393 research outputs found

    Bayesian inference of a new Mallows model for characterising symptom sequences applied in primary progressive aphasia

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    Machine learning models offer the potential to understand diverse datasets in a data-driven way, powering insights into individual disease experiences and ensuring equitable healthcare. In this study, we explore Bayesian inference for characterising symptom sequences, and the associated modelling challenges. We adapted the Mallows model to account for partial rankings and right-censored data, employing custom MCMC fitting. Our evaluation, encompassing synthetic data and a primary progressive aphasia dataset, highlights the model's efficacy in revealing mean orderings and estimating ranking variance. This holds the potential to enhance clinical comprehension of symptom occurrence. However, our work encounters limitations concerning model scalability and small dataset sizes.Comment: Extended Abstract presented at Machine Learning for Health (ML4H) symposium 2023, December 10th, 2023, New Orleans, United States, 8 page

    Effects of Storage Conditions on the Morphology and Titer of Lentiviral Vectors

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    Lentiviral vectors are commonly used in laboratory experiments to stably integrate transgenes into host genomes. It has long been observed that storage of virus stocks leads to a decrease in viral titer, but the mechanisms driving this decrease have yet to be identified. To that end, lentiviral vector stocks were generated and stored as follows: room temperature for less than one hour, -80ºC for 24 hours, 4ºC for three days and 4ºC for 7 days. These stocks were subsequently evaluated with regard to their transducing ability and their morphology, specifically particle diameter. The vector that was stored at room temperature served as the control with viral morphology similar to other VSV-G pseudotyped viruses. These stocks were able to transduce ~100% of HEK 293T cells. Particles were unstable under the storage conditions tested, as evidenced by the fact that all stocks stored at -80°C and 4°C required concentration with an ultracentrifuge to generate a preparation suitable for visualization with TEM. The vector stored at -80°C for 24 hours exhibited some morphological changes, but only a slight decrease in titer. The morphology of vectors stored at 4°C for 3 and 7 days was not significantly different from the room temperature control, although titer was reduced to 60% and 30-40%, respectively. Thus, the decrease in titer observed in the lentiviral stocks generated and stored during this investigation appears to be the result of viral particle instability rather than morphological changes to individual particles

    The Addition of Arachidin 1 or Arachidin 3 to Human Rotavirus-infected Cells Inhibits Viral Replication and Alters the Apoptotic Cell Death Pathway

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    Rotavirus (RV) infections are a leading cause of severe gastroenteritis in infants and children under the age of five. There are two vaccines available in the United States and one in India that can be administered early in childhood, however they only protect against specific strains1. From our previous work, both arachidin-1 (A1) and arachidin-3 (A3) from peanut (Arachis hypogaea) hairy root cultures significantly inhibit simian RV replication2,3,4. The purpose of this study was to determine if a human intestinal cell line, HT29.f8, infected with a human RV, Wa, was affected by A1 and A3. Cell viability assays were utilized to determine if A1 and A3 affect the HT29.f8 cells with/without RV infections. At eighteen hours post infection (hpi), supernatants from the RV-infected HT29.f8 cells with/without the arachidins were used in plaque forming assays to quantify and compare the amount of infectious RV particles that are produced during an infection. Transmission electron microscopy (TEM) was used to visualize cell ultrastructure and individual RV particles. Additionally, tunable resistive pulse sensing technology (TRPS) using the qNano system by IZON was employed to quantify and measure virus particle sizes, and display the size distribution of RV particles. Likewise, quantitative real time polymerase chain reactions (qRT-PCR) were performed to determine if A1 and A3 regulated cell death pathways in the HT29.f8 cell line. This data will guide our future studies to determine the antiviral mechanism(s) of action of A1 and A3

    Susceptibility of Primary HTLV-1 Isolates from Patients with HTLV-1-Associated Myelopathy to Reverse Transcriptase Inhibitors

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    Since human T-lymphotropic virus type 1 (HTLV-1)-associated diseases are associated with a high HTLV-1 load, reducing this load may treat or prevent disease. However, despite in vitro evidence that certain nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs) are active against HTLV-1, in vivo results have been disappointing. We therefore assayed the sensitivity of HTLV-1 primary isolates to a panel of RT inhibitors. HTLV-1 primary isolates were obtained, pre- and post- NRTI treatment, from patients with HTLV-1-associated myelopathy. Sensitivity to azidothymidine (AZT), lamivudine (3TC), tenofovir (TDF) and three phosphonated carbocyclic 2’-oxa-3’aza nucleosides (PCOANs) was assessed in a RT inhibitor assay. With the exception of 3TC, HTLV RT from primary isolates was less sensitive to all tested inhibitors than HTLV-1 RT from MT-2 cells. HTLV-1 RT from primary isolates and from chronically infected, transformed MT-2 cells was insensitive to 3TC. Sensitivity of primary isolates to RT inhibitors was not reduced following up to 12 months of patient treatment with AZT plus 3TC. The sensitivity of HTLV-1 primary isolates to NRTIs differs from that of cell lines and may vary among patients. Failure of NRTIs to reduce HTLV-1 viral load in vivo was not due to the development of phenotypic NRTI resistance. AZT and the three PCOANs assayed all consistently inhibited primary isolate HTLV-1 RT

    Assessing infant cognition in field settings using eye-tracking: A pilot cohort trial in Sierra Leone

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    OBJECTIVES: To investigate the feasibility of eye-tracking-based testing of the speed of visual orienting in malnourished young children at rural clinics in Sierra Leone. DESIGN: Prospective dual cohort study nested in a cluster-randomised trial. SETTING: 8 sites participating in a cluster-randomised trial of supplementary feeding for moderate acute malnutrition (MAM). PARTICIPANTS: For the MAM cohort, all infants aged 7-11 months at the eight sites were enrolled, 138 altogether. For controls, a convenience sample of all non-malnourished infants aged 7-11 months at the same sites were eligible, 60 altogether. A sample of 30 adults at the sites also underwent eye-tracking tests as a further control. INTERVENTIONS: Infants with MAM were provided with supplementary feeding. OUTCOME MEASURES: The primary outcomes were feasibility and reliability of eye-tracking-based testing of saccadic reaction time (SRT). Feasibility was assessed by the percent of successful tests in the infants. Reliability was measured with intraclass correlation coefficients (ICCs). Secondary outcomes were mean SRT based on nutritional state as well as and changes in mean SRT after supplementary feeding of MAM children. RESULTS: Infants exhibited consistent orienting to targets on a computer screen (\u3e95% of valid trials). Mean SRTs had moderate stability within visits (ICCs 0.60-0.69) and across the 4-week test-retest interval (0.53) in infants; the adult control group had greater SRT stability (within visit ICC=0.92). MAM infants had a trend toward higher adjusted SRT at baseline (difference=12.4 ms, 95% CI -2 to 26.9, p=0.09) and improvement in SRT 4 weeks thereafter (difference=-14 ms, 95% CI -26.2 to -1.7, p=0.025) compared with age-matched controls. CONCLUSIONS: The results demonstrate the feasibility of eye-tracking-based testing in a resource-poor field setting and suggest eye-tracking measures have utility in the detection of group level effects of supplementary feeding

    Quality of life in lung cancer survivors treated with tyrosine-kinase inhibitors (TKI) : results from the multi-centre cross-sectional German study LARIS

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    Purpose We aimed at exploring the quality of life (QOL) of lung cancer survivors with proven tyrosine-kinase receptor (RTK) genetic alterations and targeted tyrosine-kinase inhibitors (TKI) therapy, compared to lung cancer survivors with no-RTK alterations and no-TKI therapy. Methods Data were collected in a cross-sectional multi-centre study. Primary lung cancer survivors were asked about their socio-demographic and clinical information, QOL, symptom burden, and distress. QOL and symptom burden were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), and distress with the Patient Health Questionnaire-4 (PHQ-4). Demographic and clinical characteristics were reported in absolute and relative frequencies, QOL, and symptom burden using mean scores. Diferences in mean scores with relative 95% confdence intervals were used for comparison. Results Three groups of survivors were defned: group A with proven RTK alterations, TKI therapy at any time during therapy, and stage IV lung cancer at diagnosis (n=49); group B: non-TKI therapy and stage IV lung cancer (n=121); group C: non-TKI therapy and stage I–III lung cancer (n=495). Survivors in group A reported lower QOL (mean score diference=-11.7 vs. group B) and symptom burden for dyspnoea (diference=-11.5 vs. group C), and higher symptom burden for appetite loss (diference= +11.4 vs. group C), diarrhoea and rash (diferences= +25.6,+19.6 and+13.2,+13.0, respectively, vs. both groups). Conclusions Our results suggest that the specifc side efects of TKI therapy can impair QOL among lung cancer survivors. Therefore, specifc focus towards the optimal management of these side efects should be considered
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