bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of regucalcin blocks the migration, invasion, and bone metastatic activity of human prostate cancer cells: Crosstalk between cancer cells and bone cells
Authors: Yamaguchi Masayoshi , Murata Tomiyasu , Ramos Joe W.
Published: April 2022

Background

Prostate cancer is a bone metastatic cancer and is the second leading cause of cancer‐related death in men. Prolonged progression‐free survival of prostate cancer patients is associated with high regucalcin expression in the tumor tissues. This study investigates the underlying mechanism by which regucalcin prevents bone metastatic activity of prostate cancer cells.

Methods

Human prostate cancer PC‐3 or DU‐145 wild‐type cells or regucalcin‐overexpressing PC‐3 or DU‐145 cells (transfectants) were cultured in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum.

Results

Overexpressed regucalcin suppressed the migration and invasion of bone metastatic human prostate cancer cells in vitro, and it reduced the levels of key proteins in metastasis including Ras, Akt, MAPK, RSK‐2, mTOR, caveolin‐1, and integrin β1. Invasion of prostate cancer cells was promoted by coculturing with preosteoblastic MC3T3‐E1 or preosteoclastic RAW264.7 cells. Coculturing with cancer cells and bone cells repressed the growth of preosteoblastic cells and enhanced osteoclastogenesis of preosteoclastic cells, and these alterations were caused by a conditioned medium from cancer cell culture. Disordered differentiation of bone cells was prevented by regucalcin overexpression. Production of tumor necrosis factor‐α (TNF‐α) in cancer cells was blocked by overexpressed regucalcin. Of note, the effects of conditioned medium on bone cells were prevented by NF‐κB inhibitor. TNF‐α may be important as a mediator in the crosstalk between cancer cells and bone cells.

Conclusion

Overexpression of regucalcin suppressed the migration, invasion, and bone metastatic activity of human prostate cancer cells. This study may provide a new strategy for therapy with the regucalcin gene transfer.
Combined application of entomopathogenic nematodes and fungi against fruit flies, Bactrocera zonata and B. dorsalis (Diptera: Tephritidae): laboratory cups to field study
Authors: Wakil Waqas , Usman Muhammad , Piñero Jaime C , Wu Shaohui , Toews Michael D , Shapiro‐Ilan David I
Published: April 2022

BACKGROUND

The peach fruit fly, Bactrocera zonata, and the Oriental fruit fly, B. dorsalis (Diptera: Tephritidae), are economically important fruit fly species in various regions of the world. We evaluated the effects of separate and combined applications of the entomopathogenic fungi (EPF) Beauveria bassiana (WG‐18) and Metarhizium anisopliae (WG‐02), and the entomopathogenic nematodes (EPNs) Heterorhabditis bacteriophora (VS strain) and Steinernema carpocapsae (ALL strain) against larvae, pupae and pharate adults, of B. zonata and B. dorsalis under laboratory, glasshouse and field cage conditions.

RESULTS

Combined applications of EPF and EPNs produced greater mortality than individual treatments under all conditions. Against both species, the combination of B. bassiana and H. bacteriophora consistently exerted strong effects that were similar to the combined application of B. bassiana and S. carpocapsae whereas M. anisopliae applied with S. carpocapsae was least effective in all combinations. In a laboratory bioassay, synergistic interactions were detected between B. bassiana and H. bacteriophora applied against larvae and pharate adults of both fly species, between B. bassiana and S. carpocapsae against larvae of both species and pharate adults of B. zonata, and between M. anisopliae and H. bacteriophora against B. zonata larvae. Other combined treatments resulted in additive effects, especially against fly pupae. In a potted soil bioassay, there were only additive interactions in all combinations against different stages of both flies. The 3rd instar of both flies was more susceptible than pharate adult and pupal stages. Additive interactions between EPNs and EPF were detected in the glasshouse against 3rd instars and pupae, and under field conditions against 3rd instars of both fly species.

CONCLUSION

These results indicate how particular combinations of entomopathogenic fungi and nematodes could be deployed in integrated pest management of tephritid fruit flies in orchard agro‐ecosystems. © 2022 Society of Chemical Industry.
Prediction is easy; change is hard
Authors: Price Lawrence H.
Published: April 2022

As in my last commentary in the March issue, three studies in this month's issue of the Update struck me as especially comment‐worthy. This time, the common thread is obvious: ketamine. It's a topic that reminded me of a commentary I wrote back in July 2019, one I now look back on with no small measure of chagrin…
Traffic flow control on cascaded roads by event‐triggered output feedback
Authors: Espitia Nicolas , Auriol Jean , Yu Huan , Krstic Miroslav
Published: April 2022

In this article, we propose an event‐triggered output‐feedback controller that guarantees the simultaneous stabilization of traffic flow on two connected roads. The density and velocity traffic dynamics are described with the linearized Aw‐Rascle‐Zhang macroscopic traffic partial differential equation model, which results in a coupled hyperbolic system. The control objective is to simultaneously stabilize the upstream and downstream traffic to a given spatially uniform constant steady‐state that is in the congested regime. To suppress stop‐and‐go traffic oscillations on the cascaded roads, we consider a ramp metering strategy that regulates the traffic flow rate entering from the on‐ramp to the mainline freeway. The ramp metering is located at the outlet with only boundary measurements of flow rate and velocity. Under the event‐triggered scheme, the control signal is only updated when an event triggering condition is satisfied. Compared with the continuous input signal, the event‐triggered boundary output control presents a more realistic setting to implement by ramp metering on a digital platform. The event‐triggered control design relies on the emulation of the backstepping boundary output feedback and on a dynamic event‐triggered strategy to determine the time instants at which the control value must be updated. We prove that there is a uniform minimal dwell‐time (independent of initial conditions), thus avoiding the Zeno phenomenon. We guarantee the exponential convergence of the closed‐loop system under the proposed event‐triggered control. A numerical example illustrates the results.
Long‐term ground cover affects soil bacterial community and carbon metabolism in the Loess Plateau, China
Authors: Zhang Wenting , Wang Yi , Li Chunyue , Chang Shun , Xue Yinglong , Dang Tinhui , Zeng Xiaomin
Published: April 2022

Farmland mulching can maintain soil nutrients, which plays a positive role in agricultural planting in the arid area. However, the composition of the soil microbial community and the C cycle involved is unclear under farmland mulching. Based on the Changwu Agro‐Ecological Experiment Station, this study set up a long‐term positioning experiment to explore the effect on soil bacterial community structure and C metabolism capacity. In this study, we include five treatments: control uncovered (CK), plastic film mulching (PF), high amount of straw mulching carried out in July, August, and September every year (St90), low amount of straw mulch throughout the growth period (S45), and high amount of straw cover throughout the growth period (S90). We combined Illumina MiSeq sequencing and Biolog‐ECO technology to analyze the functional characterization of soil bacterial community composition in terms of C source metabolism. The results indicated that the soil bacteria showed a high degree of epistatic clustering, and the operational taxonomic unit numbers of soil bacteria decrease as St90, S45, PF, CK, and S90. Redundancy analysis showed that soil available P, NH4+–N, soil moisture content were the main environmental factors affecting bacterial community composition. Proteobacteria, Acidobacteria, and Actinobacteria are the main dominant flora in this area. Soil bacterial C metabolism was highest under PF treatment. Structural equation modeling (SEM) shows that surface cover has direct and indirect effects on bacterial C metabolism capacity and diversity through soil physicochemical properties. Reasonable mulching methods have a positive effect on the sustainable development of agro‐ecosystems in arid areas.
Effects of Achnatherum inebrians ecotypes and endophyte status on plant growth, plant nutrient, soil fertility and soil microbial community
Authors: Jin Yuanyuan , Chen Zhenjiang , He Yali , White James F. , Malik Kamran , Chen Taixiang , Li Chunjie
Published: April 2022

Effects of endophytes infection on bacterial and fungal communities in soil have been extensively studied. However, how the presence of Epichloë endophytes and environmental factors influence the nitrifying genes abundance of ammonia‐oxidizing archaea (amoA‐AOA) and bacteria (amoA‐AOB), and denitrifying genes abundances of N reduction (nirS and nirK) and nitrous oxide reduction (nosZ) in soil is unclear. In the study, the copy number of 16S rRNA, 18S rRNA, amoA‐AOB, amoA‐AOA, nirS, nirK, and nosZ genes in rhizosphere soils of drunken horse grass [Achnatherum inebrians (Hance) Keng] with the infected (E+) and uninfected (E–)endophyte five ecotypes after 3 yr field cultivation were investigated using quantitative polymerase chain reaction (PCR). The effects of A. inebrians in geographic source on plant growth, soil fertility, and microbial community was greater than in different endophyte status. The copy number of the 16S rRNA, amoA‐AOA, nirK, and nosZ genes from different ecotypes (Qinghai, QH; and Tianzhu, TZ) were significantly affected by Epichloë endophyte. The copy number of the 16S rRNA, 18S rRNA, amoA‐AOB. amoA‐AOA, nirS, nirK, and nosZ genes positively related to soil pH, moisture, C/N ratio, and soil ammonium nitrogen (NH4+), and soil organic carbon (SOC) contents. Endophyte infection significantly increased plant biomass of A. inebrians from QH ecotype. Plant total chlorophyll and soil nitrate nitrogen (NO3–) were the main factor for the Epichloë endophyte and ecotype to affect plant dry weight. Further studies are required to confirm the regulation of soil NO3– as an important factor in Epichloë endophyte affecting plant growth and the soil microbial community structure in relation to N cycling.
Moving beyond the boilerplate: Reflections on equity‐centered reviewing for granting organizations
Authors: Marshall Stefanie L. , Salter Amy O.
Published: April 2022

This essay centers on the voices of leading scholars in science and STEM education on how equity can and should be centered in reviewing proposals for granting organizations. As the decisions made as a result of the reviewing process significantly impact the future directions of the field, we recognize the urgency in considering how equity is considered in this process. Through their experiences, four researchers offer the science and STEM community a call to action. The scholars interviewed highlighted that equitable reviewing and funding research and professional development will require changes within the science education and STEM funding ecosystem. Three overarching themes include (1) changing the ideologies and culture of science and STEM education research funding will require centering the needs of the communities being served; (2) institutions and granting organizations should adopt equity‐focused and holistic rubrics and models; and 3) we each have an individual responsibility to employ equity during the review process. Thus, this essay has the potential to both inspire and provide explicit examples of how we can all center equity as we strive to transform the future of science and STEM education.
Strength capacity of prismatic specimens for masonry constructions made of concrete voussoirs
Authors: Pomares Torres Juan Carlos , González Sánchez Antonio , Pereiro‐Barceló Javier , Saura Gómez Pascual , Torres Benjamín
Published: April 2022

This research shows the results of an experimental campaign of masonry specimens tested until failure. The masonry is made of special voussoirs for the construction of arches and vaults. The voussoirs were made of plain concrete. The experimental campaign focused on obtaining the flexural and the compressive strength of this type of masonry specimens. Specimens were subjected to compressive loads with different eccentricities to obtain the axial load–bending moment interaction diagrams, which indicate the strength of these pieces against eccentric compression. The ultimate purpose of this research is to foresee the behavior of structural elements, such as arches and lowered vaults with a circular directrix, built using this type of voussoirs. These structural elements aim to reintroduce anti‐funicular structural elements in bridges, culvert, tunnel, floor, and roof of buildings. Constructions that solve the basic needs of the population in any country. This innovative idea on a new block geometry, designed specifically for construction of arches, allows covering distances up to 6–7 m. The use of steel is not necessary; therefore, the risk of corrosion is eliminated. Finally, a study on the use of this new masonry type on the statics of arches is assessed.
Intergeneric relationships within the tribe Alsineae (Caryophyllaceae) as inferred from nrDNA ITS and cpDNArps16 sequences: A step toward a phylogenetically based generic system
Authors: Arabi Zahra , Ghahremaninejad Farrokh , Rabeler Richard K. , Sokolova Irina , Weigend Maximilian , Zarre Shahin
Published: April 2022

The tribe Alsineae is a large monophyletic group in the family Caryophyllaceae especially found across Eurasia and the Americas, but with a center of diversity in the Mediterranean region. Several previous molecular phylogenetic studies have focused on the delimitation of genera and tribes of Caryophyllaceae, especially the subfamily Alsinoideae or the tribe Alsineae in a broader sense than now recognized. However, there are still many open questions regarding the subdivision of the tribe and genus delimitation. In the present study, we sampled 191 (148 species) and 149 (125 species) accessions of Alsineae representing almost all (Adenonema and Pseudocerastium were not available to us) recognized genera in the tribe for nuclear DNA internal transcribed spacer (ITS) and plastid marker rps16 sequences, respectively. A combined matrix of 103 species was built for taxa with both sequences available. Maximum parsimony and Bayesian inference analyses retrieved Cerastium and Stellaria (including Myosoton) as the largest monophyletic genera, while other genera were medium‐sized (10–20 spp.) or small (<10 spp.). Our expanded sampling of Pseudostellaria and its relatives suggests a broader circumscription of this genus. Major divergence in morphology, particularly of the seeds, observed in the “Protostellaria”‐clade, allows recognition of some taxonomic changes. A total of 16 genera are recognized in Alsineae including Cerastium, Dichodon, Hartmaniella, Holosteum, Lepyrodiclis, Mesostemma, Moenchia, Nubelaria, Odontostemma, Pseudostellaria, Rabelera, Schizotechium, Shivparvatia, and Stellaria, along with Adenonema and Pseudocerastium that could not be analyzed and are, therefore, kept as distinct genera. A diagnostic key to these genera, as well as notes on their relationships, distribution, and nomenclature, is provided.
Inferential‐ and measurement‐based methods to estimate rooftop “solar city” potential in megacity Seoul, South Korea
Authors: Taminiau Job , Byrne John , Kim Jongkyu , Kim Min‐Hwi , Seo Jeongseok
Published: April 2022

Data analysis and collection techniques now allow for detailed inventory‐building of urban rooftops for the purposes of identifying solar energy potential within geographically defined boundaries, including those of cities. The complexity and inherent diversity of a city's building stock has propelled the introduction of many so‐called “solar city” assessment methods that, with varying levels of accuracy, scalability, and ease of use, seek to characterize the citywide solar photovoltaic (PV) resource potential. A review of the landscape of available methods supports a fundamental distinction across two classes of methods. First, “solar city” assessment methods can principally rely on inference to identify and characterize rooftop solar potential. Such inferential methods can establish estimates of citywide solar potential without needing direct insight into rooftop conditions or morphology, Second, measurement‐based methods estimate rooftop solar opportunities based on the direct measurement of rooftop conditions, often conducted through remote sensing. Comparative performance testing of several inferential‐ and measurement‐based methods using case study analysis underscores the importance of measurement‐based methods. In particular, measurement‐based methods are likely better positioned to support the needs of policy‐makers and investors interested in transforming a city or metropolitan area into a sustainable city whose buildings serve as the host of a new solar PV‐powered distributed electricity service system.

This article is categorized under:

Sustainable Energy > Solar Energy

Energy and Power Systems > Energy Infrastructure

Cities and Transportation > Smart Cities
The width difference in $$ B-\overline{B} $$ beyond mixing at order αs and
Authors: Gerlach Marvin , Nierste Ulrich , Shtabovenko Vladyslav , Steinhauser Matthias
Published: April 2022

Abstract

We complete the calculation of the element $$ {\Gamma}_{12}^q $$

Γ
12
q

of the decay matrix in $$ {B}_q-{\overline{B}}_q $$

B
q

−

B
¯

q

mixing, q = d, s, to order αs in the leading power of the Heavy Quark Expansion. To this end we compute one- and two-loop contributions involving two four-quark penguin operators. Furthermore, we present two-loop QCD corrections involving a chromomagnetic operator and either a current-current or four-quark penguin operator. Such contributions are of order $$ {\alpha}_s^2 $$

α
s
2

, i.e. next-to-next-to-leading-order. We also present one-loop and two-loop results involving two chromomagnetic operators which are formally of next-to-next-to-leading and next-to-next-to-next-to-leading-order, respectively. With our new corrections we obtain the Standard-Model prediction ∆Γs/∆Ms = (5.20 ± 0.69) · 10−3 if $$ {\Gamma}_{12}^s $$

Γ
12
s

is expressed in terms of the $$ \overline{\mathrm{MS}} $$

MS
¯

b-quark mass, while we find ∆Γs/∆Ms = (4.70 ± 0.96) · 10−3 instead for the use of the pole mass.
Negligible effect of surgeon experience on the accuracy and time to perform unrestricted caliper verified kinematically aligned TKA with manual instruments
Authors: Howell Stephen M. , Nedopil Alexander J. , Hull Maury L.
Published: April 2022

Purpose

Surgeons performing total knee arthroplasty (TKA) are interested in the accuracy and time it takes to make the four femoral resections that determine the setting of the femoral component. A method for quantifying the error of each resection is the thickness, measured by a caliper, minus the femoral target. The present study tested the hypothesis that the mean deviation of the resection from the femoral target, the percentage of resections with a deviation of ± 0.5, 1.0, 1.5, and 2.0 mm, and the time to complete the femoral cuts were not different between experienced (E) and less-experienced (LE) surgeons performing unrestricted caliper verified kinematically aligned (KA) TKA with manual instruments.

Methods

This study analyzed intraoperative verification worksheets from 203 patients treated by ten E surgeons and 58 patients treated by four LE surgeons. The worksheet recorded (1) the thickness of the femoral target for the distal medial (DM), distal lateral (DL), posterior medial (PM), and posterior lateral (PL) resections and the caliper thickness of the resections with a resolution of 0.5 mm, and (2) the time to complete them. The most accurate resection has a mean difference ± standard deviation of 0 ± 0.0 mm.

Results

The accuracy of the 1044 initial resections (261 patients) was significantly closer to the femoral target for E vs. the LE surgeons: 0.0 ± 0.4 vs. − 0.3 ± 0.5 for the DM, 0.0 ± 0.5 vs. − 0.4 ± 0.6 for the DL, − 0.1 ± 0.5 vs. − 0.2 ± 0.5 PM, and − 0.1 ± 0.5 vs. − 0.4 ± 0.6 for the PL resections (p ≤ 0.0248). E surgeons completed the femoral resections in 12 min; 5 min faster than LE surgeons (p < 0.0001).

Conclusions

Because the mean difference in femoral resections with manual instruments for E vs. LE surgeons was < 0.5 mm which is within the caliper’s resolution, differences in accuracy were not clinically relevant. Surgeons exploring other alignment options and robotic, navigation, and patient-specific instrumentation might find these values helpful when deciding to change.

Level of evidence

III; case–control study.
Formal Gevrey solutions: in analytic germs—for higher order holomorphic PDEs
Authors: Carrillo Sergio A. , Lastra Alberto
Published: April 2022

We consider a family of holomorphic PDEs whose singular locus is given by the zero set of an analytic map P with $$P(0)=0$$

P
(
0
)
=
0

. Our goal is to establish conditions for the existence and uniqueness of formal power series solutions and to determine their divergence rate. In fact, we prove that the solution is Gevrey in P, giving new information on divergency while compared to the classical Gevrey classes. If P is not singular at 0, we also provide Poincaré conditions to recover convergent solutions. Our strategy is to extend the dimension and lift the given PDE to a problem where results of singular PDEs can be applied. Finally, examples where the Gevrey class in P is optimal are included.
Quantitative assessment of myelin density using [11C]MeDAS PET in patients with multiple sclerosis: a first-in-human study
Authors: van der Weijden Chris W. J. , Meilof Jan F. , van der Hoorn Anouk , Zhu Junqing , Wu Chunying , Wang Yanming , Willemsen Antoon T. M. , Dierckx Rudi A. J. O. , Lammertsma Adriaan A. , de Vries Erik F. J.
Published: April 2022

Purpose

Multiple sclerosis (MS) is a disease characterized by inflammatory demyelinated lesions. New treatment strategies are being developed to stimulate myelin repair. Quantitative myelin imaging could facilitate these developments. This first-in-man study aimed to evaluate [11C]MeDAS as a PET tracer for myelin imaging in humans.

Methods

Six healthy controls and 11 MS patients underwent MRI and dynamic [11C]MeDAS PET scanning with arterial sampling. Lesion detection and classification were performed on MRI. [11C]MeDAS time-activity curves of brain regions and MS lesions were fitted with various compartment models for the identification of the best model to describe [11C]MeDAS kinetics. Several simplified methods were compared to the optimal compartment model.

Results

Visual analysis of the fits of [11C]MeDAS time-activity curves showed no preference for irreversible (2T3k) or reversible (2T4k) two-tissue compartment model. Both volume of distribution and binding potential estimates showed a high degree of variability. As this was not the case for 2T3k-derived net influx rate (Ki), the 2T3k model was selected as the model of choice. Simplified methods, such as SUV and MLAIR2 correlated well with 2T3k-derived Ki, but SUV showed subject-dependent bias when compared to 2T3k. Both the 2T3k model and the simplified methods were able to differentiate not only between gray and white matter, but also between lesions with different myelin densities.

Conclusion

[11C]MeDAS PET can be used for quantification of myelin density in MS patients and is able to distinguish differences in myelin density within MS lesions. The 2T3k model is the optimal compartment model and MLAIR2 is the best simplified method for quantification.

Trial registration.

NL7262. Registered 18 September 2018.
Livestock Use on Public Lands in the Western USA Exacerbates Climate Change: Implications for Climate Change Mitigation and Adaptation
Authors: Kauffman J. Boone , Beschta Robert L. , Lacy Peter M. , Liverman Marc
Published: April 2022

Public lands of the USA can play an important role in addressing the climate crisis. About 85% of public lands in the western USA are grazed by domestic livestock, and they influence climate change in three profound ways: (1) they are significant sources of greenhouse gases through enteric fermentation and manure deposition; (2) they defoliate native plants, trample vegetation and soils, and accelerate the spread of exotic species resulting in a shift in landscape function from carbon sinks to sources of greenhouse gases; and (3) they exacerbate the effects of climate change on ecosystems by creating warmer and drier conditions. On public lands one cow-calf pair grazing for one month (an “animal unit month” or “AUM”) produces 875 kg CO2e through enteric fermentation and manure deposition with a social carbon cost of nearly $36 per AUM. Over 14 million AUMs of cattle graze public lands of the western USA each year resulting in greenhouse gas emissions of 12.4 Tg CO2e year−1. The social costs of carbon are > $500 million year−1or approximately 26 times greater than annual grazing fees collected by managing federal agencies. These emissions and social costs do not include the likely greater ecosystems costs from grazing impacts and associated livestock management activities that reduce biodiversity, carbon stocks and rates of carbon sequestration. Cessation of grazing would decrease greenhouse gas emissions, improve soil and water resources, and would enhance/sustain native species biodiversity thus representing an important and cost-effective adaptive approach to climate change.
Automated artifact detection in abbreviated dynamic contrast-enhanced (DCE) MRI-derived maximum intensity projections (MIPs) of the breast
Authors: Kapsner Lorenz A. , Ohlmeyer Sabine , Folle Lukas , Laun Frederik B. , Nagel Armin M. , Liebert Andrzej , Schreiter Hannes , Beckmann Matthias W. , Uder Michael , Wenkel Evelyn , Bickelhaupt Sebastian
Published: April 2022

Objectives

To automatically detect MRI artifacts on dynamic contrast-enhanced (DCE) maximum intensity projections (MIPs) of the breast using deep learning.

Methods

Women who underwent clinically indicated breast MRI between October 2015 and December 2019 were included in this IRB-approved retrospective study. We employed two convolutional neural network architectures (ResNet and DenseNet) to detect the presence of artifacts on DCE MIPs of the left and right breasts. Networks were trained on images acquired up to and including the year 2018 using a 5-fold cross-validation (CV). Ensemble classifiers were built with the resulting CV models and applied to an independent holdout test dataset, which was formed by images acquired in 2019.

Results

Our study sample contained 2265 examinations from 1794 patients (median age at first acquisition: 50 years [IQR: 17 years]), corresponding to 1827 examinations of 1378 individuals in the training dataset and 438 examinations of 416 individuals in the holdout test dataset with a prevalence of image-level artifacts of 53% (1951/3654 images) and 43% (381/876 images), respectively. On the holdout test dataset, the ResNet and DenseNet ensembles demonstrated an area under the ROC curve of 0.92 and 0.94, respectively.

Conclusion

Neural networks are able to reliably detect artifacts that may impede the diagnostic assessment of MIPs derived from DCE subtraction series in breast MRI. Future studies need to further explore the potential of such neural networks to complement quality assurance and improve the application of DCE MIPs in a clinical setting, such as abbreviated protocols.

Key Points

• Deep learning classifiers are able to reliably detect MRI artifacts in dynamic contrast-enhanced protocol-derived maximum intensity projections of the breast.

• Automated quality assurance of maximum intensity projections of the breast may be of special relevance for abbreviated breast MRI, e.g., in high-throughput settings, such as cancer screening programs.
Screen-detected and interval breast cancer after concordant and discordant interpretations in a population based screening program using independent double reading
Authors: Martiniussen Marit A. , Sagstad Silje , Larsen Marthe , Larsen Anne Sofie F. , Hovda Tone , Lee Christoph I. , Hofvind Solveig
Published: April 2022

Objectives

To analyze rates, odds ratios (OR), and characteristics of screen-detected and interval cancers after concordant and discordant initial interpretations and consensus in a population-based screening program.

Methods

Data were extracted from the Cancer Registry of Norway for 487,118 women who participated in BreastScreen Norway, 2006–2017, with 2 years of follow-up. All mammograms were independently interpreted by two radiologists, using a score from 1 (negative) to 5 (high suspicion of cancer). A score of 2+ by one of the two radiologists was defined as discordant and 2+ by both radiologists as concordant positive. Consensus was performed on all discordant and concordant positive, with decisions of recall for further assessment or dismiss. OR was estimated with logistic regression with 95% confidence interval (CI), and histopathological tumor characteristics were analyzed for screen-detected and interval cancer.

Results

Among screen-detected cancers, 23.0% (697/3024) had discordant scores, while 12.8% (117/911) of the interval cancers were dismissed at index screening. Adjusted OR was 2.4 (95% CI: 1.9–2.9) for interval cancer and 2.8 (95% CI: 2.5–3.2) for subsequent screen-detected cancer for women dismissed at consensus compared to women with concordant negative scores. We found 3.4% (4/117) of the interval cancers diagnosed after being dismissed to be DCIS, compared to 20.3% (12/59) of those with false-positive result after index screening.

Conclusion

Twenty-three percent of the screen-detected cancers was scored negative by one of the two radiologists. A higher odds of interval and subsequent screen-detected cancer was observed among women dismissed at consensus compared to concordant negative scores. Our findings indicate a benefit of personalized follow-up.

Key Points

• In this study of 487,118 women participating in a screening program using independent double reading with consensus, 23% screen-detected cancers were detected by only one of the two radiologists.

• The adjusted odds ratio for interval cancer was 2.4 (95% confidence interval: 1.9, 2.9) for cases dismissed at consensus using concordant negative interpretations as the reference.

• Interval cancers diagnosed after being dismissed at consensus or after concordant negative scores had clinically less favorable prognostic tumor characteristics compared to those diagnosed after false-positive results.
The learning curve in bladder MRI using VI-RADS assessment score during an interactive dedicated training program
Authors: da Silva Miguel Correia , Pecoraro Martina , Pisciotti Martina Lucia , Dehghanpour Ailin , Forookhi Ali , Lucciola Sara , Bicchetti Marco , Messina Emanuele , Catalano Carlo , Panebianco Valeria
Published: April 2022

Objective

The purpose of the study was to evaluate the effect of an interactive training program on the learning curve of radiology residents for bladder MRI interpretation using the VI-RADS score.

Methods

Three radiology residents with minimal experience in bladder MRI served as readers. They blindly evaluated 200 studies divided into 4 subsets of 50 cases over a 3-month period. After 2 months, the first subset was reassessed, resulting in a total of 250 evaluations. An interactive training program was provided and included educational lessons and case-based practice. The learning curve was constructed by plotting mean agreement as the ratio of correct evaluations per batch. Inter-reader agreement and diagnostic performance analysis were performed with kappa statistics and ROC analysis.

Results

As for the VI-RADS scoring agreement, the kappa differences between pre-training and post-training evaluation of the same group of cases were 0.555 to 0.852 for reader 1, 0.522 to 0.695 for reader 2, and 0.481 to 0.794 for reader 3. Using VI-RADS ≥ 3 as cut-off for muscle invasion, sensitivity ranged from 84 to 89% and specificity from 91 to 94%, while the AUCs from 0.89 (95% CI:0.84, 0.94) to 0.90 (95% CI:0.86, 0.95). Mean evaluation time decreased from 5.21 ± 1.12 to 3.52 ± 0.69 min in subsets 1 and 5. Mean grade of confidence improved from 3.31 ± 0.93 to 4.21 ± 0.69, in subsets 1 and 5.

Conclusion

An interactive dedicated education program on bladder MRI and the VI-RADS score led to a significant increase in readers’ diagnostic performance over time, with a general improvement observed after 100–150 cases.

Key Points

• After the first educational lesson and 100 cases were interpreted, the concordance on VI-RADS scoring between the residents and the experienced radiologist was significantly higher.

• An increase in the grade of confidence was experienced after 100 cases.

• We found a decrease in the evaluation time after 150 cases.
Characterization of low levels of turbulence generated by grids in the settling chamber of a laminar wind tunnel
Authors: Romblad Jonas , Greiner Michael , Guissart Amandine , Würz Werner
Published: April 2022

Wind tunnel investigations of how Natural Laminar Flow (NLF) airfoils respond to atmospheric turbulence require the generation of turbulence, whose relevant characteristics resemble those in the atmosphere. The lower, convective part of the atmospheric boundary layer is characterized by low to medium levels of turbulence. The current study focuses on the small scales of this turbulence. Detailed hot-wire measurements have been performed to characterize the properties of the turbulence generated by grids mounted in the settling chamber of the Laminar Wind Tunnel (LWT). In the test section, the very low base turbulence level of Tuu ≅ 0.02% (10 ≤ f ≤ 5000 Hz) is incrementally increased by the grids up to Tuu ≅ 0.5%. The turbulence spectrum in the u-direction shows the typical suppression of larger scales due to the contraction between grids and test section. Still, the generated turbulence provides a good mapping of the spectrum measured in flight for most of the frequency range 500 ≤ f ≤ 3000 Hz, where Tollmien-Schlichting (TS)-amplification occurs for typical NLF airfoils. The spectra in v and w-direction exhibit distinct inertial subranges with slopes being less steep compared to the − 5/3 slope of the Kolmogorov spectrum. The normalized spectra in u-direction collapse together well for all grids, whereas in v- and w-directions the inertial- and dissipative subranges are more clearly distinguished for the coarser grids. It is demonstrated that the dissipation rate ε is a suitable parameter for comparing the wind tunnel turbulence with the atmospheric turbulence in the frequency range of interest. By employing the grids, turbulence in the range 4.4 × 10–7 ≤ ε ≤ 0.40 m2/s3 at free-stream velocity U∞ = 40 m/s can be generated in the LWT, which covers representative dissipation rates of free flight NLF applications. In the x-direction, the spectra of the v and w-components develop progressively more pronounced inertial- and dissipative subranges, and the energy below f ≈ 400 Hz decreases. In contrast, the spectral energy of the u-component increases across the whole frequency range, when moving downstream. This behavior can be explained by the combination of energy transport along the Kolmogorov cascade and the incipient return to an isotropic state.

Graphic Abstract
Effect of caffeine on muscle oxygen saturation during short-term all-out exercise: a double-blind randomized crossover study
Authors: Ruiz-Moreno Carlos , Gutiérrez-Hellín Jorge , Lara Beatriz , Del Coso Juan
Published: April 2022

Purpose

The ergogenic effect of oral caffeine administration on short-term all-out exercise performance is well established. However, the potential mechanisms associated with caffeine’s ergogenicity in this type of exercise are poorly understood. The aim of this study was to investigate whether caffeine intake modifies muscle oxygen saturation during the 15-s Wingate Anaerobic Test.

Methods

Fifteen moderately trained individuals (body mass = 67.4 ± 12.3 kg; height 171.3 ± 6.9 cm; age 31 ± 6 years) took part in two identical experimental trials after the ingestion of (a) 3 mg/kg of caffeine or (b) 3 mg/kg of cellulose (placebo). After 60 min for substances absorption, participants performed a 15-s Wingate test on a cycle ergometer against a load representing 7.5% of participant’s body mass. Muscle oxygen saturation was continuously measured during exercise with near-infrared spectroscopy and blood lactate concentration was measured 1 min after exercise.

Results

In comparison to the placebo, the oral administration of caffeine increased peak power by 2.9 ± 4.5% (from 9.65 ± 1.38 to. 9.92 ± 1.40 W/kg, P = 0.038; effect size (ES), 95% confidence intervals = 0.28, 0.05–0.51), mean power by 3.5 ± 6.2% (from 8.30 ± 1.08 to 8.57 ± 1.12 W/kg, P = 0.044; ES = 0.36, 0.01–0.71) and blood lactate concentration by 20.9 ± 24.7% (from 12.4 ± 2.6 to 14.8 ± 4.0 mmol/L, P = 0.005; ES = 0.59, 0.16–1.02). However, caffeine did not modify the curve of muscle oxygen desaturation during exercise (lowest value was 23.1 ± 14.1 and 23.4 ± 14.1%, P = 0.940).

Conclusion

Caffeine’s ergogenic effect during short-term all-out exercise seems to be associated with an increased glycolytic metabolism with no influence of enhanced muscle oxygen saturation.
Patterns of amygdala region pathology in LATE-NC: subtypes that differ with regard to TDP-43 histopathology, genetic risk factors, and comorbid pathologies
Authors: Cykowski Matthew D. , Arumanayagam Anithachristy S. , Powell Suzanne Z. , Rivera Andreana L. , Abner Erin L. , Roman Gustavo C. , Masdeu Joseph C. , Nelson Peter T.
Published: April 2022

Transactive response (TAR) DNA-binding protein 43 kDa (TDP-43) pathology is a hallmark of limbic-predominant age-related TDP-43 encephalopathy (LATE). The amygdala is affected early in the evolution of LATE neuropathologic change (LATE-NC), and heterogeneity of LATE-NC in amygdala has previously been observed. However, much remains to be learned about how LATE-NC originates and progresses in the brain. To address this, we assessed TDP-43 and other pathologies in the amygdala region of 184 autopsied subjects (median age = 85 years), blinded to clinical diagnoses, other neuropathologic diagnoses, and risk genotype information. As previously described, LATE-NC was associated with older age at death, cognitive impairment, and the TMEM106B risk allele. Pathologically, LATE-NC was associated with comorbid hippocampal sclerosis (HS), myelin loss, and vascular disease in white matter (WM). Unbiased hierarchical clustering of TDP-43 inclusion morphologies revealed discernable subtypes of LATE-NC with distinct clinical, genetic, and pathologic associations. The most common patterns were: Pattern 1, with lamina II TDP-43 + processes and preinclusion pathology in cortices of the amygdala region, and frequent LATE-NC Stage 3 with HS; Pattern 2, previously described as type-β, with neurofibrillary tangle-like TDP-43 neuronal cytoplasmic inclusions (NCIs), high Alzheimer’s disease neuropathologic change (ADNC), frequent APOE ε4, and usually LATE-NC Stage 2; Pattern 3, with round NCIs and thick neurites in amygdala, younger age at death, and often comorbid Lewy body disease; and Pattern 4 (the most common pattern), with tortuous TDP-43 processes in subpial and WM regions, low ADNC, rare HS, and lower dementia probability. TDP-43 pathology with features of patterns 1 and 2 were often comorbid in the same brains. Early and mild TDP-43 pathology was often best described to be localized in the “amygdala region” rather than the amygdala proper. There were also important shared attributes across patterns. For example, all four patterns were associated with the TMEM106B risk allele. Each pattern also demonstrated the potential to progress to higher LATE-NC stages with confluent anatomical and pathological patterns, and to contribute to dementia. Although LATE-NC showed distinct patterns of initiation in amygdala region, there was also apparent shared genetic risk and convergent pathways of clinico-pathological evolution.
Post-enucleation socket syndrome—a novel pathophysiological definition
Authors: Rokohl Alexander C. , Kopecky Adam , Trester Marc , Wawer Matos Philomena A. , Pine Keith R. , Heindl Ludwig M.
Published: April 2022

Background

The last definition of the post-enucleation socket syndrome (PESS) by Tyers and Collin—formulated almost 40 years ago in 1982—is predominantly based on the clinical characteristics and does not include the insights of newer studies into the pathophysiological mechanism of the PESS.

Methods

A systematic PubMed literature review regarding the pathophysiological mechanism of the PESS was performed, and results were comprised to give an overview of the current knowledge of the PESS including the exact pathophysiological mechanism.

Results

The primarily postulated pathophysiological mechanism of the PESS was the atrophy of orbital tissues, especially of fat, resulting in variable clinical findings. Newer studies using high-resolution computed tomography and magnetic resonance imaging or performing histopathological analyses found no orbital fat atrophy but rather a rotatory displacement of the orbital tissues from superior to posterior and from posterior to inferior together with the retraction of the extraocular muscles and a possible volume loss of the orbital implant by resorption if it is manufactured from hydroxyapatite. PESS results in a backward tilt of the superior fornix, a deep superior sulcus, a pseudo-ptosis, a lower eyelid elongation and laxity, a shallower inferior fornix, as well as enophthalmos and may lead to an inability of wearing ocular prostheses.

Conclusions

A novel and comprehensive definition of the PESS is proposed: PESS is a multifactorial and variable syndrome caused by a rotatory displacement of orbital contents together with the retraction of the extraocular muscles and possible resorption of the orbital implant if it is manufactured from hydroxyapatite.
Interferon antagonists encoded by SARS-CoV-2 at a glance
Authors: Lee Jung-Hyun , Koepke Lennart , Kirchhoff Frank , Sparrer Konstantin M. J.
Published: April 2022

The innate immune system is a powerful barrier against invading pathogens. Interferons (IFNs) are a major part of the cytokine-mediated anti-viral innate immune response. After recognition of a pathogen by immune sensors, signaling cascades are activated that culminate in the release of IFNs. These activate cells in an autocrine or paracrine fashion eventually setting cells in an anti-viral state via upregulation of hundreds of interferon-stimulated genes (ISGs). To evade the anti-viral effect of the IFN system, successful viruses like the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolved strategies to counteract both IFN induction and signaling. In fact, more than half of the about 30 proteins encoded by SARS-CoV-2 target the IFN system at multiple levels to escape IFN-mediated restriction. Here, we review recent insights into the molecular mechanisms used by SARS-CoV-2 proteins to suppress IFN production and the establishment of an anti-viral state.
Programmed death receptor ligand-2 (PD-L2) bearing extracellular vesicles as a new biomarker to identify early triple-negative breast cancer patients at high risk for relapse
Authors: Hoffmann Oliver , Wormland Sebastian , Bittner Ann-Kathrin , Collenburg Monika , Horn Peter A. , Kimmig Rainer , Kasimir-Bauer Sabine , Rebmann Vera
Published: April 2022

Purpose

Based on the tumor-promoting features of extracellular vesicles (EV) and PD-L1/2-bearing EV subpopulations (PD-L1/2EV), we evaluated their potential as surrogate markers for disease progression or eligibility criteria for PD-1 immune checkpoint inhibition (ICI) approaches in early triple-negative breast cancer (TNBC).

Methods

After enrichment of EV from plasma samples of 56 patients before and 50 after chemotherapy (CT), we determined levels of EV particle number and PD-L1/2EV by nanoparticle tracking analysis or ELISA and associated the results with clinical status/outcome and the presence of distinct circulating tumor cells (CTC) subpopulations.

Results

Compared to healthy controls, patients had a tenfold higher EV concentration and significantly elevated PD L2EV but not PD L1EV levels. The most important clinical implications were found for PD-L2EV. High PD-L2EV levels were associated with a significantly reduced 3-year progression-free and overall survival (PFS and OS). A loss of PD-L2EV after CT was significantly more prominent in patients achieving pathological complete response (pCR). Increased pre-CT PD-L2EV levels were found in patients having NOTCH1-positive or ERBB3-positive CTC. The presence of ERBB3-positive CTC combined with high pre-CT PD-L2EV resulted in a shorter PFS.

Conclusion

This study highlights PD L2EV as a promising biomarker for risk assessment of TNBC patients and represents the basic for additional studies introducing PD-L2EV as an eligibility criterion for PD-1 ICI approaches.
Body condition scores, fluke intensity, liver pathology, and carcass quality of different dairy cattle genotypes infected with Fasciola species at high throughput abattoirs in South Africa
Authors: Mpisana Zuko , Jaja Ishmael Festus , Byaruhanga Charles , Marufu Munyaradzi Christopher
Published: April 2022

Milk is an essential commodity whose demand far exceeds supply. However, dairy animal productivity is constantly hampered by parasitic diseases such as fasciolosis, affecting milk production. Despite the negative impact of liver fluke on milk production, there is little information on liver fluke infection and associated abattoir losses (body weight, condition score, liver pathology, and carcass quality) in culled dairy cattle. This study aimed to determine body condition scores, fluke intensity, liver pathology, and carcass quality of different cattle genotypes infected withFasciolaspecies at three commercial abattoirs. A longitudinal study was conducted from September 2019 to October 2020 to determine body condition score, liver fluke intensity, liver pathology in 3065 dairy cattle slaughtered in CA1, CA2, and CA3, of the Eastern Cape Province South Africa. Liver fluke intensity significantly increased with cattle age (P < 0.0001). Cattle ≥ 7 years old (59.93 ± 6.42) and those 4 to 6 years old (49.78 ± 9.98) had higher infection than those 2 to 3 years old (27.55 ± 13.68). The liver fluke infection was significantly (P < 0.001) the highest when sampling was conducted in summer, followed by autumn and winter, and least for spring. The differences in carcass weights or body condition scores decreased by 0.99 units (P < 0.0001) or 0.97 units (P < 0.0001) respectively. Therefore, this study suggests that fluke infection could be responsible for considerable economic and production losses mainly due to condemnation and weight loss in dairy cattle. This study recommended a combination of holistic and grazing management to control infection rates in dairy herds.
Mobile games success and failure: mining the hidden factors
Authors: Kerim Abdulrahman , Genç Burkay
Published: April 2022

Predicting the success of a mobile game is a prime issue in game industry. Thousands of games are being released each day. However, a few of them succeed while the majority fail. Toward the goal of investigating the potential correlation between the success of a mobile game and its specific attributes, this work was conducted. More than 17 thousand games were considered for that reason. We show that IAPs (In-App Purchases), genre, number of supported languages, developer profile, and release month have a clear effect on the success of a mobile game. We also develop a novel success score reflecting multiple objectives. Furthermore, we show that game icons with certain visual characteristics tend to be associated with more rating counts. We employ different machine learning models to predict a novel success score metric of a mobile game given its attributes. The trained models were able to predict this score, as well as the expected rating average and rating count for a mobile game with 70% accuracy.