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Echocardiographic evaluation is a diagnostic tool for the in vivo diagnosis of heart diseases. Specific and unique anatomical characteristics of the ophidian heart such as the single ventricular cavity, a tubular sinus venosus opening into the right atrium, the presence of three arterial trunks and extreme mobility in the coelomic cavity during the cardiac cycle directly affect echocardiographic examination. Twenty‐one awake, healthy ball pythons (Python regius) were analysed based on guidelines for performing echocardiographic examinations. Imaging in the sagittal plane demonstrated the caudal vena cava, sinus venosus valve (SVV) and right atrium and the various portions of the ventricle, horizontal septum, left aortic arch and pulmonary artery. Transverse imaging depicted the spatial relationship of the left and right aortic arches, the pulmonary artery and the horizontal septum. Basic knowledge of cardiac blood flow in reptiles is necessary to understand the echocardiographic anatomy. The flow of the arterial trunks and SVV was analysed using pulsed‐wave Doppler based on the approach used for humans and companion mammals. The walls and diameters of the cavum arteriosum, cavum venosum and cavum pulmonale were also evaluated. This study should improve the veterinarian's knowledge of ophidian heart basal physiology and contribute to the development of cardiology in reptiles., Echocardiography improves the opportunity to diagnose before necropsy, thanks to the evaluation of intracardiac flows. Physiological range allow the clinician an ante‐mortem diagnosis and an appropriate treatment for the individual subject.

PURPOSE Despite its increasing application, radiomics has not yet demonstrated a solid reliability, due to the difficulty in replicating analyses. The extraction of radiomic features from clinical MRI (T1w/T2w) presents even more challenges because of the absence of well-defined units (e.g. HU). Some preprocessing steps are required before the estimation of radiomic features and one of this is the intensity normalization, that can be performed using different methods. The aim of this work was to evaluate the effect of three different normalization techniques, applied on T2w-MRI images of the pelvic region, on radiomic features reproducibility. METHODS T2w-MRI acquired before (MRI1) and 12 months after radiotherapy (MRI2) from 14 patients treated for prostate cancer were considered. Four different conditions were analyzed: (a) the original MRI (No_Norm); (b) MRI normalized by the mean image value (Norm_Mean); (c) MRI normalized by the mean value of the urine in the bladder (Norm_ROI); (d) MRI normalized by the histogram-matching method (Norm_HM). Ninety-one radiomic features were extracted from three organs of interest (prostate, internal obturator muscles and bulb) at both time-points and on each image discretized using a fixed bin-width approach and the difference between the two time-points was calculated (Δfeature). To estimate the effect of normalization methods on the reproducibility of radiomic features, ICC was calculated in three analyses: (a) considering the features extracted on MRI2 in the four conditions together and considering the influence of each method separately, with respect to No_Norm; (b) considering the features extracted on MRI2 in the four conditions with respect to the inter-observer variability in region of interest (ROI) contouring, considering also the effect of the discretization approach; (c) considering Δfeature to evaluate if some indices can recover some consistency when differences are calculated. RESULTS Nearly 60% of the features have shown poor reproducibility (ICC

The field of particle physics is at the crossroads. The discovery of a Higgs-like boson completed the Standard Model (SM), but the lacking observation of convincing resonances Beyond the SM (BSM) offers no guidance for the future of particle physics. On the other hand, the motivation for New Physics has not diminished and is, in fact, reinforced by several striking anomalous results in many experiments. Here we summarise the status of the most significant anomalies, including the most recent results for the flavour anomalies, the multi-lepton anomalies at the LHC, the Higgs-like excess at around 96 GeV, and anomalies in neutrino physics, astrophysics, cosmology, and cosmic rays. While the LHC promises up to 4 ab - 1 of integrated luminosity and far-reaching physics programmes to unveil BSM physics, we consider the possibility that the latter could be tested with present data, but that systemic shortcomings of the experiments and their search strategies may preclude their discovery for several reasons, including: final states consisting in soft particles only, associated production processes, QCD-like final states, close-by SM resonances, and SUSY scenarios where no missing energy is produced. New search strategies could help to unveil the hidden BSM signatures, devised by making use of the CERN open data as a new testing ground. We discuss the CERN open data with its policies, challenges, and potential usefulness for the community. We showcase the example of the CMS collaboration, which is the only collaboration regularly releasing some of its data. We find it important to stress that individuals using public data for their own research does not imply competition with experimental efforts, but rather provides unique opportunities to give guidance for further BSM searches by the collaborations. Wide access to open data is paramount to fully exploit the LHCs potential., The European Physical Journal C, 82 (8), ISSN:1434-6044, ISSN:1434-6052

Recent high precision determinations of $V_{us}$ and $V_{ud}$ indicate towards anomalies in the first row of the CKM matrix. Namely, determination of $V_{ud}$ from superallowed beta decays and of $V_{us}$ from kaon decays imply a violation of first row unitarity at about $4\sigma$ level. Moreover, there is tension between determinations of $V_{us}$ obtained from leptonic $K\mu2$ and semileptonic $K\ell3$ kaon decays. These discrepancies can be explained if there exist extra vector-like quarks at the TeV scale, which have large enough mixings with the lighter quarks. In particular, extra vector-like weak singlets quarks can be thought as a solution to the CKM unitarity problem and an extra vector-like weak doublet can in principle resolve all tensions. The implications of this kind of mixings are examined against the flavour changing phenomena and SM precision tests. We consider separately the effects of an extra down-type isosinglet, up-type isosinglet and an isodoublet containing extra quarks of both up and down type, and determine available parameter spaces for each case. We find that the experimental constraints on flavor changing phenomena become more stringent with larger masses, so that the extra species should have masses no more than few TeV. Moreover, only one type of extra multiplet cannot entirely explain all the discrepancies, and some their combination is required. We show that these scenarios are testable with future experiments. Namely, if extra vector-like quarks are responsible for CKM anomalies, then at least one of them should be found at scale of few TeV, and anomalous weak isospin violating $Z$-boson couplings with light quarks should be detected if the experimental precision on $Z$ hadronic decay rate is improved by a factor of $2$ or so., Comment: 92 pages, 24 figures

We explore a new mechanism for reproducing the Dark Matter (DM) abundance: scatterings of one DM particle on light Standard Model particles. Strong bounds on its decays can be satisfied if DM undergoes freeze-in and has a mass around or below the pion mass. This happens, for example, in theories with a right-handed neutrino interacting with charged fermions through a leptoquark exchange. These leptoquarks can be linked to the ones motivated by the B-physics anomalies if assumptions about the flavour structure are made. DM signals are unusual, with interesting possibilities for direct and indirect detection. Achieving thermal freeze-out instead requires models with more than one DM flavour, and couplings parametrically smaller than what needed by the usual pair annihilations., Comment: 27 pages + appendices, 8 figures, 1 table; Some clarifications and references added, conclusion unchanged. Matching published version on JHEP

Previous work identified gene product 56 (gp56), encoded by the lytic bacteriophage SP01, as being responsible for inhibition of Bacillus subtilis cell division during its infection. Assembly of the essential tubulin-like protein FtsZ into a ring-shaped structure at the nascent site of cytokinesis determines the timing and position of division in most bacteria. This FtsZ ring serves as a scaffold for recruitment of other proteins into a mature division-competent structure permitting membrane constriction and septal cell wall synthesis. Here, we show that expression of the predicted 9.3-kDa gp56 of SP01 inhibits later stages of B. subtilis cell division without altering FtsZ ring assembly. Green fluorescent protein-tagged gp56 localizes to the membrane at the site of division. While its localization does not interfere with recruitment of early division proteins, gp56 interferes with the recruitment of late division proteins, including Pbp2b and FtsW. Imaging of cells with specific division components deleted or depleted and two-hybrid analyses suggest that gp56 localization and activity depend on its interaction with FtsL. Together, these data support a model in which gp56 interacts with a central part of the division machinery to disrupt late recruitment of the division proteins involved in septal cell wall synthesis. IMPORTANCE Studies over the past decades have identified bacteriophage-encoded factors that interfere with host cell shape or cytokinesis during viral infection. The phage factors causing cell filamentation that have been investigated to date all act by targeting FtsZ, the conserved prokaryotic tubulin homolog that composes the cytokinetic ring in most bacteria and some groups of archaea. However, the mechanisms of several phage factors that inhibit cytokinesis, including gp56 of bacteriophage SP01 of Bacillus subtilis, remain unexplored. Here, we show that, unlike other published examples of phage inhibition of cytokinesis, gp56 blocks B. subtilis cell division without targeting FtsZ. Rather, it utilizes the assembled FtsZ cytokinetic ring to localize to the division machinery and to block recruitment of proteins needed for septal cell wall synthesis.

Previous work identified gp56, encoded by the lytic bacteriophage SP01, as responsible for inhibition of Bacillus subtilis cell division during its infection. Assembly of the essential tubulin-like protein FtsZ into a ring-shaped structure at the nascent site of cytokinesis determines the timing and position of division in most bacteria. This FtsZ ring serves as a scaffold for recruitment of other proteins into a mature division-competent structure permitting membrane constriction and septal cell wall synthesis. Here we show that expression of the predicted 9.3-kDa gene product 56 (gp56) of SP01 inhibits latter stages of B. subtilis cell division without altering FtsZ ring assembly. GFP-tagged gp56 localizes to the membrane at the site of division. While its localization permits recruitment of early division proteins, gp56 interferes with the recruitment of late division proteins, including Pbp2b and FtsW. Imaging of cells with specific division components deleted or depleted and two-hybrid analysis suggest that gp56 localization and activity depends on its interaction with mid-recruited proteins DivIC and/or FtsL. Together these data support a model where gp56 interacts with a central part of the division machinery to disrupt late recruitment of the division proteins involved in septal cell wall synthesis.IMPORTANCEResearch over the past decades has uncovered bacteriophage-encoded factors that interfere with host cell shape or cytokinesis during viral infection. Phage factors that cause cell filamentation that have been investigated to date all act by targeting FtsZ, the conserved prokaryotic tubulin homolog that composes the cytokinetic ring in most bacteria and some groups of archaea. However, the mechanism of several identified phage factors that inhibit cytokinesis remain unexplored, including gp56 of bacteriophage SP01 of Bacillus subtilis. Here, we show that unlike related published examples of phage inhibition of cyotkinesis, gp56 blocks B. subtilis cell division without targeting FtsZ. Rather, it utilizes the assembled FtsZ cytokinetic ring to localize to the division machinery and block recruitment of proteins needed for the septal cell wall synthesis.

Purpose Mathematical modeling is a powerful and flexible method to investigate complex phenomena. It discloses the possibility of reproducing expensive as well as invasive experiments in a safe environment with limited costs. This makes it suitable to mimic tumor evolution and response to radiotherapy although the reliability of the results remains an issue. Complexity reduction is therefore a critical aspect in order to be able to compare model outcomes to clinical data. Among the factors affecting treatment efficacy, tumor oxygenation is known to play a key role in radiotherapy response. In this work, we aim at relating the oxygenation dynamics, predicted by a macroscale model trained on tumor volumetric data of uterine cervical cancer patients, to vascularization and blood flux indices assessed on Ultrasound Doppler images. Methods We propose a macroscale model of tumor evolution based on three dynamics, namely active portion, necrotic portion, and oxygenation. The model parameters were assessed on the volume size of seven cervical cancer patients administered with 28 fractions of intensity modulated radiation therapy (IMRT) (1.8 Gy/fraction). For each patient, five Doppler ultrasound tests were acquired before, during, and after the treatment. The lesion was manually contoured by an expert physician using 4D View® (General Electric Company - Fairfield, Connecticut, United States), which automatically provided the overall tumor volume size along with three vascularization and/or blood flow indices. Volume data only were fed to the model for training purpose, while the predicted oxygenation was compared a posteriori to the measured Doppler indices. Results The model was able to fit the tumor volume evolution within 8% error (range: 3-8%). A strong correlation between the intrapatient longitudinal indices from Doppler measurements and oxygen predicted by the model (about 90% or above) was found in three cases. Two patients showed an average correlation value (50-70%) and the remaining two presented poor correlations. The latter patients were the ones featuring the smallest tumor reduction throughout the treatment, typical of hypoxic conditions. Moreover, the average oxygenation value predicted by the model was close to the average vascularization-flow index (average difference: 7%). Conclusions The results suggest that the modeled relation between tumor evolution and oxygen dynamics was reasonable enough to provide realistic oxygenation curves in five cases (correlation greater than 50%) out of seven. In case of nonresponsive tumors, the model failed in predicting the oxygenation trend while succeeded in reproducing the average oxygenation value according to the mean vascularization-flow index. Despite the need for deeper investigations, the outcomes of the present work support the hypothesis that a simple macroscale model of tumor response to radiotherapy is able to predict the tumor oxygenation. The possibility of an objective and quantitative validation on imaging data discloses the possibility to translate them as decision support tools in clinical practice and to move a step forward in the treatment personalization.

Survival of pediatric patients with brain tumor has increased over the past 20 years, and increasing evidence of iatrogenic toxicities has been reported. In follow-ups, images are acquired at different time points where substantial changes of brain morphology occur, due to childhood physiological development and treatment effects. To address the image registration complexity, we propose two multi-metric approaches (Mplus, Mdot), combining mutual information (MI) and normalized gradient field filter (NGF). The registration performance of the proposed metrics was assessed on a simulated dataset (Brainweb) and compared with those obtained by MI and NGF separately, using mean magnitude and mean angular errors. The most promising metric (Mplus) was then selected and tested on a retrospective dataset comprising 45 pediatric patients who underwent focal radiotherapy for brain cancer. The quality of the realignment was scored by a radiation oncologist using a perceived misalignment metric (PM). All patients but one were assessed as PM ≤ 2 (good alignment), but the remaining one, severely affected by hydrocephalus and pneumocephalus at the first MRI acquisition, scored PM = 5 (unacceptable). These preliminary findings suggest that Mplus might improve the registration accuracy in complex applications such as pediatric oncology, when data are acquired throughout the years of follow-up, and is worth investigating.