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Abstract Coronavirus and other prevailing viruses continue to remain a health threat and challenge the efforts of institutions to promote vaccination acceptance. The current study’s aim is to propose a conceptual framework explaining the role of individual motivators (such as self-interest and collective interest) in shaping attitudes toward vaccination while emphasizing the pivotal role of institutional trust as a mediator and gender as a moderator. Data were collected via an online panel survey among Israelis (N = 464), and SEM statistics were used to test the model empirically. The path analysis model supports the positive direct effect of collective interest and the negative effect of self-interest. Additionally, it shows an indirect effect through the mediation effect of institutional trust and gender moderation. Therefore, institutional trust may significantly influence self-interest people’s attitudes toward vaccines. Furthermore, since females process information more comprehensively, their developed trustworthiness in institutions has an increased impact on vaccine acceptance. Theoretical and practical implications are discussed.

We determine the gravito-magnetic Love numbers of non-rotating black holes in all spacetime dimensions through a novel and direct derivation. The Ishibashi-Kodama master field and its associated field equation are avoided. The matching to the EFT variables is simple. This method allows us to correct the values in the literature. Moreover, we highlight a parity-based selection rule for nonlinear terms that include both electric-type and magnetic-type gravitational field tensors, enabling us to conclude that many of the nonlinear response coefficients in the Schwarzschild black hole effective action vanish. [ABSTRACT FROM AUTHOR]

Coronavirus and other prevailing viruses continue to remain a health threat and challenge the efforts of institutions to promote vaccination acceptance. The current study's aim is to propose a conceptual framework explaining the role of individual motivators (such as self-interest and collective interest) in shaping attitudes toward vaccination while emphasizing the pivotal role of institutional trust as a mediator and gender as a moderator. Data were collected via an online panel survey among Israelis (N = 464), and SEM statistics were used to test the model empirically. The path analysis model supports the positive direct effect of collective interest and the negative effect of self-interest. Additionally, it shows an indirect effect through the mediation effect of institutional trust and gender moderation. Therefore, institutional trust may significantly influence self-interest people's attitudes toward vaccines. Furthermore, since females process information more comprehensively, their developed trustworthiness in institutions has an increased impact on vaccine acceptance. Theoretical and practical implications are discussed. [ABSTRACT FROM AUTHOR]

The objective of the present paper is to investigate the behaviour of exciton-polariton condensates using the modulational instability mechanism. The study incorporates a complex state that involves quintic order nonlinearity due to polariton energy shift effects, as well as nonlinear dispersion effects. The investigation considers both constant and temporally variable wave numbers and cubic dispersion parameters. The results of the study indicate that various factors, including the physical parameters of the system, wave number, time variability, and construction constants of the field vector, influence the amplitude and configuration of the breather wave function. [ABSTRACT FROM AUTHOR]

Luteinizing hormone (LH) is present throughout the natural follicular phase. However, the debate is still not settled on whether LH is needed during ovarian stimulation in IVF. This commentary looks at the evolution of this debate, mentioning three elephants in the room that were ignored by the Pharma industry, professional organizations, and clinicians alike: The different endocrinology between the long agonist and the antagonist protocols. The fixed dose of the two most widely commercially available antagonist preparations, namely cetrorelix and ganirelix. The fact that most research in this area uses population-based criteria, ignoring endocrine parameters. Individual genetics of the LH receptor gene may also serve to individualize LH needs during stimulation; however, the jury is still out regarding this approach. Conclusions: Individual endocrine and genetics parameters may shed meaningful light on the question of LH supplemental during ovarian stimulation. [ABSTRACT FROM AUTHOR]

The flux-based statistical theory of the non-hierarchical three-body system predicts that the chaotic outcome distribution reduces to the chaotic emissivity function times a known function, the asymptotic flux. Here, we measure the chaotic emissivity function (or equivalently, the absorptivity) through simulations. More precisely, we follow millions of scattering events only up to the point when it can be decided whether the scattering is regular or chaotic. In this way, we measure a trivariate absorptivity function. Using it, we determine the flux-based prediction for the chaotic outcome distribution over both binary binding energy and angular momentum, and we find good agreement with the measured distribution. This constitutes a detailed confirmation of the flux-based theory and demonstrates a considerable reduction in computation to determine the chaotic outcome distribution. [ABSTRACT FROM AUTHOR]

Since the inception of in vitro fertilization (IVF), monitoring of controlled ovarian stimulation (COS) has traditionally involved numerous appointments for ultrasound and laboratory testing to guide medication use and dosing, determine trigger timing, and allow for measures to reduce the risk of ovarian hyperstimulation syndrome (OHSS). Recent advances in the field of assisted reproductive technology (ART) have called into question the timing and frequency of COS monitoring appointments, as discussed in this commentary. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a common chronic metabolic disease in humans and household cats that is characterized by persistent hyperglycemia. DM is associated with dysfunction of the intestinal barrier. This barrier is comprised of an epithelial monolayer that contains a network of tight junctions that adjoin cells and regulate paracellular movement of water and solutes. The mechanisms driving DM-associated barrier dysfunction are multifaceted, and the direct effects of hyperglycemia on the epithelium are poorly understood. Preliminary data suggest that fenofibrate, An FDA-approved peroxisome proliferator-activated receptor-alpha (PPARα) agonist drug attenuates intestinal barrier dysfunction in dogs with experimentally-induced DM. We investigated the effects of hyperglycemia-like conditions and fenofibrate treatment on epithelial barrier function using feline intestinal organoids. We hypothesized that glucose treatment directly increases barrier permeability and alters tight junction morphology, and that fenofibrate administration can ameliorate these deleterious effects. We show that hyperglycemia-like conditions directly increase intestinal epithelial permeability, which is mitigated by fenofibrate. Moreover, increased permeability is caused by disruption of tight junctions, as evident by increased junctional tortuosity. Finally, we found that increased junctional tortuosity and barrier permeability in hyperglycemic conditions were associated with increased protein kinase C-α (PKCα) activity, and that fenofibrate treatment restored PKCα activity to baseline levels. We conclude that hyperglycemia directly induces barrier dysfunction by disrupting tight junction structure, a process that is mitigated by fenofibrate. We further propose that counteracting modulation of PKCα activation by increased intracellular glucose levels and fenofibrate is a key candidate regulatory pathway of tight junction structure and epithelial permeability. [ABSTRACT FROM AUTHOR]

Background: CD103 is an integrin specifically expressed on the surface of cancer-reactive T cells. The number of CD103+ T cells significantly increases during successful immunotherapy and might therefore be an attractive biomarker for noninvasive PET imaging of immunotherapy response. Since the long half-life of antibodies preclude repeat imaging of CD103+ T cell dynamics early in therapy, we therefore here explored PET imaging with CD103 Fab fragments radiolabeled with a longer (89Zr) and shorter-lived radionuclide (68Ga). Methods: Antihuman CD103 Fab fragment Fab01A was radiolabeled with 89Zr or 68Ga, generating [89Zr]Zr-hCD103.Fab01A and [68Ga]Ga-hCD103.Fab01A, respectively. In vivo evaluation of these tracers was performed in male nude mice (BALB/cOlaHsd-Foxn1nu) with established CD103-expressing CHO (CHO.CD103) or CHO-wildtype (CHO.K1) xenografts, followed by serial PET imaging and ex vivo bio-distribution. Results: [89Zr]Zr-hCD103.Fab01A showed high tracer uptake in CD103+ xenografts as early as 3 h post-injection. However, the background signal remained high in the 3- and 6-h scans. The background was relatively low at 24 h after injection with sufficient tumor uptake. [68Ga]Ga-hCD103.Fab01Ashowed acceptable uptake and signal-to-noise ratio in CD103+ xenografts after 3 h, which decreased at subsequent time points. Conclusion: [89Zr]Zr-hCD103.Fab01A demonstrated a relatively low background and high xenograft uptake in scans as early as 6 h post-injection and could be explored for repeat imaging during immunotherapy in clinical trials. 18F or 64Cu could be explored as alternative to 68Ga in optimizing half-life and radiation burden of the tracer. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate at 1.5 and 3 T MRI the safety and performance of trademarked ENO®, TEO®, or OTO® pacing systems with automated MRI Mode and the image quality of non-enhanced MR examinations. Methods: A total of 267 implanted patients underwent MRI examination (brain, cardiac, shoulder, cervical spine) at 1.5 (n = 126) or 3 T (n = 141). MRI-related device complications, lead electrical performances stability at 1-month post-MRI, proper functioning of the automated MRI mode and image quality were evaluated. Results: Freedom from MRI-related complications at 1 month post-MRI was 100% in both 1.5 and 3 T arms (both p < 0.0001). The stability of pacing capture threshold was respectively at 1.5 and 3 T (atrial:: 98.9% (p = 0.001) and 100% (p < 0.0001); ventricular: both 100% (p < 0001)). The stability of sensing was respectively at 1.5 and 3 T (atrial: 100% (p = 0.0001) and 96.9% (p = 0.01); ventricular: 100% (p < 0.0001) and 99.1% (p = 0.0001)). All devices switched automatically to the programmed asynchronous mode in the MRI environment and to initially programmed mode after the MRI exam. While all MR examinations were assessed as interpretable, artifacts deteriorated a subset of examinations including mostly cardiac and shoulder ones. Conclusion: This study demonstrates the safety and electrical stability of ENO®, TEO®, or OTO® pacing systems at 1 month post-MRI at 1.5 and 3 T. Even if artifacts were noticed in a subset of examinations, overall interpretability was preserved. Clinical relevance statement: ENO®, TEO®, and OTO® pacing systems switch to MR-mode when detecting magnetic field and switch back on conventional mode after MRI. Their safety and electrical stability at 1 month post MRI were shown at 1.5 and 3 T. Overall interpretability was preserved. Key Points: • Patients implanted with an MRI conditional cardiac pacemaker can be safely scanned under 1.5 or 3 Tesla MRI with preserved interpretability. • Electrical parameters of the MRI conditional pacing system remain stable after a 1.5 or 3 Tesla MRI scan. • The automated MRI mode enabled the automatic switch to asynchronous mode in the MRI environment and to initial settings after the MRI scan in all patients. [ABSTRACT FROM AUTHOR]

The three-body problem is a fundamental long-standing open problem, with applications in all branches of physics, including astrophysics, nuclear physics and particle physics. In general, conserved quantities allow to reduce the formulation of a mechanical problem to fewer degrees of freedom, a process known as dynamical reduction. However, extant reductions are either non-general, or hide the problem's symmetry or include unexplained definitions. This paper presents a general and natural dynamical reduction, which avoids these issues. Any three-body configuration defines a triangle, and its orientation in space. Accordingly, we decompose the dynamical variables into the geometry (shape + size) and orientation of the triangle. The geometry variables are shown to describe the motion of an abstract point in a curved 3d space, subject to a potential-derived force and a magnetic-like force with a monopole charge. The orientation variables are shown to obey a dynamics analogous to the Euler equations for a rotating rigid body; only here the moments of inertia depend on the geometry variables, rather than being constant. The reduction rests on a novel symmetric solution to the center of mass constraint inspired by Lagrange's solution to the cubic. The formulation of the orientation variables is novel and rests on a partially known generalization of the Euler–Lagrange equations to non-coordinate velocities. Applications to global features, to the statistical solution, to special exact solutions and to economized simulations are presented. A generalization to the four-body problem is presented. [ABSTRACT FROM AUTHOR]

We examine pattern formations of the spatiotemporal dynamics of tumor growth model. The system is modeled by three-species reaction–diffusion equations of healthy cells, cancer cells and acid concentrations. The equilibrium points of the model are determined, the Routh–Hurwitz criteria allowed us to assess the stability of the system by deducing the conditions of existence of Turing models. Numerical results are presented in order to appreciate how biological processes have been affected by the formation of spatiotemporal patterns and highlight the impact of diffusion term on areas of healthy cells, cancer cells and acid concentrations through Turing and non-Turing models. Our results may be used to better describe the relationship between acidity and pattern formation as metastases during tumor growth through different sequence of diffusive cancer dynamics. [ABSTRACT FROM AUTHOR]

The micro-canonical phase-space volume for the three-body problem is an elementary quantity of intrinsic interest, and within the flux-based statistical theory, it sets the scale of the disintegration time. While the bare phase-volume diverges, we show that a regularized version can be defined by subtracting a reference phase-volume, which is associated with hierarchical configurations. The reference quantity, also known as a counter-term, can be chosen from a 1-parameter class. The regularized phase-volume of a given (negative) total energy, σ ¯ (E) , is evaluated. First, it is reduced to a function of the masses only, which is sensitive to the choice of a regularization scheme only through an additive constant. Then, analytic integration is used to reduce the integration to a sphere, known as shape sphere. Finally, the remaining integral is evaluated numerically and presented by a contour plot in parameter space. Regularized phase-volumes are presented for both the planar three-body system and the full 3d system. In the test mass limit, the regularized phase-volume is found to become negative, thereby signaling the breakdown of the non-hierarchical statistical theory. This work opens the road to the evaluation of σ ¯ (E , L) , where L is the total angular momentum, and in turn to comparison with simulation determined disintegration times. [ABSTRACT FROM AUTHOR]

It is known that acetyl derivatives, Schiff bases, and Mannich bases obtained from 1,2,4-triazol-5-ones have significant antibacterial and antioxidant activities. Herein, 27 new 1,2,4-triazole derivatives were synthesized, and their antioxidant and antibacterial properties were investigated. The metal chelating activity of the synthesized compounds and especially the effect against gram-positive bacteria were found to be significant. The effect against gram-negative strains was also important. Structure determination of the synthesized com-pounds was performed on the basis of their 1H and 13C NMR, IR, and high-resolution mass spectra. [ABSTRACT FROM AUTHOR]

The aim of this work is to study the stress distributions and the location of hot spots stress in the vicinity of the intersection lines of the tubular elements of the tubular TY-joints. Using the finite element models, we analyze the effects of geometrical parameters on the stress concentration factor in the case of in-plane bending and out-of-plane bending loads, around the weld toe of the tubular joints. Our results reveal the location of the maximum stress concentration factor at the heel or toe in the case of in-plane bending loads and at the saddle point in the case of out-of-plane bending loads. Six parametric equations are established and used to calculate the stress concentration factor at critical locations using the non-linear regression method. The results obtained from the finite element analysis are close to the results of the parametric equations and the experimental data from the previous work. [ABSTRACT FROM AUTHOR]

The synthesis of 2-ethoxy-4-[(3-alkyl-4,5-dihydro-1H-1,2,4-triazol-5-one-4-yl)-azomethine]-phenyl 2-methylbenzoates (4) from the reactions of 3-alkyl-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (2) with 3-ethoxy-4-(2-methylbenzoxy)-benzaldehyde (3) is described. The acetylation reactions of compounds 4 were investigated, and 5 type N-acetyl derivatives were obtained and the newly synthesized compounds were fully characterized. Also, in vitro antibacterial activities of the fourteen new compounds were screened against six bacteria such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Bacillus cereus and Klebsiella pneumonia according to agar well diffusion method. In addition, the newly synthesized 14 novel compounds were tested for their antioxidant activities using three different methods. Furthermore, to investigate the effects of solvents and molecular structure upon acidity, the compounds 4 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents (isopropyl alcohol, tert-butyl alcohol, N,N-dimethylformamide and acetone). [ABSTRACT FROM AUTHOR]

ATL1-related spastic paraplegia SPG3A is a pure form of hereditary spastic paraplegia. Rare complex phenotypes have been described, but few data concerning cognitive evaluation or molecular imaging of these patients are available. We relate a retrospective collection of patients with SPG3A from the Neurology Department of Nancy University Hospital, France. For each patient were carried out a 18F-FDG PET (positron emission tomography), a electromyography (EMG), a sudoscan®, a cerebral and spinal cord MRI (magnetic resonance imaging) with measurement of cervical and thoracic surfaces, a neuropsychological assessment. The present report outlines standardised clinical and paraclinical data of five patients from two east-France families carrying the same missense pathogenic variation, NM_015915.4(ATL1): c.1483C > T p.(Arg495Trp) in ATL1. Mean age at onset was 14 ± 15.01 years. Semi-quantitatively and in comparison to healthy age-matched subjects, PET scans showed a significant cerebellar and upper or mild temporal hypometabolism in all four adult patients and hypometabolism of the prefrontal cortex or precuneus in three of them. Sudoscan® showed signs of small fibre neuropathy in three patients. Cervical and thoracic patients' spinal cords were significantly thinner than matched-control, respectively 71 ± 6.59mm2 (p = 0.01) and 35.64 ± 4.35mm2 (p = 0.015). Two patients presented with a dysexecutive syndrome. While adding new clinical and paraclinical signs associated with ATL1 pathogenic variations, we insist here on the variable penetrance and expressivity. We report small fibre neuropathy, cerebellar hypometabolism and dysexecutive syndromes associated with SPG3A. These cognitive impairments and PET findings may be related to a cortico-cerebellar bundle axonopathy described in the cerebellar cognitive affective syndrome (CCAS). [ABSTRACT FROM AUTHOR]

Objectives: Enlarged lateral lymph nodes (LLNs) are associated with increased (lateral) local recurrence rates. Size and anatomical location should therefore always be reported by radiologists and discussed during multidisciplinary meetings. The objective was to investigate how often LLNs are mentioned in MRI reports in a tertiary referral centre. Methods: A single - centre, retrospective study of 202 patients treated for primary rectal cancer between 2012 and 2020, with at least a T2 tumour located within 12cm of the anorectal junction. The radiology reports were written by 30–40 consultant radiologists. MRI scans were independently re-assessed by an expert radiologist. The primary outcome was how often the presence or absence of LLNs was mentioned in the initial report. Results: Primary MRI reports explicitly mentioned the presence or absence of LLNs in 89 (44%) cases. Of the 43 reports with present LLNs, only one (1%) reported on all features such as size, location or malignant features. Expert review revealed 17 LLNs which were ≥ 7 mm (short-axis); two of these were not mentioned in the original reports. In 14/43 (33%) cases, LLNs were discussed during the primary multidisciplinary meeting, while 17/43 (40%) restaging MRI reports failed to report on the previously visible LLN. Reporting LLNs increased significantly with higher N-stage (p =.010) and over time (p =.042). Conclusions: Though improving with time, there is still limited consistency in reporting LLNs. Only 44% of primary MRI reports mentioned LLNs and relevant features of those LLNs were seldomly reported. Given the importance of this information for subsequent treatment; increased awareness, proper training and the use of templates are needed. Key Points: • Comprehensive reporting of lateral lymph nodes in primary MRI reports was limited to less than 50%. • Lateral lymph nodes are not always discussed during primary multidisciplinary meetings or mentioned in restaging reports. • Improvements in the awareness and knowledge of lateral lymph nodes are needed to ensure adequate multidisciplinary treatment decisions. [ABSTRACT FROM AUTHOR]

The small intestinal mucosa constitutes a physical barrier separating the gut lumen from sterile internal tissues. Junctional complexes between cells regulate transport across the barrier, preventing water loss and the entry of noxious molecules or pathogens. Inflammatory diseases in cattle disrupt this barrier; nonetheless, mechanisms of barrier disruption in cattle are poorly understood. We investigated the direct effects of three inflammatory cytokines, TNFα, IFNγ, and IL-18, on the bovine intestinal barrier utilizing intestinal organoids. Flux of fluorescein isothiocyanate (FITC)-labeled dextran was used to investigate barrier permeability. Immunocytochemistry and transmission electron microscopy were used to investigate junctional morphology, specifically tortuosity and length/width, respectively. Immunocytochemistry and flow cytometry was used to investigate cellular turnover via proliferation and apoptosis. Our study shows that 24-h cytokine treatment with TNFα or IFNγ significantly increased dextran permeability and tight junctional tortuosity, and reduced cellular proliferation. TNFα reduced the percentage of G2/M phase cells, and IFNγ treatment increased cell apoptotic rate. IL-18 did not directly induce significant changes to barrier permeability or cellular turnover. Our study concludes that the inflammatory cytokines, TNFα and IFNγ, directly induce intestinal epithelial barrier dysfunction and alter the tight junctional morphology and rate of cellular turnover in bovine intestinal epithelial cells. [ABSTRACT FROM AUTHOR]

Background: Genetic kidney diseases contribute a significant portion of kidney diseases in children and young adults. Nephrogenetics is a rapidly evolving subspecialty; however, in the clinical setting, increased use of genetic testing poses implementation challenges. Consequently, we established a national nephrogenetics clinic to apply a multidisciplinary model. Methods: Patients were referred from different pediatric or adult nephrology units across the country if their primary nephrologist suspected an undiagnosed genetic kidney disease. We determined the diagnostic rate and observed the effect of diagnosis on medical care. We also discuss the requirements of a nephrogenetics clinic in terms of logistics, recommended indications for referral, and building a multidisciplinary team. Results: Over 24 months, genetic evaluation was completed for a total of 74 unrelated probands, with an age range of 10 days to 72 years. The most common phenotypes included congenital anomalies of the kidneys and urinary tract, nephrotic syndrome or unexplained proteinuria, nephrocalcinosis/nephrolithiasis, tubulopathies, and unexplained kidney failure. Over 80% of patients were referred due to clinical suspicion of an undetermined underlying genetic diagnosis. A molecular diagnosis was reached in 42/74 probands, yielding a diagnostic rate of 57%. Of these, over 71% of diagnoses were made via next generation sequencing (gene panel or exome sequencing). Conclusions: We identified a substantial fraction of genetic kidney etiologies among previously undiagnosed individuals which influenced subsequent clinical management. Our results support that nephrogenetics, a rapidly evolving field, may benefit from well-defined multidisciplinary co-management administered by a designated team of nephrologist, geneticist, and bioinformatician. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

In this paper, the influence of geometric parameters on the stress concentration factors due to three different types of axial loading on 81 TY tubular structures is studied. Our results reveal that, geometric parameters have a considerable impact on the variation of stress concentration factors on tubular TY-joints under axial loads. Thus, the highest stress concentration factor values are observed on the vertical brace than on the inclined one. The finite element results of the tubular structures were verified by parametric equations and experimental data. A parametric study was carried out by analyses using the non-linear regression method to obtain parametric equations. These equations are used to calculate stress concentration factors and to analyse the fatigue resistance of TY-joints due to axial loads. [ABSTRACT FROM AUTHOR]

Electric-magnetic duality, the Newman-Janis shift, and the double copy all act by elementary operations on three-point amplitudes. At the same time, they generate a network of interesting classical solutions spanning from the Coulomb charge via the dyon to the Kerr-Taub-NUT spacetime. We identify the amplitudes corresponding to each of these solutions, working to all orders in spin, but to leading perturbative order. We confirm that the amplitudes double-copy when the solutions are related by the classical double copy. Along the way we show that the Kerr-Taub-NUT solution corresponds to a gravitational electric-magnetic duality rotation acting on the Kerr solution, again to all orders in spin, and demonstrate that the asymptotic charges also transform simply under our operations. [ABSTRACT FROM AUTHOR]

We present an explicit formula for Lorentz boosts and rotations that commute with BMS supertranslations in asymptotically flat spacetimes. Key to the construction is the use of infrared regularizations and of a unitary transformation that makes observables commute with the soft degrees of freedom. We explicitly verify that our charges satisfy the Lorentz algebra and we check that they are consistent with expectations by evaluating them on the supertranslated Minkowski space and on the boosted Kerr black hole. [ABSTRACT FROM AUTHOR]

The extended BMS group includes supertranslation, dual supertranslation and Lorentz transformations. The generators of these symmetries can be classified according to their parity into "electric" and "magnetic" types. Using a multipole expansion of gravitational sources in the Newman-Penrose formalism, we associate each one of these charges with a particular moment. At leading order, the "electric" and "magnetic" monopole moments correspond respectively to supertranslations and dual supertranslations. At the first subleading order, the "electric" and "magnetic" dipole moments correspond respectively to boosts and rotations, therefore comprising the entire Lorentz group. Electric-magnetic type of duality then rotates the boost and rotation generators into each other. [ABSTRACT FROM AUTHOR]

Purpose : Multiparametric magnetic resonance imaging (mpMRI) is a well-established imaging method for localizing primary prostate cancer (PCa) and for guiding targeted prostate biopsies. [18F]DCFPyL positron emission tomography combined with MRI (PSMA-PET/MRI) might be of additional value to localize primary PCa. The aim of this study was to assess the diagnostic performance of [18F]DCFPyL-PET/MRI vs. mpMRI in tumour localization based on histopathology after robot-assisted radical-prostatectomy (RARP), also assessing biopsy advice for potential image-guided prostate biopsies. Methods: Thirty prospectively included patients with intermediate to high-risk PCa underwent [18F]DCFPyL-PET/MRI and mpMRI prior to RARP. Two nuclear medicine physicians and two radiologists assessed tumour localization on [18F]DCFPyL-PET/MRI and on mpMRI respectively, and gave a prostate biopsy advice (2 segments) using a 14-segment model of the prostate. The uro-pathologist evaluated the RARP specimen for clinically significant PCa (csPCa) using the same model. csPCa was defined as any PCa with Grade Group (GG) ≥ 2. The biopsy advice based on imaging was correlated with the final histology in the RARP specimen for a total-agreement analysis. An additional near-agreement correlation was performed to approximate clinical reality. Results: Overall, 142 of 420 (33.8%) segments contained csPCa after pathologic examination. The segments recommended for targeted biopsy contained the highest GG PCa segment in 27/30 patients (90.0%) both for [18F]DCFPyL-PET/MRI and mpMRI. Areas under the receiver operating characteristics curves (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the total-agreement detection of csPCa per segment using [18F]DCFPyL-PET/MRI were 0.70, 50.0%, 89.9%, 71.7%, and 77.9%, respectively. These results were 0.75, 54.2%, 94.2%, 82.8%, and 80.1%, respectively, for mpMRI only. Conclusion: Both [18F]DCFPyL-PET/MRI and mpMRI were only partly able to detect csPCa on a per-segment basis. An accurate detection (90.0%) of the highest GG lesion at patient-level was observed when comparing both [18F]DCFPyL-PET/MRI and mpMRI biopsy advice with the histopathology in the RARP specimen. So, despite the finding that [18F]DCFPyL-PET/MRI adequately detects csPCa, it does not outperform mpMRI. [ABSTRACT FROM AUTHOR]

We extract the relativistic classical radial action from scattering amplitudes, to all orders in perturbation theory, in the probe limit. Our sources include point charges and monopoles, as well as the Schwarzschild and pure-NUT gravitational backgrounds. A characteristic relativistic effect, that scattering trajectories may wind around these sources any number of times, can be recovered when all-order amplitudes are available. We show that the amplitude for scattering a probe off a pure NUT is given by the solution of a transcendental equation involving continued fractions, and explain how to solve this equation to any desired loop order. [ABSTRACT FROM AUTHOR]

Multipotent stromal cells (MSCs) are widely utilized in therapy for their immunomodulatory properties, but their usage in infectious viral diseases is less explored. This review aimed to collate the current novel use of MSCs in virus-associated conditions, including MSC's susceptibility to virus infection, antiviral properties of MSCs and their effects on cell-based immune response and implementation of MSC therapy in animal models and human clinical trials of viral diseases. Recent discoveries shed lights on MSC's capability in suppressing viral replication and augmenting clearance through enhancement of antiviral immunity. MSC therapy may maintain a crucial balance between aiding pathogen clearance and suppressing hyperactive immune response. [ABSTRACT FROM AUTHOR]

The prevalent m6Am mRNA cap modification was recently identified as a valid target for removal by the human obesity gene FTO along with the previously established m6A mRNA modification. However, the deposition and dynamics of m6Am in regulating obesity are unknown. Here, we investigate the liver m6A/m methylomes in mice fed on a high fat Western-diet and in ob/ob mice. We find that FTO levels are elevated in fat mice, and that genes which lost m6Am marking under obesity are overly downregulated, including the two fatty-acid-binding proteins FABP2, and FABP5. Furthermore, the cellular perturbation of FTO correspondingly affect protein levels of its targets. Notably, generally m6Am- but not m6A-methylated genes, are found to be highly enriched in metabolic processes. Finally, we deplete all m6A background via Mettl3 knockout, and unequivocally uncover the association of m6Am methylation with increased mRNA stability, translation efficiency, and higher protein expression. Together, these results strongly implicate a dynamic role for m6Am in obesity-related translation regulation. m6A and m6Am are two prevalent mRNA modifications which are target for removal by the fat mass and obesity gene FTO. Here the authors capture the differential profile of these two modifications in the liver of obese mice and identify dynamic translation regulation by the m6Am modification. [ABSTRACT FROM AUTHOR]

In retailing, it is recognized that prominent differences exist between generational cohorts. As such, analysis of varying patterns of personality traits and their effects between generations is essential for understanding consumer behaviors. This research focuses on the association between the Big Five personality traits and m-shopping intentions of hedonic products among four generational cohorts: baby boomers and Generations X, Y, and Z. Generational cohort theory, the Big Five Personality Model, and resistance to innovations theory are integrated in a theoretical framework. The research was conducted by online survey of 1241 Internet users aged 14–72. Different patterns of effects of personality traits between generations were found. For baby boomers and Generation X, a positive association between openness to experience and m-shopping intention was found. Moreover, in these generations, personality traits were more powerful in predicting m-shopping intention, compared to younger generations. Among Generation Y, extraversion was positively correlated with m-shopping intention. Among Generation Z, a negative correlation between agreeableness and m-shopping intention was found. Based on our findings, we propose a generational approach to marketing strategy and suggest specific practical implications. [ABSTRACT FROM AUTHOR]

Since Poincaré, the three-body problem is known to be chaotic and is believed to lack a general deterministic solution. Instead, decades ago a statistical solution was marked as a goal. Yet, despite considerable progress, all extant approaches display two flaws. First, probability was equated with phase space volume, thereby ignoring the fact that significant regions of phase space describe regular motion, including post-decay motion. Secondly and relatedly, an adjustable parameter, the strong interaction region, which is a sort of cutoff, was a central ingredient of the theory. This paper introduces remedies and presents for the first time a statistical prediction of decay rates, in addition to outcomes. Based on an analogy with a particle moving within a leaky container, the statistical distribution is presented in an exactly factorized form. One factor is the flux of phase-space volume, rather than the volume itself, and it is given in a cutoff-independent closed form. The other factors are the chaotic absorptivity and the regularized phase space volume. The situation is analogous to Kirchhoff's law of thermal radiation, also known as greybody radiation. In addition, an equation system for the time evolution of the statistical distribution is introduced; it describes the decay rate statistics while accounting for sub-escape excursions. Early numerical tests indicate a leap in accuracy. [ABSTRACT FROM AUTHOR]

Plasma gelsolin (pGSN) is the secreted isoform of an intracellular actin remodeling protein found in high concentrations in human plasma. Clinical studies demonstrate reduced pGSN concentrations in several disease states, including severe trauma, burns, and sepsis. Markedly decreased pGSN concentrations in these conditions precede and predict adverse clinical outcomes. In this study, we measured pGSN in patients with chronic granulomatous disease (CGD), a primary immunodeficiency characterized by recurrent infections and dysregulated inflammation. pGSN was quantified using a sandwich ELISA in plasma from healthy volunteers, clinically stable CGD patients, and X-linked CGD carriers and in sera from 12 CGD patients undergoing bone marrow transplantation. pGSN was also quantified in healthy volunteers challenged with intravenous endotoxin. pGSN concentrations were lower in CGD patients without active infection or systemic inflammation compared with healthy control subjects. In CGD patients undergoing bone marrow transplantation, pGSN concentrations increased significantly following successful transplant. X-linked carriers of CGD had normal pGSN. Despite reduction of pGSN in CGD patients, we did not detect significant changes in pGSN over 24 h following challenge of healthy volunteers with intravenous endotoxin (4 ng/kg) that elicited a febrile response. We describe, for the first time, significantly lower pGSN in clinically stable patients with CGD compared with age- and sex-matched healthy volunteers. Low pGSN levels in CGD patients significantly increased following bone marrow transplantation. X-linked carriers of CGD had normal pGSN. In healthy volunteers challenged with intravenous endotoxin, pGSN is not an acute phase reactant. [ABSTRACT FROM AUTHOR]

The Symmetries of Feynman Integrals (SFI) method is extended for the first time to incorporate an irreducible numerator. This is done in the context of the so-called vacuum and propagator seagull diagrams, which have 3 and 2 loops, respectively, and both have a single irreducible numerator. For this purpose, an extended version of SFI (xSFI) is developed. For the seagull diagrams with general masses, the SFI equation system is found to extend by two additional equations. The first is a recursion equation in the numerator power, which has an alternative form as a differential equation for the generating function. The second equation applies only to the propagator seagull and does not involve the numerator. We solve the equation system in two cases: over the singular locus and in a certain 3 scale sector where we obtain novel closed-form evaluations and epsilon expansions, thereby extending previous results for the numerator-free case. [ABSTRACT FROM AUTHOR]

Inhalation injury is predictive of dysphagia post burns; however, the nature of dysphagia associated with inhalation burns is not well understood. This study describes the clinical profile and recovery pattern of swallowing following inhalation burn injury. All patients admitted 2008-2017 with confirmed inhalation burns on laryngoscopy and managed by speech-language pathology (SLP) were included. Initial dysphagia presentation and dysphagia recovery pattern were documented using the FOIS. Co-presence of dysphonia was determined clinically and rated present/absent. Persistent laryngeal/pharyngeal injury at 6 months was documented using laryngoscopy. Data were compared to published data from a large adult burn cohort. All patients with confirmed inhalation burns during the study period received SLP input, enabling review of 38 patients (68% male; m = 40.8 years). Percent Total Body Surface Area burn ranged 1-90%, 100% had head and neck burns, 97% required mechanical ventilation (mean 9.4 days), 18% required tracheostomy and 100% had dysphonia. Comparing to non-inhalation burn patients, the inhalation cohort had significantly (p < 0.01) higher dysphagia incidence (89.47% vs 5.6%); more with severe dysphagia at presentation (78.9% vs 1.7%); increased duration to initiate oral intake (m = 24.69 vs 0.089 days); longer duration of enteral feeding (m = 45.03 vs 1.96 days); and longer duration to resolution of dysphagia (m = 29.79 vs 1.67 days). Persistent laryngeal pathology was present in 47.37% at 6 months. This study shows dysphagia incidence in burn patients with inhalation injury is 16 times greater than for those without inhalation injury. Laryngeal pathology due to inhalation injury increases dysphagia severity and duration to dysphagia recovery. [ABSTRACT FROM AUTHOR]

Host cell proteins (HCPs) are process-related impurities generated during biotherapeutic protein production. HCPs can be problematic if they pose a significant metabolic demand, degrade product quality, or contaminate the final product. Here, we present an effort to create a "clean" Chinese hamster ovary (CHO) cell by disrupting multiple genes to eliminate HCPs. Using a model of CHO cell protein secretion, we predict that the elimination of unnecessary HCPs could have a non-negligible impact on protein production. We analyze the HCP content of 6-protein, 11-protein, and 14-protein knockout clones. These cell lines exhibit a substantial reduction in total HCP content (40%-70%). We also observe higher productivity and improved growth characteristics in specific clones. The reduced HCP content facilitates purification of a monoclonal antibody. Thus, substantial improvements can be made in protein titer and purity through large-scale HCP deletion, providing an avenue to increased quality and affordability of high-value biopharmaceuticals. Host cell proteins can contaminate biotherapeutics and compromise and degrade their quality. Here the authors use modelling and CRISPR to delete secreted host proteins in CHO cells, leading to improved monoclonal antibody production and purity. [ABSTRACT FROM AUTHOR]

We study the most general triangle diagram through the Symmetries of Feynman Integrals (SFI) approach. The SFI equation system is obtained and presented in a simple basis. The system is solved providing a novel derivation of an essentially known expression. We stress a description of the underlying geometry in terms of the Distance Geometry of a tetrahedron discussed by Davydychev-Delbourgo [1], a tetrahedron which is the dual on-shell diagram. In addition, the singular locus is identified and the diagram’s value on the locus’s two components is expressed as a linear combination of descendant bubble diagrams. The massless triangle and the associated magic connection are revisited. [ABSTRACT FROM AUTHOR]

The numerical relation of cast iron chill characteristics (distance of chilled layer H and volume quota of ledeburite in it Ql) with its carbon equivalent СE was investigated. This data helps forecast the evolution of the surface chilled layer forming at the casting production with different thickness from cast iron of various chemical compositions. The study focuses on the unalloyed induction-melted cast iron with eight chemical-composition variants with carbon equivalent from 3.30 up to 5.53%. From these cast irons, step-by-step castings were made with steps sizes of 10 × 60 mm and thickness of 5, 10, 20, and 40 mm. The chilled-layer distance (depth) was measured at the casting fractures and gaged on thickness of full chill zone. Ledeburite volume quota was detected by a metallographic method using the "Nexsys-Image expert pro 3" computer program. According to experimental data, when the casting thickness is 5 and 10 mm, the through (at all thickness) full chill is formed at a carbon equivalent ≤4.08% and ≤3.67%, consequently. At the castings with 20- and 40-mm thickness, the zone of full chill is absent. In this case, the chilled layer depth increases with a decrease of carbon equivalent and decreases with an increase of casting's thickness X. The dependence of H from CE have the exponential character and can be described by the equation H = Aexp(–kCE), where A and k are empirical coefficients. Ledeburite volume quota near the contact casting surface with chiller is near 90%, but it decreases with different intensity depending on changes of carbon equivalent and casting's thickness with an increase in the distance from the surface. By mathematical processing of the experimental data received for the 5-mm distance from the contact surface of the casting with chiller, a numerical relation Ql in casting chilled layer with value of CE can be described by the exponential dependence: Ql = 1000(7/(X + 10))exp(–CE). [ABSTRACT FROM AUTHOR]

We consider two known lower bounds on randomized communication complexity: the smooth rectangle bound and the logarithm of the approximate nonnegative rank. Our main result is that they are the same up to a multiplicative constant and a small additive term.The logarithm of the nonnegative rank is known to be a nearly tight lower bound on the deterministic communication complexity. Our result indicates that proving an analogous result for the randomized case, namely that the log approximate nonnegative rank is a nearly tight bound on randomized communication complexity, would imply the tightness of the information complexity bound.Another corollary of our result is the existence of a Boolean function with a quasipolynomial gap between its approximate rank and approximate nonnegative rank.We also show that our method yields an alternative simple proof of the equivalence between the approximate rank and the approximate μ norm, first shown by Lee and Shraibman. [ABSTRACT FROM AUTHOR]

Methods for site-selective chemistry on proteins are in high demand for the synthesis of chemically modified biopharmaceuticals, as well as for applications in chemical biology, biosensors and more. Inadvertent N-terminal gluconoylation has been reported during expression of proteins with an N-terminal His tag. Here we report the development of this side-reaction into a general method for highly selective N-terminal acylation of proteins to introduce functional groups. We identify an optimized N-terminal sequence, GHHHn− for the reaction with gluconolactone and 4-methoxyphenyl esters as acylating agents, facilitating the introduction of functionalities in a highly selective and efficient manner. Azides, biotin or a fluorophore are introduced at the N-termini of four unrelated proteins by effective and selective acylation with the 4-methoxyphenyl esters. This Gly-Hisn tag adds the unique capability for highly selective N-terminal chemical acylation of expressed proteins. We anticipate that it can find wide application in chemical biology and for biopharmaceuticals. [ABSTRACT FROM AUTHOR]

Recently it has been shown that infrared divergences in the conventional S-matrix elements of gauge and gravitational theories arise from a violation of the conservation laws associated with large gauge symmetries. These infrared divergences can be cured by using the Faddeev-Kulish (FK) asymptotic states as the basis for S-matrix elements. Motivated by this connection, we study the action of BMS supertranslations on the FK asymptotic states of perturbative quantum gravity. We compute the BMS charge of the FK states and show that it characterizes the superselection sector to which the state belongs. Conservation of the BMS charge then implies that there is no transition between different superselection sectors, hence showing that the FK graviton clouds implement the necessary transition induced by the scattering process. [ABSTRACT FROM AUTHOR]

We analytically investigate the formation of the Kuznetsov-Ma breather, the Akhmediev breather and the Peregrine breather in one-dimensional exciton-polariton condensates under homogeneous pumping. We show that the breather polariton solitons obtained in this study present deformations which are completely controlled by the physical parameters of the system. The maximal intensity of these breathers is controlled by the strength of the interaction amongst polaritons. In addition, we observe that the maximal population of polaritons is obtained at the highest concentration of breathers during the condensation. [ABSTRACT FROM AUTHOR]

Adenosine deaminase acting on RNA 1 (ADAR1) is the master RNA editor, catalyzing the deamination of adenosine to inosine. RNA editing is vital for preventing abnormal activation of cytosolic nucleic acid sensing pathways by self-double-stranded RNAs. Here we determine, by parallel analysis of RNA secondary structure sequencing (PARS-seq), the global RNA secondary structure changes in ADAR1 deficient cells. Surprisingly, ADAR1 silencing resulted in a lower global double-stranded to single-stranded RNA ratio, suggesting that A-to-I editing can stabilize a large subset of imperfect RNA duplexes. The duplexes destabilized by editing are composed of vastly complementary inverted Alus found in untranslated regions of genes performing vital biological processes, including housekeeping functions and type-I interferon responses. They are predominantly cytoplasmic and generally demonstrate higher ribosomal occupancy. Our findings imply that the editing effect on RNA secondary structure is context dependent and underline the intricate regulatory role of ADAR1 on global RNA secondary structure. [ABSTRACT FROM AUTHOR]

In this paper, we use the similarity transformation method to investigate the generation and the control of rogue wave solutions in nonlinear optical cavities described by a (2 + 1) -dimensional Lugiato-Lefever equation with varying coefficients. For a periodic distribution of the diffraction parameter, first-order and second-order rogue wave solutions with multiple compression points are generated. Our results reveal that multiple compression points depend on the values of the modulation amplitude of the diffraction parameter and are independent of the spatial distribution in the cavities. [ABSTRACT FROM AUTHOR]

Purpose: c-MET and its ligand hepatocyte growth factor are often dysregulated in human cancers. Dynamic changes in c-MET expression occur and might predict drug efficacy or emergence of resistance. Noninvasive visualization of c-MET dynamics could therefore potentially guide c-MET-directed therapies. We investigated the feasibility of Zr-labelled one-armed c-MET antibody onartuzumab PET for detecting relevant changes in c-MET levels induced by c-MET-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib resistance or heat shock protein-90 (HSP90) inhibitor NVP-AUY-922 treatment in human non-small-cell lung cancer (NSCLC) xenografts. Methods: In vitro membrane c-MET levels were determined by flow cytometry. HCC827ErlRes, an erlotinib-resistant clone with c-MET upregulation, was generated from the exon-19 EGFR-mutant human NSCLC cell line HCC827. Mice bearing HCC827 and HCC827ErlRes tumours in opposite flanks underwent Zr-onartuzumab PET scans. The HCC827-xenografted mice underwent Zr-onartuzumab PET scans before treatment and while receiving biweekly intraperitoneal injections of 100 mg/kg NVP-AUY-922 or vehicle. Ex vivo, tumour c-MET immunohistochemistry was correlated with the imaging results. Results: In vitro, membrane c-MET was upregulated in HCC827ErlRes tumours by 213 ± 44% in relation to the level in HCC827 tumours, while c-MET was downregulated by 69 ± 9% in HCC827 tumours following treatment with NVP-AUY-922. In vivo, Zr-onartuzumab uptake was 26% higher ( P < 0.05) in erlotinib-resistant HCC827ErlRes than in HCC827 xenografts, while HCC827 tumour uptake was 33% lower ( P < 0.001) following NVP-AUY-922 treatment. Conclusion: The results show that Zr-onartuzumab PET effectively discriminates relevant changes in c-MET levels and could potentially be used clinically to monitor c-MET status. [ABSTRACT FROM AUTHOR]

Developing strategies to mitigate or to adapt to the threats of floods is an important topic in the context of climate changes. Many of the world's cities are endangered due to rising ocean levels and changing precipitation patterns. It is therefore crucial to develop analytical tools that allow us to evaluate the threats of floods and to investigate the influence of mitigation and adaptation measures, such as stronger dikes, adaptive spatial planning, and flood disaster plans. Up until the present, analytical tools have only been accessible to domain experts, as the involved simulation processes are complex and rely on computational and data-intensive models. Outputs of these analytical tools are presented to practitioners (i.e., policy analysts and political decision-makers) on maps or in graphical user interfaces. In practice, this output is only used in limited measure because practitioners often have different information requirements or do not trust the direct outcome. Nonetheless, literature indicates that a closer collaboration between domain experts and practitioners can ensure that the information requirements of practitioners are better aligned with the opportunities and limitations of analytical tools. The objective of our work is to present a step forward in the effort to make analytical tools in flood management accessible for practitioners to support this collaboration between domain experts and practitioners. Our system allows the user to interactively control the simulation process (addition of water sources or influence of rainfall), while a realistic visualization allows the user to mentally map the results onto the real world. We have developed several novel algorithms to present and interact with flood data. We explain the technologies, discuss their necessity alongside test cases, and introduce a user study to analyze the reactions of practitioners to our system. We conclude that, despite the complexity of flood simulation models and the size of the involved data sets, our system is accessible for practitioners of flood management so that they can carry out flood simulations together with domain experts in interactive work sessions. Therefore, this work has the potential to significantly change the decision-making process and may become an important asset in choosing sustainable flood mitigations and adaptation strategies. [ABSTRACT FROM AUTHOR]

We show that in the model of zero-error communication complexity, direct sum fails for average communication complexity as well as for external information complexity. Our example also refutes a version of a conjecture by Braverman et al. that in the zero-error case amortized communication complexity equals external information complexity. In our examples the underlying distributions do not have full support. One interpretation of a distribution of non full support is as a promise given to the players (the players have a guarantee on their inputs). This brings up the issue of promise versus non-promise problems in this context. [ABSTRACT FROM AUTHOR]

Purpose: Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is an extremely rare autosomal recessive disease. The immune phenotype is characterized by hypogammaglobulinemia in the presence of B cells. T cell lymphopenia also develops in some patients. We sought to further investigate the immune defect in an ICF patient with a novel missense mutation in DNMT3B and a severe phenotype. Methods: Patient lymphocytes were examined for subset counts, immunoglobulin levels, T and B cell de novo production (via excision circles) and receptor repertoire diversity. Mutated DNMT3B protein structure was modeled to assess the effect of a mutation located outside of the catalytic region on protein function. Results: A novel homozygous missense mutation, Ala585Thr, was found in DNMT3B. The patient had decreased B cell counts with hypogammaglobulinemia, and normal T cell counts. CD4 T cells decreased over time, leading to an inversion of the CD4 to CD8 ratio. Excision circle copy numbers were normal, signifying normal de novo lymphocyte production, but the ratio between naïve and total B cells was low, indicating decreased in vivo B cell replication. T and B cell receptor repertoires displayed normal diversity. Computerized modeling of the mutated Ala585 residue suggested reduced thermostability, possibly affecting the enzyme kinetics. Conclusions: Our results highlight the existence of a T cell defect that develops over time in ICF patient, in addition to the known B cell dysfunction. With intravenous immunoglobulin (IVIG) treatment ameliorating the B cell defect, the extent of CD4 lymphopenia may determine the severity of ICF immunodeficiency. [ABSTRACT FROM AUTHOR]