Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of PCR and Microscopy for Detection of Cryptosporidium parvum in Human Fecal Specimens: Clinical Trial

ABSTRACT PCR technology offers alternatives to conventional diagnosis ofCryptosporidium for both clinical and environmental samples. We compared microscopic examination by a conventional acid-fast staining procedure with a recently developed PCR test that can not only detect Cryptosporidium but is also able to differentiate between what appear to be host-adapted genotypes of the parasite. Examinations were performed on 511 stool specimens referred for screening on the basis of diarrhea. PCR detected a total of 36 positives out of the 511 samples, while routine microscopy detected 29 positives. Additional positives detected by PCR were eventually confirmed to be positive by microscopy. A total of five samples that were positive by routine microscopy at Western Diagnostic Pathology but negative by PCR and by microscopy in our laboratory were treated as false positives. Microscopy therefore exhibited 83.7% sensitivity and 98.9% specificity compared to PCR. PCR was more sensitive and easier to interpret but required more hands-on time to perform and was more expensive than microscopy. PCR, however, was very adaptable to batch analysis, reducing the costs considerably. Bulk buying of reagents and modifications to the procedure would decrease the cost of the PCR test even more. An important advantage of the PCR test, its ability to directly differentiate between different Cryptosporidiumgenotypes, will assist in determining the source of cryptosporidial outbreaks. Sensitivity, specificity, ability to genotype, ease of use, and adaptability to batch testing make PCR a useful tool for future diagnosis and studies on the molecular epidemiology ofCryptosporidium infections.
Production of Active Chimeric Pediocin AcH inEscherichia coli in the Absence of Processing and Secretion Genes from the Pediococcus pap Operon

ABSTRACT Minimum requirements have been determined for synthesis and secretion of the Pediococcus antimicrobial peptide, pediocin AcH, in Escherichia coli. The functional mature domain of pediocin AcH (Lys+1 to Cys+44) is targeted into the E. coli sec machinery and secreted to the periplasm in active form when fused in frame to the COOH terminus of the secretory protein maltose-binding protein (MBP). The PapC-PapD specialized secretion machinery is not required for secretion of the MBP-pediocin AcH chimeric protein, indicating that inPediococcus, PapC and PapD probably are required for recognition and processing of the leader peptide rather than for translocation of the mature pediocin AcH domain across the cytoplasmic membrane. The chimeric protein displays bactericidal activity, suggesting that the NH2 terminus of pediocin AcH does not span the phospholipid bilayer in the membrane-interactive form of the molecule. However, the conserved Lys+1-Tyr-Tyr-Gly-Asn-Gly-Val+7-sequence at the NH2 terminus is important because deletion of this sequence abolishes activity. The secreted chimeric protein is released into the culture medium when expressed in a periplasmic leaky E. coli host. The MBP fusion-periplasmic leaky expression system should be generally advantageous for production and screening of the activity of bioactive peptides.
Meta-analysis of limb salvage versus amputation for treating high-grade and localized osteosarcoma in patients with pathological fracture

The goal of this study was to determine outcomes related to limb salvage vs. amputation for treating high-grade and localized osteosarcoma in patients with pathological fractures. Literature search was conducted using Medline, Embase and the Cochrane Database. Two reviewers independently assessed all eligible publications. The primary outcome measurement was pooled odds ratio (OR) and 95% confidence interval (CI) for the risk of local recurrence, 5-year overall survival rate and metastatic occurrence calculated through the fixed-effects method. Seven eligible studies were identified, which included a total of 284 patients. The risk for local recurrence and 5-year overall survival rate did not differ significantly (P>0.05) between the limb salvage group and amputation group, with an OR of 1.48 (95% CI, 0.67–3.30) and 1.85 (95% CI, 0.86–3.98), respectively. The risk for metastatic occurrence differed significantly (P<0.05), with an OR of 0.30 (95% CI, 0.10–0.91). The occurrence of a pathological fracture is not regarded as an absolute contraindication to limb salvage in patients with high-grade and localized osteosarcoma. Limb salvage as an alternative for treating high-grade and localized osteosarcoma in patients with pathological fracture does not greatly increase the risk for local recurrence or 5-year overall survival rate compared to amputation and has a lower risk for metastatic occurrence.
OBSERVATIONAL QUANTIFICATION OF THE ENERGY DISSIPATED BY ALFVÉN WAVES IN A POLAR CORONAL HOLE: EVIDENCE THAT WAVES DRIVE THE FAST SOLAR WIND

We present a measurement of the energy carried and dissipated by Alfvén waves in a polar coronal hole. Alfvén waves have been proposed as the energy source that heats the corona and drives the solar wind. Previous work has shown that line widths decrease with height in coronal holes, which is a signature of wave damping, but have been unable to quantify the energy lost by the waves. This is because line widths depend on both the non-thermal velocity v nt and the ion temperature T i. We have implemented a means to separate the T i and v nt contributions using the observation that at low heights the waves are undamped and the ion temperatures do not change with height. This enables us to determine the amount of energy carried by the waves at low heights, which is proportional to v nt. We find the initial energy flux density present was 6.7 ± 0.7 × 105 erg cm−2 s−1, which is sufficient to heat the coronal hole and accelerate the solar wind during the 2007–2009 solar minimum. Additionally, we find that about 85% of this energy is dissipated below 1.5 R ☉, sufficiently low that thermal conduction can transport the energy throughout the coronal hole, heating it and driving the fast solar wind. The remaining energy is roughly consistent with what models show is needed to provide the extended heating above the sonic point for the fast solar wind. We have also studied T i, which we found to be in the range of 1–2 MK, depending on the ion species.
The Development, Characterization, and Application of an OATP1B1 Inhibition Assay in Drug Discovery

The pivotal role of organic anion-transporting polypeptide 1B1 (OATP1B1) in drug disposition has become clear over the last decade. Therefore, an OATP1B1 inhibition assay suitable for use within early drug discovery was developed and characterized. IC50 estimates for 10 literature compounds using pitavastatin and estradiol-17β-glucuronide as substrates were within 2-fold of each other. In addition, the IC50 estimates using pitavastatin uptake agreed well with literature values (r2 = 0.92, average fold error = 1.3). However, when estrone-3-sulfate was used, OATP1B1 inhibition was underpredicted by as much as 10-fold. A comparison of uptake in human hepatocytes and OATP1B1 inhibition showed a significant correlation (r2 = 0.53, P < 0.001) for more than 40 compounds. These data suggest that, for discrete chemical series, OATP1B1 inhibition data may be used as a surrogate for more costly and time-consuming uptake studies in hepatocytes. OATP1B1 inhibition data, determined for over 260 compounds representing both internal AstraZeneca and literature chemistry, were also used to generate a continuous in silico model. The robustness of the model was demonstrated by accurately predicting OATP1B1 inhibition for external test sets using 50 AstraZeneca compounds (root mean square error = 0.45) and 12 literature drugs (RMSE = 0.32). The most important molecular descriptors for the prediction of OATP1B1 inhibition were maximal hydrogen bonding strength followed by cLogP. This study has shown that a well validated OATP1B1 inhibition assay in conjunction with an in silico approaches has the potential to influence significantly the design-make-test cycle and subsequently reduce the propensity of OATP1B1 ligands.
Angioimmunoblastic T-cell Lymphomas With the RHOA p.Gly17Val Mutation Have Classic Clinical and Pathologic Features

Angioimmunoblastic T-cell lymphoma (AITL) is a nodal-based mature T-cell lymphoma with distinctive clinical symptomatology and histology. Research into its pathogenesis supports a cellular derivation from follicular helper T cells and overexpression of genes related to B cells, follicular dendritic cells, and vascular growth. Recently, a novel recurring somatic mutation in RHOA, encoding p.Gly17Val, was discovered in nearly 70% of AITLs and in a smaller proportion of peripheral T-cell lymphomas, not otherwise specified (PTCL-NOS). We investigated a series of AITLs to compare RHOA mutated with wild-type case for clinicopathologic differences. Targeted exome and Sanger sequencing was performed on 27 AITLs and 10 PTCL-NOS. The RHOA G17V mutation was identified in 63% of the AITL cases and in none of the PTCL-NOS cases. The median variant allelic frequency was 14%, with a range of 0.4 to 50% in positive cases. RHOA G17V-mutated cases had a significantly higher incidence of splenomegaly and B symptoms at diagnosis, but there was no difference in overall survival between mutated and wild-type subgroups. Cases with the RHOA G17V mutation had a significantly higher mean microvessel density (P<0.01) and expressed a greater number of follicular helper T-cell markers (P<0.05) than wild-type cases. RHOA G17V is present in a significant proportion of angioimmunoblastic lymphomas and is associated with classic pathologic features of AITL. Additional studies are needed to provide a biological or functional link between altered RHOA function and these pathologic features.
In vitro pharmacoregulation of CC chemokine ligand 5 and its receptor CCR5 in diffuse lung diseases.

BACKGROUND: CC chemokine ligand (CCL)5 and its receptor CCR5 contribute to leukocyte migration into lungs of patients with diffuse lung diseases (DLD). Pharmacological regulation of CCL5 and CCR5 expression was therefore explored in bronchoalveolar cells obtained from patients with DLD. METHODS: Cells from 21 patients were co-cultivated in vitro with tumour necrosis factor-alpha and dexamethasone, cyclosporin A (CyA) or pentoxifylline. Chemokine mRNA expression and protein production was assessed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: Dexamethasone altered CCL5 mRNA expression and suppressed its protein levels. CyA inhibited chemokine mRNA expression but not protein production. Pentoxifylline did not affected chemokine expression. Both dexamethasone and CyA suppressed CCR5 mRNA transcripts. CONCLUSION: In conclusion, while dexamethasone downregulates the CCL5 functional form, CyA and pentoxifylline have no effects on CCL5 protein. These data provide in vitro correlation for clinical applications of immunomodulators in therapy of DLD.
Future Changes in European Severe Convection Environments in a Regional Climate Model Ensemble

The occurrence of environmental conditions favorable for severe convective storms was assessed in an ensemble of 14 regional climate models covering Europe and the Mediterranean with a horizontal grid spacing of 0.448. These conditions included the collocated presence of latent instability and strong deep-layer (surface to 500 hPa) wind shear, which is conducive to the severe andwell-organized convective storms. The occurrence of precipitation in the models was used as a proxy for convective initiation. Two climate scenarios (RCP4.5 and RCP8.5) were investigated by comparing two future periods (2021–50 and 2071–2100) to a historical period (1971–2000) for each of these scenarios. The ensemble simulates a robust increase (change larger than twice the ensemble sample standard deviation) in the frequency of occurrence of unstable environments (lifted index 15 m/s) deep-layer shear were found to be small and not robust, except across far northern Europe, where a decrease in shear is projected. By the end of the century, the simultaneous occurrence of latent instability, strong deep-layer shear, andmodel precipitation is simulated to increase by up to 100% across central and eastern Europe in the RCP8.5 and by 30%–50% in the RCP4.5 scenario. Until midcentury, increases in the 10%–25%range are forecast formost regions.Alarge intermodel variability is present in the ensemble and is primarily due to the uncertainties in the frequency of the occurrence of unstable environments.
Real-time Eulerian water simulation using a restricted tall cell grid

We present a new Eulerian fluid simulation method, which allows real-time simulations of large scale three dimensional liquids. Such scenarios have hitherto been restricted to the domain of off-line computation. To reduce computation time we use a hybrid grid representation composed of regular cubic cells on top of a layer of tall cells. With this layout water above an arbitrary terrain can be represented without consuming an excessive amount of memory and compute power, while focusing effort on the area near the surface where it most matters. Additionally, we optimized the grid representation for a GPU implementation of the fluid solver. To further accelerate the simulation, we introduce a specialized multi-grid algorithm for solving the Poisson equation and propose solver modifications to keep the simulation stable for large time steps. We demonstrate the efficiency of our approach in several real-world scenarios, all running above 30 frames per second on a modern GPU. Some scenes include additional features such as two-way rigid body coupling as well as particle representations of sub-grid detail.
Ultrasound-targeted microbubble destruction enhances gene transduction of adeno-associated virus in a less-permissive cell type, NIH/3T3

Adeno-associated virus (AAV) is a common vector utilized in gene therapy. The NIH/3T3 cell line, which is a potential induced pluripotent stem (iPS) cell type, was identified to be a less-permissive cell type to AAV due to its defective endosomal processing. Ultrasound-targeted microbubble destruction (UTMD) enhanced the gene transduction of AAV in permissive cells. However, there are no data concerning UTMD enhancement in less-permissive cells, and the exact mechanism of UTMD enhancement in cellular uptake is unclear. Greater knowledge concerning the rate-limiting steps in NIH/3T3 cells would aid in the elucidation of the mechanism of UTMD enhancement in the gene transduction of AAV. In the present study, UTMD enhanced the gene transduction of AAV in NIH/3T3 cells, suggesting that UTMD-enhanced AAV-mediated gene transduction may be beneficial for gene therapy in iPS cells. The dose dependence of UTMD enhancement indicated that mechanisms other than sonoporation were involved in the cellular uptake of AAV. However, UTMD did not greatly increase the gene transduction of AAV in NIH/3T3 cells. Additionally, the similar degree of enhancement in the two cell types resulted in no correlation between UTMD and endosomal processing. Future studies on UTMD-mediated AAV transduction in other non- or less-permissive cell types may aid in elucidating the exact mechanism of UTMD enhancement in cellular uptake.
Characteristics and development trends of ecohydrology in lakes and reservoirs: Insights from bibliometrics

Ecohydrology, an interdisciplinary subject connecting ecology and hydrology, has developed rapidly in recent years. Because lakes and reservoirs are responsible for the drinking water supply of billions of people and water issues are becoming increasingly severe, the importance of these water bodies is self‐evident. Lake (reservoir) ecohydrology has thus attracted considerable attention. This study aimed to analyse the characteristics and development trends of ecohydrology using a bibliometric analysis based on the Science Citation Index database. A total of 21,753 papers from 1900 to 2017 on lake (reservoir) ecohydrology were published in 2,323 journals, and the large majority of them were published in the past three decades. Most research has been concentrated in Europe (40.0%) and North America (31.0%). Among these studies, a few key lakes, for example, Lake Taihu, Lake Erie, Lake Michigan, and Lake Ontario, have been analysed in detail by numerous researchers. The results of a word frequency analysis show that the topics related to ecohydrology have transformed from the microcosmic perspective to the macroscopic perspective, and major topics include eutrophication, global change, models, and ecosystem management. The results of a principal component analysis show that the scope of lake (reservoir) ecohydrology research in Europe and North America has stagnated in recent years, whereas in China, ecohydrology research has developed rapidly over the same period. The development of ecohydrology research around the world is not even, and we need to push for more research on major lakes that are outside of Europe, the United States, and China.
Spatiotemporal properties of sensory integration in the mouse barrel cortex

While rodents explore their environment they actively contact surrounding objects with their array of whiskers, resulting in a complex pattern of multiwhisker deflections. Despite this complexity, the whisker system is able to extract relevant information from the spatiotemporal sequence of deflections to generate touch-dependent behavior. The question that arises is: How is global multiwhisker information encoded? Whiskers are mapped onto layer 4 of the primary somatosensory cortex (S1) as discrete units named “barrels”. Each barrel-related vertical column processes information coming primarily from its corresponding principal whisker (PW). Previous experiments in our lab done with extracellular recordings have revealed that neurons in the rat S1 and thalamus not only show a preferred direction for the local deflection of the PW but also for the direction of a global motion across the whisker pad. To further understand how the cortical network processes global tactile scenes, we built a set-up that enables to perform voltage sensitive dye imaging of the mouse barrel cortex while applying precise tactile stimuli using a 24-multi-whisker stimulator. We further developed a technical method to map the recorded functional data onto the cortical structure. We first studied whether local direction selectivity is spatially distributed within the barrel-related column. Responses to different directions were slightly segregated on space close to the barrel center, but the distribution differed from the one previously described in rat S1, namely a pinwheel-like structure. We then showed that global direction selectivity is spatially organized in the barrel cortex. Columns related to rostral whiskers were more selective to the global direction than columns related to caudal whiskers. Moreover, the columns related to dorsal whiskers preferred ventral global directions, while the columns related to ventral whiskers preferred caudal global directions. Overall the responses to the caudo-ventral global directions were the strongest in average for all the columns. We showed that the spatial distribution of the global direction selectivity can be explained neither by the high salience of the starting position of the deflections on the whiskerpad (a border effect), nor by the linear summation of the responses to deflections of several whiskers. Responses to the global motion of the whisker array are indeed highly sublinear independently of the direction of stimulation. In conclusion, we show here that stepping aside from the classical view of the whisker-to-barrel cortex system allows a better understanding of how different features of complex stimuli are processed and how the emergent properties of the cortex, like the global direction selectivity, are built-up.
A longitudinal study of human cytomegalovirus serology and viruria fails to detect active viral infection in 20 systemic lupus erythematosus patients

In this study, we investigated whether active human cytomegalovirus infection could be detected in 20 systemic lupus erythematosus (SLE) patients over a one-year observation period by polymerase chain reaction on serial urine specimens and by monitoring of IgG and IgM HCMV-specific antibody profiles in serial serum samples. Of 788 urine samples analysed for the presence of human cytomegalovirus DNA, only 2 specimens (0.25%) collected from two different patients contained genuine human cytomegalovirus sequences as determined by polymerase chain reaction and subsequent sequencing of the PCR products. These two patients had one positive sample out of 36 samples or 40 samples, respectively. Nineteen of the patients (95%) possessed IgG antibodies against human cytomegalovirus, while 9 (45%) produced IgM antibodies. However, none of the patients showed signs of an active virus infection as judged by the stable anti-HCMV IgG or IgM antibody levels during the observation period, nor was any correlation between disease activity and HCMV serology/viruria observed. Of single serum samples of 26 age-and sex-matched blood donors, 21 (81%) were HCMV IgG positive and 1 (3.8%) was IgM seropositive. In conclusion, our data fail to establish an active human cytomegalovirus infection in SLE patients.
Bacteriological profile and safety of Soured Milk in Uganda

Background: Soured milk has an outstanding nutritional quality and highly consumed by people in Kampala and Uganda. However, it is an excellent medium for pathogen bacterial growth and an important source of bacterial infections when poorly handled. A cross sectional study was carried out to assess for occurrence of pathological bacterial species in soured milk sold in retail dairy shops in Makindye, Kampala, Uganda. A total of 174 soured milk samples were purposively collected and analyzed using by standard bacteriological methods. 89.1% of the samples showed significant bacterial contamination. The most commonly isolated organisms were E coli (47.1%), Klebsiella spp (28.4%) Shigella Spp (11.6%), Salmonella Spp (7.1%) and Enterobacteria faecalis (5.8%). Factors associated with contamination included; age, level of education, working experience, source of information on milk handling, longevity of soured milk, presence of pests at facility, availability of hand washing equipment and general cleanliness.
Eliminating a Region of Respiratory Syncytial Virus Attachment Protein Allows Induction of Protective Immunity without Vaccine-enhanced Lung Eosinophilia

In a murine model of respiratory syncytial virus disease, prior sensitization to the attachment glycoprotein (G) leads to pulmonary eosinophilia and enhanced illness. Three different approaches were taken to dissect the region of G responsible for enhanced disease and protection against challenge. First, mutant viruses, containing frameshifts that altered the COOH terminus of the G protein, were used to challenge mice sensitized by scarification with recombinant vaccinia virus (rVV) expressing wild-type G. Second, cDNA expressing these mutated G proteins were expressed by rVV and used to vaccinate mice before challenge with wild-type respiratory syncytial virus (RSV). These studies identified residues 193–205 to be responsible for G-induced weight loss and lung eosinophilia and showed that this region was not was not necessary for induction of protective immunity. Third, mice were sensitized using an rVV that expressed only amino acids 124–203 of the G protein. Upon RSV challenge, mice sensitized with this rVV developed enhanced weight loss and eosinophilia. This is the first time that a region within RSV (amino acids 193–203) has been shown to be responsible for induction of lung eosinophilia and disease enhancement. Moreover, we now show that it is possible to induce protective immunity with an altered G protein without inducing a pathological response.