Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of mineral source and mannan oligosaccharide supplements on zinc and copper digestibility in growing pigs

This study aimed to compare the effects of organic (proteinate) and inorganic (sulphate) copper (Cu) and zinc (Zn) supplements, in presence or absence of a mannan oligosaccharide (MOS) supplement, on mineral solubility and digestibility in pigs. Twenty-eight barrows (25 ± 4 kg) assigned randomly to four treatment groups were fed a corn-wheat-soya bean meal diet with 10 mg/kg of Cu and 100 mg/kg of Zn supplied as organic or inorganic supplement, and supplemented or not with 0.1% MOS. After an adaptation period, total faeces and urine were collected for a period of 6–7 days. Pigs were then euthanatised and digesta from ileum and caecum were collected. Apparent digestibility was calculated in ileum and caecum using titanium dioxide. The organic mineral supplement improved total (faecal) digestibility and retained/ingested ratio of Cu (p < 0.05) while reducing apparent digestibility of Zn in the ileum (p < 0.05) without effect on total digestibility of Zn. Solubilities of Cu and Zn in liquid fraction of ileum and caecum were not affected by mineral sources. Although MOS supplement increased Cu solubility in the ileum (p < 0.05), it had no effect on digestibility of Zn and Cu in ileum, caecum and faeces, retained/ingested ratio of Zn and Cu, or pH and volatile fatty acid concentration in ileal and caecal digesta. In conclusion, organic mineral supplement improved total digestibility and retained/ingested ratio of Cu in pigs but this cannot be attributed to its solubility in ileal and caecal digesta. The MOS supplement did not interfere with digestibility or dietary utilisation of Zn and Cu in pigs fed above the Zn and Cu requirements.
Potent in vivo anticancer activity and stability of liposomes encapsulated with semi-purified Job’s tear (Coix lacryma-jobi Linn.) extracts on human colon adenocarcinoma (HT-29) xenografted mice

Abstract The in vivo anticancer activity and stability of liposomes encapsulated with semi-purified Job’s tear (Coix lacryma-jobi Linn.) extracts (S5L), prepared by supercritical carbon dioxide fluid technique, on human colon adenocarcinoma (HT29) xenografted mice were investigated. For the stability and the physicochemical characteristics, S5L showed a high stability of pH, good dispersibility, small particle size and stable zeta potential. Liposomes can protect linoleic acid in the extract comparing with the free S5. S5L kept at 4 °C for 3 months showed the highest linoleic acid content of 63.50%, whereas at 45 °C, the lowest linoleic acid content of 42.66% was observed. The anticancer activity and toxicity on xenografted mice were observed for 14 days. At the end of the experiment, the relative tumor volume (RTV) in the S5L-treated xenografted mice showed a significant RTV reduction. The high dose of S5 and S5L were potent with the highest inhibition of tumor growth of 48.67 and 54.75%, which was 86.94% and 97.81% of 5-fluorouracil, respectively. The apoptotic activity was shown in xenografted mice treated with S5 at medium and high dose, S5L, 5-fluorouracil and commercial product. All treated xenografted mice showed no toxic signs and symptoms, abnormality of internal organs histopathology and blood chemistry. This study has demonstrated the high physicochemical stability of liposomes encapsulated with semi-purified Job’s tear extract and their potent anticancer activity on human colon adenocarcinoma xenografted model with the potential for further development to anticolon cancer drug.
Autophagy promotes degradation of polyethyleneimine–alginate nanoparticles in endothelial progenitor cells

Polyethyleneimine (PEI)–alginate (Alg) nanoparticle (NP) is a safe and effective vector for delivery of siRNA or DNA. Recent studies suggest that autophagy is related to cytotoxicity of PEI NPs. However, contribution of autophagy to degradation of PEI–Alg NPs remains unknown. CD34+VEGFR-3+ endothelial progenitor cells isolated from rat bone marrow were treated with 25 kDa branched PEI modified by Alg. After treatment with the NPs, morphological changes and distribution of the NPs in the cells were examined with scanning and transmission electron microscopies. Cytotoxicity of the NPs was analyzed by reactive oxygen species (ROS) production, lactate dehydrogenase leakage and induction of apoptosis. The level of autophagy was assessed with expression of Beclin-1 and LC3 and formation of autophagic structures and amphisomes. Colocalization of LC3-positive puncta and the NPs was determined by LC3–GFP tracing. Cytotoxicity of PEI NPs was reduced greatly after modification with Alg. PEI–Alg NPs were distributed in mitochondria, rough endoplasmic reticula and nuclei as well as cytoplasm. After phagocytosis of the NPs, expression of Beclin-1 mRNA and LC3 protein was upregulated, and the number of LC3-positive puncta, autophagic structures and amphisomes increased significantly. The number of lysosomes also increased obviously. There were LC3-positive puncta in nuclei, and some puncta were colocalized with the NPs. These results demonstrate that the activated autophagy promotes degradation of PEI–Alg NPs via multiple pathways.
A Spectral Probe for Detection of Aluminum (III) Ions Using Surface Functionalized Gold Nanoparticles

A simple green route has been developed for the synthesis of casein peptide functionalized gold nanoparticles (AuNPs), in which casein peptide acts as a reducing as well as the stabilizing agent. In this report, AuNPs have been characterized on the basis of spectroscopic and microscopic results; which showed selective and sensitive response toward Al3+ in aqueous media, and Al3+ induces aggregation of AuNPs. The sensing study performed for Al3+ revealed that the color change from red to blue was due to a red-shift in the surface plasmon resonance (SPR) band and the formation of aggregated species of AuNPs. The calibration curve determines the detection limit (LOD) for Al3+ about 20 ppb (0.067 μM) is presented using both decrease and increase in absorbance at 530 and 700 nm, respectively. This value is considerably lower than the higher limit allowed for Al3+ in drinking water by the world health organization (WHO) (7.41 μM), representing enough sensitivity to protect water quality. The intensity of the red-shifted band increases with linear pattern upon the interaction with different concentrations of Al3+, thus the possibility of producing unstable AuNPs aggregates. The method is successfully used for the detection of Al3+ in water samples collected from various sources, human urine and ionic drink. The actual response time required for AuNPs is about 1 min, this probe also have several advantages, such as ease of synthesis, functionalization and its use, high sensitivity, and enabling on-site monitoring.
Medication Adherence in Rheumatoid Arthritis Patients: Older Is Wiser

OBJECTIVES: To create a profile of individuals nonadherent to their medications in an age‐stratified sample (ages 34–84) of community‐dwelling rheumatoid arthritis patients. The relative contributions of age, cognitive function, disability, emotional state, lifestyle, and beliefs about illness to nonadherence were assessed.
In vivo effect of surfactant on inflammatory cytokines during endotoxin-induced lung injury in rodents

Lipopolysaccharide (LPS) is a known inducer of acute respiratory distress syndrome (ARDS) in humans and animals. In this study, ARDS was developed in rats by intratracheal instillation of LPS and the effect of two types of surfactant (natural vs. synthetic) was examined to determine their potential corrective roles in general, as well as to compare the two surfactants against one another in particular, in endotoxin-induced lung injury. Sprague–Dawley male rats were divided into four groups, i.e., rats given: buffer controls; 055:B5 E. coli LPS only; LPS and then porcine surfactant (P-SF); or, LPS and then synthetic surfactant (S-SF). In vivo administration of LPS led to an increase in expression of the cytokines tumor necrosis factor-α, interleukin (IL)-1β, IL-2, IL-4, interferon-γ, monocyte chemotactic protein-1, and macrophage inflammatory protein-1β in the lungs of rats. These effects were confirmed by immunofluorescence in lung tissue sections and/or by protein (Western immunoblot) and mRNA expression (reverse transcription polymerase chain reaction) analyses of tissue samples. Apart from IL-4, concentrations of each of these cytokines in bronchoalveolar lavage fluid recovered from the animals were significantly increased in the LPS-treated hosts. Instillation of either surfactant (70 h after the LPS) into the airways diminished the expression of each of the inducible-cytokines, with the porcine (natural) form seeming having the greater inhibitory effect. These data suggest that surfactant can play an important role in the treatment of endotoxin-induced lung injury and might possess robust anti-inflammatory effects. Further, it seems that both the natural and synthetic surfactants prevent inflammatory outcomes in the lungs by controlling cytokine(s) production by various inflammatory cells. Last, the studies here clearly indicated that in this aspect, natural surfactant appears to be more beneficial compared to synthetic surfactant.
Rational plasmid design and bioprocess optimization to enhance recombinant adeno‐associated virus (AAV) productivity in mammalian cells

Viral vectors used for gene and oncolytic therapy belong to the most promising biological products for future therapeutics. Clinical success of recombinant adeno‐associated virus (rAAV) based therapies raises considerable demand for viral vectors, which cannot be met by current manufacturing strategies. Addressing existing bottlenecks, we improved a plasmid system termed rep/cap split packaging and designed a minimal plasmid encoding adenoviral helper function. Plasmid modifications led to a 12‐fold increase in rAAV vector titers compared to the widely used pDG standard system. Evaluation of different production approaches revealed superiority of processes based on anchorage‐ and serum‐dependent HEK293T cells, exhibiting about 15‐fold higher specific and volumetric productivity compared to well‐established suspension cells cultivated in serum‐free medium. As for most other viral vectors, classical stirred‐tank bioreactor production is thus still not capable of providing drug product of sufficient amount. We show that manufacturing strategies employing classical surface‐providing culture systems can be successfully transferred to the new fully‐controlled, single‐use bioreactor system IntegrityTM iCELLisTM. In summary, we demonstrate substantial bioprocess optimizations leading to more efficient and scalable production processes suggesting a promising way for flexible large‐scale rAAV manufacturing.
Charge Neutralization of the Central Lysine Cluster in Prion Protein (PrP) Promotes PrPSc-like Folding of Recombinant PrP Amyloids*

Background: Key factors modulating conversion of prion protein into prions remain unclear. Results: Neutralization of a cluster of lysines within residues 101–110 promoted formation of an N-terminally extended recombinant prion protein amyloid core. Conclusion: A central lysine cluster strongly modulates folding of prion protein amyloids. Significance: These findings highlight a key structural factor in the PrPSc-like folding of prion protein. The structure of the infectious form of prion protein, PrPSc, remains unclear. Most pure recombinant prion protein (PrP) amyloids generated in vitro are not infectious and lack the extent of the protease-resistant core and solvent exclusion of infectious PrPSc, especially within residues ∼90–160. Polyanionic cofactors can enhance infectivity and PrPSc-like characteristics of such fibrils, but the mechanism of this enhancement is unknown. In considering structural models of PrPSc multimers, we identified an obstacle to tight packing that might be overcome with polyanionic cofactors, namely, electrostatic repulsion between four closely spaced cationic lysines within a central lysine cluster of residues 101–110. For example, in our parallel in-register intermolecular β-sheet model of PrPSc, not only would these lysines be clustered within the 101–110 region of the primary sequence, but they would have intermolecular spacings of only ∼4.8 Å between stacked β-strands. We have now performed molecular dynamics simulations predicting that neutralization of the charges on these lysine residues would allow more stable parallel in-register packing in this region. We also show empirically that substitution of these clustered lysine residues with alanines or asparagines results in recombinant PrP amyloid fibrils with extended proteinase-K resistant β-sheet cores and infrared spectra that are more reminiscent of bona fide PrPSc. These findings indicate that charge neutralization at the central lysine cluster is critical for the folding and tight packing of N-proximal residues within PrP amyloid fibrils. This charge neutralization may be a key aspect of the mechanism by which anionic cofactors promote PrPSc formation.
Enhancement of Low Light Level Images with coupled dictionary learning

Low Light Level Images (LLLIs) are captured with exceptionally low brightness and low contrast, and cannot be enhanced satisfactorily with ordinary methods. In this paper, we propose a LLLI enhancement method using coupled dictionary learning. During the training stage, a pair of dictionaries and a linear mapping function are learned simultaneously. The dictionary pair aims to describe the raw LLLIs and their enhanced versions, and the linear mapping function models the correspondence between the representations of the dictionary pair. In the enhancement process, the resulting image is generated through dictionary mapping from patches of the input LLLI. We adopt a clustering strategy to improve the robustness of coupled dictionary learning, and propose an improved algorithm for fast implementation. Experimental results on real images demonstrate the effectiveness of our method.
Hypermethylated DNA as a biomarker for colorectal cancer: a systematic review

Improved methods for early detection of colorectal cancer (CRC) are essential for increasing survival. Hypermethylated DNA in blood or stool has been proposed as a biomarker for CRC. Biochemical methods have improved in recent years, and several hypermethylated genes that are sensitive and specific for CRC have been proposed. Articles describing the use of hypermethylated promoter regions in blood or stool as biomarkers for CRC were systematically reviewed.
Impact of Immigration on Pulmonary Tuberculosis in Spanish Children: A Three-Decade Review

Background: Tuberculosis causes significant morbidity and mortality worldwide. In the last years, international travel and immigration have led to important changes in the epidemiology of this disease. Drug resistance has emerged as an important threat to tuberculosis control. Data regarding the impact of immigration and the incidence of drug-resistant strains in children are lacking. Methods: Retrospective review of patients diagnosed with pulmonary tuberculosis at La Paz Children's Hospital in a 30-year period. Data were collected with regard to the clinical, radiologic, microbiologic, and demographic characteristics of patients, and data from the 3 decades of the study were compared using &khgr;2 test and Fisher exact test. Results: A total of 507 cases of tuberculosis were identified, 414 of which had pulmonary involvement. During the study, there was a significant decrease in tuberculous meningitis: 10.4% in 1978–1987, 5.6% in 1988–1997, and 2.9% in 1998–2007 (P < 0.05). The most frequent reason for a consultation was case contact investigation. The adult source case was identified in 64% of patients. We observed an increase in extrafamilial contacts (8% in 1978–1987 and 18% in 1998–2007, P < 0.01), including 4 cases of immigrant caretakers. Tuberculosis in immigrant children has increased with time: 2% in the period 1978–1987, 6% in 1988–1997, and 46% in 1998–2007 (P < 0.001). The primary resistance rate to isoniazid in our population was 6.5%. Conclusions: Tuberculosis in our area continues to be a major health problem, especially among foreign-born children. As drug-resistant strains are increasing, initial therapy with 4 drugs is recommended in our population.
A novel segmental challenge model for bleomycin-induced pulmonary fibrosis in sheep

ABSTRACT Background: Idiopathic Pulmonary fibrosis (IPF) is a fatal respiratory disease, characterized by a progressive fibrosis and worsening lung function. While the outcomes of recent clinical trials have resulted in therapies to slow the progression of the disease, there is still a need to develop alternative therapies, which are able to prevent fibrosis. Aim: This study uses a segmental lung infusion of bleomycin (BLM) to investigate pulmonary fibrosis in a physiologically relevant large animal species. Methods: Two separate lung segments in eight sheep received two fortnightly challenges of either 3U or 30U BLM per segment, and a third segment received saline (control). Lung function was assessed using a wedged-bronchoscope procedure. Bronchoalveolar lavage fluid and lung tissue were assessed for inflammation, fibrosis and collagen content two weeks after the final dose of BLM. Results: Instillation of both BLM doses resulted in prominent fibrosis in the treated lobes. More diffuse fibrosis and loss of alveolar airspace was observed in high-dose BLM-treated segments, while multifocal fibrosis was seen in low-dose BLM-treated segments. Extensive and disorganised collagen deposition occurred in the BLM-treated lobes, compared to controls. Significant loss of lung compliance was also observed in the BLM-treated lobes, which did not occur in controls. Conclusions: Fibrosis comparable to IPF was induced into isolated lung segments, without compromising the respiratory functioning of the animal. This model may have potential for investigating novel therapies for IPF by allowing direct comparison of multiple treatments with internal controls, and sampling and drug delivery that are clinically relevant.
Automatized spleen segmentation in non-contrast-enhanced MR volume data using subject-specific shape priors

To develop the first fully automated 3D spleen segmentation framework derived from T1-weighted magnetic resonance (MR) imaging data and to verify its performance for spleen delineation and volumetry. This approach considers the issue of low contrast between spleen and adjacent tissue in non-contrast-enhanced MR images. Native T1-weighted MR volume data was performed on a 1.5 T MR system in an epidemiological study. We analyzed random subsamples of MR examinations without pathologies to develop and verify the spleen segmentation framework. The framework is modularized to include different kinds of prior knowledge into the segmentation pipeline. Classification by support vector machines differentiates between five different shape types in computed foreground probability maps and recognizes characteristic spleen regions in axial slices of MR volume data. A spleen-shape space generated by training produces subject-specific prior shape knowledge that is then incorporated into a final 3D level set segmentation method. Individually adapted shape-driven forces as well as image-driven forces resulting from refined foreground probability maps steer the level set successfully to the segment the spleen. The framework achieves promising segmentation results with mean Dice coefficients of nearly 0.91 and low volumetric mean errors of 6.3%. The presented spleen segmentation approach can delineate spleen tissue in native MR volume data. Several kinds of prior shape knowledge including subject-specific 3D prior shape knowledge can be used to guide segmentation processes achieving promising results.
Critical role of Wnt/β-catenin signaling in driving epithelial ovarian cancer platinum resistance

Resistance to platinum-based chemotherapy is the major barrier to treating epithelial ovarian cancer. To improve patient outcomes, it is critical to identify the underlying mechanisms that promote platinum resistance. Emerging evidence supports the concept that platinum-based therapies are able to eliminate the bulk of differentiated cancer cells, but are unable to eliminate cancer initiating cells (CIC). To date, the relevant pathways that regulate ovarian CICs remain elusive. Several correlative studies have shown that Wnt/β-catenin pathway activation is associated with poor outcomes in patients with high-grade serous ovarian cancer (HGSOC). However, the functional relevance of these findings remain to be delineated. We have uncovered that Wnt/β-catenin pathway activation is a critical driver of HGSOC chemotherapy resistance, and targeted inhibition of this pathway, which eliminates CICs, represents a novel and effective treatment for chemoresistant HGSOC. Here we show that Wnt/β-catenin signaling is activated in ovarian CICs, and targeted inhibition of β-catenin potently sensitized cells to cisplatin and decreased CIC tumor sphere formation. Furthermore, the Wnt/β-catenin specific inhibitor iCG-001 potently sensitized cells to cisplatin and decreased stem-cell frequency in platinum resistant cells. Taken together, our data is the first report providing evidence that the Wnt/β-catenin signaling pathway maintains stem-like properties and drug resistance of primary HGSOC PDX derived platinum resistant models, and therapeutic targeting of this pathway with iCG-001/PRI-724, which has been shown to be well tolerated in Phase I trials, may be an effective treatment option.
A novel genetic algorithm-based clustering technique and its suitability for knowledge discovery from a brain data set

In this paper we demonstrate that some recent clustering techniques do not produce sensible clusters and fail to discover knowledge from underlying data sets. Sometimes, they obtain a huge number of clusters from few records and sometimes they obtain only two clusters from many records, where one cluster contains one record and the other cluster contains all remaining records. Interestingly, these clustering solutions often achieve high fitness values based on existing evaluation criteria. We in this paper propose a Genetic Algorithm-based Clustering technique called CSClust that produces sensible clusters with high fitness values, which are also useful for knowledge discovery. CSClust learns necessary properties of a sensible clustering solution for a data set from a high-quality initial population, without requiring any user input. It then disqualifies the chromosomes that do not satisfy the properties and replaces them by high-quality chromosomes through its cloning operation in each generation. As a result, it finally produces sensible clusters of high quality that are useful in knowledge discovery from a data set. We apply CSClust on a brain data set and demonstrate its ability in knowledge discovery compared to some existing techniques. We also compare it with five (5) existing techniques on ten (10) publicly available data sets in terms of two well-known evaluation criteria: Silhouette Coefficient and DB Index. Our experimental results demonstrate statistically significant superiority of CSClust over existing techniques.
Target motion compensation in MRI-guided prostate biopsy with static images

Purpose: MRI-guided prostate needle biopsy requires compensation for organ motion between target planning and needle placement. Methods: We propose slice-to-volume registration algorithms for tracking the prostate motion. Three orthogonal intra-operative slices are acquired in the approximate center of the prostate and registered with a high-resolution target planning volume. Both rigid and deformable scenarios were implemented. MRI-guided robotic prostate biopsy cases were analyzed retrospectively. Results: Average registration errors were 2.55mm for the rigid algorithm and 2.05mm for the deformable algorithm. Conclusion: Slice-based tracking appears to be promising. Deformable registration does not seem warranted.