bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of an adeno‐associated virus serotype Anc80 to provide durable cure of phenylketonuria in a mouse model
Authors: Kaiser Robert A. , Weber Nicholas D. , Trigueros‐Motos Laia , Allen Kari L. , Martinez Michael , Cao William , VanLith Caitlin J. , Hillin Lori G. , Douar Anne , González‐Aseguinolaza Gloria , Aldabe Rafael , Lillegard Joseph B.
Published: April 2021

Phenylketonuria (PKU) is the most common inborn error of metabolism of the liver, and results from mutations of both alleles of the phenylalanine hydroxylase gene (PAH). As such, it is a suitable target for gene therapy via gene delivery with a recombinant adeno‐associated virus (AAV) vector. Here we use the synthetic AAV vector Anc80 via systemic administration to deliver a functional copy of a codon‐optimized human PAH gene, with or without an intron spacer, to the Pahenu2 mouse model of PKU. Dose‐dependent transduction of the liver and expression of PAH mRNA were present with both vectors, resulting in significant and durable reduction of circulating phenylalanine, reaching near control levels in males. Coat color of treated Pahenu2 mice reflected an increase in pigmentation from brown to the black color of control animals, further indicating functional restoration of phenylalanine metabolism and its byproduct melanin. There were no adverse effects associated with administration of AAV up to 5 × 1012 VG/kg, the highest dose tested. Only minor and/or transient variations in some liver enzymes were observed in some of the AAV‐dosed animals which were not associated with pathology findings in the liver. Finally, there was no impact on cell turnover or apoptosis as evaluated by Ki‐67 and TUNEL staining, further supporting the safety of this approach. This study demonstrates the therapeutic potential of AAV Anc80 to safely and durably cure PKU in a mouse model, supporting development for clinical consideration.
Raman spectral peak positions of olivine (Fo‐Fa) as fast methodology for classifying chondrites
Authors: do Nascimento‐Dias Bruno Leonardo , Donato Tatiane Peters , Zucolotto Maria Elizabeth , dos Anjos Virgílio de Carvalho
Published: April 2021

Chondrites are the most common meteorites in the world. However, the carbonaceous chondrites represent only a small fraction of those. Among them, Allende meteorite is one of the most studied carbonaceous chondrites. The main objective of this paper is to use the Raman spectral peak positions of olivine as a parameter to chondrite classification, here, specifically, Allende meteorite. Although these correlations are not new in the literature, this approach has not been used to classify carbonaceous chondrites yet. To develop the olivine calibration, only the peak positions of the doublet in the 700–1100 cm−1 region were analyzed in this study. The typical Raman spectrum of olivine displays two major peaks, here called Peak A, with Raman shifting in the 814–824 cm−1 range, and Peak B, in the 836–857 cm−1 range. The results of measurements found were perfectly matched to a linear correlation between Peak A and Peak B. The peak position versus composition plot shows a good correlation between the samples used as reference. The correlation curve obtained from the reference olivines is consistent with the data found in literature, as well as the peak versus peak plot. Finally, from the analysis of the olivine Raman spectral peak positions present in Allende meteorite, it is possible to conclude that there is little Fe in its matrix. Actually, the proportion of metallic Fe is less than 3% when the range of fayalite content is between Fa26–32.Thus, although the exact amount of iron present in the sample is not entirely clear, this kind of methodology quickly and effectively provides a response regarding the Fa ratio in the meteorite.
Regional‐level prediction model with difference equation model and fine particulate matter (PM2.5) concentration data
Authors: Han Xiaoling , Lei Ceyu
Published: April 2021

Accurate reporting and prediction of PM2.5 concentration is very important for improving public health. In this article, we use spectral clustering algorithm to cluster 15 cities in the Pearl River Delta. On this basis, we propose a special difference equation model, especially the use of nonlinear diffusion equations to characterize the temporal and spatial dynamic characteristics of PM2.5 propagation between and within clusters for real‐time prediction. For example, through the analysis of PM2.5 concentration data for 91 consecutive days in the Pearl River Delta, and according to different accuracy definitions, the average prediction accuracy of the difference equation model in all city clusters is 97% or 88%. The mean absolute error (MAE) of the forecast data for each urban agglomeration is within 7 units (
). Experimental results show that the difference equation model can effectively reduce the prediction time and improve the prediction accuracy. Therefore, based on the spectral clustering algorithm and the difference equation model, the fastest prediction speed and the best prediction result can be obtained, and the problem of PM2.5 concentration prediction can be effectively solved. The research can provide decision support for local air pollution early warning and urban integrated management.
13C NMR of glutamate for monitoring the pentose phosphate pathway in myocardium
Authors: Jin Eunsook S. , Lee Min H. , Malloy Craig R.
Published: April 2021

After administration of 13C‐labeled glucose, the activity of the pentose phosphate pathway (PPP) is often assessed by the distribution of 13C in lactate. However, in some tissues, such as the well‐oxygenated heart, the concentration of lactate may be too low for convenient analysis by NMR. Here, we examined 13C‐labeled glutamate as an alternative biomarker of the PPP in the heart. Isolated rat hearts were perfused with media containing [2,3‐13C2]glucose and the tissue extracts were analyzed. Metabolism of [2,3‐13C2]glucose yields [1,2‐13C2]pyruvate via glycolysis and [2,3‐13C2]pyruvate via the PPP. Pyruvate is in exchange with lactate or is further metabolized to glutamate through pyruvate dehydrogenase and the TCA cycle. A doublet from [4,5‐13C2]glutamate, indicating flux through the PPP, was readily detected in 13C NMR of heart extracts even when the corresponding doublet from [2,3‐13C2]lactate was minimal. Benfotiamine, known to induce the PPP, caused an increase in production of [4,5‐13C2]glutamate. In rats receiving [2,3‐13C2]glucose, brain extracts showed well‐resolved signals from both [2,3‐13C2]lactate and [4,5‐13C2]glutamate in 13C NMR spectra. Assessment of the PPP in the brain based on glutamate had a strong linear correlation with lactate‐based assessment. In summary, 13C NMR analysis of glutamate enabled detection of the low PPP activity in isolated hearts. This analyte is an alternative to lactate for monitoring the PPP with the use of [2,3‐13C2]glucose.
Association Between Longitudinal Trajectories of Lifestyle Pattern and BMI in Early Childhood
Authors: Zheng Miaobing , Lioret Sandrine , Hesketh Kylie D. , Spence Alison , Taylor Rachael , Campbell Karen J.
Published: April 2021

Objective

This study examined the association between longitudinal trajectories of lifestyle patterns (LPs) and BMI z score in early childhood.

Methods

Data of children (n = 439) who participated in the 18‐, 42‐, and 60‐month follow‐ups of the Melbourne InFANT Program were used. Multitrajectory modeling identified groups of children following similar LPs and BMI z score trajectories, and multinomial logistic regression assessed the determinants of the trajectory groups.

Results

Three trajectory groups of child LPs and BMI z scores were identified: “Unhealthy LP, Low BMIz” (30%), “Healthy LP, Mid BMIz” (53%), and “Unhealthy LP, High BMIz” (17%). Relative to the “Unhealthy LP, Low BMIz” group, the maternal “Fruit and vegetables” dietary pattern was associated with higher odds (odds ratio [OR] 1.22, 95% CI: 1.01‐1.47) of children following the “Healthy LP, Mid BMIz” group. Maternal prepregnancy BMI (≥25 kg/m2) (OR 2.50, 95% CI: 1.31‐4.75) and maternal TV‐viewing time ≥130 min/d (OR 2.55, 95% CI: 1.13, 5.72) increased the odds of children following the “Unhealthy LP, High BMIz” group. Child sex, breastfeeding duration, and maternal physical activity were not associated with the identified trajectory groups.

Conclusions

Three trajectory groups of LPs and BMI z scores in early childhood were revealed, with maternal prepregnancy BMI, dietary pattern, and TV‐viewing time being identified as significant determinants.
Comments on the Bellman functional for linear time‐delay systems
Authors: Ortega‐Martínez Jorge‐Manuel , Santos‐Sánchez Omar‐Jacobo , Mondié Sabine
Published: April 2021

In this note, we present some complementary results on the infinite horizon optimal control for linear time‐delay systems. We formally establish some properties of the matrices arising in the Bellman functional, and we prove that any admissible linear control law generates only a class of Bellman functional for addressed systems. Additionally, experimental results are presented, which illustrate a satisfactory control performance when is compared with an optimal proportional integral industrial control.
Acclimation to cold stress reduces injury from low temperature and bispyribac‐sodium on rice
Authors: FD Martini Luiz , Roma‐Burgos Nilda , Tseng Te‐Ming , V Fipke Marcus , A Noldin José , A de Avila Luis
Published: April 2021

BACKGROUND

In subtropical areas, early planting exposes rice seedlings to cold stress, impairing seedling growth and making them more vulnerable to other stresses including herbicide injury. The objectives of this work were: to evaluate the effect of cold stress on bispyribac‐sodium selectivity in rice; to determine the mechanisms of cold tolerance in sensitive (‘Epagri 109’) and tolerant (‘IRGA 424’) rice cultivars; and to ascertain that cold acclimatization influences bispyribac‐sodium selectivity in rice.

RESULTS

Prolonged cold stress caused high lipid peroxidation, increased rice injury, and stunted growth. Short‐term acclimation with cold stress reduced rice injury with bispyribac‐sodium. Total phenols were upregulated in rice exposed to cold stress. Prolonged cold stress increased the superoxide dismutase and catalase activity in IRGA 424. Antioxidant activity was higher in the cold‐tolerant than in the cold‐sensitive cultivar. Only catalase activity was responsive to bispyribac‐sodium. OsRAN2, OsGSTL2, and CYP72A21 were upregulated by cold and herbicide stress in both cultivars. OsGSTL2 was upregulated more in IRGA 424 than in Epagri 109. OsFAD8 was upregulated in cold‐sensitive rice exposed to short‐duration cold stress but was not responsive to bispyribac‐sodium.

CONCLUSION

Cold stress reduces bispyribac‐sodium selectivity in rice. Short‐term acclimation to cold stress reduces the effect of cold stress and enhances bispyribac‐sodium selectivity. The tolerance of rice (IRGA 424) to cold stress is due to differential induction of protection genes CYP72A21 and OsGSTL2 associated with herbicide metabolism, together with the accumulation of total phenols and higher activity of antioxidant enzymes.
Long‐term monitoring of lipophilic acaricide residues in commercial Swiss beeswax
Authors: Kast Christina , Kilchenmann Verena , Charrière Jean‐Daniel
Published: April 2021

BACKGROUND

A national survey on pesticides in recycled beeswax originating from beekeeping has been conducted in Switzerland for almost three decades. It allowed obtaining a good overview of the lipophilic products used for beekeeping within the last 30 years.

RESULTS

The use of the veterinary drugs containing bromopropylate or tau‐fluvalinate two decades ago led to substantial residues in commercial beeswax. These contaminants are still detectable although in Switzerland the corresponding products have been out of use for many years. The level of coumaphos substantially increased in 2015 up to an annual value of 3.25 mg·kg−1, suggesting that at least a few beekeepers used coumaphos‐containing products. Consequently, an information campaign was launched, and the annual value decreased again. Maximal levels of thymol up to an annual value of 87.5 mg·kg−1 were measured in 2009. Since that time, a steady decrease of thymol residues suggests that beekeepers less frequently use thymol‐containing products. Twenty‐five years ago, 1,4‐dichlorobenzene (PDCB) was widely used for the control of the wax moth, resulting in residues in beeswax up to an annual value of 10.9 mg·kg−1 whereas nowadays, PDCB residues are rarely detected in Swiss beeswax.

CONCLUSIONS

Our survey illustrates that several beekeeping‐associated pesticides persist in recycled beeswax for many years. Most recent analyses show lower residue levels in Swiss beeswax as compared to previous years. Nowadays Swiss beekeepers mostly use hydrophilic substances for treatment against the Varroa destructor that do not accumulate in beeswax, thus reducing exposure of the honey bees to lipophilic contaminants.
Increasing Anthonomus grandis susceptibility to Metarhizium anisopliae through RNAi‐induced AgraRelish knockdown: a perspective to combine biocontrol and biotechnology
Authors: Moreira‐Pinto Clidia E , Coelho Roberta R , Leite Ana G B , Silveira Daniela A , de Souza Daniela A , Lopes Rogerio B , Macedo Leonardo L P , Silva Maria C M , Ribeiro Thuanne P , Morgante Carolina V , Antonino José D , Grossi‐de‐Sa Maria F
Published: April 2021

BACKGROUND

The hemolymph and insect gut together have an essential role in the immune defense against microorganisms, including the production of antimicrobial peptides (AMP). AMPs are mainly induced by two specific signaling pathways, Toll and immune deficiency (IMD). Here, we characterize the expression profile of four genes from both pathways and describe the importance of AgraRelish in the immune defense of Anthonomus grandis against the entomopathogenic fungus Metarhizium anisopliae by RNA interference (RNAi).

RESULTS

To characterize the pathway that is activated early during the A. grandis–M. anisopliae interaction, we assessed the expression profiles of AgraMyD88 and AgraDorsal (Toll pathway), AgraIMD and AgraRelish (IMD pathway), and several AMP genes. Interestingly, we found that IMD pathway genes are upregulated early, and Toll pathway genes are upregulated just 3 days after inoculation (DAI). Furthermore, nine AMPs were upregulated 24 h after fungus inoculation, including attacins, cecropins, coleoptericins, and defensins. AgraRelish knockdown resulted in a reduction in median lethal time (LT50) for M. anisopliae‐treated insects of around 2 days compared to control treatments. In addition, AgraRelish remained knocked down at 3 DAI. Finally, we identified that AgraRelish knockdown increased fungal loads at 2 DAI compared to control treatments, possibly indicating a faster infection.

CONCLUSIONS

Our data indicate the influence of the IMD pathway on the antifungal response in A. grandis. Combining biocontrol and RNAi could significantly improve cotton boll weevil management. Hence, AgraRelish is a potential target for the development of biotechnological tools aimed at improving the efficacy of M. anisopliae against A. grandis.
Overexpression of ATP‐binding cassette transporters associated with sulfoxaflor resistance in Aphis gossypii glover
Authors: Wang Li , Zhu Junshu , Cui Li , Wang Qinqin , Huang Weiling , Ji Xuejiao , Yang Qingjie , Rui Changhui
Published: April 2021

BACKGROUND

Sulfoxaflor is a new insecticide for controlling against Aphis gossypii in the field. ATP‐binding cassette (ABC) transporters belong to a large superfamily of proteins and play an important role in the detoxification process. However, the potential role of ABC transporters in sulfoxaflor resistance in A. gossypii is unknown.

RESULTS

In this study, an ABC transporter inhibitor, verapamil, dramatically increased the toxicity of sulfoxaflor in the resistant population with a synergistic ratio of 8.55. However, verapamil did not synergize sulfoxaflor toxicity in the susceptible population. The contents of ABC transporters were significantly increased in the Sul‐R population. Based on RT‐qPCR analysis, 10 of 23 ABC transcripts, ABCA1, ABCA2, ABCB1, ABCB5, ABCD1, ABCG7, ABCG16, ABCG26, ABCG27, and MRP7, were up‐regulated in the Sul‐R population compared to the Sus population. Meanwhile, inductive effects of ABCA1, ABCD1, ABCG7 and ABCG26 by sulfoxaflor were found in A. gossypii. Furthermore, knockdown of ABCA1 and ABCD1 using RNAi significantly increased the sulfoxaflor sensitivity in Sul‐R aphids.

CONCLUSION

These results suggested that ABC transporters, especially the ABCA1 and ABCD1 genes, might be related with sulfoxaflor resistance in A. gossypii. This study will promote further work to validate the functional roles of these ABCs in sulfoxaflor resistance and might be helpful for the management of sulfoxaflor‐resistant A. gossypii.
Sequential knockoffs for continuous and categorical predictors: With application to a large psoriatic arthritis clinical trial pool
Authors: Kormaksson Matthias , Kelly Luke J. , Zhu Xuan , Haemmerle Sibylle , Pricop Luminita , Ohlssen David
Published: April 2021

Knockoffs provide a general framework for controlling the false discovery rate when performing variable selection. Much of the Knockoffs literature focuses on theoretical challenges and we recognize a need for bringing some of the current ideas into practice. In this paper we propose a sequential algorithm for generating knockoffs when underlying data consists of both continuous and categorical (factor) variables. Further, we present a heuristic multiple knockoffs approach that offers a practical assessment of how robust the knockoff selection process is for a given dataset. We conduct extensive simulations to validate performance of the proposed methodology. Finally, we demonstrate the utility of the methods on a large clinical data pool of more than 2000 patients with psoriatic arthritis evaluated in four clinical trials with an IL‐17A inhibitor, secukinumab (Cosentyx), where we determine prognostic factors of a well established clinical outcome. The analyses presented in this paper could provide a wide range of applications to commonly encountered datasets in medical practice and other fields where variable selection is of particular interest.
Photoelectrochemical Reduction of CO2 at Poly(4‐Vinylpyridine)‐Stabilized Copper(I) Oxide Semiconductor: Feasibility of Interfacial Decoration with Palladium Cocatalyst
Authors: Seta-Wiaderek Ewelina , Szaniawska Ewelina , Wadas Anna , Rutkowska Iwona A. , Jurczakowski Rafal , Lewera Adam , Gorzkowski Maciej , Rajeshwar Krishnan , Kulesza Pawel J.
Published: April 2021

Poly(4‐vinylpyridine)‐modified copper(I) oxide photocathodes, bare or decorated with palladium nanoparticles, can be used for the visible‐light‐driven selective reduction of CO2, mostly to methanol and carbon monoxide (in the absence of Pd cocatalyst) or formic acid and carbon monoxide (in the presence of Pd cocatalyst). The photocathode materials, which are composed of hierarchically deposited (onto transparent fluorine‐doped conducting glass electrode) Cu2O (inner layer) and poly(4‐vinylpyridine) (P4VP) polyelectrolyte film (outer‐layer), with or without dispersed Pd nanoparticles, have been fabricated and examined using electrochemical methodology, atomic force microscopy, and various spectroscopic techniques, including the Raman approach. While the physicochemical characteristics of Cu2O, including the oxide identity and its semiconducting properties, are not largely affected by the interfacial modification with P4VP, the photostability of the hybrid photocathode is significantly improved. The P4VP‐modified Cu2O exhibits reasonable durability during photoelectrochemical reduction of CO2 upon illumination with sunlight in semi‐neutral medium (Na2SO4). While Cu2O can be identified using Raman spectroscopy as the sole bulk component of the semiconducting film, the XPS data imply that the Cu2O surface is likely to be partially reduced during prolonged operation. Introduction of palladium cocatalyst seems to improve distribution (collection and transport) of photoelectrons at the photoelectrochemical interface and affects the CO2‐electroreduction mechanism.
Six-loop beta functions in general scalar theory
Authors: Bednyakov A. , Pikelner A.
Published: April 2021

Abstract

We consider general renormalizable scalar field theory and derive six-loop beta functions for all parameters in d = 4 dimensions within the $$ \overline{\mathrm{MS}} $$

MS
¯

-scheme. We do not explicitly compute relevant loop integrals but utilize O(n)-symmetric model counter-terms available in the literature. We consider dimensionless couplings and parameters with a mass scale, ranging from the trilinear self-coupling to the vacuum energy. We use obtained results to extend renormalization-group equations for several vector, matrix, and tensor models to the six-loop order. Also, we apply our general expressions to derive new contributions to beta functions and anomalous dimensions in the scalar sector of the Two-Higgs-Doublet Model.
Boson stars and solitons confined in a Minkowski box
Authors: Dias Oscar J. C. , Masachs Ramon , Rodgers Paul
Published: April 2021

Abstract

We consider the static charged black hole bomb system, originally designed for a (uncharged) rotating superradiant system by Press and Teukolsky. A charged scalar field confined in a Minkowski cavity with a Maxwell gauge field has a quantized spectrum of normal modes that can fit inside the box. Back-reacting non-linearly these normal modes, we find the hairy solitons, a.k.a boson stars (depending on the chosen U(1) gauge), of the theory. The scalar condensate is totally confined inside the box and, outside it, we have the Reissner-Nordström solution. The Israel junction conditions at the box surface layer determine the stress tensor that the box must have to confine the scalar hair. Some of these horizonless hairy solutions exist for any value of the scalar field charge and not only above the natural critical charges of the theory (namely, the critical charges for the onset of the near-horizon and superradiant instabilities of the Reissner-Nordström black hole). However, the ground state solutions have a non-trivial intricate phase diagram with a main and a secondary family of solitons (some with a Chandrasekhar mass limit but others without) and there are a third and a fourth critical scalar field charges where the soliton spectra changes radically. Most of these intricate properties are not captured by a higher order perturbative analysis of the problem where we simply back-react a normal mode of the system.
Stability results and separations theorems
Authors: Badora Roman
Published: April 2021

The presented work summarizes the relationships between stability results and separation theorems. We prove the equivalence between different types of theorems on separation by an additive map and different types of stability results concerning the stability of the Cauchy functional equation.
On the Raşa Inequality for Higher Order Convex Functions
Authors: Komisarski Andrzej , Rajba Teresa
Published: April 2021

We study the following $$(q-1)$$

(
q
-
1
)

th convex ordering relation for qth convolution power of the difference of probability distributions $$\mu $$
μ
and $$\nu $$
ν
$$\begin{aligned} (\nu -\mu )^{*q}\ge _{(q-1)cx} 0 , \quad q\ge 2, \end{aligned}$$

(
ν
-
μ
)

∗
q

≥

(
q
-
1
)
c
x

0
,

q
≥
2
,

and we obtain the theorem providing a useful sufficient condition for its verification. We apply this theorem for various families of probability distributions and we obtain several inequalities related to the classical interpolation operators. In particular, taking binomial distributions, we obtain a new, very short proof of the inequality given recently by Abel and Leviatan (2020).
Dielectric and surface properties of wood modified with NaCl aqueous solutions and treated with FE-DBD atmospheric plasma
Authors: Žigon Jure , Petrič Marko , Dahle Sebastian
Published: April 2021

The hygroscopic and electrical properties of the wood surface of Norway spruce (Picea abies (L.) Karst.) and common beech (Fagus sylvatica L.) were altered by the application of differently concentrated NaCl aqueous solutions. The presence of Na+ and Cl– ions increased the equilibrium moisture content in both woods in environments with a relative humidity of 75% to a nearly saturated state. The electrical resistance of the wood decreased, while the electrical capacitance of the wood increased with increasing amounts of NaCl introduced. Inverse trends were observed for both properties in wood modified with the two most concentrated solutions (18 and 36% molality). Microscopic analysis of the outer layers of the wood samples using scanning electron microscopy and energy-dispersive X-ray spectroscopy showed that the amount of NaCl decreased linearly up to about 1 mm from the modified surface. The presence of Na+ and Cl– ions in wood increased the intensity and improved the homogeneity of the plasma discharge generated during treatment of samples in air at atmospheric pressure. Both modification of wood with NaCl and subsequent treatment with plasma increased the surface roughness of the substrates. Finally, it was shown that the wettability of wood with a waterborne coating was improved after plasma treatment, regardless of the presence of NaCl on the surface. These findings have a good potential not only for the study of surface treatment processes of wood with plasma discharges, but also for other technical applications of lignocellulosic materials.
The safest time to fly: pandemic response in the era of Fox News
Authors: Ananyev Maxim , Poyker Michael , Tian Yuan
Published: April 2021

We document a causal effect of the conservative Fox News Channel in the USA on physical distancing during COVID-19 pandemic. We measure county-level mobility covering all US states and District of Columbia produced by GPS pings to 15–17 million smartphones and zip-code-level mobility using Facebook location data. Using the historical position of Fox News Channel in the cable lineup as the source of exogenous variation, we show that increased exposure to Fox News led to a smaller reduction in distance traveled and a smaller increase in the probability of staying home after the national emergency declaration in the USA. Our results show that slanted media can have a harmful effect on containment efforts during a pandemic by affecting people’s behavior.
Systematic review and meta-analysis of genetic association studies of pelvic organ prolapse
Authors: Allen-Brady Kristina , Chua John W. F. , Cuffolo Romana , Koch Marianne , Sorrentino Felice , Cartwright Rufus
Published: April 2021

Introduction and hypothesis

Family and twin studies demonstrate that pelvic organ prolapse (POP) is heritable, but the genetic etiology is poorly understood. This review aimed to identify genetic loci and specific polymorphisms associated with POP, while assessing the strength, consistency, and risk of bias among reported associations.

Methods

Updating an earlier systematic review, PubMed and HuGE Navigator as well as relevant conference abstracts were searched using genetic and phenotype keywords from 2015 to 2020. Screening and data extraction were performed in duplicate. Fixed and random effects meta-analyses were conducted using co-dominant models of inheritance. We assessed credibility of pooled associations using interim Venice criteria.

Results

We screened 504 new abstracts and included 46 published and 7 unpublished studies. In pooled analyses we found significant associations for four polymorphisms: rs2228480 at theESR1gene (OR 0.67 95% CI 0.46–0.98, I2 = 0.0%, Venice rating BAB), rs12589592 at theFBLN5gene (OR 1.46 95% CI 1.11–1.82, I2 = 36.3%, Venice rating BBB), rs484389 in thePGRgene (OR 0.61 95% CI 0.39–0.96, I2 = 32.4%, Venice rating CBB), and rs1800012 at theCOL1A1gene (OR 0.80 95% CI 0.66–0.96, I2 = 0.0%, Venice rating BAB). Further credible novel variants have also been recently identified in genome-wide association studies.

Conclusion

The genetic contributions to POP remain poorly understood. Several biologically plausible variants have been identified, but much work is required to establish the role of these genes in the pathogenesis of POP or to establish a role for genetic testing in clinical practice.
On the Diffusive-Mean Field Limit for Weakly Interacting Diffusions Exhibiting Phase Transitions
Authors: Delgadino Matias G. , Gvalani Rishabh S. , Pavliotis Grigorios A.
Published: April 2021

The objective of this article is to analyse the statistical behaviour of a large number of weakly interacting diffusion processes evolving under the influence of a periodic interaction potential. We focus our attention on the combined mean field and diffusive (homogenisation) limits. In particular, we show that these two limits do not commute if the mean field system constrained to the torus undergoes a phase transition, that is to say, if it admits more than one steady state. A typical example of such a system on the torus is given by the noisy Kuramoto model of mean field plane rotators. As a by-product of our main results, we also analyse the energetic consequences of the central limit theorem for fluctuations around the mean field limit and derive optimal rates of convergence in relative entropy of the Gibbs measure to the (unique) limit of the mean field energy below the critical temperature.
Vitamin D Supplementation for Patients with Chronic Kidney Disease: A Systematic Review and Meta-analyses of Trials Investigating the Response to Supplementation and an Overview of Guidelines
Authors: Christodoulou Marilena , Aspray Terence J. , Schoenmakers Inez
Published: April 2021

A large proportion of patients with chronic kidney disease (CKD) are vitamin D deficient (plasma 25-hydroxyvitamin D (25(OH)D) < 25 or 30 nmol/L per UK and US population guidelines) and this contributes to the development of CKD–mineral bone disease (CKD–MBD). Gaps in the evidence-base for the management of vitamin D status in relation to CKD–MBD are hindering the formulation of comprehensive guidelines. We conducted a systemic review of 22 RCTs with different forms of vitamin D or analogues with CKD–MBD related outcomes and meta-analyses for parathyroid hormone (PTH). We provide a comprehensive overview of current guidelines for the management of vitamin D status for pre-dialysis CKD patients. Vitamin D supplementation had an inconsistent effect on PTH concentrations and meta-analysis showed non- significant reduction (P = 0.08) whereas calcifediol, calcitriol and paricalcitol consistently reduced PTH. An increase in Fibroblast Growth Factor 23 (FGF23) with analogue administration was found in all 3 studies reporting FGF23, but was unaltered in 4 studies with vitamin D or calcifediol. Few RCTS reported markers of bone metabolism and variations in the range of markers prevented direct comparisons. Guidelines for CKD stages G1–G3a follow general population recommendations. For the correction of deficiency general or CKD-specific patient guidelines provide recommendations. Calcitriol or analogues administration is restricted to stages G3b–G5 and depends on patient characteristics. In conclusion, the effect of vitamin D supplementation in CKD patients was inconsistent between studies. Calcifediol and analogues consistently suppressed PTH, but the increase in FGF23 with calcitriol analogues warrants caution.
Cetacean occurrence in the Gulf of Alaska from long-term passive acoustic monitoring
Authors: Rice Ally , Širović Ana , Trickey Jennifer S. , Debich Amanda J. , Gottlieb Rachel S. , Wiggins Sean M. , Hildebrand John A. , Baumann-Pickering Simone
Published: April 2021

The Gulf of Alaska is an important habitat for a diverse array of marine mammals, many of which were severely depleted by historical whaling. To study current cetacean distributions in this region, passive acoustic monitoring was used to detect species-specific call types between 2011 and 2015 at five locations spanning the continental shelf, slope, and offshore seamounts. Spatial and temporal detection patterns were examined for nine species to compare differences in behavior and habitat use. Mysticetes showed seasonal increases in calling that indicated possible behavioral shifts between feeding and breeding in blue (Balaenoptera musculus), fin (B. physalus), and humpback (Megaptera novaeangliae) whales, and matched known migration timing of gray whales (Eschrichtius robustus). Interannual changes in blue and fin whale calling may relate to the marine heat wave that began in 2013 and lasted through the end of the monitoring period. Odontocete detections revealed unique spatial distributions, with killer whales (Orcinus orca) most common on the continental shelf and sperm whales (Physeter macrocephalus) most common on the continental slope, where detections occurred year-round. Beaked whales showed both spatial and temporal separation: Baird’s beaked whale (Berardius bairdii) detections were highest at Quinn Seamount in the spring, Cuvier’s (Ziphius cavirostris) at Pratt Seamount in winter, and Stejneger’s (Mesoplodon stejnegeri) on the continental slope in the fall. The year-round presence of many species highlights the ecological importance of the Gulf of Alaska and the spatiotemporal information reported here should inform future conservation efforts.
The impact of susceptibility correction on diffusion metrics in adolescents
Authors: Lahti Katri , Parkkola Riitta , Jääsaari Päivi , Haataja Leena , Saunavaara Virva ,   On behalf of the PIPARI Study Group, Ahtola Annarilla , Ekblad Mikael , Ekblad Satu , Ekholm Eeva , Grönroos Linda , Haataja Leena , Huhtala Mira , Jaakkola Jere , Joensuu Eveliina , Karukivi Max , Kero Pentti , Korja Riikka , Lahti Katri , Lapinleimu Helena , Lehtonen Liisa , Lehtonen Tuomo , Leppänen Marika , Lind Annika , Manninen Hanna , Koivisto Mari , Mattson Mira , Maunu Jonna , Munck Petriina , Määttänen Laura , Niemi Pekka , Nyman Anna , Palo Pertti , Parkkola Riitta , Ripatti Liisi , Rautava Päivi , Saarinen Katriina , Saarinen Tiina , Saunavaara Virva , Setänen Sirkku , Sillanpää Matti , Stolt Suvi , Tuomikoski-Koiranen Päivi , Tuovinen Timo , Uusitalo Karoliina , Väliaho Anniina , Ylijoki Milla
Published: April 2021

Background

Diffusion tensor imaging is a widely used imaging method of brain white matter, but it is prone to imaging artifacts. The data corrections can affect the measured values.

Objective

To explore the impact of susceptibility correction on diffusion metrics.

Materials and methods

A cohort of 27 healthy adolescents (18 boys, 9 girls, mean age 12.7 years) underwent 3-T MRI, and we collected two diffusion data sets (anterior–posterior). The data were processed both with and without susceptibility artifact correction. We derived fractional anisotropy, mean diffusivity and histogram data of fiber length distribution from both the corrected and uncorrected data, which were collected from the corpus callosum, corticospinal tract and cingulum bilaterally.

Results

Fractional anisotropy and mean diffusivity values significantly differed when comparing the pathways in all measured tracts. The fractional anisotropy values were lower and the mean diffusivity values higher in the susceptibility-corrected data than in the uncorrected data. We found a significant difference in total tract length in the corpus callosum and the corticospinal tract.

Conclusion

This study indicates that susceptibility correction has a significant effect on measured fractional anisotropy, and on mean diffusivity values and tract lengths. To receive reliable and comparable results, the correction should be used systematically.
Performance of a new natural oral contrast agent (LumiVision®) in dynamic MR swallowing
Authors: Kulinna-Cosentini Christiane , Arnoldner Michael A. , Schima Wolfgang , Kristo Ivan , Schoppmann Sebastian F. , Weber Michael , Cosentini Enrico P.
Published: April 2021

Objectives

To evaluate image quality by first use of LumiVision® in dynamic MR swallowing, a contrast medium consisting of biological substances versus a gadolinium-buttermilk mixture in patients who underwent Nissen fundoplication due to gastroesophageal reflux disease (GERD).

Methods

The protocol of this retrospective study was approved by the local Institutional Review Board. A hundred twenty-nine patients (146 examinations) underwent a dynamic MR swallowing study (at 1.5 T or 3.0 T) and received an oral contrast agent. Two readers evaluated the distention of the esophagus, contrast, and traceability of the bolus in a 3-point scale. A steady-state coherent sequence (B-FFE, TrueFISP) was used. The patients were divided into 3 different groups: 53 patients received gadolinium chelate (Dotarem®)–buttermilk mixture (GBM) in a dilution of 1:40 as an oral contrast agent; 44 patients received LumiVision® water mixture (LWM) in a dilution of 1:1 and 49 patients received LumiVision® (L) undiluted.

Results

GBM showed significantly better results in overall evaluation for both readers in contrast to LWM (p = .003, p = .002). L also reached significantly better results in overall evaluation than LWM in both readers (p = .004, p = .042). There was no significant difference in the overall evaluation between L and GBM (p = .914, p = .376).According to Landis and Koch, interobserver agreement was “substantial” (Cohen’s kappa = 0.738) between both readers.

Conclusion

LumiVision® undiluted showed equal image quality compared to gadolinium-buttermilk mixture. The constellation of LumiVision® water mixture led to a clearly negative result in relation to the image quality compared to LumiVision® undiluted. Therefore, oral ingestion of LumiVision® undiluted is recommended for MR swallowing examinations.

Key Points

• LumiVision® undiluted shows significantly better image quality in comparison to LumiVision® diluted in oral application in swallowing MRI.

• LumiVision® undiluted shows equal image quality in comparison to gadolinium-buttermilk mixture in oral application.

• Oral ingestion of LumiVision® undiluted can replace gadolinium-buttermilk mixture in oral MR examinations.
Aeroacoustic noise reduction by application of end plates on wall-mounted finite airfoils
Authors: Schneehagen Erik , Geyer Thomas F. , Sarradj Ennes , Moreau Danielle J.
Published: April 2021

One known method to reduce vortex shedding from the tip of a blade is the use of end plates or winglets. Although the aerodynamic impact of such end plates has been investigated in the past, no studies exist on the effect of such end plates on the far-field noise. The aeroacoustic noise reduction of three different end-plate geometries is experimentally investigated. The end plates are applied to the free end of a wall-mounted symmetric NACA 0012 airfoil and a cambered NACA 4412 airfoil with an aspect ratio of 2 and natural boundary layer transition. Microphone array measurements are taken in the aeroacoustic open-jet wind tunnel at BTU Cottbus-Senftenberg for chord-based Reynolds numbers between 75,000 and 225,000 and angles of attack from 0$$^\circ$$

∘

to 30$$^\circ$$

∘

. The obtained acoustic spectra show a broad frequency hump for the airfoil base configurations at higher angles of attack that is attributed to tip noise. Hot-wire measurements taken for one configuration show that the application of an end plate diffuses the vorticity at the tip. The aeroacoustic noise contribution of the tip can be reduced when the endplates are applied. This reduction is most effective for higher angles of attack, when the tip vortex is the dominant sound source.

Graphic abstract
Gynecological and psycho-sexual aspects of women with history of anorectal malformations
Authors: Bicelli Noemi , Trovalusci Emanuele , Zannol Monica , Gamba Piergiorgio , Bogana Gianna , Zanatta Cinzia , Midrio Paola
Published: April 2021

Purpose

Women with anorectal malformation (ARM) are expected to have a normal life span, therefore, gynecological and psycho-sexual issues are also important. Aim of the study was to assess these aspects in adult females with history of ARM.

Methods

Thirty-seven women from two ARM referral centers, aged ≥ 16, were identified. Gynecologic visit, cervicovaginal swab, pelvic ultrasound, FSH, LH, prolactin, progesterone, 17–β–estradiol, DHEAS, testosterone, TSH during follicular and luteal phases, and administration of FSFI questionnaire to screen the female sexual functioning were performed. Data were compared with six controls.

Results

Nineteen patients, mean age 21.7 (16–45), participated to the study. Associated anomalies, mostly affecting limbs, vertebrae and genitalia, were present in 57.8% of cases. Mullerian anomalies were retrieved in 36.8%. Hormones’ levels were normal. Concerning sexual functioning, four women (21%) reported dyspareunia or impossible penetration, four did not answer the FSFI questionnaire due to lack of confidence about their sexuality, and three scored lower than the cut-off value for female sexual function.

Conclusion

This study confirms the importance of a multidisciplinary long-term follow-up for ARM patients, including a careful study of the reproductive tract to detect and treat those conditions that could affect the fertility. Moreover, an appropriate psychological support should be provided.
Transmissible α-synuclein seeding activity in brain and stomach of patients with Parkinson’s disease
Authors: Thomzig Achim , Wagenführ Katja , Pinder Phillip , Joncic Marion , Schulz-Schaeffer Walter J. , Beekes Michael
Published: April 2021

Cerebral deposition of abnormally aggregated α-synuclein (αSyn) is a neuropathological hallmark of Parkinson’s disease (PD). PD-associated αSyn (αSynPD) aggregates can act as proteinaceous nuclei (“seeds”) able of self-templated propagation. Since this is strikingly reminiscent to properties of proteinaceous infectious particles (prions), lessons learned from prion diseases suggest to test whether transferred αSynPD can propagate and induce neurological impairments or disease in a new host. Two studies that addressed this question provided divergent results. Intracerebral (i.c.) injection of Lewy body extracts from PD patients caused cerebral αSyn pathology, as well as nigrostriatal neurodegeneration, of wild-type mice and macaques, with the mice also showing motor impairments (Recasens et al. 2014, Ann Neurol 75:351–362). In contrast, i.c. transmission of homogenates from PD brains did not stimulate, after “> 360” days post-injection (dpi), pathological αSyn conversion or clinical symptoms in transgenic TgM83+/− mice hemizygously expressing mutated (A53T) human αSyn (Prusiner et al. 2015, PNAS 112:E5308–E5317). To advance the assessment of possible αSynPD hazards by providing further data, we examined neuropathological and clinical effects upon i.c. transmission of brain, stomach wall and muscle tissue as well as blood from PD patients in TgM83+/− mice up to 612 dpi. This revealed a subtle, yet distinctive stimulation of localized αSyn aggregation in the somatodendritic compartment and dystrophic neurites of individual or focally clustered cerebral neurons after challenge with brain and stomach wall homogenates. No such effect was observed with transmitted blood or homogenized muscle tissue. The detected stimulation of αSyn aggregation was not accompanied by apparent motor impairments or overt neurological disease in TgM83+/− mice. Our study substantiated that transmitted αSynPD seeds, including those from the stomach wall, are able to propagate in new mammalian hosts. The consequences of such propagation and potential safeguards need to be further investigated.
Abelchia: inability to belch/burp—a new disorder? Retrograde cricopharyngeal dysfunction (RCPD)
Authors: Karagama Yakubu
Published: April 2021

Case series

This is retrospective case series involving 72 patients who presented with symptoms associated with inability to burp. The following symptoms was described by almost all the patients; retrosternal pain after eating or drinking, bloating feeling in the stomach, gurgling noise in the throat, excessive flatulence. These symptoms are worse with fizzy/carbonated drinks and beer. A full clinical history and examination plus endoscopic and in some cases barium a swallow radiological investigation was done.

Procedure

The surgery was performed under a general anaesthesia for all cases. Suspension pharyngoscopy in supine position using a Weerda diverticuloscope to identify the cricopharyngeal bar muscle. High dose of botulinum toxin A (botox) 100 iu was injected into the cricopharynxgeus muscle under a general anaesthesia.

Results

A total of 72 patients were diagnosed and undergone surgery between November 2016 and December 2020. There were 50 male and 22 female patients. Their average age was 30 (range 18–68 years old). All patients were able to burp again within first 4 weeks of the injection. This persisted even after the Botox worn off beyond the 3 months in 96% of cases. The average follow-up was 24 months post injection with longest follow-up 48 months (range 1–48 months).

Conclusion

The author reported a new condition of inability to burp due to failure of the cricopharyngeal sphincter to relax spontaneously and outcome of treatment using botulinum toxin A injection into the cricopharyngeus muscle. It is expected that the paralysing action of botulinum toxin injection last approximately 3 months. However, this group of patients seem to be cured even after the effect of the botox is worn off. The author therefore postulated that there might me some neural dysfunction that inhibits the brain to send signals to the cricopharyngeal sphincter to initiate burping. Once burping is re-established with the help of botox injection, spontaneous burping seems to occur and sustained even after the botox is worn off.
Re-evaluation of single nucleotide variants and identification of structural variants in a cohort of 45 sudden unexplained death cases
Authors: Neubauer Jacqueline , Wang Shouyu , Russo Giancarlo , Haas Cordula
Published: April 2021

Sudden unexplained death (SUD) takes up a considerable part in overall sudden death cases, especially in adolescents and young adults. During the past decade, many channelopathy- and cardiomyopathy-associated single nucleotide variants (SNVs) have been identified in SUD studies by means of postmortem molecular autopsy, yet the number of cases that remain inconclusive is still high. Recent studies had suggested that structural variants (SVs) might play an important role in SUD, but there is no consensus on the impact of SVs on inherited cardiac diseases. In this study, we searched for potentially pathogenic SVs in 244 genes associated with cardiac diseases. Whole-exome sequencing and appropriate data analysis were performed in 45 SUD cases. Re-analysis of the exome data according to the current ACMG guidelines identified 14 pathogenic or likely pathogenic variants in 10 (22.2%) out of the 45 SUD cases, whereof 2 (4.4%) individuals had variants with likely functional effects in the channelopathy-associated genes SCN5A and TRDN and 1 (2.2%) individual in the cardiomyopathy-associated gene DTNA. In addition, 18 structural variants (SVs) were identified in 15 out of the 45 individuals. Two SVs with likely functional impairment were found in the coding regions of PDSS2 and TRPM4 in 2 SUD cases (4.4%). Both were identified as heterozygous deletions, which were confirmed by multiplex ligation-dependent probe amplification. In conclusion, our findings support that SVs could contribute to the pathology of the sudden death event in some of the cases and therefore should be investigated on a routine basis in suspected SUD cases.