Identification of hip fracture patients from radiographs using Fourier analysis of the trabecular structure: a cross-sectional study

Peer reviewedPublisher PD

Bacteriological and cytological findings during the late puerperal period after two different treatments of retained placenta followed by acute puerperal metritis

The aim of the study was to compare the effect of two acute puerperal metritis (APM) treatment protocols on uterine condition during the late puerperal period (5th to 7th week). Late gestation healthy cows (n = 21) were divided randomly in three equal groups. Parturitions were induced. Treatments of APM were started on the third day postpartum (PP). Group A was treated with an oxytocin analogue carbetocin for three days and intrauterine administration of cephapirin between days 15 and 17. Group B was given intramuscular injection of ceftiofur for five days followed by two injections of prostaglandin F2α, at an interval of 12 h, on the eighth day PP. Group C served as the control group with no treatment. Body temperature was recorded daily for 14 days PP. Uterine biopsies for bacteriology, and uterobrush samples for cytology, were taken once a week from the 5th to 7th week postpartum. No differences were found in body temperature on day 14 PP, presence of bacteriological infections and disappearance of uterine inflammatory signs diagnosed by cytological examination between experimental groups

Exploratory Analysis of TP53\textit{TP53} Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study

$\textbf{Background:}$ Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic $\textit{TP53}$ mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP). $\textbf{Methods and Findings:}$ We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment. Patient-specific $\textit{TP53}$ assays were developed for 31 unique mutations identified in formalin-fixed paraffin-embedded tumour DNA from these patients. These assays were used to quantify ctDNA in 318 plasma samples using microfluidic digital PCR. The $\textit{TP53}$ mutant allele fraction (TP53MAF) was compared to serum CA-125, the current gold-standard response marker for HGSOC in blood, as well as to disease volume on computed tomography scans by volumetric analysis. Changes after one cycle of treatment were compared with TTP. The median TP53MAF prior to treatment in 51 relapsed treatment courses was 8% (interquartile range [IQR] 1.2%-22%) compared to 0.7% (IQR 0.3%-2.0%) for seven untreated newly diagnosed stage IIIC/IV patients. TP53MAF correlated with volumetric measurements (Pearson $r$ = 0.59, $p$ 32 cm$^3$, ctDNA was detected at ≥20 amplifiable copies per millilitre of plasma. In 49 treatment courses for relapsed disease, pre-treatment TP53MAF concentration, but not CA-125, was associated with TTP. Response to chemotherapy was seen earlier with ctDNA, with a median time to nadir of 37 d (IQR 28-54) compared with a median time to nadir of 84 d (IQR 42-116) for CA-125. In 32 relapsed treatment courses evaluable for response after one cycle of chemotherapy, a decrease in TP53MAF of >60% was an independent predictor of TTP in multivariable analysis (hazard ratio 0.22, 95% CI 0.07-0.67, $p$ = 0.008). Conversely, a decrease in TP53MAF of ≤60% was associated with poor response and identified cases with TTP < 6 mo with 71% sensitivity (95% CI 42%-92%) and 88% specificity (95% CI 64%-99%). Specificity was improved when patients with recent drainage of ascites were excluded. Ascites drainage led to a reduction of TP53MAF concentration. The limitations of this study include retrospective design, small sample size, and heterogeneity of treatment within the cohort. $\textbf{Conclusions:}$ In this retrospective study, we demonstrated that ctDNA is correlated with volume of disease at the start of treatment in women with HGSOC and that a decrease of ≤60% in TP53MAF after one cycle of chemotherapy was associated with shorter TTP. These results provide evidence that ctDNA has the potential to be a highly specific early molecular response marker in HGSOC and warrants further investigation in larger cohorts receiving uniform treatment.This work was supported by Cancer Research UK Grant numbers: A15601 (JDB), A11906 (NR), A20240 (NR), A18072 (JDB). JDB was supported by the National Institute for Health Research Cambridge Biomedical Research Centre. CAP was supported in part by the Academy of Medical Sciences, the Wellcome Trust, British Heart Foundation and Arthritis Research UK

Catecholaminergic depletion in nucleus accumbens enhances trace conditioning

Purpose: To examine the effect of dopamine depletion in nucleus accumbens on trace conditioning; to distinguish the role of core and shell sub-regions, as far as possible. Material/Methods: 6-hydroxydopamine was used to lesion dopamine terminals within the core and shell accumbens. Experiment 1 assessed conditioning to a tone conditioned stimulus that had previously been paired with footshock (unconditioned stimulus) at a 30s trace interval. Experiment 2 subsequently assessed contiguous conditioning (at 0s trace) using a light conditioned stimulus directly followed by the unconditioned stimulus. Results: Both sham and shell-lesioned animals showed the normal trace effect of reduced conditioning to the trace conditioned stimulus but 6-hydroxydopamine injections targeted on the core subregion of the nucleus accumbens abolished this effect and enhanced conditioning to the trace conditioned stimulus. However, the depletion produced by this lesion placement extended to the shell. In Experiment 2 (at 0s trace), there was no effect of either lesion placement as all animals showed comparable levels of conditioning to the light conditioned stimulus. Neurochemical analysis across core, shell and comparison regions showed some effects on noradrenalin as well as dopamine. Conclusions: The pattern of changes in noradrenalin did not systematically relate to the observed behavioural changes after core injections. The pattern of changes in dopamine suggested that depletion in core mediated the increased conditioning to the trace conditioned stimulus seen in the present study. However, the comparison depletion restricted to the shell subregion was less substantial, and a role for secondarily affected brain regions cannot be excluded

Prediction of preterm birth with and without preeclampsia using mid-pregnancy immune and growth-related molecular factors and maternal characteristics.

OBJECTIVE:To evaluate if mid-pregnancy immune and growth-related molecular factors predict preterm birth (PTB) with and without (±) preeclampsia. STUDY DESIGN:Included were 400 women with singleton deliveries in California in 2009-2010 (200 PTB and 200 term) divided into training and testing samples at a 2:1 ratio. Sixty-three markers were tested in 15-20 serum samples using multiplex technology. Linear discriminate analysis was used to create a discriminate function. Model performance was assessed using area under the receiver operating characteristic curve (AUC). RESULTS:Twenty-five serum biomarkers along with maternal age &lt;34 years and poverty status identified &gt;80% of women with PTB ± preeclampsia with best performance in women with preterm preeclampsia (AUC = 0.889, 95% confidence interval (0.822-0.959) training; 0.883 (0.804-0.963) testing). CONCLUSION:Together with maternal age and poverty status, mid-pregnancy immune and growth factors reliably identified most women who went on to have a PTB ± preeclampsia

A High Diffusive Model for Nanomaterials

Considerable attention is today devoted to the engineering of films widely used in photocatalytic, solar energy converters, photochemical and photoelectrochemical cells, dye-sensitized solar cells (DSSCs), to optimize electronic time response following photogeneration. However, the precise nature of transport processes in these systems has remained unresolved. To investigate such aspects of carrier dynamics, we have suggested a model for the calculation of correlation functions, expressed as the Fourier transform of the frequency-dependent complex conductivity σ(ω). Results are presented for the velocity correlation functions, the mean square deviation of position and the diffusion coefficient in systems, like TiO2 and doped Si, of large interest in present devices. Fast diffusion occurs in short time intervals of the order of few collision times. Consequences for efficiency of this fast response are discussed in relation to nanostructured devices

Plant-RRBS, a bisulfite and next-generation sequencing-based methylome profiling method enriching for coverage of cytosine positions

Background: Cytosine methylation in plant genomes is important for the regulation of gene transcription and transposon activity. Genome-wide methylomes are studied upon mutation of the DNA methyltransferases, adaptation to environmental stresses or during development. However, from basic biology to breeding programs, there is a need to monitor multiple samples to determine transgenerational methylation inheritance or differential cytosine methylation. Methylome data obtained by sodium hydrogen sulfite (bisulfite)-conversion and next-generation sequencing (NGS) provide genome- wide information on cytosine methylation. However, a profiling method that detects cytosine methylation state dispersed over the genome would allow high-throughput analysis of multiple plant samples with distinct epigenetic signatures. We use specific restriction endonucleases to enrich for cytosine coverage in a bisulfite and NGS-based profiling method, which was compared to whole-genome bisulfite sequencing of the same plant material. Methods: We established an effective methylome profiling method in plants, termed plant-reduced representation bisulfite sequencing (plant-RRBS), using optimized double restriction endonuclease digestion, fragment end repair, adapter ligation, followed by bisulfite conversion, PCR amplification and NGS. We report a performant laboratory protocol and a straightforward bioinformatics data analysis pipeline for plant-RRBS, applicable for any reference-sequenced plant species. Results: As a proof of concept, methylome profiling was performed using an Oryza sativa ssp. indica pure breeding line and a derived epigenetically altered line (epiline). Plant-RRBS detects methylation levels at tens of millions of cytosine positions deduced from bisulfite conversion in multiple samples. To evaluate the method, the coverage of cytosine positions, the intra-line similarity and the differential cytosine methylation levels between the pure breeding line and the epiline were determined. Plant-RRBS reproducibly covers commonly up to one fourth of the cytosine positions in the rice genome when using MspI-DpnII within a group of five biological replicates of a line. The method predominantly detects cytosine methylation in putative promoter regions and not-annotated regions in rice. Conclusions: Plant-RRBS offers high-throughput and broad, genome- dispersed methylation detection by effective read number generation obtained from reproducibly covered genome fractions using optimized endonuclease combinations, facilitating comparative analyses of multi-sample studies for cytosine methylation and transgenerational stability in experimental material and plant breeding populations

Appraisals, emotions and emotion regulation: An integrative approach

The present work aims to investigate the relation between appraisals, emotions, and emotion regulation strategies by creating a structural equation model which integrates these three aspects of the emotion process. To reach this aim, Italian students (N = 610) confronted with their high school diploma examination completed a questionnaire 3 weeks before the beginning of the exam. Results showed that they experienced primarily three types of emotions—anxiety/fear, frustration/powerlessness, positive emotions—which were related to specific appraisal profiles. Importantly, these appraisal profiles and emotions were associated with the use of different strategies for regulating emotions: anxiety/fear was associated with focusing on the exam, drug use, and an inability to distance oneself from the exam; frustration/powerlessness, with use of suppression, distancing, and drugs; positive emotion, with reappraisal and problem focused strategies. The effectiveness of these different strategies will be discussed

Sharing Detailed Research Data Is Associated with Increased Citation Rate

BACKGROUND: Sharing research data provides benefit to the general scientific community, but the benefit is less obvious for the investigator who makes his or her data available. PRINCIPAL FINDINGS: We examined the citation history of 85 cancer microarray clinical trial publications with respect to the availability of their data. The 48% of trials with publicly available microarray data received 85% of the aggregate citations. Publicly available data was significantly (p = 0.006) associated with a 69% increase in citations, independently of journal impact factor, date of publication, and author country of origin using linear regression. SIGNIFICANCE: This correlation between publicly available data and increased literature impact may further motivate investigators to share their detailed research data