bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiology of Plasmodium knowlesi malaria in north-east Sabah, Malaysia: family clusters and wide age distribution
Authors: Barber Bridget E , William Timothy , Dhararaj Prabakaran , Anderios Fread , Grigg Matthew J , Yeo Tsin W , Anstey Nicholas M 
Published: December 2012

Abstract

Background
The simian parasite Plasmodium knowlesi is a common cause of human malaria in Malaysian Borneo, with a particularly high incidence in Kudat, Sabah. Little is known however about the epidemiology in this substantially deforested region.

Methods
Malaria microscopy records at Kudat District Hospital were retrospectively reviewed from January 2009-November 2011. Demographics, and PCR results if available, were recorded for each positive result. Medical records were reviewed for patients suspected of representing family clusters, and families contacted for further information. Rainfall data were obtained from the Malaysian Meteorological Department.

Results

“Plasmodium malariae” mixed or mono-infection was diagnosed by microscopy in 517/653 (79%) patients. Of these, PCR was performed in 445 (86%) and was positive for P. knowlesi mono-infection in 339 (76%). Patients with knowlesi malaria demonstrated a wide age distribution (median 33, IQR 20–50, range 0.7-89 years) with P. knowlesi predominating in all age groups except those <5 years old, where numbers approximated those of Plasmodium falciparum and Plasmodium vivax. Two contemporaneous family clusters were identified: a father with two children (aged 10–11 years); and three brothers (aged one-11 years), all with PCR-confirmed knowlesi malaria. Cases of P. knowlesi demonstrated significant seasonal variation, and correlated with rainfall in the preceding three to five months.

Conclusions

Plasmodium knowlesi is the most common cause of malaria admissions to Kudat District Hospital. The wide age distribution and presence of family clusters suggest that transmission may be occurring close to or inside people’s homes, in contrast to previous reports from densely forested areas of Sarawak. These findings have significant implications for malaria control. Prospective studies of risk factors, vectors and transmission dynamics of P. knowlesi in Sabah, including potential for human-to-human transmission, are needed.
Wait, treat and see: echocardiographic monitoring of brain-dead potential donors with stunned heart
Authors: Casartelli Marilena , Bombardini Tonino , Simion Davide , Gaspari Maria Grazia , Procaccio Francesco 
Published: December 2012

Abstract

Background
Heart transplantation is limited by a severe donor organ shortage. Potential donors with brain death (BD) and left ventricular dysfunction due to neurogenic stunning are currently excluded from donation – although such abnormalities can be reversible with aggressive treatment including Hormonal Treatment (HT) and deferred organ retrieval.

Aim
To assess the recovery of left ventricular dysfunction in potential brain-dead donors with hemodynamic instability treated by aggressive treatment and HT.

Methods
In a single-center, observational study design, we evaluated 15 consecutive brain-dead potential donors (DBD) (8 males, age = 48 ± 15 years) with hemodynamic instability. All underwent standard hemodynamic monitoring and transthoracic 2-dimensional echo (2-DE) with assessment of Ejection Fraction (EF). Measurements were obtained before BD and after BD within 6 h, at 24 h and within 48 h. HT (with insulin, methylprednisolone, vasopressin and T3) was started as soon as possible to treat hemodynamic instability and avoid administration of norepinephrine (NE). Eligible potential heart donors underwent coronary angiography.

Results
After HT, we observed a normalization of hemodynamic conditions with improvement of mean arterial pressure (pre = 68 ± 8 mmHg vs post = 83 ± 13 mmHg, p < .01), cardiac index (pre = 2.4 ± 0.6 L/min/m2 vs post 3.7 ± 1.2 L/min/m2, p < .05), EF (pre = 48 ± 15 vs post = 59 ± 3%, p < .01) without administration of norepinephrine (NE) in 67% of cases. Five potential donors were excluded from donation (opposition, n = 3, tubercolosis n = 1, malignancy n = 1). At pre-harvesting angiography, coronary artery stenosis was present in 2 of the 10 consented donors. Eight hearts were uneventfully transplanted. No early graft failure occurred and all eight recipients were alive at 6-month follow-up.

Conclusion
In BD donors, intensive treatment including HT is associated with improvement of regional and global LV function and reverse remodeling detectable by transthoracic 2DE. Donor hearts with recovered LV function may be eligible for uneventful heart transplant. The wait (in brain death), treat (with HT) and see (with 2D echo) strategy can help rescue organs suitable for heart donation.
Glutamate-induced obesity leads to decreased sperm reserves and acceleration of transit time in the epididymis of adult male rats
Authors: Fernandes Glaura SA , Arena Arielle C , Campos Kleber E , Volpato Gustavo T , Anselmo-Franci Janete A , Damasceno Débora C , Kempinas Wilma G 
Published: December 2012

AbstractBackgroundGiven the established fact that obesity interferes with male reproductive functions, the present study aimed to evaluate sperm production in the testis and storage in the epididymis in a glutamate-induced model of obesity.MethodsMale rats were treated neonatally with monosodium glutamate (MSG) at doses of 4 mg/kg subcutaneously, or with saline solution (control group), on postnatal days 2, 4, 6, 8 and 10. On day 120, obesity was confirmed by the Lee index in all MSG-treated rats. After this, all animals from the two experimental groups were anesthetized and killed to evaluate body and reproductive organ weights, sperm parameters, plasma hormone levels (FSH, LH and testosterone), testicular and epididymal histo-morphometry and histopathology.ResultsSignificant reductions in absolute and relative weights of testis, epididymis, prostate and seminal vesicle were noted in MSG-treated animals. In these same animals plasma testosterone and follicle-stimulating hormone (FSH) concentrations were decreased, as well as sperm counts in the testis and epididymis and seminiferous epithelium height and tubular diameter. The sperm transit time was accelerated in obese rats. However, the number of Sertoli cells per seminiferous tubule and stereological findings on the epididymis were not markedly changed by obesity.ConclusionsNeonatal MSG-administered model of obesity lowers sperm production and leads to a reduction in sperm storage in the epididymis of adult male rats. The acceleration of sperm transit time can have implications for the sperm quality of these rats.
Overexpression of the secretory small GTPase Rab27B in human breast cancer correlates closely with lymph node metastasis and predicts poor prognosis
Authors: Zhang Jia-Xing , Huang Xiao-Xia , Cai Man-Bo , Tong Zhu-Ting , Chen Jie-Wei , Qian Dong , Liao Yi-Ji , Deng Hai-Xia , Liao Ding-Zhun , Huang Ma-Yan , Zeng Yi-Xin , Xie Dan , Mai Shi-Juan 
Published: December 2012

Abstract

Background
The secretory small GTPase Rab27b was recently identified as an oncogene in breast cancer (BC) in vivo and in vitro studies. This research was designed to further explore the clinical and prognostic significance of Rab27B in BC patients.

Methods
The mRNA/protein expression level of Rab27B was examined by performing Real-time PCR, western blot, and immunohistochemistry (IHC) assays in 12 paired BC tissues and matched adjacent noncancerous tissues (NAT). Then we carried out IHC assay in a large cohort of 221 invasive BC tissues, 22 normal breast tissues, 40 fibroadenoma (FA), 30 ductual carcinoma in situ (DCIS) and 40 metastatic lymph nodes (LNs). The receiver operating characteristic curve method was applied to obtain the optimal cutoff value for high Rab27B expression. Epithelial-mesenchymal transition (EMT) marker expression levels were detected in relation to Rab27B expression.

Results
We observed that the increased expression of Rab27B was dependent upon the magnitude of cancer progression (P < 0.001). The elevated expression of Rab27B was closely correlated with lymph node metastasis, advanced clinical stage, ascending pathology classification, and positive ER status. Furthermore, patients with high expression of Rab27B had inferior survival outcomes. Multivariate Cox regression analysis proved that Rab27B was a significantly independent risk factor for patients’ survival (P < 0.001). Furthermore, a significant positive relationship was observed between Rab27B expression and elevated mesenchymal EMT markers.

Conclusion
Our findings suggest that overexpression of Rab27B in BC coincides with lymph node metastasis and acquisition of a poor prognostic phenotype.
A comparison of the ability of rilpivirine (TMC278) and selected analogues to inhibit clinically relevant HIV-1 reverse transcriptase mutants
Authors: Johnson Barry C , Pauly Gary T , Rai Ganesha , Patel Disha , Bauman Joseph D , Baker Heather L , Das Kalyan , Schneider Joel P , Maloney David J , Arnold Eddy , Thomas Craig J , Hughes Stephen H 
Published: December 2012

Abstract

Background
The recently approved anti-AIDS drug rilpivirine (TMC278, Edurant) is a nonnucleoside inhibitor (NNRTI) that binds to reverse transcriptase (RT) and allosterically blocks the chemical step of DNA synthesis. In contrast to earlier NNRTIs, rilpivirine retains potency against well-characterized, clinically relevant RT mutants. Many structural analogues of rilpivirine are described in the patent literature, but detailed analyses of their antiviral activities have not been published. This work addresses the ability of several of these analogues to inhibit the replication of wild-type (WT) and drug-resistant HIV-1.

Results
We used a combination of structure activity relationships and X-ray crystallography to examine NNRTIs that are structurally related to rilpivirine to determine their ability to inhibit WT RT and several clinically relevant RT mutants. Several analogues showed broad activity with only modest losses of potency when challenged with drug-resistant viruses. Structural analyses (crystallography or modeling) of several analogues whose potencies were reduced by RT mutations provide insight into why these compounds were less effective.

Conclusions
Subtle variations between compounds can lead to profound differences in their activities and resistance profiles. Compounds with larger substitutions replacing the pyrimidine and benzonitrile groups of rilpivirine, which reorient pocket residues, tend to lose more activity against the mutants we tested. These results provide a deeper understanding of how rilpivirine and related compounds interact with the NNRTI binding pocket and should facilitate development of novel inhibitors.
Seroprevalence of porcine torovirus (PToV) in Spanish farms
Authors: Alonso-Padilla Julio , Pignatelli Jaime , Simon-Grifé Meritxell , Plazuelo Susana , Casal Jordi , Rodríguez Dolores 
Published: December 2012

Abstract

Background
Torovirus infections have been associated with gastroenteritis and diarrhea in horses, cows, pigs and humans, especially in young animals and in children. Although asymptomatic in a large percentage of cases, however toroviruses may pose a potential threat to worsen disease outcome in concurrent infections with other enteric pathogens. Previous studies based on the analysis of limited numbers of samples indicated high seroprevalences against porcine torovirus (PToV) in various European countries. The aim of this work was to perform a seroepidemiological survey of PToV in Spanish farms in order to define the seroprevalence against this virus.

Results
Serum samples (n = 2664) from pigs of different ages were collected from 100 Spanish farms coming from 10 regions that concentrate 96.1% of the 3392 farms with 80 or more sows censused in Spain. Samples were screened by means of an indirect enzyme-linked immune-sorbent assay (ELISA) based on a recombinant PToV nucleocapsid protein as antigen. The analysis of the whole serum collection yielded a total of 95.7% (2550/2664) seropositive samples. The highest prevalence (99.6%, 1382/1388) and ELISA values (average O.D. ± standard deviation) were observed in the sows (1.03±0.36) and the lowest prevalence (59.4%, 98/165) and anti-PToV IgG levels (0.45±0.16) were found amongst 3-week-old piglets. Both ELISA reactivity values and seroprevalence percentages rose quickly with piglet’s age from 3 to 11 weeks of age; the seroprevalence was 99.3% (2254/2270) when only the samples from sows and pigs over 11-weeks of age were considered. Antibodies against PToV were detected in all analyzed farms.

Conclusions
This report describes the results of the largest torovirus seroepidemiological survey in farmed swine performed so far. Overall, the seroprevalence against PToV in animals older than 11 weeks of age was >99%, indicating that this virus is endemic in pig herds from Spain.
Strong purifying selection in endogenous retroviruses in the saltwater crocodile (Crocodylus porosus) in the Northern Territory of Australia
Authors: Chong Amanda Yoon-Yee , Atkinson Sarah Jane , Isberg Sally , Gongora Jaime 
Published: December 2012

Abstract

Background
Endogenous retroviruses (ERVs) are remnants of exogenous retroviruses that have integrated into the nuclear DNA of a germ-line cell. Here we present the results of a survey into the ERV complement of Crocodylus porosus, the saltwater crocodile, representing 45 individuals from 17 sampling locations in the Northern Territory of Australia. These retroelements were compared with published ERVs from other species of Crocodylia (Crocodilians; alligators, caimans, gharials and crocodiles) as well as representatives from other vertebrates. This study represents one of the first in-depth studies of ERVs within a single reptilian species shedding light on the diversity of ERVs and proliferation mechanisms in crocodilians.

Results
Analyses of the retroviral pro-pol gene region have corroborated the presence of two major clades of ERVs in C. porosus and revealed 18 potentially functional fragments out of the 227 recovered that encode intact pro-pol ORFs. Interestingly, we have identified some patterns of diversification among those ERVs as well as a novel sequence that suggests the presence of an additional retroviral genus in C. porosus. In addition, considerable diversity but low genetic divergence within one of the C. porosus ERV lineages was identified.

Conclusions
We propose that the ERV complement of C. porosus has come about through a combination of recent infections and replication of ancestral ERVs. Strong purifying selection acting on these clades suggests that this activity is recent or still occurring in the genome of this species. The discovery of potentially functional elements is an interesting development that warrants further investigation.
Verification and validation of ICME methods and models for aerospace applications
Authors: Cowles Bradford , Backman Dan , Dutton Rollie 
Published: December 2012

AbstractIntegrated Computational Materials Engineering (ICME) model verification and validation (V&V) is difficult because materials processing, microstructural evolution, and property development contain a rich mix of length and time scales with an equally complex set of interacting phenomena and mechanisms. Beyond these difficulties, engineers who adapt these models rarely generate independent validation data sets to confirm model adequacy, quantify uncertainty, and identify potential error sources. Even when a validation data set is produced and applied, the range of model applicability is limited by the range on input model parameters contained within the data set. In this paper we provide a summary of a recommended approach to ICME V&V and include descriptions of V&V planning checklists, an ICME Tool Maturity Level assessment guide and examples of how such practitioner aids might be employed.
Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood
Authors: Davies Matthew N , Volta Manuela , Pidsley Ruth , Lunnon Katie , Dixit Abhishek , Lovestone Simon , Coarfa Cristian , Harris R Alan , Milosavljevic Aleksandar , Troakes Claire , Al-Sarraj Safa , Dobson Richard , Schalkwyk Leonard C , Mill Jonathan 
Published: December 2012

Abstract
Background
Dynamic changes to the epigenome play a critical role in establishing and maintaining cellular phenotype during differentiation, but little is known about the normal methylomic differences that occur between functionally distinct areas of the brain. We characterized intra- and inter-individual methylomic variation across whole blood and multiple regions of the brain from multiple donors.

Results
Distinct tissue-specific patterns of DNA methylation were identified, with a highly significant over-representation of tissue-specific differentially methylated regions (TS-DMRs) observed at intragenic CpG islands and low CG density promoters. A large proportion of TS-DMRs were located near genes that are differentially expressed across brain regions. TS-DMRs were significantly enriched near genes involved in functional pathways related to neurodevelopment and neuronal differentiation, including BDNF, BMP4, CACNA1A, CACA1AF, EOMES, NGFR, NUMBL, PCDH9, SLIT1, SLITRK1 and SHANK3. Although between-tissue variation in DNA methylation was found to greatly exceed between-individual differences within any one tissue, we found that some inter-individual variation was reflected across brain and blood, indicating that peripheral tissues may have some utility in epidemiological studies of complex neurobiological phenotypes.

Conclusions
This study reinforces the importance of DNA methylation in regulating cellular phenotype across tissues, and highlights genomic patterns of epigenetic variation across functionally distinct regions of the brain, providing a resource for the epigenetics and neuroscience research communities.
Intraoperative Frozen Section Analysis of Margins in Breast Conserving Surgery Significantly Decreases Reoperative Rates
Authors: Jorns Julie M. , Visscher Daniel , Sabel Michael , Breslin Tara , Healy Patrick , Daignaut Stephanie , Myers Jeffrey L. , Wu Angela J. 
Published: December 2012

Abstract
Intraoperative frozen section (FS) margin evaluation is not common practice for patients undergoing breast conservation therapy (BCT), but offers a significant reduction in reoperation. In this study, a technique to allow for more effective freezing of breast tissue was developed to perform FS evaluation of lumpectomy margins (FSM) for all patients undergoing BCT at an ambulatory surgery center. FS evaluation of sentinel lymph node biopsy specimens was performed concurrently. One hundred eighty-one study and 188 control patients, with and without FS evaluation, were compared. Reexcision was reduced 34% (from 48.9% to 14.9%) and reoperation was reduced 36% (from 55.3% to 19.3%) with FS evaluation. Most of the decrease in reoperative rate was because of a decrease in the need for margin reexcision. The number of patients requiring 1, 2, or 3 operations to complete therapy was 84, 92, and 12, respectively, in the control group, and 146, 33, and 2, respectively, in the study group. Lobular subtype, multifocal disease, and larger tumor size (≥2 cm) were significantly associated with failure of FSM to prevent reoperation, but reoperation rates were still significantly decreased in this subgroup of patients (from 75.5% to 43.8%) with FSM. This study highlights an innovative yet simple and adaptable FS approach that resulted in a nearly 3-fold reduction in reoperation for patients undergoing BCT.
Molecular Diagnostics of Melanoma Fine-Needle Aspirates
Authors: Bernacki Kurt D. , Betz Bryan L. , Weigelin Helmut C. , Lao Christopher D. , Redman Bruce G. , Knoepp Stewart M. , Roh Michael H. 
Published: December 2012

Abstract
Patients with advanced-stage melanoma harboring a BRAF mutation are candidates for BRAF inhibition as a therapeutic strategy. The use of fine-needle aspiration (FNA) to diagnose metastatic melanoma is increasing. Studies examining the predictive value of BRAF mutation analysis on melanoma FNAs via correlation with follow-up excision findings are lacking. We examined 37 consecutive FNA cases of metastatic melanoma in which the aspirated lesion was subsequently excised. DNA was purified from Diff-Quik–stained FNA smears and tissue blocks from corresponding excisions in parallel. BRAF mutation status was successfully obtained from both specimen types in 34 (92%) of 37 cases. BRAF mutations were detected in 12 (35%) of 34 cases—11 V600E and 1 V600K. Results of BRAF mutational analysis were concordant in all 34 FNA smear/tissue excision pairs. Thus, melanoma FNA for molecular diagnostics represents a rapid, minimally invasive, and effective management strategy in this era of precision medicine.
Prognostic Significance of the Ratio of Absolute Neutrophil Count to Absolute Lymphocyte Count in Classic Hodgkin Lymphoma
Authors: Koh Young Wha , Kang Hyo Jeong , Park Chansik , Yoon Dok Hyun , Kim Shin , Suh Cheolwon , Kim Ji Eun , Kim Chul-Woo , Huh Jooryung 
Published: December 2012

Abstract
The aim of this study was to determine the prognostic effect of the absolute neutrophil count/absolute lymphocyte count ratio (ANC/ALC ratio) in patients with classic Hodgkin lymphoma (cHL). We performed a retrospective analysis of 312 patients with cHL. Univariate analysis revealed that a high ANC/ALC ratio (≥4.3) correlated with poor overall survival (OS) (P &lt; .001). Subgroup analysis of advanced-stage disease showed that the ANC/ALC ratio was significant for OS (P = .032). Multivariate analysis revealed the ANC/ALC ratio to be an independent prognostic factor for OS (P = .048). The ANC/ALC ratio allowed further risk stratification in patients who were considered to be at low risk on the basis of an International Prognostic Score less than 4 (P = .002). The ANC/ALC ratio is a simple, inexpensive, and independent prognostic factor for OS that may improve the ability to identify high-risk patients with cHL.
Patterned Deposition of Allophane Nanoparticles on Silicon Substrates
Authors: Fuchs Marco , Abidin Zaenal , Kübel Christian , Weidler Peter G. , Matsue Naoto , Henmi Teruo , Köster Rainer , Gliemann Hartmut 
Published: December 2012

AbstractIn order to obtain nanopatterned surfaces, natural allophane particles originating from Japanese soils were immobilized as single particles on Si wafer substrates.When derived from aqueous suspensions, only a few nanoparticles were deposited and detected on the surface due to the weak adsorption of allophanes on the substrate. The amount of immobilized allophane was increased significantly, however, by using an organic solvent in combination with a micelle-based technique to suspend the allophane particles. The micelles were formed from a tailored, aliphatic diblock copolymer that was dissolved in toluene and contained several allophane particles. A cleaned silica chip was used as a substrate on which a monolayer of micelles was immobilized equidistant from each other by dip coating. To remove the polymer from the substrate and to produce free, single allophane nanoparticles, ultraviolet (UV) irradiation was used. After UV treatment, single allophane particles formed ring-shaped deposition patterns with a high surface density. Transmission electron microscopy (TEM) was used to verify the presence of single allophane nanoparticles in the Japanese samples which came from natural sources. The single allophane particles as well as the allophane-containing di-block copolymer micelles, both immobilized on Si substrates and TEM sample grids, were imaged by atomic force microscopy and TEM. In this way, the diameters of the single allophane particles, as well as the distances between the immobilized micelles and the particles and their topography on the substrates, were determined.