) morphology are associated with morbidity and mortality in heart and lung disease. We examined the association of abnormal RV structure and function with the risk of heart failure or cardiovascular death in a population-based multiethnic sample free of clinical cardiovascular disease at baseline.

Methods and Results—

The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on 5098 participants between 2000 and 2002 with follow-up for incident heart failure and cardiovascular death (“death”) until January 2008. RV volumes and mass were available for 4204 participants. The study sample (n=4144) was 61.4±10.1 years old and 47.6% male. The presence of RV hypertrophy (increased RV mass) was associated with more than twice the risk of heart failure or death after adjustment for demographics, body mass index, education, C-reactive protein level, hypertension, and smoking status (hazard ratio, 2.52; 95% confidence interval, 1.55–4.10;
P
<0.001) and a doubling (or more) of risk with left ventricular mass at the mean value or lower (
P
for interaction=0.05).

Conclusions—
RV hypertrophy was associated with the risk of heart failure or death in a multiethnic population free of clinical cardiovascular disease at baseline.
Physiological-based pharmacokinetic modeling of endotoxin in the rat
Authors: Hutter Joseph C , Kim Chung S 
Published: August 2012

We have previously measured the distribution and pharmacokinetics of biosynthetically radiolabeled endotoxin of Salmonella typhimurium following intraperitoneal (IP) dosing (200 μg/kg) in Sprague-Dawley rats. In our experiments, the fatty acid residues were labeled with 3H and the glucosamine residues were labeled with 14C. To predict the dynamics of endotoxin exposure, we developed a physiological-based pharmacokinetic model using our measured distribution results. The model was validated with published low-dose (30 μg/kg) IP exposure results in rats. Endotoxin pharmacokinetics depended on dose and route. At high IP doses, absorption was followed by biphasic decay over 48 h in plasma. There were tissue accumulations of the fatty acid and glucosamine residues in various target organs, including the brain. We also found that the glucosamine and fatty acid components separated in vivo about 3 h after IP injection. At the lower IP dose, a smaller fraction of the dose was distributed to the tissues, with most of the dose remaining in the blood. Each component had its own dynamic behavior and target tissue distribution in the rat. The fatty acid components tended to remain in the brain stem, caudate nucleus, cerebellum, frontal cortex, hippocampus, and hypothalamus. Other organs (spleen, kidney, meninges, and choroid plexus) had similar biphasic distribution. The liver had the unique accumulation of both glucosamine and fatty acid residues.
Conditional TRF1 knockout in the hematopoietic compartment leads to bone marrow failure and recapitulates clinical features of dyskeratosis congenita
Authors: Beier Fabian , Foronda Miguel , Martinez Paula , Blasco Maria A. 
Published: August 2012

Abstract
TRF1 is part of the shelterin complex, which binds telomeres and it is essential for their protection. Ablation of TRF1 induces sister telomere fusions and aberrant numbers of telomeric signals associated with telomere fragility. Dyskeratosis congenita is characterized by a mucocutaneous triad, bone marrow failure (BMF), and presence of short telomeres because of mutations in telomerase. A subset of patients, however, show mutations in the shelterin component TIN2, a TRF1-interacting protein, presenting a more severe phenotype and presence of very short telomeres despite normal telomerase activity. Allelic variations in TRF1 have been found associated with BMF. To address a possible role for TRF1 dysfunction in BMF, here we generated a mouse model with conditional TRF1 deletion in the hematopoietic system. Chronic TRF1 deletion results in increased DNA damage and cellular senescence, but not increased apoptosis, in BM progenitor cells, leading to severe aplasia. Importantly, increased compensatory proliferation of BM stem cells is associated with rapid telomere shortening and further increase in senescent cells in vivo, providing a mechanism for the very short telomeres of human patients with mutations in the shelterin TIN2. Together, these results represent proof of principle that mutations in TRF1 lead to the main clinical features of BMF.
Interphase Chromosome Flow-FISH
Authors: Keyvanfar Keyvan , Weed Jason , Swamy Prashanth , Kajigaya Sachiko , Calado Rodrigo T. , Young Neal S. 
Published: August 2012

Abstract
A 2-day method using flow cytometry and FISH for interphase cells was developed to detect monosomy 7 cells in myelodysplastic syndrome patients. The method, Interphase Chromosome Flow-FISH (IC Flow-FISH), involves fixation of leukocytes from blood, membrane permeabilization, hybridization of cellular DNA with peptide nucleic acid probes with cells intact, and analysis by flow cytometry. Hundreds to thousands of monosomy 7 cells were consistently detected from 10-20 mL of blood in patients with monosomy 7. Proportions of monosomy 7 cells detected in IC Flow-FISH were compared with results from conventional cytogenetics; identification of monosomy 7 populations was verified with FACS; and patient and donor cells were mixed to test for sensitivity. IC Flow-FISH allows for detecting monosomy 7 without requiring bone marrow procurement or the necessity of metaphase spreads, and wider applications to other chromosomal abnormalities are in development.
Comment on ‘Approximate ∗-derivations and approximate quadratic ∗-derivations on "Equation missing" -algebras’ [Jang, Park, J. Inequal. Appl. 2011 (2011), Article ID 55]
Authors: Park Choonkil , Shin Dong Yun , Lee Jung Rye , Lee Sung Jin 
Published: August 2012

Abstract
In (J. Inequal. Appl. 2011:Article ID 55, Section 4, 2011), Jang and Park proved the Hyers-Ulam stability of quadratic ∗-derivations on Banach ∗-algebras. One can easily show that all the quadratic ∗-derivations δ in Section 4 must be trivial. So the results are trivial. In this paper, we correct the statements and prove the corrected results.

MSC:39B52, 47B47, 39B72.
Urinary N-acetyl-β-D glucosaminidase as a surrogate marker for renal function in autosomal dominant polycystic kidney disease: 1 year prospective cohort study
Authors: Park Hayne Cho , Hwang Jin Ho , Kang Ah-Young , Ro Han , Kim Myung-Gyu , An Jung Nam , In Park Ji , Kim Seung Hyup , Yang Jaeseok , Oh Yun Kyu , Oh Kook-Hwan , Noh Jung Woo , Cheong Hae Il , Hwang Young-Hwan , Ahn Curie 
Published: August 2012

Abstract

Background
Renal failure is one of the most serious complications associated with autosomal dominant polycystic kidney disease (ADPKD). To date, early markers have failed to predict renal function deterioration at the early stages. This 1-year prospective study evaluated N-acetyl-β-D-glucosaminidase (NAG) as a new surrogate marker for renal function in ADPKD.

Methods
A total of 270 patients were enrolled in the study, and we measured urinary NAG, β2-microglobulin, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) prospectively for 1 year to compare their predictive values for renal function.

Results
Baseline urinary NAG/Cr was negatively correlated with estimated glomerular filtration rate (GFR) (r

2
= 0.153, P < 0.001) and positively correlated with total kidney volume (TKV) (r

2
= 0.113, P < 0.001). Among other biomarkers, urinary NAG/Cr better discriminated patients with decreased renal function from those with conserved renal function, showing the largest area under the curve (AUC 0.794). Immunohistochemical study revealed strong staining along the cyst-lining epithelial cells as well as the nearby compressed tubular epithelial cells. However, both single and repeated measurements of urinary NAG/Cr failed to predict renal function decline in 1 year.

Conclusions
Urinary NAG/Cr may be a useful surrogate marker for renal function in ADPKD patients.
Prevalence of KRAS, BRAF, and PIK3CA somatic mutations in patients with colorectal carcinoma may vary in the same population: clues from Sardinia
Authors: Palomba Grazia , Colombino Maria , Contu Antonio , Massidda Bruno , Baldino Giovanni , Pazzola Antonio , Ionta MariaTeresa , Capelli Francesca , Trova Vittorio , Sedda Tito , Sanna Giovanni , Tanda Francesco , Budroni Mario ,   Sardinian Translational Oncology Group (STOG), Palmieri Giuseppe , Cossu Antonio 
Published: August 2012

Abstract

Background
Role of KRAS, BRAF and PIK3CA mutations in pathogenesis of colorectal cancer (CRC) has been recently investigated worldwide. In this population-based study, we evaluated the incidence rates and distribution of such somatic mutations in genetically isolated population from Sardinia.

Methods
From April 2009 to July 2011, formalin-fixed paraffin-embedded tissues (N = 478) were prospectively collected from Sardinian CRC patients at clinics across the entire island. Genomic DNA was isolated from tissue sections and screened for mutations in KRAS, BRAF, and PIK3CA genes by automated DNA sequencing.

Results
Overall, KRAS tumour mutation rate was 30% (145/478 positive cases). Distribution of mutation carriers was surprisingly different within the island: 87/204 (43%) in North Sardinia vs. 58/274 (21%) in Middle-South Sardinia (p<0.001). Among 384 CRC cases whose DNA was available, only one (0.3%) patient carried a mutation in BRAF gene; PIK3CA was found mutated in 67 (17%) patients. A significant inverse distribution of PIK3CA mutation rates was observed within Sardinian population: 19/183 (10%) cases from northern vs. 48/201 (24%) cases from central-southern island (p<0.001). This heterogeneity in frequencies of KRAS/PIK3CA somatic mutations is consistent with already-reported discrepancies in distribution of germline mutations for other malignancies within Sardinian population. Preliminary clinical evaluation of 118 KRAS wild-type patients undergoing anti-EGFR-based treatment indicated lack of role for PIK3CA in predicting response to therapy.

Conclusions
Our findings support the hypothesis that differences in patients’ origins and related genetic backgrounds may contribute to even determine the incidence rate of somatic mutations in candidate cancer genes.
Optimization for image transmission over varying channel with MCMC
Authors: Wu Xiaobin , Cao Lei , Goggans Paul 
Published: August 2012

Abstract

Abstract
Existing work in media transmission generally assumes that the channel condition is stationary. However, communication channels are often varying with time in practice. Adaptive design needs frequent feedback for channel updates, which is often impractical due to the complexity and delay. In this article, we design the unequal error protection for image transmission over noisy varying channels based on their distribution functions. Since the channel effect must be marginalized in order to find the appropriate rate allocation, the optimization problem is very complex. We propose to solve this problem using the Markov Chain Monte Carlo (MCMC) method. The cost function is first mapped into a multi-variable probability distribution. Then, with the “detailed balance”, MCMC is designed to generate samples from the mapped stationary probability distribution so that the optimal solution is the one that gives the lowest data distortion. We also show that the rate allocation design considering the channel probability function works better than the design considering the mean value of the channel.
Direct path detection using multipath interference cancelation for communication-based positioning system
Authors: Yang Jiaxin , Wang Xianbin , Park Sung Ik , Kim Heung Mook 
Published: August 2012

Abstract

Abstract
Recent development in wireless communication-based positioning technology brings significant challenge of detecting the weak signal component arriving from the direct propagation path for time-of-arrival (TOA)-based approach. Due to the common obstruction of the direct propagation path in dense multipath environments, identification of the weak direct path in these environments can be very difficult via the classical correlation-based estimator in the presence of interference from significant later arriving multipath components. A new direct path detection scheme using the multipath interference cancelation is presented in this article. For data communication purpose, an iterative estimator with improved accuracy for joint channel and data estimation is first developed; based on which, the interference of multipath components are reconstructed and subtracted from the original received signal. With the aid of the detected data, an enhanced preamble is formulated. The accuracy of direct path detection is substantially improved by using the correlation between the multipath interference-suppressed signal and the enhanced preamble. Semi-analytical expression of the performance of the iterative estimator is derived. The analysis enables the system to determine an automatic stopping criterion to reduce the computational complexity of the iterative process. The performance of the direct path detection is also analyzed in terms of the signal-to-interference-noise ratio (SINR) and compared with that of the conventional approach. Computer simulation results show the superiority of the proposed direct path detection. The accuracy of the positioning system using the proposed method is also evaluated in dense multipath environments.
Molecular correlates and prognostic significance of SATB1 expression in colorectal cancer
Authors: Nodin Björn , Johannesson Henrik , Wangefjord Sakarias , O’Connor Darran P , Lindquist Kajsa Ericson , Uhlén Mathias , Jirström Karin , Eberhard Jakob 
Published: August 2012

AbstractBackgroundSpecial AT-rich sequence-binding protein 1 (SATB1) is a global gene regulator that has been reported to confer malignant behavior and associate with poor prognosis in several cancer forms. SATB1 expression has been demonstrated to correlate with unfavourable tumour characteristics in rectal cancer, but its association with clinical outcome in colorectal cancer (CRC) remains unclear. In this study, we examined the prognostic impact of SATB1 expression in CRC, and its association with important molecular characteristics; i.e. beta-catenin overexpression, microsatellite instability (MSI) screening status, and SATB2 expression.MethodsImmunohistochemical expression of SATB1 and beta-catenin was assessed in tissue microarrays with tumours from 529 incident CRC cases in the prospective population-based Malmö Diet and Cancer Study, previously analysed for SATB2 expression and MSI screening status. Spearmans Rho and Chi-Square tests were used to explore correlations between SATB1 expression, clinicopathological and investigative parameters. Kaplan Meier analysis and Cox proportional hazards modelling were used to explore the impact of SATB1 expression on cancer specific survival (CSS) and overall survival (OS).ResultsSATB1 was expressed in 222 (42%) CRC cases and negative, or sparsely expressed, in adjacent colorectal mucosa (n = 16). SATB1 expression was significantly associated with microsatellite stable tumours (p < 0.001), beta-catenin overexpression (p < 0.001) and SATB2 expression (p < 0.001). While not prognostic in the full cohort, SATB1 expression was significantly associated with poor prognosis in SATB2 negative tumours (HR = 2.63; 95% CI 1.46-4.71; pinteraction = 0.011 for CSS and HR = 2.31; 95% CI 1.32-4.04; pinteraction = 0.015 for OS), remaining significant in multivariable analysis.ConclusionsThe results of this study demonstrate that SATB1 expression in CRC is significantly associated with beta-catenin overexpression, microsatellite stability and SATB2 expression. Furthermore, SATB1 expression is a factor of poor prognosis in SATB2 negative tumours. Altogether, these data indicate an important role for SATB1 in colorectal carcinogenesis and suggest prognostically antagonistic effects of SATB1 and SATB2. The mechanistic basis for these observations warrants further study.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1922643082772076
Distribution and viability of spermatozoa in the canine female genital tract during post-ovulatory oocyte maturation
Authors: Karre Inga , Meyer-Lindenberg Andrea , Urhausen Carola , Beineke Andreas , Meinecke Burkhard , Piechotta Marion , Beyerbach Martin , Günzel-Apel Anne-Rose 
Published: August 2012

AbstractBackgroundUnlike other domestic mammals, in which metaphase-II oocytes are ovulated, canine ovulation is characterized by the release of primary oocytes, which may take 12 to up to 36 hours. Further 60 hours are needed for maturation to secondary oocytes which then remain fertile for about 48 hours. Oestrus takes 7 to 10 days on average and may start as early as a week before ovulation. This together with the prolonged process of post-ovulatory oocyte maturation requires an according longevity of spermatozoa in the female genital tract in order to provide a population of fertile sperm when oocytes have matured to fertilizability. Therefore the distribution and viability of spermatozoa in the bitch genital tract was examined during post-ovulatory oocyte maturation.MethodsThirteen beagle bitches were inseminated on the day of sonographically verified ovulation with pooled semen of two beagle dogs containing one billion progressively motile spermatozoa. Ovariohysterectomy was performed two days later (group 1, n = 6) and four days later (group 2, n = 7). The oviduct and uterine horn of one side were flushed separately and the flushing’s were checked for the presence of gametes. The oviducts including the utero-tubal junction and the uterine horns, both the flushed and unflushed, were histologically examined for sperm distribution.ResultsThe total number of spermatozoa recovered by flushing was low and evaluation of viability was limited. Prophase-I oocytes were collected from oviduct flushing in group 1, whereas unfertilized metaphase-II oocytes were detected in group 2. From day 2 to day 4 after ovulation a significant decrease in the percentage of glands containing sperm (P<0.05) and a marked reduction of the mean sperm number in uterine horn glands were observed. A concomitant diminution of spermatozoa was indicated in the utero-tubal junction accompanied by a slight increase in sperm numbers in the mid oviduct.ConclusionsOocyte maturation to metaphase-II stage is accompanied by a continuous sperm detachment and elimination in the uterine horns. Entrance of spermatozoa into the caudal oviduct seems to be steadily controlled by the utero-tubal junction thus providing a selected sperm population to be shifted towards the site of fertilization when oocyte maturation is completed.
Cost-effectiveness of adding-on new antiepileptic drugs to conventional regimens in controlling intractable seizures in children
Authors: Gharibnaseri Zahra , Kebriaeezadeh Abbas , Nikfar Shekoufeh , Zamani Gholamreza , Abdollahiasl Akbar 
Published: August 2012

Abstract

Background and purpose of the study
Intractable seizures are a subgroup of epileptic disorders challenging the physicians’ skills to become controlled. Showing resistance towards common pharmacotherapy, they demand newer antiepileptic drugs acquired at higher costs. 0.06% of children around the world are estimated to suffer from epilepsy and its consequences. The aim of the present study has been to evaluate the cost-effectiveness of these drugs in the treatment of intractable seizures in children.

Methods
Clinical and cost data were collected from medical and cost records preserved at a neurologist office and a referral pharmacy respectively. Based on the new AED which are accessible in Iran, regimens were categorized into eight groups. The first group consisting of conventional AEDs was considered as comparator and the effectiveness of other groups was compared with it. Incremental Cost-effectiveness Ratio (ICER) of adding-on each new antiepileptic drug was calculated in terms of Rials per consequence (Rls/consq) and compared with each other. Furthermore ICER of the regimens was compared with the GDP per capita (Gross Domestic Product) of the year (2010).

Results
the ICER of the adding-on regimens range from negative values for Gabapentin, Levetiracetam and Zonisamide to low values for Lamotrigine (~ 6.4 million Rials/consequence [mil Rls/consq]) and Oxcarbazepine (~7.7 mil Rls/consq) and followed by high values for Topiramate (~21 mil Rls/consq) and Vigabatrin (~43.7 mil Rls/consq) considering the three months of remaining on regimen. By increasing the limit of remaining time to six months, the previously mentioned regimens persist on negative values. However Oxcarbazepine (~28.7 mil Rls/consq) and Lamotrigine (~13.8 mil Rls/consq) show a steep increase. Topiramate (~23.6 mil Rls/consq) displays a less change. Opposite to other regimens, the ICER value of Vigabatrin (~17.26 mil Rls/consq) has shown an important increase.

Major conclusions
Adding-on new antiepileptics to conventional regimens are cost-effective and justified considering the GDP per capita.