Miracle-dz/UniFAR-FTUs huggingface dataset:
Continuation of Antibiotics Is Associated With Failure of Metronidazole for Clostridium difficile-Associated Diarrhea

Background: Metronidazole is first-line therapy for C. difficile-associated diarrhea primarily because of its low cost relative to vancomycin. Currently, it is unknown which patients will fail metronidazole therapy. Our goal was to prospectively evaluate risk factors for metronidazole failure. Study: Included patients had symptomatic C. difficile-associated diarrhea, either mild or severe. Once enrolled, detailed baseline data were gathered. All interviews were performed daily while the patient was in the hospital for up to 14 days. If discharged prior to 14 days, the patient received a follow-up phone call on day 5 and day 14. Enrolled patients were given a daily stool survey to complete. Results: We enrolled 27 patients with C. difficile-associated diarrhea. All patients (10 of 10) who had their offending antibiotic(s) discontinued had symptomatic resolution of diarrhea by day 14 of metronidazole treatment. Conversely, 59% (10 of 17) of patients who remained on antibiotics during treatment had symptomatic resolution by day 14 (P = 0.02). The risk ratio for treatment failure was 2.0 (95% confidence interval, 1.29-3.10) in patients who remained on antibiotics. In our treatment group, there would be one additional metronidazole treatment success for every 2.4 patients who discontinued antibiotics. Conclusion: Patients who remain on antibiotics while undergoing treatment of C. difficile-associated diarrhea have a high likelihood of treatment failure with metronidazole.
Effect of human osteopontin on proliferation, transmigration and expression of MMP-2 and MMP-9 in osteosarcoma cells.

BACKGROUND To explore the effect of human osteopontin (hOPN) on the proliferation, transmigration and expression of matrix metallproteinase-2 (MMP-2) and matrix metallproteinase-9 (MMP-9) in osteosarcoma (OS) cells in vitro. METHODS The prokaryotic-expression vector of hOPN was produced. hOPN was then subcloned into E. coli BL21 (DE3) cells and purified with ProBond trade mark Columns. The proliferation, cell cycle and the expression of cyclin A in OS cells were investigated by using MTT assay, flow cytometry and Western blot respectively. The transmigration of OS cells was checked by using transwell cell culture chamber. The micro-pore-filter-membrane system was used to study the chemiotaxis of hOPN to OS cells. The levels of total protein were examined according to Coomassie Brilliant Blue manuals. The expression of MMP-2 and MMP-9 were evaluated by detecting the volume of degradation of gelatin on SDS-PAGE gel. RESULTS The prokaryotic-expression vector of hOPN and purified hOPN protein were achieved hOPN promoted OS cells proliferation in a dose-dependent manner, and stimulated cyclin A expression in OS cells to accelerate cell division cycle. hOPN facilitated the trans-membrane migration of OS cells. hOPN also enhanced the secretion of MMP-2 and MMP-9 in OS cells. CONCLUSION hOPN could stimulate cyclin A expression in OS cells. hOPN has chemiotaxis to OS cells and increases their transmigration. hOPN enhances the secretion of MMP-2 and MMP-9 in OS cells.
Cowpox Virus Outbreak in Banded Mongooses (Mungos mungo) and Jaguarundis (Herpailurus yagouaroundi) with a Time-Delayed Infection to Humans

Background Often described as an extremely rare zoonosis, cowpox virus (CPXV) infections are on the increase in Germany. CPXV is rodent-borne with a broad host range and contains the largest and most complete genome of all poxviruses, including parts with high homology to variola virus (smallpox). So far, most CPXV cases have occurred individually in unvaccinated animals and humans and were caused by genetically distinguishable virus strains. Methodology/Principal Findings Generalized CPXV infections in banded mongooses (Mungos mungo) and jaguarundis (Herpailurus yagouaroundi) at a Zoological Garden were observed with a prevalence of the affected animal group of 100% and a mortality of 30%. A subsequent serological investigation of other exotic animal species provided evidence of subclinical cases before the onset of the outbreak. Moreover, a time-delayed human cowpox virus infection caused by the identical virus strain occurred in a different geographical area indicating that handling/feeding food rats might be the common source of infection. Conclusions/Significance Reports on the increased zoonotic transmission of orthopoxviruses have renewed interest in understanding interactions between these viruses and their hosts. The list of animals known to be susceptible to CPXV is still growing. Thus, the likely existence of unknown CPXV hosts and their distribution may present a risk for other exotic animals but also for the general public, as was shown in this outbreak. Animal breeders and suppliers of food rats represent potential multipliers and distributors of CPXV, in the context of increasingly pan-European trading. Taking the cessation of vaccination against smallpox into account, this situation contributes to the increased incidence of CPXV infections in man, particularly in younger age groups, with more complicated courses of clinical infections.
Coupling modes of gold trimer superstructures

An experimental and theoretical examination of the coupling modes within superstructures of gold nanorod trimers is presented. The experimentally determined spectrum of the nanorod trimers is reported and the modes are elucidated using an electrostatic eigenmode method based on the coupling of evanescent electric fields. The theory is able to reproduce the experimental spectrum well, and the nature of the modes and interactions are discussed.
Tetrahedral Element Shape Optimization via the Jacobian Determinant and Condition Number

We present a new shape measure for tetrahedral elements that is optimal in the sense that it gives the distance of a tetrahedron from the set of inverted elements. This measure is constructed from the condition number of the linear transformation between a unit equilateral tetrahedron and any tetrahedron with positive volume. We use this shape measure to formulate two optimization objective functions that are differentiated by their goal: the first seeks to improve the average quality of the tetrahedral mesh; the second aims to improve the worst-quality element in the mesh. Because the element condition number is not defined for tetrahedral with negative volume, these objective functions can be used only when the initial mesh is valid. Therefore, we formulate a third objective function using the determinant of the element Jacobian that is suitable for mesh untangling. We review the optimization techniques used with each objective function and present experimental results that demonstrate the effectiveness of the mesh improvement and untangling methods. We show that a combined optimization approach that uses both condition number objective functions obtains the best-quality meshes.
Effect of local binding on stochastic transport in ion channels

Ionic Coulomb blockade is an electrostatic phenomenon recently discovered in low-capacitance ion channels/ nanopores. Depending on the fixed charge that is present, Coulomb blockade strongly and selectively influences the ease with which a given type of ion can permeate the pore. The phenomenon arises from the discreteness of the charge-carriers and it manifests itself strongly for divalent ions (e.g. Ca2+). Ionic Coulomb blockade is closely analogous to electronic Coulomb blockade in quantum dots. In addition to the non-local 1D Coulomb interaction considered in the standard Coulomb blockade model, we now propose a correction to take account of the singular part of the attraction to the binding site (i.e. local site binding) and of the local ion-ion repulsion. We show that this correction leads to a geometry-dependent shift of the single-ion barrier-less resonant conduction points M0. We also show that local repulsion accounts for a splitting of Ca2+ profiles observed earlier in Brownian dynamics simulations.
Pathways between childhood victimization and psychosis-like symptoms in the ALSPAC birth cohort.

BACKGROUND Several large population-based studies have demonstrated associations between adverse childhood experiences and later development of psychotic symptoms. However, little attention has been paid to the mechanisms involved in this pathway and the few existing studies have relied on cross-sectional assessments. METHODS Prospective data on 6692 children from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) were used to address this issue. Mothers reported on children's exposure to harsh parenting and domestic violence in early childhood, and children self-reported on bullying victimization prior to 8.5 years. Presence of children's anxiety at 10 years and their depressive symptoms at 9 and 11 years were ascertained from mothers, and children completed assessments of self-esteem and locus of control at 8.5 years. Children were interviewed regarding psychotic symptoms at a mean age of 12.9 years. Multiple mediation analysis was performed to examine direct and indirect effects of each childhood adversity on psychotic symptoms. RESULTS The association between harsh parenting and psychotic symptoms was fully mediated by anxiety, depressive symptoms, external locus of control, and low self-esteem. Bullying victimization and exposure to domestic violence had their associations with psychotic symptoms partially mediated by anxiety, depression, locus of control, and self-esteem. Similar results were obtained following adjustment for a range of confounders and when analyses were conducted for boys and girls separately. CONCLUSIONS These findings tentatively suggest that specific cognitive and affective difficulties in childhood could be targeted to minimize the likelihood of adolescents exposed to early trauma from developing psychotic symptoms.
Detection of Interaural Time Differences in the Alligator

The auditory systems of birds and mammals use timing information from each ear to detect interaural time difference (ITD). To determine whether the Jeffress-type algorithms that underlie sensitivity to ITD in birds are an evolutionarily stable strategy, we recorded from the auditory nuclei of crocodilians, who are the sister group to the birds. In alligators, precisely timed spikes in the first-order nucleus magnocellularis (NM) encode the timing of sounds, and NM neurons project to neurons in the nucleus laminaris (NL) that detect interaural time differences. In vivo recordings from NL neurons show that the arrival time of phase-locked spikes differs between the ipsilateral and contralateral inputs. When this disparity is nullified by their best ITD, the neurons respond maximally. Thus NL neurons act as coincidence detectors. A biologically detailed model of NL with alligator parameters discriminated ITDs up to 1 kHz. The range of best ITDs represented in NL was much larger than in birds, however, and extended from 0 to 1000 μs contralateral, with a median ITD of 450 μs. Thus, crocodilians and birds employ similar algorithms for ITD detection, although crocodilians have larger heads.
Effects of the Mediterranean diet supplemented with coenzyme q10 on metabolomic profiles in elderly men and women.

BACKGROUND Characterization of the variations in the metabolomic profiles of elderly people is a necessary step to understand changes associated with aging. This study assessed whether diets with different fat quality and supplementation with coenzyme Q10 (CoQ) affect the metabolomic profile in urine analyzed by proton nuclear magnetic resonance spectroscopy from elderly people. METHODS Ten participants received, in a cross-over design, four isocaloric diets for 4-week periods each: Mediterranean diet supplemented with CoQ (Med + CoQ diet); Mediterranean diet; Western diet rich in saturated fat diet; low-fat, high-carbohydrate diet enriched in n-3 polyunsaturated fat. RESULTS Multivariate analysis showed differences between diets when comparing Med + CoQ diet and saturated fat diet, with greater hippurate urine levels after Med + CoQ diet and higher phenylacetylglycine levels after saturated fat diet in women. Following consumption of Med + CoQ, hippurate excretion was positively correlated with CoQ and β-carotene plasma levels and inversely related to Nrf2, thioredoxin, superoxide dismutase 1, and gp91(phox) subunit of NADPH oxidase gene expression. After saturated fat diet consumption, phenylacetylglycine excretion was inversely related to CoQ plasma level and positively correlated with isoprostanes urinary level. CONCLUSIONS The association between hippurate excretion and antioxidant biomarkers along with the relationship between phenylacetylglycine excretion and oxidant biomarkers suggests that the long-term consumption of a Med + CoQ diet could be beneficial for healthy aging and a promising challenge in the prevention of processes related to chronic oxidative stress, such as cardiovascular and neurodegenerative disease.
A mid- to late-Holocene record of vegetation decline and erosion triggered by monsoon weakening and human adaptations in the south-east Indian Peninsula

The mid- to late-Holocene monsoon decline led to aridification of the Indian Peninsula impacting the early agricultural practices in the region. Our analysis of organic carbon, mineral magnetic properties and AMS 14C dating of a 54.2-m-long sediment core (CY) from the Godavari Delta, India, showed changes in the organic carbon source and sediment provenance, which are linked to the changes in vegetation and soil/rock erosion caused by widespread aridification and associated human adaptation in central India. Our results show a decline in the concentration of ferrimagnetic minerals, indicating reduced input from the basalts of the Deccan Plateau after ~6.0 cal. ka BP in response to the weaker Indian monsoon. δ13C values show a distinct increase from ~4.9 cal. ka BP, indicating an increase in C4 plant sources under the continued weak monsoon phase, whereas a higher ferrimagnetic mineral concentration in the sediment suggested an increased Deccan basalt source. Abrupt increase in δ13C values and decrease in TOC content accompanied with a significant increase in ferrimagnetic mineral concentration from ~3.2 to 3.1 cal. ka BP reflected a shift of organic carbon and sediment source and a severe decline in vegetation coverage. Such phenomena indicate intensified deforestation and soil/rock erosion in the Deccan Plateau producing higher ferrimagnetic mineral inputs, which is in agreement with significant expansion of agricultural activities in the Deccan Chalcolithic cultural period. In addition, C3 plants recovered and magnetic concentration declined during the wet events (4.6 and 4.0 cal. ka BP) of Neolithic time, while both C3 plants and magnetic parameters increased during the wet events (3.1–2.8 and 2.1 cal. ka BP) of the Chalcolithic cultural period. This implies increased agricultural activity and the onset of human modification of the ecosystem.
Visualization of Intracellular Transport of Vesicular Stomatitis Virus Nucleocapsids in Living Cells

ABSTRACT The phosphoprotein (P) of vesicular stomatitis virus (VSV) is a subunit of the viral RNA polymerase. In previous studies, we demonstrated that insertion of 19 amino acids in the hinge region of the protein had no significant effect on P protein function. In the present study, we inserted full-length enhanced green fluorescent protein (eGFP) in frame into the hinge region of P and show that the fusion protein (PeGFP) is functional in viral genome transcription and replication, albeit with reduced activity. A recombinant vesicular stomatitis virus encoding PeGFP in place of the P protein (VSV-PeGFP), which possessed reduced growth kinetics compared to the wild-type VSV, was recovered. Using the recombinant VSV-PeGFP, we show that the viral replication proteins and the de novo-synthesized RNA colocalize to sites throughout the cytoplasm, indicating that replication and transcription are not confined to any particular region of the cytoplasm. Real-time imaging of the cells infected with the eGFP-tagged virus revealed that, following synthesis, the nucleocapsids are transported toward the cell periphery via a microtubule (MT)-mediated process, and the nucleocapsids were seen to be closely associated with mitochondria. Treatment of cells with nocodazole or Colcemid, drugs known to inhibit MT polymerization, resulted in accumulation of the nucleocapsids around the nucleus and also led to inhibition of infectious-virus production. These findings are compatible with a model in which the progeny viral nucleocapsids are transported toward the cell periphery by MT and the transport may be facilitated by mitochondria.
Assessing Motivations for Sports Volunteerism

Drawing on recent conceptual models on volunteer motivations developed mainly in social psychology, this study proposes that motivation for sports volunteerism is a multidimensional construct that comprises five distinct components, namely (1) Altruistic Value, (2) Personal Development, (3) Community Concern, (4) Ego Enhancement, and (5) Social Adjustment. A 20-item scale measuring motivations for sports volunteerism was developed using survey data from 935 qualified respondents. Results of confirmatory factor analysis via LISREL software provided reasonably adequate support for the five-factor dimensionality, reliability, convergent validity, and discriminant validity of the measurement scale.
An exploration of improvements to semi-supervised fuzzy c-means clustering for real-world biomedical data

This thesis explores various detailed improvements to semi-supervised learning (using labelled data to guide clustering or classification of unlabelled data) with fuzzy c-means clustering (a ‘soft’ clustering technique which allows data patterns to be assigned to multiple clusters using membership values), with the primary aim of creating a semi-supervised fuzzy clustering algorithm that shows good performance on real-world data. Hence, there are two main objectives in this work. The first objective is to explore novel technical improvements to semi-supervised Fuzzy c-means (ssFCM) that can address the problem of initialisation sensitivity and can improve results. The second objective is to apply the developed algorithm on real biomedical data, such as the Nottingham Tenovus Breast Cancer (NTBC) dataset, to create an automatic methodology for identifying stable subgroups which have been previously elicited semi-manually. Investigations were conducted into detailed improvements to the ss-FCM algorithm framework, including a range of distance metrics, initialisation and feature selection techniques and scaling parameter values. These methodologies were tested on different data sources to demonstrate their generalisation properties. Evaluation results between methodologies were compared to determine suitable techniques on various University of California, Irvine (UCI) benchmark datasets. Results were promising, suggesting that initialisation techniques, feature selection and scaling parameter adjustment can increase ssFCM performance. Based on these investigations, a novel ssFCM framework was developed, applied to the NTBC dataset, and various statistical and biological evaluations were conducted. This demonstrated highly significant improvement in agreement with previous classifications, with solutions that are biologically useful and clinically relevant in comparison with Sorias study [141]. On comparison with the latest NTBC study by Green et al. [63], similar clinical results have been observed, confirming stability of the subgroups. Two main contributions to knowledge have been made in this work. Firstly, the ssFCM framework has been improved through various technical refinements, which may be used together or separately. Secondly, the NTBC dataset has been successfully automatically clustered (in a single algorithm) into clinical sub-groups which had previously been elucidated semi-manually. While results are very promising, it is important to note that fully, detailed validation of the framework has only been carried out on the NTBC dataset, and so there is limit on the general conclusions that may be drawn. Future studies include applying the framework on other biomedical datasets and applying distance metric learning into ssFCM. In conclusion, an enhanced ssFCM framework has been proposed, and has been demonstrated to have highly significant improved accuracy on the NTBC dataset.
Therapeutic Efficacy of Human Hepatocyte Transplantation in a SCID/uPA Mouse Model with Inducible Liver Disease

Background Severe Combined Immune Deficient (SCID)/Urokinase-type Plasminogen Activator (uPA) mice undergo liver failure and are useful hosts for the propagation of transplanted human hepatocytes (HH) which must compete with recipient-derived hepatocytes for replacement of the diseased liver parenchyma. While partial replacement by HH has proven useful for studies with Hepatitis C virus, complete replacement of SCID/uPA mouse liver by HH has never been achieved and limits the broader application of these mice for other areas of biomedical research. The herpes simplex virus type-1 thymidine kinase (HSVtk)/ganciclovir (GCV) system is a powerful tool for cell-specific ablation in transgenic animals. The aim of this study was to selectively eliminate murine-derived parenchymal liver cells from humanized SCID/uPA mouse liver in order to achieve mice with completely humanized liver parenchyma. Thus, we reproduced the HSVtk (vTK)/GCV system of hepatic failure in SCID/uPA mice. Methodology/Principal Findings In vitro experiments demonstrated efficient killing of vTK expressing hepatoma cells after GCV treatment. For in vivo experiments, expression of vTK was targeted to the livers of FVB/N and SCID/uPA mice. Hepatic sensitivity to GCV was first established in FVB/N mice since these mice do not undergo liver failure inherent to SCID/uPA mice. Hepatic vTK expression was found to be an integral component of GCV-induced pathologic and biochemical alterations and caused death due to liver dysfunction in vTK transgenic FVB/N and non-transplanted SCID/uPA mice. In SCID/uPA mice with humanized liver, vTK/GCV caused death despite extensive replacement of the mouse liver parenchyma with HH (ranging from 32–87%). Surprisingly, vTK/GCV-dependent apoptosis and mitochondrial aberrations were also localized to bystander vTK-negative HH. Conclusions/Significance Extensive replacement of mouse liver parenchyma by HH does not provide a secure therapeutic advantage against vTK/GCV-induced cytotoxicity targeted to residual mouse hepatocytes. Functional support by engrafted HH may be secured by strategies aimed at limiting this bystander effect.
Condom use for disease prevention among unmarried U.S. women.

Among a nationally representative sample of 932 sexually experienced unmarried women aged 17-44, 41% reported using condoms for protection against sexually transmitted diseases, and 30% said they used condoms for this reason every time or most times they had intercourse. While 67% of unmarried condom users cited disease prevention as their primary motivation for choosing this method, only 4% said contraception was their sole reason for using condoms; the remaining 29% gave both reasons. Condom use for disease prevention appeared most common among young women, never-married women, those with the highest incomes, women at an early stage of their reproductive career, women who had not been surgically sterilized and were not using oral contraceptives, those who believed in the effectiveness of condoms and women who had intercourse infrequently. Results of logistic regression analysis showed that black women and those who believed condoms and spermicides are effective in protecting against disease were about twice as likely as their counterparts to use condoms for disease prevention every time or most times they had sex; women who had intercourse two or more times a week, who used the pill or who had been pregnant were about half as likely as others to do so.