bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID‐19 Vaccination and Obesity: Optimism and Challenges
Authors: Townsend Matthew J. , Kyle Theodore K. , Stanford Fatima Cody
Published: January 2021

Researchers have speculated that vaccines to prevent coronavirus disease 2019 (COVID‐19) may be less effective for individuals with obesity, a major risk factor for mortality and morbidity from COVID‐19. Initial results from the Pfizer‐BioNTech and Moderna COVID‐19 vaccine trials, though limited by inadequate power to compare subgroups and incomplete stratification of high‐risk groups, appear to have similar efficacy among individuals with and without obesity. Careful follow‐up in placebo‐controlled studies is required to generate data on long‐term vaccine immunogenicity, particularly in high‐risk groups. Subsequent analyses should stratify safety and efficacy results by each class of obesity. Speculation about variable effectiveness of COVID‐19 vaccines in obesity likely increases vaccine hesitancy among individuals with obesity, who face not only a higher risk of severe outcomes from COVID‐19 but also weight stigma, which reduces health care engagement at baseline. Clinical and public health messaging must be data driven, transparent, and sensitive to these biological and sociological vulnerabilities.
Minimizing the probability of absolute ruin under the mean‐variance premium principle
Authors: Han Xia , Liang Zhibin , Yuen Kam C.
Published: January 2021

In this article, we assume that the insurer can purchase per‐loss reinsurance and invest its surplus in a financial market consisting of a risk‐free asset and a risky asset. It is also assumed that the investment amount of the risky asset is capped at a fixed level and that short‐selling is prohibited. Our objective is to minimize the probability of absolute ruin, and the reinsurance premium is computed according to the mean‐variance premium principle, that is, a combination of the expected‐value and variance premium principles. By solving the corresponding Hamilton–Jacobi–Bellman equation, we derive explicit expressions for the S‐shaped minimum absolute ruin function and its associated optimal reinsurance‐investment strategy. We further study the same optimization problem for a slightly modified version of absolute ruin, and the corresponding optimal results are obtained as well. To gain insights into the optimal problems, we investigate the reason for the S‐shaped value function and discover that the constraint on investment control can result in the kink of minimum absolute ruin function. Finally, some properties and numerical examples are presented to show the impact of model parameters on the optimal results.
A reevaluation of human capital accumulation and economic growth in OECD
Authors: Ogbeifun Lawrence , Shobande Olatunji Abdul
Published: January 2021

Over the last three decades, the renewed interest in key drivers of economic growth in OECD countries has been the central discourse. The argument is whether physical or human capital matters for the economic growth in these countries. This study contributes to the ongoing debate by exploring the connection between human capital accumulation and economic growth between 1986 and 2018 for a panel of 24 OECD countries. The empirical evidence is based on the fixed effect and two‐stage lease squares (2SLS). The result indicates that growth does not converge between countries. Further evidence shows that human capital, the savings rate, and the openness of trade play a vital role in OECD countries' economic growth. On the contrary, the findings show that life expectancy and inflation have adverse effects on growth. Thus, the study recommends the urgent need for intervention programs tailored toward improving research and development combined with investment in the well‐being of the people and the effective utilization of human capital to promote growth while mitigating inflationary pressure. Highlights

The study flashlight on the link between human capital accumulation and economic growth

It highlights various issues surrounding the gaps in Solow model.

The evidenced is based on Pooled OLS, G2SLS, and FE‐IV regression.

Our results indicate that human capital accumulation (education and health) has a positive and significant relationship with economic growth.
Effects of financial status on major depressive disorder and complicated grief among bereaved family members of patients with cancer
Authors: Aoyama Maho , Sakaguchi Yukihiro , Igarashi Naoko , Morita Tatsuya , Shima Yasuo , Miyashita Mitsunori
Published: January 2021

Objective

To examine current financial status, changes before and after bereavement, and their effects on possible major depressive disorder (MDD) and complicated grief (CG) among bereaved family members of patients with cancer.

Methods

We conducted a nationwide cross‐sectional questionnaire survey on 787 bereaved family members of patients with cancer in 71 palliative care institutions in Japan from May to July 2016. The survey assessed perceived level of concern regarding current financial status and whether it changed after bereavement. We also collected information on demographic factors and assessed the possible MDD and CG using the Patient Health Questionnaire‐9 and Brief Grief Questionnaire, respectively. We then conducted bivariate analysis to examine the relationship between these factors and financial status.

Results

A total of 491 (62%) questionnaires were returned. The majority of the participants (n = 382, 78%) reported having no or mild concerns about their livelihood, whereas 19% (n = 95) had moderate to severe concerns. Regarding the change in financial status after bereavement, 7% (n = 35) reported improvement, 28% (n = 131) reported worsening, and 65% (n = 308) reported no change. The prevalences of possible MDD and CG were 22% (n = 108) and 9% (n = 41), respectively, and were significantly lower among participants with less concern regarding their livelihood and whose financial status had not changed after bereavement (both p < 0.05).

Conclusions

About one‐fifth of the bereaved family members reported financial difficulties to some extent; these were significantly associated with MDD and CG. These findings provide evidence of the need for psychosocial support including financial consultation for bereaved family members.
Recent thermokarst evolution in the Italian Central Alps
Authors: Guglielmin Mauro , Ponti Stefano , Forte Emanuele , Cannone Nicoletta
Published: January 2021

Thermokarst depressions are widespread phenomena due to permafrost degradation in the Arctic, whereas only few are known from mountain permafrost of the mid‐latitudes. In the Italian Central Alps, close to the Stelvio Pass (2,763 m above sea level), a ski run was built in 1987. Since 1981, statistically significant air warming has been recorded, especially during summer (+0.65°C per decade). Permafrost temperature recorded at the nearby Share Stelvio Borehole between 1990 and 2011 exhibited a rapid increase (> 0.8°C per decade) and an active‐layer thickening (7 cm/year). Between the years 1999 and 2003, some thermokarst depressions started to develop, initially in the lower part of the ski run and then extending to higher elevations. The depressions increased in number, size, and depth with time. Since ski‐run construction, the area remained free of vegetation until early 2000, when vegetation colonization started, showing a coupling with the onset of thermokarst development and summer warming. Vegetation changes accelerated with the ingress of pioneer and early‐successional as well as of late‐successional species. Moreover, the ingress of shrub species (Salix spp.) typical of lower elevation belts (subalpine and even montane) was dated to 2004. All the observed features show a rapid and coupled response of the abiotic and biotic components of this ecosystem to climate warming. Our data also confirm the similarity of the observed responses and dynamics of the alpine tundra with the Arctic tundra with regard to both permafrost and vegetation.
Nanostructures Composed of Dual Plasmonic Materials Exhibiting High Thermal Stability and SERS Enhancement
Authors: Wang Le , Wang Shengyan , Mei Lin , Sun Jie , Shi Feng , Zhang Nan , Jiang Ruibin
Published: January 2021

As one kind of alternative to conventional metals, titanium nitride offers many advantages in the rapidly growing fields of plasmonics and metamaterials. However, the development of TiNx‐based plasmonics is severally limited by the difficulty in the preparation. Herein, a facial approach is developed for the preparation of Au@TiNx core‐shell nanostructures. The synthesis starts with colloidal Au nanospheres, followed by the growth of amorphous TiO2 shells. The obtained Au@a‐TiO2 nanostructures convert into Au@TiNx through nitridation at high temperature in ammonia atmosphere. The prepared Au@TiNx nanostructures have strong plasmonic scatting in the visible region and strong field enhancement at the surface of nanostructures. Au@TiNx nanostructures also exhibit a relatively large enhancement for Raman scattering. The developed preparation method can produce TiNx nanostructures with relatively uniform size and thus will be very helpful to the development of TiNx‐base plasmonics.
Moduli Stabilization with Non‐Geometric Fluxes — Comments on Tadpole Contributions and de‐Sitter Vacua
Authors: Plauschinn Erik
Published: January 2021

We study moduli stabilization for type IIB orientifold compactifications on Calabi‐Yau three‐folds with (non‐)geometric fluxes. For this setting it is possible to stabilize all closed‐string moduli classically without the need for non‐perturbative contributions, and examples of stable de‐Sitter constructions can be found in the literature which violate a prominent swampland conjecture. In this paper we derive general properties of non‐geometric flux‐compactifications, we argue that the contribution of fluxes to the tadpole cancellation conditions should be similar to D‐branes (and not anti‐D‐branes), and we exclude supersymmetric Minkowski vacua for certain cases. We also reassess known stable de‐Sitter constructions with (non‐)geometric H‐, F‐, Q‐ and R‐fluxes and argue that these are not consistent in string theory.
An effective ‘push–pull’ control strategy for European tarnished plant bug, Lygus rugulipennis (Heteroptera: Miridae), in strawberry using synthetic semiochemicals
Authors: Fountain Michelle T , Deakin Greg , Farman Dudley , Hall David , Jay Chantelle , Shaw Bethan , Walker Adam
Published: January 2021

BACKGROUND

European tarnished plant bug, Lygus rugulipennis (Heteroptera: Miridae), is a polyphagous pest damaging a range of arable and horticultural crops. Management is reliant upon chemical insecticides for control. These studies developed a synthetic semiochemical push–pull control strategy to reduce numbers of L. rugulipennis and subsequent fruit damage in UK strawberry crops. Using a series of small field experiments and testing in commercial strawberry crops we explored the efficacy of hexyl butyrate (HB) as the push element and female sex pheromone combined with phenylacetaldehyde as the pull element.

RESULTS

HB dispensers placed 1.0, 3.5, 5.0 and 7.0 m from all‐green Unitraps baited with L. rugulipennis female sex pheromone significantly reduced male catches by 99%, 54%, 44% and 20% compared with untreated control, respectively. Subsequently, in commercial crops, HB dispensers at 2‐m intervals along the crop row (the push) combined with a perimeter pull reduced numbers of adult and nymph L. rugulipennis by up to 80% in organic strawberry crops compared with the untreated control. Finally, the push–pull system halved fruit damage (8%) compared with untreated areas (16%) in conventional crops. In organic strawberry crops, 90% of untreated strawberries had some mirid damage compared with only 41–51% in push–pull‐treated areas.

CONCLUSION

To our knowledge, this is the first demonstration of a push–pull approach using synthetic semiochemicals giving a significant reduction in crop damage by mirids and paves the way for non‐pesticide control of a range of mirid species on multiple crops.

© 2021 Society of Chemical Industry
Seed traits correlate with herbicide resistance in Italian ryegrass (Lolium perenne ssp. multiflorum)
Authors: Maity Aniruddha , Singh Vijay , Jessup Russell , Bagavathiannan Muthukumar
Published: January 2021

BACKGROUND

Italian ryegrass (Lolium perenne ssp. multiflorum) is one of the major winter annual weeds worldwide. In this research, diversity for seed morpho‐physiological traits such as seed weight, seed size, awnedness, dormancy, speed of germination, and seed vigor among Italian ryegrass populations collected from the Texas Blacklands region were assessed, and potential association with herbicide resistance was investigated.

RESULTS

A high degree of diversity was observed among the populations for 100‐seed weight (125–256 mg), seed length (4.8–6.6 mm), awn length (0–6 mm), and total seedling length (9–14 cm at 21 days after seed germination). Inter‐population range for seed dormancy was higher in the freshly harvested seed (31–85%), which reduced to 18 to 62% at 9 months after harvest. Populations with high initial seed dormancy (> 70% dormancy) released dormancy at a faster rate than the low dormancy group (< 40%). Percent survival status to multiple postemergence herbicides was positively correlated with 100‐seed weight and fresh or initial seed dormancy.

CONCLUSION

Early emerging cohorts are easily controlled by pre‐plant tillage and preemergence herbicides, whereas late emerging cohorts (facilitated by seed dormancy) are exposed to postemergence herbicides wherein greater opportunities exist for resistance evolution, likely explaining the occurrence of high seed dormancy in Italian ryegrass populations resistant to postemergence herbicides. High seed weights can further allow seedling emergence from greater burial depth, thereby exposing more seedlings to postemergence herbicides and increasing the likelihood of resistance evolution. Results provide unique insights into the association between seed traits and herbicide resistance in this species.

© 2021 Society of Chemical Industry
Fitness studies of insecticide resistant strains: lessons learned and future directions
Authors: Freeman Jamie C , Smith Letícia B , Silva Juan J , Fan Yinjun , Sun Haina , Scott Jeffrey G
Published: January 2021

The evolution of insecticide resistance is generally thought to be associated with a fitness cost in the absence of insecticide exposure. However, it is not clear how these fitness costs manifest or how universal this phenomenon is. To investigate this, we conducted a literature review of publications that studied fitness costs of insecticide resistance, selected papers that met our criteria for scientific rigor, and analyzed each class of insecticides separately as well as in aggregate. The more than 170 publications on fitness costs of insecticide resistance show that in 60% of the experiments there is a cost to having resistance, particularly for measurements of reversion of resistance and reproduction. There were differences between classes of insecticides, with fitness costs seen less commonly for organochlorines. There was considerable variation in the experiments performed. We suggest that future papers will have maximum value to the community if they quantitatively determine resistance levels, identify the resistance mechanisms present (and the associated mutations), have replicated experiments, use related strains (optimally congenic with the resistance mutation introgressed into different genetic backgrounds) and measure fitness by multiple metrics. Studies on the fitness costs of insecticide resistance will continue to enlighten our understanding of the evolutionary process and provide valuable information for resistance management. © 2021 Society of Chemical Industry
Reversible crosslinked assembly of a trimeric coiled‐coil peptide into a three‐dimensional matrix for cell encapsulation and release
Authors: Jorgensen Michael D. , Chmielewski Jean
Published: January 2021

Mimicking the extracellular matrix (ECM) continues to be a goal in the field of regenerative medicine. Herein, we report a modified trimeric GCN4 coiled‐coil sequence containing three ligands for metal ions specifically positioned for crosslinked assembly (TriCross). In the presence of metal ions, TriCross assembles into a three‐dimensional (3D) matrix with significant cavities to accommodate cells. The matrix was found to be stable in media with serum, and mild removal of the metal leads to disassembly. By assembling TriCross with a suspension of cells in media, the matrix encapsulates cells during the assembly process leading to high cell viability. Further disassembly under mild conditions allows for the release of cells from the scaffold. As such, this peptide‐based material displays many of the characteristics necessary for successful 3D cell culture.
Novel anoplin‐based (lipo)‐peptide models show potent antimicrobial activity
Authors: Stergiou Vasileios , Krikorian Dimitrios , Koukkou Anna‐Irini , Sakarellos‐Daitsiotis Maria , Panou‐Pomonis Eugenia
Published: January 2021

The subject of this study is the synthesis and biological evaluation of anoplin‐based (Gly‐Leu‐Leu3‐Lys‐Arg5‐Ile‐Lys‐Thr8‐Leu‐Leu‐NH2)—designed (lipo)‐peptides, aiming at the development of new antibiotic substances. The design of synthetic compounds based on natural bioactive molecules is an optimistic strategy for the development of new pharmaceutics. Antimicrobial peptides (AMPs) and (lipo)‐peptides are two classes of promising compounds, with characteristics that allow them to express their activity by differentiated mechanisms of action. On this basis, anoplin, a natural AMP, was used as a scaffold to design five peptides and seven lipopeptide analogs of them. Substitutions were made on residues Leu3 and Arg5 of the interphase and on Thr8 of the polar phase, as well as N‐terminus conjunctions with octanoic and decanoic acid. The outcome of the biological evaluation revealed that some analogs might have substantial clinical potential. Specifically, Ano 1‐F, Ano 3‐F, Ano 4‐C10, and Ano 5‐F are strongly active against Gram‐negative bacteria at minimum inhibitory concentration (MIC) values of 3 μg/ml, while Ano 4‐F is active against Gram‐positive bacteria at 1 μg/ml. Ano 2‐C10, C10‐Gly‐Leu‐Lys3‐Lys‐Ile5‐Ile‐Lys‐Lys8‐Leu‐Leu‐NH2, is the most promising compound (MIC = 0.5 μg/ml) for the development of new pharmaceutics. The conformational features of the synthetic peptides were investigated by circular dichroism spectroscopy, and their physicochemical parameters were calculated. Our study shows that appropriate substitutions in the anoplin sequence in combination with Nα‐acylation may lead to new effective AMPs.
Distributed adaptive Nash equilibrium seeking and disturbance rejection for noncooperative games of high‐order nonlinear systems with input saturation and input delay
Authors: Ai Xiaolin , Wang Long
Published: January 2021

This article aims to investigate Nash equilibrium seeking problems for noncooperative games played by high‐order nonlinear multiagent systems subject to input saturation, input delay, and external disturbances. Based on the gradient play technique, an adaptive Nash equilibrium seeking algorithm is designed in a distributed fashion via backstepping, where a fixed‐time sliding mode observer is used to tackle the problem of “explosion of terms.” In the proposed algorithm, an extended‐state observer and an adaptive distributed observer are included for state/disturbance estimates and information sharing, respectively. Detailed convergence results are presented by leveraging Lyapunov stability theory. Finally, the effectiveness of the proposed approach is numerically verified through simulation results.
A puzzle for evaluation theories of desire
Authors: Grzankowski Alex ,   Philosophy Documentation Center
Published: January 2021

How we evaluate things and what we desire are closely connected. In typical cases, the things we desire are things that we evaluate as good or desirable. According to evaluation theories of desire, this connection is a very tight one: desires are evaluations of their objects as good or as desirable. There are two main varieties of this view. According to Doxastic Evaluativism, to desire that p is to believe or judge that p is good. According to Perceptual Evaluativism, to desire that p is to perceive p as being good (or for p to seem good). The present paper poses a puzzle for such views. The puzzle should be familiar to theorists interested in the normativity and metaphysics of the emotions, but I am unaware of its application to desire. The aim of the present paper is to present the puzzle as it applies to desire, which should be of independent interest, but I also hope that by shining a light on the puzzle in this domain, we might put ourselves in a better position to offer a solution in all cases. At the end of the paper, I gesture towards a promising way ahead that departs from relying on contradictory contents.
Ba3[Rh(OH)6]2 ⋅ H2O – a Precursor to Barium Oxorhodates with One‐dimensional Hydrogen Bonding Systems
Authors: Albrecht Ralf , Bretschneider Vincent , Doert Thomas , Ruck Michael
Published: January 2021

Orange‐colored single‐crystals of barium hexahydroxo‐rhodate(III) monohydrate, Ba3[Rh(OH)6]2 ⋅ H2O, were synthesized in a PTFE‐lined autoclave at 200 °C starting from Ba(NO3)2, RhI3 and concentrated sodium hydroxide solution (water‐base ratio 4 : 1). Single‐crystal X‐ray diffraction revealed the triclinic space group
(no. 2) with lattice parameters a=824.60(6) pm, b=852.78(5) pm, c=885.34(6) pm, α=94.294(3)°, β=92.422(3)°, γ=91.673(3)° at 100(1) K. The crystal structure consists of [Rh(OH)6]3− octahedra surrounded by barium cations and water molecules. Hydrogen bonds with a wide range of donor‐acceptor distances are located between hydroxide groups and water molecules to form one‐dimensional hydrogen bonding networks in c direction. Upon heating in air, Ba3[Rh(OH)6]2 ⋅ H2O decomposes first to “BaRhO3” with a superstructure of the hexagonal perovskite type, which undergoes a phase transition to the 2H hexagonal perovskite Ba9Rh8O24 above 900 °C.
Introduction: Relational Empires
Authors: Lahti Janne
Published: January 2021

This anthology examines German and United States colonialism through their previously under examined shared and entangled histories in a global setting of empires. It grapples with and elaborates on the range, form, and intensity of connectedness between the two empires, seeing them as relational. It also sees that the German-US entanglements were not exceptional, but emblematic of an interconnected, competitive, and increasingly integrated worlds of empires.
Numerator seagull and extended Symmetries of Feynman Integrals
Authors: Kol Barak , Schiller Amit , Shir Ruth
Published: January 2021

Abstract

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.
Exploring new physics with O(keV) electron recoils in direct detection experiments
Authors: Bloch Itay M. , Caputo Andrea , Essig Rouven , Redigolo Diego , Sholapurkar Mukul , Volansky Tomer
Published: January 2021

Abstract

Motivated by the recent XENON1T results, we explore various new physics models that can be discovered through searches for electron recoils in $$ \mathcal{O} $$
O
(keV)-threshold direct-detection experiments. First, we consider the absorption of axion-like particles, dark photons, and scalars, either as dark matter relics or being produced directly in the Sun. In the latter case, we find that keV mass bosons produced in the Sun provide an adequate fit to the data but are excluded by stellar cooling constraints. We address this tension by introducing a novel Chameleon-like axion model, which can explain the excess while evading the stellar bounds. We find that absorption of bosonic dark matter provides a viable explanation for the excess only if the dark matter is a dark photon or an axion. In the latter case, photophobic axion couplings are necessary to avoid X-ray constraints. Second, we analyze models of dark matter-electron scattering to determine which models might explain the excess. Standard scattering of dark matter with electrons is generically in conflict with data from lower-threshold experiments. Momentum-dependent interactions with a heavy mediator can fit the data with dark matter mass heavier than a GeV but are generically in tension with collider constraints. Next, we consider dark matter consisting of two (or more) states that have a small mass splitting. The exothermic (down)scattering of the heavier state to the lighter state can fit the data for keV mass splittings. Finally, we consider a subcomponent of dark matter that is accelerated by scattering off cosmic rays, finding that dark matter interacting though an $$ \mathcal{O} $$
O
(100 keV)-mass mediator can fit the data. The cross sections required in this scenario are, however, typically challenged by complementary probes of the light mediator. Throughout our study, we implement an unbinned Monte Carlo analysis and use an improved energy reconstruction of the XENON1T events.
Neutrino masses, vacuum stability and quantum gravity prediction for the mass of the top quark
Authors: Domènech Guillem , Goodsell Mark , Wetterich Christof
Published: January 2021

Abstract

A general prediction from asymptotically safe quantum gravity is the approximate vanishing of all quartic scalar couplings at the UV fixed point beyond the Planck scale. A vanishing Higgs doublet quartic coupling near the Planck scale translates into a prediction for the ratio between the mass of the Higgs boson MH and the top quark Mt. If only the standard model particles contribute to the running of couplings below the Planck mass, the observed MH∼ 125 GeV results in the prediction for the top quark mass Mt∼ 171 GeV, in agreement with recent measurements. In this work, we study how the asymptotic safety prediction for the top quark mass is affected by possible physics at an intermediate scale. We investigate the effect of an SU(2) triplet scalar and right-handed neutrinos, needed to explain the tiny mass of left-handed neutrinos. For pure seesaw II, with no or very heavy right handed neutrinos, the top mass can increase to Mt ∼ 172.5 GeV for a triplet mass of M∆ ∼ 108GeV. Right handed neutrino masses at an intermediate scale increase the uncertainty of the predictions of Mt due to unknown Yukawa couplings of the right-handed neutrinos and a cubic interaction in the scalar potential. For an appropriate range of Yukawa couplings there is no longer an issue of vacuum stability.
Single-top final states as a probe of top-flavoured dark matter models at the LHC
Authors: Blanke Monika , Pani Priscilla , Polesello Giacomo , Rovelli Giulia
Published: January 2021

Abstract

Models incorporating flavoured dark matter provide an elegant solution to the dark matter problem, evading the tight LHC and direct direction constraints on simple WIMP models. In Dark Minimal Flavour Violation, a simple framework of flavoured dark matter with new sources of flavour violation, the constraints from thermal freeze-out, direct detection experiments, and flavour physics create well-defined benchmark scenarios for these models. We study the LHC phenomenology of four such scenarios, focusing on final states where a single top quark is produced accompanied by no jets, one jet from the fragmentation of light quarks or a b-tagged jet. For each of these signatures we develop a realistic LHC analysis, and we show that the proposed analyses would increase the parameter space coverage for the four benchmarks, compared to existing flavour-conserving LHC analyses. Finally we show the projected discovery potential of the considered signatures for the full LHC statistics at 14 TeV, and for the High Luminosity LHC.
T
3-invariant heterotic Hull-Strominger solutions
Authors: Acharya Bobby Samir , Kinsella Alex , Svanes Eirik Eik
Published: January 2021

Abstract

We consider the heterotic string on Calabi-Yau manifolds admitting a Strominger-Yau-Zaslow fibration. Upon reducing the system in the T3-directions, the Hermitian Yang-Mills conditions can then be reinterpreted as a complex flat connection on ℝ3 satisfying a certain co-closure condition. We give a number of abelian and non-abelian examples, and also compute the back-reaction on the geometry through the non-trivial α′-corrected heterotic Bianchi identity, which includes an important correction to the equations for the complex flat connection. These are all new local solutions to the Hull-Strominger system on T3× ℝ3. We also propose a method for computing the spectrum of certain non-abelian models, in close analogy with the Morse-Witten complex of the abelian models.
Moderate hypofractionation remains the standard of care for whole-breast radiotherapy in breast cancer: Considerations regarding FAST and FAST-Forward
Authors:   Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO), Krug David , Baumann René , Combs Stephanie E. , Duma Marciana Nona , Dunst Jürgen , Feyer Petra , Fietkau Rainer , Haase Wulf , Harms Wolfgang , Hehr Thomas , Piroth Marc D. , Sedlmayer Felix , Souchon Rainer , Strnad Vratislav , Budach Wilfried
Published: January 2021

Moderate hypofractionation is the standard of care for adjuvant whole-breast radiotherapy after breast-conserving surgery for breast cancer. Recently, 10-year results from the FAST and 5‑year results from the FAST-Forward trial evaluating adjuvant whole-breast radiotherapy in 5 fractions over 5 weeks or 1 week have been published. This article summarizes recent data for moderate hypofractionation and results from the FAST and FAST-Forward trial on ultra-hypofractionation. While the FAST trial was not powered for comparison of local recurrence rates, FAST-Forward demonstrated non-inferiority for two ultra-hypofractionated regimens in terms of local control. In both trials, the higher-dose experimental arms resulted in elevated rates of late toxicity. For the lower dose experimental arms of 28.5 Gy over 5 weeks and 26 Gy over 1 week, moderate or marked late effects were similar in the majority of documented items compared to the respective standard arms, but significantly worse in some subdomains. The difference between the standard arm and the 26 Gy of the FAST-Forward trial concerning moderate or marked late effects increased with longer follow-up in disadvantage of the experimental arm for most items. For now, moderate hypofractionation with 40–42.5 Gy over 15–16 fractions remains the standard of care for the majority of patients with breast cancer who undergo whole-breast radiotherapy without regional nodal irradiation after breast-conserving surgery.
Künstliche Intelligenz in der Mammadiagnostik
Authors: Baltzer Pascal A. T.
Published: January 2021

Klinisches/methodisches Problem

Bei der Mammadiagnostik gilt es, klinische sowie multimodal bildgebende Informationen mit perkutanen und operativen Eingriffen zu koordinieren. Aus dieser Komplexität entsteht eine Reihe von Problemen: übersehene Karzinome, Überdiagnose, falsch-positive Befunde, unnötige weiterführende Bildgebung, Biopsien und Operationen.

Radiologische Standardverfahren

Folgende Untersuchungsverfahren werden in der Mammadiagnostik eingesetzt: Röntgenmammographie, Tomosynthese, kontrastangehobene Mammographie, (multiparametrischer) Ultraschall, Magnetresonanztomographie, Computertomographie, nuklearmedizinische Verfahren sowie deren Hybridvarianten.

Methodische Innovationen

Künstliche Intelligenz (KI) verspricht Abhilfe bei praktisch allen Problemen der Mammadiagnostik. Potenziell lassen sich Fehlbefunde vermeiden, bildgebende Verfahren effizienter einsetzen und möglicherweise auch biologische Phänotypen von Mammakarzinomen definieren.

Leistungsfähigkeit

Auf KI basierende Software wird für zahlreiche Anwendungen entwickelt. Am weitesten fortgeschritten sind Systeme für das Screening mittels Mammographie. Probleme sind monozentrische sowie kurzfristig am finanziellen Erfolg orientierte Ansätze.

Bewertung

Künstliche Intelligenz (KI) verspricht eine Verbesserung der Mammadiagnostik. Durch die Vereinfachung von Abläufen, die Reduktion monotoner und ergebnisloser Tätigkeiten und den Hinweis auf mögliche Fehler ist eine Beschleunigung von dann weitgehend fehlerfreien Abläufen denkbar.

Empfehlung für die Praxis

In diesem Beitrag werden die Anforderungen der Mammadiagnostik und mögliche Einsatzgebiete der der KI beleuchtet. Je nach Definition gibt es bereits praktisch anwendbare Softwaretools für die Mammadiagnostik. Globale Lösungen stehen allerdings noch aus.
The 28 + 28 day design is an effective sampling time for analyzing mutant frequencies in rapidly proliferating tissues of MutaMouse animals
Authors: Marchetti Francesco , Zhou Gu , LeBlanc Danielle , White Paul A. , Williams Andrew , Yauk Carole L. , Douglas George R.
Published: January 2021

The Organisation for Economic Co-Operation and Development Test Guideline 488 (TG 488) uses transgenic rodent models to generate in vivo mutagenesis data for regulatory submission. The recommended design in TG 488, 28 consecutive daily exposures with tissue sampling three days later (28 + 3d), is optimized for rapidly proliferating tissues such as bone marrow (BM). A sampling time of 28 days (28 + 28d) is considered more appropriate for slowly proliferating tissues (e.g., liver) and male germ cells. We evaluated the impact of the sampling time on mutant frequencies (MF) in the BM of MutaMouse males exposed for 28 days to benzo[a]pyrene (BaP), procarbazine (PRC), isopropyl methanesulfonate (iPMS), or triethylenemelamine (TEM) in dose–response studies. BM samples were collected + 3d, + 28d, + 42d or + 70d post exposure and MF quantified using the lacZ assay. All chemicals significantly increased MF with maximum fold increases at 28 + 3d of 162.9, 6.6, 4.7 and 2.8 for BaP, PRC, iPMS and TEM, respectively. MF were relatively stable over the time period investigated, although they were significantly increased only at 28 + 3d and 28 + 28d for TEM. Benchmark dose (BMD) modelling generated overlapping BMD confidence intervals among the four sampling times for each chemical. These results demonstrate that the sampling time does not affect the detection of mutations for strong mutagens. However, for mutagens that produce small increases in MF, sampling times greater than 28 days may produce false-negative results. Thus, the 28 + 28d protocol represents a unifying protocol for simultaneously assessing mutations in rapidly and slowly proliferating somatic tissues and male germ cells.
Quantization of canonical bases and the quantum symplectic double
Authors: Allegretti Dylan G. L.
Published: January 2021

We describe a natural q-deformation of Fock and Goncharov’s canonical basis for the algebra of regular functions on a cluster variety associated to a quiver of type A. We then describe an extension of this construction involving a cluster variety called the symplectic double.
Support of BCP-ALL-cells by autologous bone marrow Th-cells involves induction of AID expression but not widespread AID off-target mutagenesis
Authors: Traxel Sabrina , Lehmann Julia , Richard Stefanie , Sidorov Semjon , Niggli Felix , Berger Christoph , Nadal David , Bürgler Simone
Published: January 2021

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common childhood malignancy. The two-step BCP-ALL pathogenesis requires in utero-induced chromosomal aberrations and additional mutagenic events for overt leukemia. In mouse models, activation-induced cytidine deaminase (AID/AICDA) was suggested to contribute to BCP-ALL pathogenesis by off-target mutagenic activity. The role of AID in patients, however, remains unclear. Moreover, AID is usually not expressed in precursor B-cells but in germinal center B-cells, where it is induced upon T-helper (Th) cell stimulation. We have previously demonstrated that autologous Th-cells supportively interacted with BCP-ALL-cells. Here, we hypothesize that this interaction additionally induces AID expression in BCP-ALL-cells, leading to off-target mutagenic activity. We show that co-culture with autologous bone marrow Th-cells induced high AICDA expression in primary BCP-ALL-cells. This induction was mediated by a mechanism similar to the induction in mature B-cells involving IL-13/Stat6, CD40L/NF-κB and TGFβ/Smad2/3 signaling. Even though Th-cell-induced AID seemed to be active in vitro in a BCP-ALL reporter cell line, extensive mutational signature analysis revealed no major contribution of AID activity to the mutational landscape in BCP-ALL patients. AID activity was neither detected in mutation clusters nor in known AID targets. Moreover, no recurrently mutated gene showed a relevant enrichment of mutations in the AID motif. Together, the lack of AID-induced mutational consequences argues towards a Th-cell-promoted yet AID-independent BCP-ALL pathogenesis and favors therapeutic research focusing on Th-cell-derived support of BCP-ALL-cells rather than AID-induced effects.
Novel Kras-mutant murine models of non-small cell lung cancer possessing co-occurring oncogenic mutations and increased tumor mutational burden
Authors: Salehi-Rad Ramin , Li Rui , Tran Linh M. , Lim Raymond J. , Abascal Jensen , Momcilovic Milica , Park Stacy J. , Ong Stephanie L. , Shabihkhani Maryam , Huang Zi Ling , Paul Manash , Shackelford David B. , Krysan Kostyantyn , Liu Bin , Dubinett Steven M.
Published: January 2021

Conditional genetically engineered mouse models (GEMMs) of non-small cell lung cancer (NSCLC) harbor common oncogenic driver mutations of the disease, but in contrast to human NSCLC these models possess low tumor mutational burden (TMB). As a result, these models often lack tumor antigens that can elicit host adaptive immune responses, which limits their utility in immunotherapy studies. Here, we establish Kras-mutant murine models of NSCLC bearing the common driver mutations associated with the disease and increased TMB, by in vitro exposure of cell lines derived from GEMMs of NSCLC [KrasG12D (K), KrasG12DTp53−/−(KP), KrasG12DTp53+/−Lkb1−/− (KPL)] to the alkylating agent N-methyl-N-nitrosourea (MNU). Increasing the TMB enhanced host anti-tumor T cell responses and improved anti-PD-1 efficacy in syngeneic models across all genetic backgrounds. However, limited anti-PD-1 efficacy was observed in the KPL cell lines with increased TMB, which possessed a distinct immunosuppressed tumor microenvironment (TME) primarily composed of granulocytic myeloid-derived suppressor cells (G-MDSCs). This KPL phenotype is consistent with findings in human KRAS-mutant NSCLC where LKB1 loss is a driver of primary resistance to PD-1 blockade. In summary, these novel Kras-mutant NSCLC murine models with known driver mutations and increased TMB have distinct TMEs and recapitulate the therapeutic vulnerabilities of human NSCLC. We anticipate that these immunogenic models will facilitate the development of innovative immunotherapies in NSCLC.
Automatic opportunistic osteoporosis screening in routine CT: improved prediction of patients with prevalent vertebral fractures compared to DXA
Authors: Löffler Maximilian T. , Jacob Alina , Scharr Andreas , Sollmann Nico , Burian Egon , El Husseini Malek , Sekuboyina Anjany , Tetteh Giles , Zimmer Claus , Gempt Jens , Baum Thomas , Kirschke Jan S.
Published: January 2021

Objectives

To compare spinal bone measures derived from automatic and manual assessment in routine CT with dual energy X-ray absorptiometry (DXA) in their association with prevalent osteoporotic vertebral fractures using our fully automated framework (https://anduin.bonescreen.de) to assess various bone measures in clinical CT.

Methods

We included 192 patients (141 women, 51 men; age 70.2 ± 9.7 years) who had lumbar DXA and CT available (within 1 year). Automatic assessment of spinal bone measures in CT included segmentation of vertebrae using a convolutional neural network (CNN), reduction to the vertebral body, and extraction of bone mineral content (BMC), trabecular and integral volumetric bone mineral density (vBMD), and CT-based areal BMD (aBMD) using asynchronous calibration. Moreover, trabecular bone was manually sampled (manual vBMD).

Results

A total of 148 patients (77%) had vertebral fractures and significantly lower values in all bone measures compared to patients without fractures (p ≤ 0.001). Except for BMC, all CT-based measures performed significantly better as predictors for vertebral fractures compared to DXA (e.g., AUC = 0.885 for trabecular vBMD and AUC = 0.86 for integral vBMD vs. AUC = 0.668 for DXA aBMD, respectively; both p < 0.001). Age- and sex-adjusted associations with fracture status were strongest for manual vBMD (OR = 7.3, [95%] CI 3.8–14.3) followed by automatically assessed trabecular vBMD (OR = 6.9, CI 3.5–13.4) and integral vBMD (OR = 4.3, CI 2.5–7.6). Diagnostic cutoffs of integral vBMD for osteoporosis (< 160 mg/cm3) or low bone mass (160 ≤ BMD < 190 mg/cm3) had sensitivity (84%/41%) and specificity (78%/95%) similar to trabecular vBMD.

Conclusions

Fully automatic osteoporosis screening in routine CT of the spine is feasible. CT-based measures can better identify individuals with reduced bone mass who suffered from vertebral fractures than DXA.

Key Points

• Opportunistic osteoporosis screening of spinal bone measures derived from clinical routine CT is feasible in a fully automatic fashion using a deep learning-driven framework (https://anduin.bonescreen.de).

• Manually sampled volumetric BMD (vBMD) and automatically assessed trabecular and integral vBMD were the best predictors for prevalent vertebral fractures.

• Except for bone mineral content, all CT-based bone measures performed significantly better than DXA-based measures.

• We introduce diagnostic thresholds of integral vBMD for osteoporosis (< 160 mg/cm3) and low bone mass (160 ≤ BMD < 190 mg/cm3) with almost equal sensitivity and specificity compared to conventional thresholds of quantitative CT as proposed by the American College of Radiology (osteoporosis < 80 mg/cm3).
Lumbar hemivertebra resection in congenital scoliosis utilizing cone-beam navigation: less radiation, more accuracy—proof of concept
Authors: Fisahn Christian , Lindemann Chris , Burgess Brittni , Strube Patrick , Zippelius Timo
Published: January 2021

Purpose

To present the first known pediatric utilization of cone-beam navigation system (CBNS) for hemivertebra resection and spondylodesis

Case presentation

A 14-year-old female with congenital scoliosis, diagnosed at 8 years of age, presenting with progressive symptoms, a Cobb angle (L3-5) of 38° at time of surgery, treated historically with conservative measures. Presence of spinal intramedullary disease was excluded prior to operation via whole spine MRI.

Results

Patient successfully underwent surgical correction utilizing the CBNS (O-arm™, Medtronic®). Post-operative Cobb angle (L3-5) was restored to 8°. Following four different pediatric patient’s radiation exposures (two receiving correction via the O-arm platform and two via the traditional method employing fluoroscopy), we show a reduction in radiation exposure using the CBNS system.

Conclusion

We present the first known pediatric case of the utilization of the CBNS system for hemivertebra correction. We demonstrate that utilizing the CBNS platform can not only increase surgical accuracy but also decrease pediatric patient’s radiation exposure as a preoperative CT scan is not needed. Future studies should continue to explore additional benefits of implementing the system into surgical practice.
The impact of snow loss and soil moisture on convective precipitation over the Rocky Mountains under climate warming
Authors: Wallace Brendan , Minder Justin R.
Published: January 2021

Warm season moist diurnal convection can be particularly sensitive to changes in land surface characteristics such as snow cover and soil moisture. Over regions of mountainous terrain, climate change is expected to reduce snow cover along the low-elevation seasonal snowpack margin. These snow reductions alter surface albedo and soil moisture content, leading to changes in surface fluxes and alterations in mesoscale orographic circulations that act to transport moisture and provide ascent. A set of convection-permitting regional climate simulations centered on the Rocky Mountains of Colorado are conducted from April through July across a period of 12 years (2002–2013). These include a reanalysis forced control run (CTR), a pseudo global warming run (PGW), and an additional altered land surface run (DSURF) used to isolate the effects of the snow albedo and soil moisture changes on orographic convection. Over the mountains, daytime hourly precipitation accumulation (0900–1800 MST) decreased in PGW by an average of 4.2% while precipitation in DSURF increased by 12.5%. On days with weak synoptic forcing, the PGW response more closely follow the DSURF response with daytime hourly increases averaging 29.7% for PGW and 28.7% for DSURF. For PGW, hourly daytime precipitation intensity increases of up to 82% overcome reductions in precipitation frequency to produce higher accumulations. DSURF shows smaller increases in intensity of up to 23% and broad increases in daytime frequency indicating that surface changes act to moderate reductions in the frequency of convective precipitation. Reduced snow cover contributes to this convective response by increasing convective instability and boundary layer moisture and decreasing lifting condensation level over the high terrain. Alterations in orographic thermal circulations contribute to this response by converging moisture over the high terrain and enhancing mesoscale ascent.
The challenging diagnosis and follow-up of skull base osteomyelitis in clinical practice
Authors: Auinger Alice B. , Dahm Valerie , Stanisz Isabella , Schwarz-Nemec Ursula , Arnoldner Christoph
Published: January 2021

Purpose

The disease activity of skull base osteomyelitis can be challenging to assess by means of conventional imaging methods and renders monitoring of the disease difficult, especially in areas with restricted access to nuclear medicine imaging. Here, we provide clinically relevant data on the management of skull base osteomyelitis including assessment, treatment, and follow-up strategies with regards to the role of imaging.

Method

A chart review was performed including 30 patients treated for SBO from 1993 to 2015. Clinical findings, treatment procedures, and complication rates were assessed. Special attention was paid to imaging procedures.

Results

The overall mortality rate was 36.7% and increased to 45% when cranial nerve palsies were present. An initial computed tomography (CT) scan was performed in all patients, MRI in 60% and nuclear imaging in 33%. CT scans failed to detect progression or regression in up to 80% after four to nine months. MRI examinations could reveal changes at a higher rate compared to CT. Nuclear medicine functional imaging was most likely to assess disease activity.

Conclusion

A combination of different imaging modalities is recommended for diagnosing SBO. For the follow-up, MRI is preferable to CT as changes can be detected more readily with MRI. If available, nuclear medicine imaging should guide the decision of treatment discontinuation.