bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Yeast Glycogen Metabolism and Sporulation by Glc7p Protein Phosphatase
Authors: Ramaswamy Nadja T , Li Li , Khalil Miriam , Cannon John F
Published: February 2021

Glc7p is an essential serine/threonine type 1 protein phosphatase (PP1) from the yeast Saccharomyces cerevisiae, which has a role in many processes including cell cycle progression, sporulation, glycogen accumulation, translation initiation, and glucose repression. Two hallmarks of PP1 enzymes are very high amino acid sequence conservation and association of the catalytic subunit with a variety of noncatalytic, regulatory subunits. We tested the hypothesis that PP1 sequence conservation was the result of each PP1 residue playing a role in multiple intermolecular interactions. Analysis of 24 glc7 mutants, isolated primarily by their glycogen accumulation traits, revealed that every mutated Glc7p residue altered many noncatalytic subunit affinities and conferred unselected sporulation traits to various degrees. Furthermore, quantitative analysis showed that Glc7p affinity for the glycogen-binding noncatalytic subunit Gac1p was not the only parameter that determines the glycogen accumulation by a glc7 mutant. Sds22p is one Glc7p noncatalytic subunit that is essential for mitotic growth. Surprisingly, several mutant Glc7p proteins had undetectable affinity for Sds22p, yet grew apparently normally. The characterization of glc7 diploid sporulation revealed that Glc7p has at least two meiotic roles. Premeiotic DNA synthesis was undetectable in glc7 mutants with the poorest sporulation. In the glc7 diploids examined, expression of the meiotic inducer IME1 was proportional to the glc7 diploid sporulation frequency. Moreover, IME1 hyperexpression could not suppress glc7 sporulation traits. The Glc7p/Gip1p holoenzyme may participate in completion of meiotic divisions or spore packaging because meiotic dyads predominate when some glc7 diploids sporulate.
Integration of genetically regulated gene expression and pharmacological library provides therapeutic drug candidates
Authors: Konuma Takahiro , Ogawa Kotaro , Okada Yukinori
Published: February 2021

Approaches toward new therapeutics using disease genomics, such as genome-wide association study (GWAS), are anticipated. Here, we developed Trans-Phar [integration of transcriptome-wide association study (TWAS) and pharmacological database], achieving in silico screening of compounds from a large-scale pharmacological database (L1000 Connectivity Map), which have inverse expression profiles compared with tissue-specific genetically regulated gene expression. Firstly we confirmed the statistical robustness by the application of the null GWAS data and enrichment in the true-positive drug–disease relationships by the application of UK-Biobank GWAS summary statistics in broad disease categories, then we applied the GWAS summary statistics of large-scale European meta-analysis (17 traits; naverage = 201 849) and the hospitalized COVID-19 (n = 900 687), which has urgent need for drug development. We detected potential therapeutic compounds as well as anisomycin in schizophrenia (false discovery rate (FDR)-q = 0.056) and verapamil in hospitalized COVID-19 (FDR-q = 0.068) as top-associated compounds. This approach could be effective in disease genomics-driven drug development.
Human Intestinal Macrophages Are Involved in the Pathology of Both Ulcerative Colitis and Crohn Disease
Authors: Dharmasiri Suranga , Garrido-Martin Eva M , Harris Richard J , Bateman Adrian C , Collins Jane E , Cummings J R Fraser , Sanchez-Elsner Tilman
Published: February 2021

Background

Intestinal macrophages are key immune cells in the maintenance of intestinal immune homeostasis and have a role in the pathogenesis of inflammatory bowel disease (IBD). However, the mechanisms by which macrophages exert a pathological influence in both ulcerative colitis (UC) and Crohn disease (CD) are not yet well understood.

Methods

We purified intestinal macrophages from gastrointestinal mucosal biopsies (patients with UC, patients with CD, and healthy donors) and analyzed their transcriptome by RNA sequencing and bioinformatics, confirming results with quantitative polymerase chain reaction and immunohistochemistry.

Results

Compared with those of healthy donors, intestinal macrophages in patients with UC and with CD showed cellular reprograming of 1287 and 840 dysregulated genes, respectively (false discovery rate ≤ 0.1). The UC and CD intestinal macrophages showed an activated M1 inflammatory phenotype and the downregulation of genes engaged in drug/xenobiotic metabolism. Only macrophages from CD showed, concomitant to an M1 phenotype, a significant enrichment in the expression of M2 and fibrotic and granuloma-related genes. For the first time, we showed (and validated by quantitative polymerase chain reaction and immunohistochemistry) that intestinal macrophages in patients with IBD present both M1 and M2 features, as recently described for tumor-associated macrophages, that affect key pathways for IBD pathology, represented by key markers such as MMP12 (fibrosis), CXCL9 (T-cell attraction), and CD40 (T-cell activation).

Conclusions

Our data support the therapeutic targeting of macrophages to maintain remission in IBD but also indicate that a shift toward an M2 program—as proposed by some reports—may not limit the recruitment and activation of T cells because M2 features do not preclude M1 activation in patients with UC or CD and could exacerbate M2-related CD-specific features such as fibrosis and the formation of granulomas.
The 3-step approach for the treatment of multisegmental thoraco-abdominal aortic pathologies
Authors: Berger Tim , Kreibich Maximilian , Rylski Bartosz , Kondov Stoyan , Fagu Albi , Beyersdorf Friedhelm , Siepe Matthias , Czerny Martin
Published: February 2021

OBJECTIVES

The goal of this study was to describe our 3-step approach to treat multisegmental thoraco-abdominal aortic disease due to aortic dissection and to present our initial clinical results.

METHODS

Nine patients with multisegmental thoraco-abdominal aortic pathology due to aortic dissection underwent our 3-step approach, which consisted of total aortic arch replacement via the frozen elephant trunk technique, thoracic endovascular aortic repair for distal extension down to the level of the thoraco-abdominal transition and, finally, open thoraco-abdominal aortic replacement for the remaining downstream aortic segments. We assessed their baseline and aortic characteristics, previous aortic procedures, intraoperative details, clinical outcomes and follow-up data.

RESULTS

The median age was 58 (42–66) years; 4 patients (44%) presented connective tissue disease. Eight patients (89%) had undergone previous aortic surgery for aortic dissection. In-hospital mortality was 0% (n = 0). None suffered symptomatic spinal cord injury or disabling stroke. During the follow-up period, 1 patient died of acute biliary septic shock 6 months after thoraco-abdominal aortic replacement.

CONCLUSIONS

The 3-step approach to treat multisegmental thoraco-abdominal aortic pathology due to aortic dissection, which involves applying both open and endovascular techniques, is associated with an excellent clinical outcome and low perioperative risk. Distal shifting of the disease process through the thoracic endovascular aortic repair extension—and thereby necessitating limited open thoraco-abdominal aortic repair—seems to be the major factor enabling these favourable results.

IRB approval

IRB approval was obtained (No. 425/15) from the institutional review board of the University of Freiburg.
The Complement Pathway Is Activated in People With Human Immunodeficiency Virus and Is Associated With Non-AIDS Comorbidities
Authors: Vujkovic-Cvijin Ivan , Sortino Ornella , Verheij Eveline , Wit Ferdinand W , Kootstra Neeltje A , Sellers Brian , Schim van der Loeff Maarten , Belkaid Yasmine , Reiss Peter , Sereti Irini
Published: February 2021

Unbiased plasma proteomics in a matched case-control study of treated people with human immunodeficiency virus (PWH) revealed the complement cascade as being among the top pathways enriched in PWH. Specific complement components, namely C5, associated significantly with non-AIDS comorbidity prevalence, and did so more strongly than previously established predictive biomarkers.
Failed Eradication Therapy of New-Onset Pseudomonas aeruginosa Infections in Children With Cystic Fibrosis Is Associated With Bacterial Resistance to Neutrophil Functions
Authors: Kwong Kelly , Benedetti Andrea , Yau Yvonne , Waters Valerie , Nguyen Dao
Published: February 2021

Background

Antibiotics, such as inhaled tobramycin, are used to eradicate new-onset Pseudomonas aeruginosa (PA) infections in patients with cystic fibrosis (CF) but frequently fail due to reasons poorly understood. We hypothesized that PA isolates’ resistance to neutrophil antibacterial functions was associated with failed eradication in patients harboring those strains.

Methods

We analyzed all PA isolates from a cohort of 39 CF children with new-onset PA infections undergoing tobramycin eradication therapy, where 30 patients had eradicated and 9 patients had persistent infection. We characterized several bacterial phenotypes and measured the isolates’ susceptibility to neutrophil antibacterial functions using in vitro assays of phagocytosis and intracellular bacterial killing.

Results

PA isolates from persistent infections were more resistant to neutrophil functions, with lower phagocytosis and intracellular bacterial killing compared to those from eradicated infections. In multivariable analyses, in vitro neutrophil responses were positively associated with twitching motility, and negatively with mucoidy. In vitro neutrophil phagocytosis was a predictor of persistent infection following tobramycin even after adjustment for clinical risk factors.

Conclusions

PA isolates from new-onset CF infection show strain-specific susceptibility to neutrophil antibacterial functions, and infection with PA isolates resistant to neutrophil phagocytosis is an independent risk factor for failed tobramycin eradication.
On bivalent semantics and natural deduction for some infectious logics
Authors: Belikov Alex
Published: February 2021

In this work, we propose a variant of so-called informational semantics, a technique elaborated by Voishvillo, for two infectious logics, Deutsch’s ${\mathbf{S}_{\mathbf{fde}}}$ and Szmuc’s $\mathbf{dS}_{\mathbf{fde}}$. We show how the machinery of informational semantics can be effectively used to analyse truth and falsity conditions of disjunction and conjunction. Using this technique, it is possible to claim that disjunction and conjunction can be rightfully regarded as such, a claim which was disputed in the recent literature. Both ${\mathbf{S}_{\mathbf{fde}}}$ and $\mathbf{dS}_{\mathbf{fde}}$ are formalized in terms of natural deduction. This allows us to solve several problems: to develop a natural deduction calculus for ${\mathbf{S}_{\mathbf{fde}}}$ containing the standard form of disjunction elimination (in contrast to the calculus by Petrukhin), to introduce the first natural deduction calculus for $\mathbf{dS}_{\mathbf{fde}}$ and to reflect the fundamental symmetry between ${\mathbf{S}_{\mathbf{fde}}}$ and $\mathbf{dS}_{\mathbf{fde}}$ on proof-theoretical level forming a convenient basis for obtaining their well-known extensions $\mathbf{K}^{\mathbf{w}}_{\mathbf{3}}$ and $\mathbf{PWK}$.
Enzymatic Hydrolysis of Defatted Antheraea pernyi (Lepidoptera: Saturniidae) Pupa Protein by Combined Neutral Protease Yield Peptides With Antioxidant Activity
Authors: Ma Shuhui , Li Xuejun , Sun Yongxin , Mi Rui , Li Yajie , Wen Zhixin , Meng Nan , Yi Li , Du Xingfan , Li Shuying
Published: February 2021

In this study, peptides were prepared from defatted Antheraea pernyi (Lepidoptera: Saturniidae) pupa protein via hydrolysis with combined neutral proteases. Single-factor tests and response surface methodology (RSM) were used to determine the optimal hydrolysis condition suitable for industrial application. Optimal hydrolysis of the defatted pupa protein was found to occur at an enzyme concentration of 4.85 g/liter, a substrate concentration of 41 g/liter, a hydrolysis temperature of 55°C, and a hydrolysis time of 10 h and 40 min. Under these conditions, the predicted and actual rates of hydrolysis were 45.82% and 45.75%, respectively. Peptides with a molecular weight of less than 2,000 Da accounted for 90.5% of the total peptides generated. Some of the peptides were antioxidant peptides as revealed by sequencing and functional analysis. The antioxidant activity of the mixed peptides was subsequently confirmed by an antioxidant activity assay. The results showed that peptides with high antioxidant activity could be obtained from the hydrolysis of A. pernyi pupa protein.
Enhancement of Temephos and Deltamethrin Toxicity by Petroselinum crispum Oil and its Main Constituents Against Aedes aegypti (Diptera: Culicidae)
Authors: Junkum Anuluck , Intirach Jitrawadee , Chansang Arpaporn , Champakaew Danita , Chaithong Udom , Jitpakdi Atchariya , Riyong Doungrat , Somboon Pradya , Pitasawat Benjawan
Published: February 2021

Previous work presented the profound antimosquito potential of Petroselinum crispum essential oil (PEO) against either the pyrethroid-susceptible or resistant strains of Aedes aegypti. This plant oil also inhibited the activity of acetylcholinesterase and mixed-function oxidases significantly, thus suggesting its potential as a synergist for improving mosquitocidal efficacy of insecticidal formulations. This study investigated the chemical composition, larvicidal activity, and potential synergism with synthetic insecticides of PEO and its main compounds for the purpose of interacting with insecticide resistance in mosquito vectors. The chemical profile of PEO, obtained by GC-MS analysis, showed a total of 17 bioactive compounds, accounting for 99.09% of the whole oil, with the most dominant constituents being thymol (74.57%), p-cymene (10.73%), and γ-terpinene (8.34%). All PEO constituents exhibited promising larvicidal effects, with LC50 values ranging from 19.47 to 59.75 ppm against Ae. aegypti, in both the pyrethroid-susceptible and resistant strains. Furthermore, combination-based bioassays revealed that PEO, thymol, p-cymene, and γ-terpinene enhanced the efficacy of temephos and deltamethrin significantly. The most effective synergist with temephos was PEO, which reduced LC50 values to 2.73, 4.94, and 3.28 ppb against MCM-S, PMD-R, and UPK-R, respectively, with synergism ratio (SR) values of 1.33, 1.38, and 2.12, respectively. The best synergist with deltamethrin also was PEO, which reduced LC50 values against MCM-S, PMD-R, and UPK-R to 0.008, 0.18, and 2.49 ppb, respectively, with SR values of 21.25, 9.00, and 4.06, respectively. This research promoted the potential for using essential oil and its principal constituents as not only alternative larvicides, but also attractive synergists for enhancing efficacy of existing conventional insecticides.
Differences between species in seed bank and vegetation helps to hold functional diversity in a floodable Neotropical savanna
Authors: de Souza Evaldo B , Bao Francielli , Damasceno Junior Geraldo A , Pott Arnildo
Published: February 2021

Aims

Our objective was to quantify the contributions of the seed bank and the established vegetation to the species composition, functional composition and diversity, and discuss the implications of these differences in regeneration and persistence of floodplain plant communities.

Methods

We sampled all ground cover vegetation up to 1.5 m height and seed bank in 25 plots (10 m × 1 m) distributed across five sites in dry and rainy seasons in a periodically flooded savanna in the Pantanal wetland, Brazil. We evaluated the soil seed bank by seedling emergence method.

Important Findings

The seed bank species had traits that conferred regeneration to the communities, while persistence traits characterized the vegetation. The seed bank had higher functional richness and lower functional evenness than the vegetation. The existence of different plant traits between seed bank and vegetation allowed the coexistence of species with functionally contrasting persistence and regeneration traits, which may help maintain functional diversity. It may allow the community to be more resilient when dealing with different environmental filters such as drought, fire and flood.
Factor Structure of Medical Autonomy Scales in Young People with Spina Bifida
Authors: Smith Zoe R , Holmbeck Grayson N
Published: February 2021

Objective

The primary goal of this study was to examine the factor structure of a spina bifida (SB) medical responsibilities measure and a medical regimen skills scale across time in families of youth with SB.

Method

One-hundred and forty youth with SB and their parents were assessed in both childhood/adolescence and adolescence/young adulthood. The Sharing of SB Medical Responsibilities Scale (SOSBMR) includes 34 items for which participants indicate who is responsible for each task. The SB Independence Survey (SBIS) is composed of 50 SB-specific medical skills items in yes-no format. Confirmatory factor analyses (CFA) were conducted to examine the factor structure of the SOSBMR and SBIS in childhood and adolescence (ages 8–15) and in adolescence/young adulthood (AYA; ages 16–25).

Results

One- and seven-factor CFAs were compared for both measures. For the SBIS, both mother- and father-report were used in childhood; self-report was employed for AYA. For the SOSBMR, only self-report was used for both age groups. Across each rater and time point, the seven-factor models of the SBIS and SOSBMR had adequate to excellent fit and reliability, indicating the ability to use each subscale. In addition, each of the corresponding subscales on the SOSBMR and SBIS were associated with each other across raters and time, showing good concurrent and predictive validity.

Conclusions

From childhood to young adulthood, the subscales of the SOSBMR can be used to examine responsibility across multiple medical tasks and the SBIS can be used to assess medical regimen skills and mastery in young people with SB.
A rare case of post-traumatic high-flow priapism requiring endovascular salvage with bilateral superselective microcoil embolization
Authors: Williams Aman B , Lax Lauren G
Published: February 2021

Post-traumatic high-flow priapism is a rare occurrence, with potentially debilitating long-term erectile dysfunction if left unaddressed. Even rarer, however, is for the priapism symptoms to be caused by a single cavernosal arterial pseudoaneurysm, with feeding vessels from the distal branched vessels of ‘both’ the left and right internal pudendal arteries. To the best of our knowledge, we present the first documented case of endovascular salvage utilizing superselective microcoil embolization in the treatment of high-flow priapism caused by a singular pseudoaneurysm with bilateral inflow. Timing of symptoms, interpretation of imaging, multidisciplinary discussions, procedural risk, arterial anatomy and choice of embolic agent were all careful considerations in this case. Following embolization, this young gentleman ultimately had a successful angiographic result, normalization of his cavernosal artery peak systolic velocity on ultrasound and a full return to normal erectile function by 6 months.
Predicting Nonresponse in Future Waves of a Probability-Based Mixed-Mode Panel with Machine Learning
Authors: Kern Christoph , Weiß Bernd , Kolb Jan-Philipp
Published: February 2021

Nonresponse in panel studies can lead to a substantial loss in data quality owing to its potential to introduce bias and distort survey estimates. Recent work investigates the usage of machine learning to predict nonresponse in advance, such that predicted nonresponse propensities can be used to inform the data collection process. However, predicting nonresponse in panel studies requires accounting for the longitudinal data structure in terms of model building, tuning, and evaluation. This study proposes a longitudinal framework for predicting nonresponse with machine learning and multiple panel waves and illustrates its application. With respect to model building, this approach utilizes information from multiple waves by introducing features that aggregate previous (non)response patterns. Concerning model tuning and evaluation, temporal crossvalidation is employed by iterating through pairs of panel waves such that the training and test sets move in time. Implementing this approach with data from a German probability-based mixed-mode panel shows that aggregating information over multiple panel waves can be used to build prediction models with competitive and robust performance over all test waves.
When junk DNA turns functional: transposon-derived non-coding RNAs in plants
Authors: Ariel Federico D , Manavella Pablo A
Published: February 2021

Transposable elements (TEs) are major contributors to genome complexity in eukaryotes. TE mobilization may cause genome instability, although it can also drive genome diversity throughout evolution. TE transposition may influence the transcriptional activity of neighboring genes by modulating the epigenomic profile of the region or by altering the relative position of regulatory elements. Notably, TEs have emerged in the last few years as an important source of functional long and small non-coding RNAs. A plethora of small RNAs derived from TEs have been linked to the trans regulation of gene activity at the transcriptional and post-transcriptional levels. Furthermore, TE-derived long non-coding RNAs have been shown to modulate gene expression by interacting with protein partners, sequestering active small RNAs, and forming duplexes with DNA or other RNA molecules. In this review, we summarize our current knowledge of the functional and mechanistic paradigms of TE-derived long and small non-coding RNAs and discuss their role in plant development and evolution.
Clade III cytokinin response factors share common roles in response to oxidative stress responses linked to cytokinin synthesis
Authors: Hughes Ariel M , Hallmark H Tucker , Plačková Lenka , Novák Ondrej , Rashotte Aaron M
Published: February 2021

Cytokinin response factors (CRFs) are transcription factors that are involved in cytokinin (CK) response, as well as being linked to abiotic stress tolerance. In particular, oxidative stress responses are activated by Clade III CRF members, such as AtCRF6. Here we explored the relationships between Clade III CRFs and oxidative stress. Transcriptomic responses to oxidative stress were determined in two Clade III transcription factors, Arabidopsis AtCRF5 and tomato SlCRF5. AtCRF5 was required for regulated expression of >240 genes that are involved in oxidative stress response. Similarly, SlCRF5 was involved in the regulated expression of nearly 420 oxidative stress response genes. Similarities in gene regulation by these Clade III members in response to oxidative stress were observed between Arabidopsis and tomato, as indicated by Gene Ontology term enrichment. CK levels were also changed in response to oxidative stress in both species. These changes were regulated by Clade III CRFs. Taken together, these findings suggest that Clade III CRFs play a role in oxidative stress response as well as having roles in CK signaling.
Is Serum-Ascites Vitamin D Gradient a Valid Marker for Diagnosing Spontaneous Bacterial Peritonitis in Patients with Cirrhotic Ascites?
Authors: Abdel Hafez Hanan , Madani Hanan , Abdel Alem Shereen , Farrag Ahmed , Fathy Wael , Abdo Mahmoud
Published: February 2021

Objective

Spontaneous bacterial peritonitis (SBP) is considered the paradigmatic model of infection in patients with liver cirrhosis. Therefore, there is a need for an accurate and rapid method for SBP diagnosis. The aim of this study was to evaluate the validity of serum-ascites 25-hydroxyvitamin D (25-OH vitamin D) gradient (SADG) as a marker for diagnosing SBP in patients with cirrhotic ascites.

Methods

We conducted a cross-sectional analytic study of 88 patients with portal hypertensive ascites resulting from liver cirrhosis of any etiology. The demographic, clinical, and laboratory characteristics of the patients were recorded. The level of 25-OH vitamin D in serum and ascitic fluid was measured using high-performance liquid chromatography autoanalyzer. The SADG was calculated with the formula: 25-OH vitamin D in serum − 25-OH vitamin D in ascites.

Results

Vitamin D deficiency was detected in 89.8% of the studied patients. The SADG values ranged between 0 and 69.2 ng/mL, with a median value of 5.58 ng/mL. It was significantly lower in patients with SBP than in those without SBP (P = .004). The area under the curve for SADG in exclusion of SBP was 0.67 at a cutoff value of ≥5.57 ng/mL.

Conclusion

We found that SADG may be a valid marker of SBP in patients with cirrhotic ascites.
RINGO3 polarimetry of very young ZTF supernovae
Authors: Maund J R , Yang Y , Steele I A , Baade D , Jermak H , Schulze S , Bruch R , Gal-Yam A , Höflich P A , Ofek E , Wang X , Amenouche M , Dekany R , Masci F J , Riddle R , Soumagnac M T
Published: February 2021

The early phases of the observed evolution of the supernovae (SNe) are expected to be dominated by the shock breakout and ‘flash’ ionization of the surrounding circumstellar medium. This material arises from the last stages of the evolution of the progenitor, such that photometry and spectroscopy of SNe at early times can place vital constraints on the latest and fastest evolutionary phases leading up to stellar death. These signatures are erased by the expansion of the ejecta within ∼5 d after explosion. Here we present the earliest constraints, to date, on the polarization of 10 transients discovered by the Zwicky Transient Facility (ZTF), between 2018 June and 2019 August. Rapid polarimetric follow-up was conducted using the Liverpool Telescope RINGO3 instrument, including three SNe observed within <1 d of detection by the ZTF. The limits on the polarization within the first 5 d of explosion, for all SN types, is generally $\lt 2{ per\ cent}$, implying early asymmetries are limited to axial ratios >0.65 (assuming an oblate spheroidal configuration). We also present polarimetric observations of the Type I Superluminous SN 2018bsz and Type II SN 2018hna, observed around and after maximum light.
Physical and kinematic conditions of the local merging galaxy NGC 1487
Authors: Buzzo M L , Ziegler B , Amram P , Verdugo M , Barbosa C E , Ciocan B , Papaderos P , Torres-Flores S , Mendes de Oliveira C
Published: February 2021

We present optical VLT/MUSE integral field spectroscopy data of the merging galaxy NGC 1487. We use fitting techniques to study the ionized gas emission of this merger and its main morphological and kinematical properties. We measured flat and sometimes inverted oxygen abundance gradients in the subsystems composing NGC 1487, explained by metal mixing processes common in merging galaxies. We also measured widespread star-forming bursts, indicating that photoionization by stars is the primary ionization source of the galaxy. The kinematic map revealed a rotating pattern in the gas in the northern tail of the system, suggesting that the galaxy may be in the process of rebuilding a disc. The gas located in the central region has larger velocity dispersion (σ ≈ 50 km s−1) than the remaining regions, indicating kinematic heating, possibly owing to the ongoing interaction. Similar trends were, however, not observed in the stellar velocity dispersion map, indicating that the galaxy has not yet achieved equilibrium, and the nebular and stellar components are still kinematically decoupled. Based on all our measurements and findings, and specially on the mass estimates, metallicity gradients, and velocity fields of the system, we propose that NGC 1487 is the result of an ongoing merger event involving smallish dwarf galaxies within a group, in a pre-merger phase, resulting in a relic with mass and physical parameters similar to a dwarf galaxy. Thus, we may be witnessing the formation of a dwarf galaxy by merging of smaller clumps at z = 0.
Successive common envelope events from multiple planets
Authors: Chamandy Luke , Blackman Eric G , Nordhaus Jason , Wilson Emily
Published: February 2021

Many stars harbour multiplanet systems. As these stars expand late in their evolutions, the innermost planet may be engulfed, leading to a common envelope (CE) event. Even if this is insufficient to eject the envelope, it may expand the star further, causing additional CE events, with the last one unbinding what remains of the envelope. This multiplanet CE scenario may have broad implications for stellar and planetary evolution across a range of systems. We develop a simplified version and show that it may be able to explain the recently observed planet WD 1856 b.
Dietary Diversification and Specialization in Neotropical Bats Facilitated by Early Molecular Evolution
Authors: Potter Joshua H T , Davies Kalina T J , Yohe Laurel R , Sanchez Miluska K R , Rengifo Edgardo M , Struebig Monika , Warren Kim , Tsagkogeorga Georgia , Lim Burton K , dos Reis Mario , Dávalos Liliana M , Rossiter Stephen J
Published: February 2021

Dietary adaptation is a major feature of phenotypic and ecological diversification, yet the genetic basis of dietary shifts is poorly understood. Among mammals, Neotropical leaf-nosed bats (family Phyllostomidae) show unmatched diversity in diet; from a putative insectivorous ancestor, phyllostomids have radiated to specialize on diverse food sources including blood, nectar, and fruit. To assess whether dietary diversification in this group was accompanied by molecular adaptations for changing metabolic demands, we sequenced 89 transcriptomes across 58 species and combined these with published data to compare ∼13,000 protein coding genes across 66 species. We tested for positive selection on focal lineages, including those inferred to have undergone dietary shifts. Unexpectedly, we found a broad signature of positive selection in the ancestral phyllostomid branch, spanning genes implicated in the metabolism of all major macronutrients, yet few positively selected genes at the inferred switch to plantivory. Branches corresponding to blood- and nectar-based diets showed selection in loci underpinning nitrogenous waste excretion and glycolysis, respectively. Intriguingly, patterns of selection in metabolism genes were mirrored by those in loci implicated in craniofacial remodeling, a trait previously linked to phyllostomid dietary specialization. Finally, we show that the null model of the widely-used branch-site test is likely to be misspecified, with the implication that the test is too conservative and probably under-reports true cases of positive selection. Our findings point to a complex picture of adaptive radiation, in which the evolution of new dietary specializations has been facilitated by early adaptations combined with the generation of new genetic variation.
Peroxisomes as redox-signaling nodes in intracellular communication and stress responses
Authors: Sandalio Luisa M , Peláez-Vico Maria Angeles , Molina-Moya Eliana , Romero-Puertas Maria C
Published: February 2021

Peroxisomes are redox nodes playing a diverse range of roles in cell functionality and in the perception of and responses to changes in their environment.
Investigation of Correlations Between Pain Modulation Paradigms
Authors: Szikszay Tibor M , Lévénez Juliette L M , von Selle Janne , Adamczyk Waclaw M , Luedtke Kerstin
Published: February 2021

Objective

Endogenous pain modulation can be quantified through the use of various paradigms. Commonly used paradigms include conditioned pain modulation (CPM), offset analgesia (OA), spatial summation of pain (SSP), and temporal summation of pain (TSP), which reflect spatial and temporal aspects of pro- and antinociceptive processing. Although these paradigms are regularly used and are of high clinical relevance, the underlying physiological mechanisms are not fully understood.

Design

The aim of this study is therefore to assess the association between these paradigms by using comparable protocols and methodological approaches.

Setting

University campus.

Subjects

Healthy and pain-free volunteers (n = 48) underwent psychophysical assessment of CPM, OA, SSP, and TSP (random order) at the same body area (volar nondominant forearm) with individualized noxious stimuli.

Methods

CPM included heat stimuli before, during, and after a noxious cold-water bath, whereas for OA, three heat stimuli were applied: baseline trial, offset trial, and constant trial. For the SSP paradigm, two differently sized heat stimulation areas were evaluated, whereas for TSP, the first and last stimulus of 10 consecutive short heat stimuli were assessed. A computerized visual analog scale was used to continuously evaluate pain intensity. The magnitudes of all associations between all paradigm pairs were analyzed with Spearman’s correlation, and individual influencing factors were assessed with a multivariate linear regression model.

Results

Weak to moderate correlations among all four paradigms were found (P > 0.05), and no distinct influencing factors were identified.

Conclusions

A limited association between pain modulation paradigms suggests that CPM, OA, SSP, and TSP assess distinct aspects of endogenous analgesia with different underlying physiological mechanisms.
Osteoarthritis and risk of hospitalization for ambulatory care-sensitive conditions: a general population-based cohort study
Authors: Kiadaliri Ali , Englund Martin
Published: February 2021

Objective

To determine the association between OA and risk of hospitalization for ambulatory care-sensitive conditions (HACSCs).

Methods

We included all individuals aged 40–85 years who resided in Skåne, Sweden on 31 December 2005 with at least one healthcare consultation during 1998–2005 (n = 515 256). We identified those with a main diagnosis of OA between 1 January 1998 and 31 December 2016. People were followed from 1 January 2006 until an HACSC, death, relocation outside Skåne, or 31 December 2016 (whichever occurred first). OA status was treated as a time-varying covariate (those diagnosed before 1 January 2006 considered as exposed for whole study period). We assessed relative [hazard ratios (HRs) using Cox proportional hazard model] and absolute (hazard difference using additive hazard model) effects of OA on HACSCs adjusted for potential confounders.

Results

Crude incidence rates of HACSCs were 239 (95% CI: 235, 242) and 151 (150, 152) per 10 000 person-years among OA and non-OA persons, respectively. The OA persons had an increased risk of HACSCs [HR (95% CI) 1.11 (1.09, 1.13)] and its subcategories of medical conditions except chronic obstructive pulmonary disease [HR (95% CI) 0.86 (0.81, 0.90)]. There were 20 (95% CI: 16, 24) more HACSCs per 10 000 person-years in OA compared with non-OA persons. While HRs for knee and hip OA were generally comparable, only knee OA was associated with increased risk of hospitalization for diabetes.

Conclusion

OA is associated with an increased risk of HACSCs, highlighting the urgent need to improve outpatient care for OA patients.
Challenging the distrust of administrative law: the case for transposition
Authors: Lui Edward , Wong Clara
Published: February 2021

It has often been said that the control of discretionary powers in trust law and administrative law should be segregated and any transposition of principles should be resisted. This article questions this orthodoxy. Two propositions will be made. First, the orthodoxy is not normatively sustainable, since both administrative law and trust law are underpinned and shaped by similar forces. Transposition should be permissible, although identical principles need not apply. Second, the extent to which the transposition of principles should occur can be readily ascertained with reference to the modified ultra vires model.
Distinct Laboratory and Clinical Features of Secondary Hemophagocytic Lymphohistiocytosis in Pediatric Visceral Leishmaniasis
Authors: López Marcos María , Ruiz Sáez Beatriz , Vílchez Pérez Juan Salvador , Moreno Pérez David , Carazo Gallego Begoña , Falcón Neyra Lola , Goycochea Valdivia Walter Alfredo , Obando Santaella Ignacio , Lucena Soto José Manuel , Díaz Martos Julio , Santos Pérez Juan Luis , Rodríguez Benjumea Margarita , Angulo González de Lara Raquel , Sánchez Codez Mª Isabel , Peromingo Matute Estrella , Cruz Cañete Marta , Calviño Molinero Jennifer , Hurtado Mingo Ángela , Lendínez Molinos Francisco , Medina Claros Antonio F. , Muñoz Vilches Mª José , Neth Olaf , Olbrich Peter ,   on behalf of the GAIP (Grupo Andaluz de Infectología e Inmunopatología Pediátrica) Network
Published: February 2021

Background:

Visceral leishmaniasis (VL) is an endemic in Southern Europe. However, details regarding disease burden, clinical presentations, laboratory markers, management and outcome in children are scarce.

Methods:

Medical records of children (<14 years) admitted with VL to 10 pediatric units in Andalusia (2004–2019) were retrospectively reviewed. VL diagnosis was based on clinical presentation, serology, microscopy and molecular methods. Diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) was established using the hemophagocytic lymphohistiocytosis-2004 criteria.

Results:

A total of 127 patients were identified. Median age was 14.5 months; the main clinical presentations were fever and splenomegaly (95.3% each). Cytopenias were the most common laboratory abnormalities. Diagnostics as well as treatment regimens varied over time and the participating centers. Liposomal amphotericin B was prescribed in 97.6%; relapses as well as adverse events were rarely observed (3.1% each). Thirty-seven patients, diagnosed with sHLH required longer hospital admission (P = 0.001), an increased number of platelet (P < 0.006) and red blood cell (P = 0.0001) transfusions and pediatric intensive care unit admission (P = 0.007). Monocytopenia (P = 0.011) and high C-reactive protein levels (P = 0.031), variables not included in the hemophagocytic lymphohistiocytosis-2004 criteria, were associated with sHLH. One patient deceased in the context of the Leishmania infection.

Conclusions:

We report data on the largest pediatric VL cohort from Europe, commonly associated with sHLH. Raised C-reactive protein levels and monocytopenia appear to be associated with sHLH. The latter may help to identify these patients and to guide decisions regarding need of additional supportive clinical care and immunomodulatory therapies. The observed high rate of heterogeneity in terms of diagnosis and management warrants the establishment of appropriate guidelines.
Comparison of clinical outcomes of 2 platforms for topography-guided LASIK in primary eyes
Authors: Li Li , Zhang Bo , Liu Shengxu , Xiong Lu , Wang Zheng
Published: February 2021

Purpose:

To compare differences in visual, refractive, and ablating outcomes between corneal topography-guided laser in situ keratomileusis (LASIK) by SCHWIND AMARIS and WaveLight Contoura for myopia and myopic astigmatism correction.

Setting:

Department of Refractive Surgery, Guangzhou Aier Eye Hospital, Guangzhou, China.

Design:

Prospective nonrandomized study.

Methods:

Patients treated with LASIK to correct ametropia and corneal higher-order aberrations (HOAs) with 6.5 mm of plan optical zone were recruited. In the AMARIS platform, there were 2 centration strategies: the symmetric (AA) and asymmetric (AS) offset modes. In the WaveLight platform, there was only symmetric offset (ES) mode. HOAs, contrast sensitivity, effective optical zone (EOZ), ablation depth, and ablating center were evaluated 3 months after the operation.

Results:

The study included 138 eyes. At 3 months after operation, the postoperative manifest refractive spherical equivalent was 0.04 ± 0.34 diopters (D), 0.06 ± 0.25 D, and −0.09 ± 0.21 D in AS, AA, and ES groups, respectively (P = .018). The EOZs of the AS and AA groups were 5.01 mm and 4.96 mm, and both were larger than 4.88 mm in the ES group (P = .04 and .03, respectively). The ablation depth of the AS group was 103.6 μm, which were larger than 86.6 μm in the AA group and 91.2 μm in the ES group.

Conclusions:

The SCHWIND AMARIS and WaveLight EX500 corneal topography-guided LASIK achieved comparable and excellent visual and refractive outcomes. The EX500 Contoura LASIK ablated less corneal tissue because of the smaller EOZ compared with the AMARIS, with a similar plan optical zone.
Cap recovery technique and double-edge sign during small-incision lenticule extraction
Authors: Carp Glenn I. , Reinstein Dan Z. , Stuart Alastair , Vida Ryan S. , Archer Timothy J. , Finkel Jake N.
Published: February 2021

Purpose:

To describe a new technique for identifying the upper (cap) interface during small-incision lenticule extraction (SMILE). If the lower interface is dissected first it can be challenging to locate the cap interface and complete the lenticule separation.

Setting:

London Vision Clinic, London, United Kingdom.

Design:

Retrospective analysis.

Methods:

The routine protocol was to open the primary small incision and separate the cap interface, followed by the lenticule interface. If the lenticule interface was dissected first, the modified Sinskey tip was inserted through the superior end of the incision, tangentially along the cap edge interface and then rotated anteriorly to engage the edge of the lenticule adherent to the underside of the cap. The Sinskey tip is then drawn inferiorly, creating a pocket of separation of the lenticule from the cap, enabling the dissection bulb and spatula to be used to dissect the upper interface.

Results:

A total of 629 consecutive eyes undergoing SMILE using the VisuMax femtosecond laser were included. The routine surgical protocol (cap interface first) was followed in 88% of eyes and the lenticule interface first in 12% of eyes. The lenticule was extracted successfully in all cases. Uncorrected distance visual acuity at the 1-day postoperative visit was 20/25 or better in 81% of the cap interface first group and 86% of the lenticule interface first group.

Conclusions:

The visual results using this cap recovery technique were equivalent to those when a routine SMILE dissection was performed. The technique allowed surgeons to rescue more challenging cases where identifying the different interfaces was difficult. This technique meant that separating the lenticule interface first should no longer be considered a complication of SMILE.
Visual outcome and optical quality of a wavefront-engineered extended depth-of-focus intraocular lens
Authors: Greve Daria , Bertelmann Eckart , Pilger Daniel , von Sonnleithner Christoph
Published: February 2021

Purpose:

To evaluate visual performance and optical quality of an extended depth-of-focus intraocular lens (EDoF IOL) compared with a monofocal aspheric IOL.

Setting:

Department of Ophthalmology, Charité-Medical University Berlin, Germany.

Design:

Prospective case series.

Methods:

After phacoemulsification, a total of 28 patients (56 eyes) underwent bilateral implantation of either the Mini Well (EDoF IOL) or the Mini 4 (monofocal IOL). Assessments including refraction, distance, intermediate and near visual acuity, defocus curves, contrast sensitivity, glare disability, higher-order aberrations (HOAs), and patient satisfaction were performed at 1 month and 3 months postoperatively.

Results:

Both study groups comprised 14 patients (28 eyes) each. At 3-month follow-up, the EDoF IOL showed better results in monocular uncorrected intermediate visual acuity (−0.04 vs 0.10 logMAR, P = .000) and in uncorrected near visual acuity (0.13 vs 0.36 logMAR, P = .000), whereas no statistically significant difference was found between groups in monocular uncorrected distance visual acuity (0.04 vs 0.00 logMAR, P = .110). The monocular depth of focus was 0.8 D greater in the Mini Well IOL group. Measurements of internal HOAs revealed a greater negative primary spherical aberration in the EDoF group at pupil sizes of 2.0 to 5.0 mm. At 5.0 mm, total internal HOAs did not differ statistically significantly (0.376 vs 0.340 μm root mean square, P = .068).

Conclusions:

The Mini Well IOL provided greater depth of focus with superior outcomes at intermediate and near distances and comparable outcomes at far distance. Although inducing higher amounts of spherical aberration, it showed good results under low lighting conditions with little subjective dysphotopsia.
Late in-the-bag intraocular lens dislocation
Authors: Kristianslund Olav , Dalby Marius , Drolsum Liv
Published: February 2021

This review aimed to evaluate the cumulative incidence, patient characteristics, predisposing conditions, and treatment outcomes for late in-the-bag intraocular lens (IOL) dislocation. Literature searches in PubMed (MEDLINE), Embase, and Cochrane Library Central database identified 1 randomized clinical trial, 1 prospective case series, 2 prospective cohort studies, and 36 retrospective studies of this condition, which showed that the cumulative incidence was 0.5% to 3%, it occurred on average 6 to 12 years after cataract surgery, and mean patient age was 65 to 85 years. Pseudoexfoliation syndrome, myopia, and previous vitreoretinal surgery were the most common predisposing conditions. Studies indicated that IOL repositioning and IOL exchange provided similar visual outcomes and were equally safe. The long-term visual outcome seemed satisfactory. However, the quality of evidence regarding treatment was in general quite low. More studies of late in-the-bag IOL dislocation are needed, and in particular, different surgical techniques should be included in high-quality clinical trials.
Clinical Validation of Automated and Rapid mariPOC SARS-CoV-2 Antigen Test
Authors: Koskinen Juha M. , Antikainen Petri , Hotakainen Kristina , Haveri Anu , Ikonen Niina , Savolainen-Kopra Carita , Sundström Kati , Koskinen Janne O.
Published: February 2021

Novel SARS coronavirus causing COVID-19 was recognized in late 2019. Diagnostics was quickly ramped up worldwide based on the detection of viral RNA. Based on the scientific knowledge for pre-existing coronaviruses, it was expected that the RNA of this novel coronavirus will be detected from symptomatic and at significant rates also from asymptomatic individuals due to persistence of non-infectious RNA. To increase the efficacy of diagnostics, surveillance, screening and pandemic control, rapid methods, such as antigen tests, are needed for decentralized testing and to assess infectiousness. The objective was to validate the analytical and clinical performance, and usability of a novel automated mariPOC SARS-CoV-2 test, which is based on the detection of structural viral proteins using sophisticated optical laser technology. Clinical performance of the test was evaluated against qRT-PCR with nasopharyngeal swab specimens collected from patients suspected of acute SARS-CoV-2 infection. Sensitivity of the mariPOC test was 100.0% (13/13) directly from swab specimens and 84.4% (38/45) from swab specimens in undefined transport mediums. Specificity of the test was 100.0% (201/201). The test’s limit of detection was 2.7 TCID50/test and had no cross-reactions with the tested respiratory microbes. Our study shows that the mariPOC can detect infectious individuals already in 20 minutes with clinical sensitivity close to qRT-PCR. The test targets conserved epitopes of SARS-CoV-2 nucleoprotein, making it robust against strain variations. The new test is a promising and versatile tool for syndromic testing of symptomatic cases and for high capacity infection control screening.