Miracle-dz/UniFAR-FTUs huggingface dataset:
A randomized clinical trial on n-3 polyunsaturated fatty acids supplementation and all-cause mortality in elderly men at high cardiovascular risk

Background The benefit of n-3 polyunsaturated fatty acids (PUFA) supplementation for mortality and cardiovascular events after myocardial infarction is well documented, but the effect of n-3 PUFA in Caucasians without established cardiovascular disease is not known. Our aim was to examine the influence of supplementation with eicosapentaenoic acid and docosahexaenoic acid on all-cause mortality and cardiovascular events in elderly men at high-risk of cardiovascular disease. Design In the Diet and Omega-3 Intervention Trial, 563 Norwegian men, 64–76-year old and 72% without overt cardiovascular disease, were randomized to a 3-year 2 × 2 factorial designed clinical trial of diet counseling and/or 2.4 g n-3 PUFA supplementation. The n-3 PUFA arm was placebo-controlled (corn oil). Methods Demographic parameters and classical risk factors were obtained at baseline. Deaths and cardiovascular events were recorded through 3 years, and the effects of n-3 PUFA-intervention on these outcomes were evaluated in pooled groups of the n-3 PUFA-arm. Results There were 38 deaths and 68 cardiovascular events. The unadjusted hazard ratios of all-cause mortality and cardiovascular events were 0.57 (95% confidence interval: 0.29–1.10) and 0.86 (0.57–1.38), respectively. Adjusted for baseline age, current smoking, hypertension, body mass index and serum glucose, hazard ratios were 0.53 (0.27–1.04, P = 0.063) and 0.89 (0.55–1.45, P = 0.641), respectively. Conclusion We observed a tendency toward reduction in all-cause mortality in the n-3 PUFA groups that, despite a low number of participants, reached borderline statistical significance. The magnitude of risk-reduction suggests that a larger trial should be considered in similar populations.
Direct Quantitation and Detection of Salmonellae in Biological Samples without Enrichment, Using Two-Step Filtration and Real-Time PCR

ABSTRACT A new two-step filtration protocol followed by a real-time PCR assay based on SYBR green I detection was developed to directly quantitate salmonellae in two types of biological samples: i.e., chicken rinse and spent irrigation water. Four prefiltration filters, one type of final filter, and six protocols for recovery of salmonellae from the final filter were evaluated to identify an effective filtration protocol. This method was then combined with a real-time PCR assay based on detection of the invA gene. The best results were obtained by subsequent filtration of 100 ml of chicken rinse or 100 ml of spent irrigation water through filters with pore diameters of >40 μm to remove large particles and of 0.22 μm to recover the Salmonella cells. After this, the Salmonella cells were removed from the filter by vortexing in 1 ml of physiological saline, and this sample was then subjected to real-time quantitative PCR. The whole procedure could be completed within 3 h from sampling to quantitation, and cell numbers as low as 7.5 × 102 CFU per 100-ml sample could be quantified. Below this limit, qualitative detection of concentrations as low as 2.2 CFU/100 ml sample was possible on occasion. This study has contributed to the development of a simple, rapid, and reliable method for quantitation of salmonellae in food without the need for sample enrichment or DNA extraction.
Information sources and perceived success in corporate finance

The work of corporate finance professionals is information intensive. In spite of that the practices and motivations of their information preferences have been researched very little. The present study investigates perceived success and how it is related to corporate finance professionals' information source use behaviour based on a web survey of 92 Finnish corporate finance professionals. The principal finding of the statistical analysis of the data is that perceptions of work success and specific types of information sources contributing to the success are related. The correlations are complex and very different types of information sources contribute to individual types of success and vice versa. The findings indicate that information sources function as measures of success and serve an instrumental purpose. Besides functional relations, the correlation of the variables suggest more comprehensive success and information source use related dependencies and preferences. The findings imply that by studying existing perceptions of success it is possible to make inferences about preferred information sources. The study also suggests that both personal and organisational perceptions of success should to be taken into account when planning information services and information literacy education for corporate finance professionals in order to increase their effectiveness and relevance for the
Cooperative Partitional-Divisive Clustering and Its Application in Gene Expression Analysis

Clustering techniques organize a collection of objects into cohesive groups called clusters such that objects in the same cluster are more similar to each other than objects in different clusters. There are many clustering approaches proposed in the literature with different quality/complexity tradeoffs. Combining multiple clustering is an approach to overcome the deficiency of single algorithms and further enhance their performances. Current approaches to combining multiple clusterings use end-result cooperation (e.g. ensemble clustering and hybrid clustering) between the clustering algorithms. Inherent drawbacks of the end-result cooperation are: the computational complexity of ensemble clustering and the idle wasted time in the hybrid approaches. In this paper, the k-means and the bisecting k-means clustering algorithms are both combined using intermediate-cooperation strategy for the aim of obtaining better clustering solutions than non-cooperative algorithms. Undertaken experimental results show that the quality of the clustering solutions obtained from the cooperative partitional-divisive clustering (CPDC) model is better than those obtained from the non-cooperative algorithms over a number of gene expression datasets.
Morphological Response of the Peritoneum and Spleen to Intraperitoneal Biomaterials

The present study was performed to evaluate the morphological response of the peritoneum and spleen to biomaterials. Silicone elastomer, knitted dacron or rubber was implanted, respectively, into a rat's peritoneal cavity and the morphology of the peritoneum and spleen was studied at 4 hours and on the 1st, 4th, 7th and 21st day after surgery. The morphological changes were identical among groups with different implanted materials. After intraperitoneal implantation of biomaterials from 4 hours and on, an infiltration of inflammatory cells was found in the slackened edematous superficial part of the peritoneum. Also noted in the spleen were stasis, vessel dilatation and fibrin deposition. With the help of scanning electron microscopy, a marked denudation and separation of the mesothelial cells, with infiltration of inflammatory cells, were observed. Peripheral leucocytes significantly increased in number one day after intraperitoneal implantation. Three weeks after intraperitoneal implantation, the materials were completely encapsulated and the morphological aberration of the peritoneum and spleen disappeared. The findings reveal the consequence and the resolution of the host-biomaterial interaction, which could contribute to the explaination of various pathophysiological alterations, including the translocation of enteric bacteria and the development of infectious complications after intraperitoneal biomaterial implantation.
DNA Vaccine-Generated Duck Polyclonal Antibodies as a Postexposure Prophylactic to Prevent Hantavirus Pulmonary Syndrome (HPS)

Andes virus (ANDV) is the predominant cause of hantavirus pulmonary syndrome (HPS) in South America and the only hantavirus known to be transmitted person-to-person. There are no vaccines, prophylactics, or therapeutics to prevent or treat this highly pathogenic disease (case-fatality 35–40%). Infection of Syrian hamsters with ANDV results in a disease that closely mimics human HPS in incubation time, symptoms of respiratory distress, and disease pathology. Here, we evaluated the feasibility of two postexposure prophylaxis strategies in the ANDV/hamster lethal disease model. First, we evaluated a natural product, human polyclonal antibody, obtained as fresh frozen plasma (FFP) from a HPS survivor. Second, we used DNA vaccine technology to manufacture a polyclonal immunoglobulin-based product that could be purified from the eggs of vaccinated ducks (Anas platyrhynchos). The natural “despeciation" of the duck IgY (i.e., Fc removed) results in an immunoglobulin predicted to be minimally reactogenic in humans. Administration of ≥5,000 neutralizing antibody units (NAU)/kg of FFP-protected hamsters from lethal disease when given up to 8 days after intranasal ANDV challenge. IgY/IgYΔFc antibodies purified from the eggs of DNA-vaccinated ducks effectively neutralized ANDV in vitro as measured by plaque reduction neutralization tests (PRNT). Administration of 12,000 NAU/kg of duck egg-derived IgY/IgYΔFc protected hamsters when administered up to 8 days after intranasal challenge and 5 days after intramuscular challenge. These experiments demonstrate that convalescent FFP shows promise as a postexposure HPS prophylactic. Moreover, these data demonstrate the feasibility of using DNA vaccine technology coupled with the duck/egg system to manufacture a product that could supplement or replace FFP. The DNA vaccine-duck/egg system can be scaled as needed and obviates the necessity of using limited blood products obtained from a small number of HPS survivors. This is the first report demonstrating the in vivo efficacy of any antiviral product produced using DNA vaccine-duck/egg system.
Molecular Requirements for Ethanol Differential Allosteric Modulation of Glycine Receptors Based on Selective Gβγ Modulation*

It is now believed that the allosteric modulation produced by ethanol in glycine receptors (GlyRs) depends on alcohol binding to discrete sites within the protein structure. Thus, the differential ethanol sensitivity of diverse GlyR isoforms and mutants was explained by the presence of specific residues in putative alcohol pockets. Here, we demonstrate that ethanol sensitivity in two ligand-gated ion receptor members, the GlyR adult α1 and embryonic α2 subunits, can be modified through selective mutations that rescued or impaired Gβγ modulation. Even though both isoforms were able to physically interact with Gβγ, only the α1 GlyR was functionally modulated by Gβγ and pharmacological ethanol concentrations. Remarkably, the simultaneous switching of two transmembrane and a single extracellular residue in α2 GlyRs was enough to generate GlyRs modulated by Gβγ and low ethanol concentrations. Interestingly, although we found that these TM residues were different to those in the alcohol binding site, the extracellular residue was recently implicated in conformational changes important to generate a pre-open-activated state that precedes ion channel gating. Thus, these results support the idea that the differential ethanol sensitivity of these two GlyR isoforms rests on conformational changes in transmembrane and extracellular residues within the ion channel structure rather than in differences in alcohol binding pockets. Our results describe the molecular basis for the differential ethanol sensitivity of two ligand-gated ion receptor members based on selective Gβγ modulation and provide a new mechanistic framework for allosteric modulations of abuse drugs.
Selected Extracts of Chinese Herbal Medicines: Their Effect on NF-κB, PPARα and PPARγ and the Respective Bioactive Compounds

Chinese herbal medicinal (CHM) extracts from fourteen plants were investigated in cell-based in vitro assays for their effect on nuclear factor κB (NF-κB), a key regulator of inflammation, as well as on peroxisome proliferator-activated receptors (PPARs) being key regulators of genes involved in lipid and glucose metabolism. 43% of the investigated CHMs showed NF-κB inhibitory and 50% PPARα and PPARγ activating effects. Apolar extracts from cortex and flos of Albizia julibrissin Durazz. and processed rhizomes of Arisaema sp. and Pinellia ternata (Thunb.) Breit. that effectively inhibited TNF-α-induced NF-κB activation and dose-dependently activated PPARα and PPARγ were further investigated. Bioassay-guided fractionation and analysis by GC-MS led to the identification of fatty acids as PPAR agonists, including linoleic and palmitic acid.
Glutathione Protects the Rat Liver Against Reperfusion Injury After Prolonged Warm Ischemia

Objective:To evaluate the potential of postischemic intravenous infusion of the endogenous antioxidant glutathione (GSH) to protect the liver from reperfusion injury following prolonged warm ischemia. Background Data:The release of reactive oxygen species (ROS) by activated Kupffer cells (KC) and leukocytes causes reperfusion injury of the liver after warm ischemia. Therefore, safe and cost-effective antioxidant strategies would appear a promising approach to prevent hepatic reperfusion injury during liver resection, but need to be developed. Methods:Livers of male Lewis rats were subjected to 60, 90, or 120 minutes of normothermic ischemia. During a 120 minutes reperfusion period either GSH (50, 100 or 200 μmol/h/kg; n= 6–8) or saline (n= 8) was continuously administered via the jugular vein. Results:Postischemic GSH treatment significantly prevented necrotic injury to hepatocytes as indicated by a 50–60% reduction of serum ALT and AST. After 1 hour of ischemia and 2 hours of reperfusion apoptotic hepatocytes were rare (0.50 ± 0.10%; mean ± SD) and not different in GSH-treated animals (0.65 ± 0.20%). GSH (200 μmol GSH/h/kg) improved survival following 2 hours of ischemia (6 of 9 versus 3 of 9 rats; P < 0.05). Intravital fluorescence microscopy revealed a nearly complete restoration of sinusoidal blood flow. This was paralleled by a reduction of leukocyte adherence to sinusoids and postsinusoidal venules. Intravenous GSH administration resulted in a 10- to 40-fold increase of plasma GSH levels, whereas intracellular GSH contents were unaffected. Plasma concentrations of oxidized glutathione (GSSG) increased up to 5-fold in GSH-treated animals suggesting counteraction of the vascular oxidant stress produced by activated KC. Conclusions:Intravenous GSH administration during reperfusion of ischemic livers prevents reperfusion injury in rats. Because GSH is well tolerable also in man, this novel approach could be introduced to human liver surgery.
Recombinational repair of chromosomal DNA double‐strand breaks generated by a restriction endonuclease

DNA double‐strand break repair can be accomplished by homologous recombination when a sister chromatid or a homologous chromosome is available. However, the study of sister chromatid double‐strand break repair in prokaryotes is complicated by the difficulty in targeting a break to only one copy of two essentially identical DNA sequences. We have developed a system using the Escherichia coli chromosome and the restriction enzyme EcoKI, in which double‐strand breaks can be introduced into only one sister chromatid. We have shown that the components of the RecBCD and RecFOR ‘pathways’ are required for the recombinational repair of these breaks. Furthermore, we have shown a requirement for SbcCD, the prokaryotic homologue of Rad50/Mre11. This is the first demonstration that, like Rad50/Mre11, SbcCD is required for recombination in a wild‐type cell. Our work suggests that the SbcCD–Rad50/Mre11 family of proteins, which have two globular domains separated by a long coiled‐coil linker, is specifically required for the co‐ordination of double‐strand break repair reactions in which two DNA ends are required to recombine at one target site.
Evaluation of the effectiveness and safety of a genetically modified live vaccine in broilers challenged with Salmonella Heidelberg

ABSTRACT Salmonellosis ranks among the major diseases of commercial poultry, and its presence in poultry flocks is responsible for economic losses and risks related to public health. Vaccines are an important tool within integrated programmes to control salmonellosis. The purpose of this study was to assess cross-protection provided by the Poulvac® ST vaccine in the control of Salmonella Heidelberg in experimentally challenged 3- and 21-day-old birds. Eighty birds were identified and separated into four treatments (T1: vaccinated and challenged at 3 days of age, T2: unvaccinated and challenged at 3 days of age, T3: vaccinated and challenged at 21 days of age, and T4: unvaccinated and challenged at 21 days of age). The inoculum was produced from a Brazilian field strain of SH. At the end of the experiment, caecum and liver/spleen samples were collected for quantitative and qualitative analysis of SH, respectively. Analysis of the liver/spleen showed that Poulvac® ST significantly (P ≤ 0.05) reduced the percentage of SH positivity in the group challenged at 3 days of age, while in the group challenged at 21 days this difference was almost considered significant (P = 0.1818). On the other hand, there was no statistically significant difference in SH count in the caecum (CFU/g) in the group challenged at 3 days, but for the group challenged at 21 days the SH counts were significantly (P ≤ 0.05) lower in the vaccinated group when compared to the positive control.
Leukemia cutis.

A 70-year-old man was referred to us for suspicion of acute leukemia. He had been treated with etoposide, ifosfamide, estramustine, and flutamide for 17 months since he underwent prostatectomy for cancer. Hematological studies of blood and bone marrow led to the diagnosis of, possibly secondary, acute monocytic leukemia (M5a). Cytochemically, the leukemic blasts were positive for nonspecific esterase and negative for myeloperoxidase; their immunophenotype was CD3, CD5, CD10, CD19, CD20, CD33, and HLA-DR. He achieved complete remission by induction chemotherapy (enocitabine, daunorubicin, 6-mercaptopurine, prednisolone) and received three cycles of consolidation chemotherapy. While he was on maintenance chemotherapy, however, scattered erythematous nodules of various sizes appeared on his trunk and four extremities. This was soon followed by hematological relapse with many monoblasts in the blood and bone marrow. The disease was refractory to further chemotherapy and the skin nodules increased in size (up to 5 cm in diameter) and number and turned dark-brown with ulceration in some (Fig. 1). The patient died 9 months after diagnosis. Postmortem examination revealed leukemic infiltration in the skin, heart, lungs, liver, spleen, stomach, pancreas, kidneys, adrenals, and bone marrow. In the skin, there was a dense leukemic infiltrate in the dermis and sub-
Combining Information Across Spatial Scales

Spatial and spatiotemporal processes in the physical, environmental, and biological sciences often exhibit complicated and diverse patterns across different space–time scales. Both scientific understanding and observational data vary in form and content across scales. We develop and examine a Bayesian hierarchical framework by which the combination of such information sources can be accomplished. Our approach is targeted to settings in which various special spatial scales arise. These scales may be dictated by the data collection methods, availability of prior information, and/or goals of the analysis. The approach restricts to a few essential scales. Hence we avoid the challenging problem of constructing a model that can be used at all scales. This means that we can provide inferences only at the preselected special scales. However, problems involving special scales are sufficiently common to justify the trade-off between our comparatively simple modeling and analysis strategy with the formidable task of forming models valid at all scales. Specifically, our approach is based on a simple idea of conditioning the spatially continuous process on an areal average of the process at some resolution of interest. In addition, the data at prescribed resolutions are then conditioned on this areal-averaged true process. These conditioning arguments fit nicely into the hierarchical Bayesian framework. The methodology is demonstrated for the spatial prediction of an important quantity known as streamfunction based on wind information from satellite observations and weather center, computer model output.
Telomeres in aging and disease: lessons from zebrafish

ABSTRACT Age is the highest risk factor for some of the most prevalent human diseases, including cancer. Telomere shortening is thought to play a central role in the aging process in humans. The link between telomeres and aging is highlighted by the fact that genetic diseases causing telomerase deficiency are associated with premature aging and increased risk of cancer. For the last two decades, this link has been mostly investigated using mice that have long telomeres. However, zebrafish has recently emerged as a powerful and complementary model system to study telomere biology. Zebrafish possess human-like short telomeres that progressively decline with age, reaching lengths in old age that are observed when telomerase is mutated. The extensive characterization of its well-conserved molecular and cellular physiology makes this vertebrate an excellent model to unravel the underlying relationship between telomere shortening, tissue regeneration, aging and disease. In this Review, we explore the advantages of using zebrafish in telomere research and discuss the primary discoveries made in this model that have contributed to expanding our knowledge of how telomere attrition contributes to cellular senescence, organ dysfunction and disease. Summary: In this Review, the authors explore the advantages of using zebrafish in telomere research and discuss the primary discoveries made in this model that have contributed to expanding our knowledge of how telomere attrition contributes to cellular senescence, organ dysfunction and disease.
Behavioral Changes and Hippocampus Glucose Metabolism in APP/PS1 Transgenic Mice via Electro-acupuncture at Governor Vessel Acupoints

Objective: Investigating the effects of electro-acupuncture (EA) treatment on mice with Alzheimer’s disease (AD), using Morris water maze (MWM) for spatial learning and memory behavior tests combined with micro-positron emission tomography (micro-PET) imaging for glucose metabolism in hippocampus. Methods: Thirty seven-month-old APP/PS1 mice were randomly divided into AD Model group (AD group), medicine group (M group) and EA group, C57BL/6 mice were used for Normal control group (N group), n = 10 in each group. Mice in M group received donepezil intervention by gavage with dose at 0.92 mg/kg. EA was applied at Baihui (GV20) and Yintang (GV29) acupoints for 20 min then pricked at Shuigou (GV26) acupoint, while mice in N, M and AD groups were received restriction for 20 min, with all treatment administrated once a day for 15 consecutive days. After the treatment, MWM was performed to observe behavioral changes in mice, then hippocampus glucose metabolism level was tested by micro-PET imaging. Results: Compared with that of AD group, the escape latency of M and EA groups declined significantly (P < 0.01), while the proportion of the platform quadrant swimming distance in total swimming distance showed an obvious increase (P < 0.01), and EA group occupied a higher percentage than that in M group. The micro-PET imaging showed that mice in AD group performed a lower glucose metabolic rate in hippocampus compared with N group (P < 0.01). Both M and EA groups presented a significant higher injected dose compared with AD group (P < 0.01), and the uptake rate of EA group was higher than M group. Conclusion: Both donepezil and EA have therapeutic effects on AD mice. To a certain extent, EA shows a better efficacy in treatment of AD by improving the spatial learning and memory ability, while also enhancing glucose metabolism in hippocampus.