Integrating CT-based radiomic model with clinical features improves long-term prognostication itpden high-risk prostate cancer

ObjectiveHigh-risk prostate cancer (PCa) is often treated by prostate-only radiotherapy (PORT) owing to its favourable toxicity profile compared to whole-pelvic radiotherapy. Unfortunately, more than 50% patients still developed disease progression following PORT. Conventional clinical factors may be unable to identify at-risk subgroups in the era of precision medicine. In this study, we aimed to investigate the prognostic value of pre-treatment planning computed tomography (pCT)-based radiomic features and clinical attributes to predict 5-year progression-free survival (PFS) in high-risk PCa patients following PORT.Materials and methodsA total of 176 biopsy-confirmed PCa patients who were treated at the Hong Kong Princess Margaret Hospital were retrospectively screened for eligibility. Clinical data and pCT of one hundred eligible high-risk PCa patients were analysed. Radiomic features were extracted from the gross-tumour-volume (GTV) with and without applying Laplacian-of-Gaussian (LoG) filter. The entire patient cohort was temporally stratified into a training and an independent validation cohort in a ratio of 3:1. Radiomics (R), clinical (C) and radiomic-clinical (RC) combined models were developed by Ridge regression through 5-fold cross-validation with 100 iterations on the training cohort. A model score was calculated for each model based on the included features. Model classification performance on 5-year PFS was evaluated in the independent validation cohort by average area-under-curve (AUC) of receiver-operating-characteristics (ROC) curve and precision-recall curve (PRC). Delong’s test was used for model comparison.ResultsThe RC combined model which contains 6 predictive features (tumour flatness, root-mean-square on fine LoG-filtered image, prostate-specific antigen serum concentration, Gleason score, Roach score and GTV volume) was the best-performing model (AUC = 0.797, 95%CI = 0.768-0.826), which significantly outperformed the R-model (AUC = 0.795, 95%CI = 0.774-0.816) and C-model (AUC = 0.625, 95%CI = 0.585-0.665) in the independent validation cohort. Besides, only the RC model score significantly classified patients in both cohorts into progression and progression-free groups regarding their 5-year PFS (p< 0.05).ConclusionCombining pCT-based radiomic and clinical attributes provided superior prognostication value regarding 5-year PFS in high-risk PCa patients following PORT. A large multi-centre study will potentially aid clinicians in implementing personalised treatment for this vulnerable subgroup in the future

Physical, psychological, and behavioral problems among children and adolescents in countries with different economic statuses during the COVID-19 pandemic: a systematic review and meta-analysis

IntroductionThe COVID-19 pandemic has impacted children and adolescents’ physical activity (PA), sleeping patterns, and psychological and behavioral health. Yet, little is known about the differences between those in countries with various economic statuses.MethodsArticles published from database inception through 16 March 2022 were retrieved using CINAHL Complete, Cochrane Library, EMBASE, Medline, PubMed, and PsycINFO. High-quality studies that reported the number of participants with parameters associated with PA, sleeping patterns, and psychological and behavioral problems in young people aged under 18 years during the pandemic were included. We referenced the Canadian 24-Hour Movement Guidelines for PA and sleep duration to provide the event rate for young people who were not compliant with the guidelines. The event rate of young people who had decreased sleep quality and experienced psychological and behavioral problems were also investigated. A subgroup analysis was conducted to identify the differences in those in countries with diverse economic statuses. Funnel plot analysis and Egger's test were also conducted to identify any risk of publication bias.ResultA total of 66 studies with 1,371,168 participants aged between 0 and 18 years, involving 27 countries, were included. During the pandemic, we identified that 41% (95% CI: 39%, 43%; I2 = 96.62) and 43% (95% CI: 34%, 52%; I2 = 99.42) of young people did not meet the PA and sleep duration recommendation guidelines. In addition, 31% (95% CI: 28%, 35%; I2 = 99.66) of young people had decreased their sleep quality. Yet, no significant difference was found across countries with different economic statuses. However, the event rates of participants with psychological and behavioral problems were 32% (95% CI: 28%, 36%; I2 = 99.85) and 19% (95% CI: 14%, 25%; I2 = 99.72), respectively. In addition, the rate of psychological problems was more severe in those who live in lower middle-income countries (p < 0.001), while the rate of behavioral problems was more severe in those who live in high-income countries (p = 0.001).DiscussionDuring the pandemic, the discouragement of PA, poor sleep quality, and high risk of psychological and behavioral problems are concerning. A large number of young people did not comply with the recommendation guidelines. Timely implementation of recovery plans is critical to address the adverse effects on young people.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=309209, identifier CRD42022309209

Systematic Identification of Spontaneous Preterm Birth-Associated RNA Transcripts in Maternal Plasma

<div><h3>Background</h3><p>Spontaneous preterm birth (SPB, before 37 gestational weeks) is a major cause of perinatal mortality and morbidity, but its pathogenesis remains unclear. Studies on SPB have been hampered by the limited availability of markers for SPB in predelivery clinical samples that can be easily compared with gestational age-matched normal controls. We hypothesize that SPB involves aberrant placental RNA expression, and that such RNA transcripts can be detected in predelivery maternal plasma samples, which can be compared with gestational age-matched controls.</p> <h3>Principal Findings</h3><p>Using gene expression microarray to profile essentially all human genes, we observed that 426 probe signals were changed by >2.9-fold in the SPB placentas, compared with the spontaneous term birth (STB) placentas. Among the genes represented by those probes, we observed an over-representation of functions in RNA stabilization, extracellular matrix binding, and acute inflammatory response. Using RT-quantitative PCR, we observed differences in the RNA concentrations of certain genes only between the SPB and STB placentas, but not between the STB and term elective cesarean delivery placentas. Notably, 36 RNA transcripts were observed at placental microarray signals higher than a threshold, which indicated the possibility of their detection in maternal plasma. Among them, the <em>IL1RL1</em> mRNA was tested in plasma samples taken from 37 women. It was detected in 6 of 10 (60%) plasma samples collected during the presentation of preterm labor (≤32.9 weeks) in women eventually giving SPB, but was detected in only 1 of 27 (4%) samples collected during matched gestational weeks from women with no preterm labor (Fisher exact test, p = 0.00056).</p> <h3>Conclusion</h3><p>We have identified 36 SPB-associated RNA transcripts, which are possibly detectable in maternal plasma. We have illustrated that the <em>IL1RL1</em> mRNA was more frequently detected in predelivery maternal plasma samples collected from women resulting in SPB than the gestational-age matched controls.</p> </div

Relativistic Binaries in Globular Clusters

Galactic globular clusters are old, dense star systems typically containing 10\super{4}--10\super{7} stars. As an old population of stars, globular clusters contain many collapsed and degenerate objects. As a dense population of stars, globular clusters are the scene of many interesting close dynamical interactions between stars. These dynamical interactions can alter the evolution of individual stars and can produce tight binary systems containing one or two compact objects. In this review, we discuss theoretical models of globular cluster evolution and binary evolution, techniques for simulating this evolution that leads to relativistic binaries, and current and possible future observational evidence for this population. Our discussion of globular cluster evolution will focus on the processes that boost the production of hard binary systems and the subsequent interaction of these binaries that can alter the properties of both bodies and can lead to exotic objects. Direct {\it N}-body integrations and Fokker--Planck simulations of the evolution of globular clusters that incorporate tidal interactions and lead to predictions of relativistic binary populations are also discussed. We discuss the current observational evidence for cataclysmic variables, millisecond pulsars, and low-mass X-ray binaries as well as possible future detection of relativistic binaries with gravitational radiation.Comment: 88 pages, 13 figures. Submitted update of Living Reviews articl

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

A MODEST review

We present an account of the state of the art in the fields explored by the research community invested in 'Modeling and Observing DEnse STellar systems'. For this purpose, we take as a basis the activities of the MODEST-17 conference, which was held at Charles University, Prague, in September 2017. Reviewed topics include recent advances in fundamental stellar dynamics, numerical methods for the solution of the gravitational N-body problem, formation and evolution of young and old star clusters and galactic nuclei, their elusive stellar populations, planetary systems, and exotic compact objects, with timely attention to black holes of different classes of mass and their role as sources of gravitational waves. Such a breadth of topics reflects the growing role played by collisional stellar dynamics in numerous areas of modern astrophysics. Indeed, in the next decade, many revolutionary instruments will enable the derivation of positions and velocities of individual stars in the Milky Way and its satellites and will detect signals from a range of astrophysical sources in different portions of the electromagnetic and gravitational spectrum, with an unprecedented sensitivity. On the one hand, this wealth of data will allow us to address a number of long-standing open questions in star cluster studies; on the other hand, many unexpected properties of these systems will come to light, stimulating further progress of our understanding of their formation and evolution.Comment: 42 pages; accepted for publication in 'Computational Astrophysics and Cosmology'. We are much grateful to the organisers of the MODEST-17 conference (Charles University, Prague, September 2017). We acknowledge the input provided by all MODEST-17 participants, and, more generally, by the members of the MODEST communit

Effects of Performing Applied Muscle Tension during Recovery after Phlebotomy in Young, First-Time Donors: A Pilot Study

Vasovagal reaction (VVR) compromises donor safety and reduces the subsequent return rates. Performing applied muscle tension (AMT) during phlebotomy may reduce the incidence of VVR. However, the effectiveness of performing AMT after phlebotomy to reduce delayed VVR remains unclear. With ethics approval, 12 young, first-time donors (YFTD) were recruited to study the effects on stroke volume (SV), cardiac output (CO) and systemic vascular resistance (SVR) while performing AMT from needle insertion to end of recovery. Measurements from 12 matched control YFTD were used for comparison. Pre-donation anxiety and VVR severity were assessed. Compared to controls, donors who performed AMT had higher SV (Control: 57 mL vs. AMT: 69 mL, p = 0.045), higher CO (Control: 3.7 L·min−1 vs. AMT: 5.2 L·min−1, p = 0.006) and lower SVR (Control: 1962 dyn·s·cm−5 vs. AMT: 1569 dyn·s·cm−5, p = 0.032) during mid-phlebotomy. During recovery, the AMT group retained higher SV, higher CO and lower SVR than the control, but not reaching statistical significance. Practicing AMT during recovery resulted in sustained haemodynamic improvements beyond the donation period, despite the reduction in delayed VVR was insignificant compared to the control group. A larger sample size is needed to validate the effectiveness of performing AMT after donation to mitigate delayed VVR

Predictive Factors for Chemoradiation-Induced Oral Mucositis and Dysphagia in Head and Neck Cancer: A Scoping Review

Despite advances in head and neck cancer treatment, virtually all patients experience chemoradiation-induced toxicities. Oral mucositis (OM) and dysphagia are among the most prevalent and have a systemic impact on patients, hampering treatment outcome and harming quality of life. Accurate prediction of severe cases is crucial for improving management strategies and, ultimately, patient outcomes. This scoping review comprehensively maps the reported predictors and critically evaluates the performance, methodology, and reporting of predictive models for these conditions. A total of 174 studies were identified from database searches, with 73 reporting OM predictors, 97 reporting dysphagia predictors, and 4 reporting both OM and dysphagia predictors. These predictors included patient demographics, tumor classification, chemoradiotherapy regimen, radiation dose to organs-at-risk, genetic factors, and results of clinical laboratory tests. Notably, many studies only conducted univariate analysis or focused exclusively on certain predictor types. Among the included studies, numerous predictive models were reported: eight for acute OM, five for acute dysphagia, and nine for late dysphagia. The area under the receiver operating characteristic curve (AUC) ranged between 0.65 and 0.81, 0.60 and 0.82, and 0.70 and 0.85 for acute oral mucositis, acute dysphagia, and late dysphagia predictive models, respectively. Several areas for improvement were identified, including the need for external validation with sufficiently large sample sizes, further standardization of predictor and outcome definitions, and more comprehensive reporting to facilitate reproducibility

RNA transcripts that were up-regulated in the SPB placentas, relative to the STB placentas, according to the microarray experiment (Mann-Whitney test, adjusted by the Benjamini and Hochberg method, adjusted p<0.05).

a<p>The RNA transcript interrogated by each probeset is shown as the gene symbol and name approved by the HUGO Gene Nomenclature Committee at the European Bioinformatics Institute (<a href="http://www.genenames.org" target="_blank">http://www.genenames.org</a>). Certain probesets interrogating the same gene may be listed as different GenBank accession numbers. This may reflect the different isoforms being interrogated. Other details on the probesets are freely accessible at <a href="http://www.netaffx.com" target="_blank">http://www.netaffx.com</a>.</p>b<p>Only 15 transcripts with the greatest fold-change values are shown. The remaining 225 transcripts are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034328#pone.0034328.s006" target="_blank">Table S5</a>.</p>c<p>Up-regulated transcripts with higher expression levels than the <i>PLAC4</i> mRNA in the placenta, according to the microarray data.</p><p>SPB, spontaneous preterm birth; STB, spontaneous term birth.</p