bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial origin of a key innovation in the evolution of the vertebrate eye
Authors: Kalluraya Chinmay A. , Weitzel Alexander J. , Tsu Brian V. , Daugherty Matthew D.
Published: April 2023

The vertebrate eye was described by Charles Darwin as one of the greatest potential challenges to a theory of natural selection by stepwise evolutionary processes. While numerous evolutionary transitions that led to the vertebrate eye have been explained, some aspects appear to be vertebrate specific with no obvious metazoan precursor. One critical difference between vertebrate and invertebrate vision hinges on interphotoreceptor retinoid-binding protein (IRBP, also known as retinol-binding protein, RBP3), which enables the physical separation and specialization of cells in the vertebrate visual cycle by promoting retinoid shuttling between cell types. While IRBP has been functionally described, its evolutionary origin has remained elusive. Here, we show that IRBP arose via acquisition of novel genetic material from bacteria by interdomain horizontal gene transfer (iHGT). We demonstrate that a gene encoding a bacterial peptidase was acquired prior to the radiation of extant vertebrates >500 Mya and underwent subsequent domain duplication and neofunctionalization to give rise to vertebrate IRBP. Our phylogenomic analyses on >900 high-quality genomes across the tree of life provided the resolution to distinguish contamination in genome assemblies from true instances of horizontal acquisition of IRBP and led us to discover additional independent transfers of the same bacterial peptidase gene family into distinct eukaryotic lineages. Importantly, this work illustrates the evolutionary basis of a key transition that led to the vertebrate visual cycle and highlights the striking impact that acquisition of bacterial genes has had on vertebrate evolution.
Lipid droplets are intracellular mechanical stressors that impair hepatocyte function
Authors: Loneker Abigail E. , Alisafaei Farid , Kant Aayush , Li David , Janmey Paul A. , Shenoy Vivek B. , Wells Rebecca G.
Published: April 2023

Matrix stiffening and external mechanical stress have been linked to disease and cancer development in multiple tissues, including the liver, where cirrhosis (which increases stiffness markedly) is the major risk factor for hepatocellular carcinoma. Patients with nonalcoholic fatty liver disease and lipid droplet–filled hepatocytes, however, can develop cancer in noncirrhotic, relatively soft tissue. Here, by treating primary human hepatocytes with the monounsaturated fatty acid oleate, we show that lipid droplets are intracellular mechanical stressors with similar effects to tissue stiffening, including nuclear deformation, chromatin condensation, and impaired hepatocyte function. Mathematical modeling of lipid droplets as inclusions that have only mechanical interactions with other cellular components generated results consistent with our experiments. These data show that lipid droplets are intracellular sources of mechanical stress and suggest that nuclear membrane tension integrates cell responses to combined internal and external stresses.
Evolution of insect innate immunity through domestication of bacterial toxins
Authors: Verster Kirsten I. , Cinege Gyöngyi , Lipinszki Zoltán , Magyar Lilla B. , Kurucz Éva , Tarnopol Rebecca L. , Ábrahám Edit , Darula Zsuzsanna , Karageorgi Marianthi , Tamsil Josephine A. , Akalu Saron M. , Andó István , Whiteman Noah K.
Published: April 2023

Toxin cargo genes are often horizontally transferred by phages between bacterial species and are known to play an important role in the evolution of bacterial pathogenesis. Here, we show how these same genes have been horizontally transferred from phage or bacteria to animals and have resulted in novel adaptations. We discovered that two widespread bacterial genes encoding toxins of animal cells,
cytolethal distending toxin subunit B
(
cdtB
) and
apoptosis-inducing protein of 56 kDa
(
aip56)
, were captured by insect genomes through horizontal gene transfer from bacteria or phages. To study the function of these genes in insects, we focused on
Drosophila ananassae
as a model. In the
D. ananassae
subgroup species,
cdtB
and
aip56
are present as singular (
cdtB
) or fused copies (
cdtB::aip56
) on the second chromosome. We found that
cdtB
and
aip56
genes and encoded proteins were expressed by immune cells, some proteins were localized to the wasp embryo’s serosa, and their expression increased following parasitoid wasp infection. Species of the
ananassae
subgroup are highly resistant to parasitoid wasps, and we observed that
D. ananassae
lines carrying null mutations in
cdtB
and
aip56
toxin genes were more susceptible to parasitoids than the wild type. We conclude that toxin cargo genes were captured by these insects millions of years ago and integrated as novel modules into their innate immune system. These modules now represent components of a heretofore undescribed defense response and are important for resistance to parasitoid wasps. Phage or bacterially derived eukaryotic toxin genes serve as macromutations that can spur the instantaneous evolution of novelty in animals.
RPL26/uL24 UFMylation is essential for ribosome-associated quality control at the endoplasmic reticulum
Authors: Scavone Francesco , Gumbin Samantha C. , Da Rosa Paul A. , Kopito Ron R.
Published: April 2023

Ribosomes that stall while translating cytosolic proteins are incapacitated by incomplete nascent chains, termed “arrest peptides” (APs) that are destroyed by the ubiquitin proteasome system (UPS) via a process known as the ribosome-associated quality control (RQC) pathway. By contrast, APs on ribosomes that stall while translocating secretory proteins into the endoplasmic reticulum (ER-APs) are shielded from cytosol by the ER membrane and the tightly sealed ribosome–translocon junction (RTJ). How this junction is breached to enable access of cytosolic UPS machinery and 26S proteasomes to translocon- and ribosome-obstructing ER-APs is not known. Here, we show that UPS and RQC-dependent degradation of ER-APs strictly requires conjugation of the ubiquitin-like (Ubl) protein UFM1 to 60S ribosomal subunits at the RTJ. Therefore, UFMylation of translocon-bound 60S subunits modulates the RTJ to promote access of proteasomes and RQC machinery to ER-APs.
75‐repetition versus sets to failure of blood flow restriction exercise on indices of muscle damage in women
Authors: Proppe Christopher E. , Aldeghi Taylor M. , Rivera Paola M. , Gonzalez‐Rojas David , Wizenberg Aaron M. , Hill Ethan C.
Published: April 2023

There is conflicting evidence regarding the prevalence and magnitude of exercise‐induced muscle damage (EIMD) following low‐load resistance exercise with blood flow restriction (LL + BFR) that may be related to exercise protocols. The purpose of this investigation was to examine the effects of 75‐repetition (BFR‐75) (1 × 30, 3 × 15) and 4 sets to failure (BFR‐4x) protocols on indices of EIMD among untrained women. Thirteen women completed this investigation. One leg was randomly assigned to BFR‐75 and the other to BFR‐4x. Each leg performed isokinetic, unilateral, concentric‐eccentric, leg extension muscle actions at 30% of maximal strength. Indices of EIMD (muscle soreness, range of motion [ROM], limb circumference, pain pressure threshold [PPT], and maximal voluntary isometric contraction [MVIC]) were recorded before exercise, 0‐, 24‐, 48‐, 72‐, and 96‐hours post‐exercise. There were no changes for ROM, circumference, or PPT. Muscle soreness increased similarly in both conditions 0‐, 24‐, and 48‐hours post‐exercise and MVIC increased 24‐, 48‐, 72‐, and 96‐hours post‐exercise. These findings suggested BFR‐75 and BFR‐4x were not associated with EIMD and elicited similar physiological responses. The increases in muscle soreness may be due to metabolic stress associated with LL + BFR protocols apart from EIMD.
Controllability of shock waves in one-dimensional polariton condensates
Authors: Wang Qi-wen , Wang Jin-ling , Wen Wen , Lin Ji , Li Hui-jun
Published: April 2023

In one-dimensional incoherent pumped exciton–polariton condensates, we realize the generation and control of supersonic shock waves. By choosing a suitable initial input wave, we obtain the region of existence of various shock waves as a function of the phase of the initial wave, the coefficient of polariton interaction, the coefficient of the interaction between polariton and reservoir and the condensation rate and intensity of pumping. Using these results, we discuss the effect of different parameters on shock waves composed of two shock waves, and find that the gain and loss will result in a sloping platform between two waves. In addition, we also consider the effect of the non-adiabatic approximation and the diffusion coefficient of the reservoir on the profiles of the shock waves. We find that the non-adiabatic approximation will result in some small oscillations on the uniform background, and the platform between two waves becomes flat; however, the diffusion effect of the reservoir will clear these small oscillations and tilt the platform. Our results may pave the way to control shock waves in an incoherent pumped exciton–polariton system.
Engineered photonic spin Hall effect of Gaussian beam in antisymmetric parity-time metamaterials
Authors: Liu 刘 Lu-Yao 露遥 , Feng 冯 Zhen-Xiao 振校 , Deng 邓 Dong-Mei 冬梅 , Wang 王 Guang-Hui 光辉
Published: April 2023

A model of the photonic spin Hall effect (PSHE) in antisymmetric parity-time (APT) metamaterials with incidence of Gaussian beams is proposed here. We derive the displacement expression of the PSHE in APT metamaterials based on the transport properties of Gaussian beams in positive and negative refractive index materials. Furthermore, detailed discussions are provided on the APT scattering matrix, eigenstate ratio, and response near exceptional points in the case of loss or gain. In contrast to the unidirectional non-reflection in parity-time (PT) symmetric systems, the transverse shift that arises from both sides of the APT structure is consistent. By effectively adjusting the parameters of APT materials, we achieve giant displacements of the transverse shift. Finally, we present a multi-layer APT structure consisting of alternating left-handed and right-handed materials. By increasing the number of layers, Bragg oscillations can be generated, leading to an increase in resonant peaks in transverse shift. This study presents a new approach to achieving giant transverse shifts in the APT structure. This lays a theoretical foundation for the fabrication of related nano-optical devices.
The Bar-Bulge Relation in Non-dwarf SB0 Galaxies in the Central Region of Coma Cluster
Authors: Poloji Nagamani , Hasan Priya , Hasan S. N.
Published: April 2023

In this paper we explore the formation of bars and present the bulge and bar properties and their correlations for a sample of lenticular barred (SB0) and lenticular unbarred (S0) galaxies in the central region of the Coma Cluster using HST/ACS data. In our sample, we identified bar features using the luminosity profile decomposition software GALFIT. We classified the bulges based on Sérsic index and Kormendy relation. We found that the average mass of the bulge in SB0 galaxies is 1.48 × 1010
M
☉ whereas the average mass of the bulge in S0 galaxies is 4.3 × 1010
M
☉. We observe that SB0 galaxies show lower bulge concentration, low mass and also smaller B/T values compared to S0 galaxies. Using the Kormendy relation, we found that among the lenticular barred galaxies, 82% have classical bulges and 18% have pseudo bulges. These classical bulges have low masses compared to the classical bulges of unbarred galaxies. S0, galaxies with massive classical bulges do not host bars. We also found that for all SB0s the bulge effective radius is less than the bar effective radius. SB0 galaxies with classical bulges suggest that the bar may have formed by mergers.
Flare Forecast Model Based on DS-SMOTE and SVM with Optimized Regular Term
Authors: Wan Jie , Fu Jun-Feng , Wen Ren-Qing , Han Ke , Yu Meng-Yao , E Peng
Published: April 2023

The research of flare forecast based on the machine learning algorithm is an important content of space science. In order to improve the reliability of the data-driven model and weaken the impact of imbalanced data set on its forecast performance, we proposes a resampling method suitable for flare forecasting and a Particle Swarm Optimization (PSO)-based Support Vector Machine (SVM) regular term optimization method. Considering the problem of intra-class imbalance and inter-class imbalance in flare samples, we adopt the density clustering method combined with the Synthetic Minority Over-sampling Technique (SMOTE) oversampling method, and performs the interpolation operation based on Euclidean distance on the basis of analyzing the clustering space in the minority class. At the same time, for the problem that the objective function used for strong classification in SVM cannot adapt to the sample noise, In this research, on the basis of adding regularization parameters, the PSO algorithm is used to optimize the hyperparameters, which can maximize the performance of the classifier. Finally, through a comprehensive comparison test, it is proved that the method designed can be well applied to the flare forecast problem, and the effectiveness of the method is proved.
Identity Formation and General and Cancer-specific Functioning in Adolescent and Emerging Adult Survivors of Childhood Cancer: A Longitudinal Study into Directionality of Effects
Authors: Vanderhaegen Janne , Prikken Sofie , Van Laere Elise , Lemiere Jurgen , Claes Laurence , Moons Philip , Uyttebroeck Anne , Jacobs Sandra , Luyckx Koen
Published: April 2023

Background

Adolescent and emerging adult survivors of childhood cancer generally adjust well psychologically similar to their peers. Nevertheless, some survivors are at greater risk for developing psychological and physical difficulties. To shed light on the psychosocial functioning of adolescent and emerging adult survivors of childhood cancer, personal identity formation and its interplay with general and cancer-specific functioning need to be investigated.

Purpose

To examine the longitudinal associations linking identity formation to general and cancer-specific functioning in adolescent and emerging adult childhood cancer survivors using three-wave data over a 2-year period.

Methods

Dutch-speaking survivors (at baseline: n = 125; 53% female; age range: 14–25 years) treated at the pediatric oncology department of the University Hospitals Leuven (Belgium), completed self-report questionnaires at three annual timepoints. Directionality of effects and correlated changes were examined using cross-lagged structural equation modeling.

Results

Regarding general functioning, bidirectional effects occurred. Life satisfaction positively predicted identity synthesis and both life satisfaction and good physical functioning negatively predicted identity confusion over time. Identity synthesis, in turn, positively predicted life satisfaction and identity confusion negatively predicted good physical functioning over time. Regarding cancer-specific functioning, mainly unidirectional effects occurred. Post-traumatic stress symptoms negatively predicted identity synthesis and positively predicted identity confusion over time, whereas the reverse pattern of associations was found for benefit finding. Several correlated changes were found linking identity formation and psychosocial functioning as well.

Conclusions

The present study uncovered clinically meaningful pathways linking identity formation to psychosocial functioning over time in adolescents and emerging adults who survived childhood cancer.
Effects of brood and group size on nestling provisioning and resource allocation in a communal bird
Authors: Savagian Amanda , Riehl Christina
Published: April 2023

Resource limitations, either due to environmental conditions or constraints on parental provisioning effort, can drive intense competition among offspring. In communal groups, resource availability may increase if parents receive assistance from other group members; however, if those caregivers also produce young, offspring demand may increase at the same time. It is possible, therefore, that the costs of intrabrood competition in large broods may outweigh the benefits of provisioning from additional caregivers. We tested the relationships between group size, brood size, and provisioning rates in the greater ani (Crotophaga major), a communally nesting cuckoo in which multiple breeding pairs and nonreproductive helpers cooperatively raise a shared brood. Crucially, brood and group size can vary independently in this species, allowing us to test changes in each variable separately. Using video footage of 2255 prey deliveries across 10 nests, we found that an increase in the number of adult caregivers within a group did not sufficiently offset a corresponding increase in the number of dependent young within a brood: prey availability per average nestling decreased with brood size, regardless of group size. In larger broods, last-hatched nestlings received significantly less prey than their broodmates, in part due to greater hatching asynchrony that exacerbated competitive asymmetries and facilitated inequality in food allocation. Our results indicate that last-hatched ani nestlings suffer a “double cost” in large broods: they must compete with more nestmates, and suffer disproportionately from asynchronous hatching. These costs may contribute to increased parent–offspring conflict and may constrain group size in communal breeders.
The anti-caste alter-network: equality labs and anti-caste activism in the US
Authors: Baishya Anirban Kapil , Mini Darshana Sreedhar , Soundararajan Thenmozhi
Published: April 2023

As a pan-South Asian phenomenon that marks certain groups and bodies as untouchable, caste-based discriminatory practices have also traveled with the South Asian diaspora. This article examines the case of anti-caste activism, especially in the context of its transnational potentials which have blossomed with the ubiquitous uptake of digital technology worldwide. We examine anti-caste activism in the US through the work of Equality Labs, an anti-caste civil rights organization that works with digital and non-digital activist strategies. Analyzing a range of material including surveys and reports, online chatter, and journalistic discourse we show how the organization’s work is part of a larger, transnational network of anti-caste activism—something we term the anti-caste alter-network.
Layer-specific stimulations of parvalbumin-positive cortical interneurons in mice entrain brain rhythms to different frequencies
Authors: David François , Borel Mélodie , Ayub Suleman , Ruther Patrick , Gentet Luc J
Published: April 2023

Neocortical interneurons provide inhibition responsible for organizing neuronal activity into brain oscillations that subserve cognitive functions such as memory, attention, or prediction. However, the interneuronal contribution to the entrainment of neocortical oscillations within and across different cortical layers was not described. Here, using layer-specific optogenetic stimulations with micro-Light-Emitting Diode arrays, directed toward parvalbumin-expressing (PV) interneurons in non-anesthetized awake mice, we found that supragranular layer stimulations of PV neurons were most efficient at entraining supragranular local field potential (LFP) oscillations at gamma frequencies (γ: 25–80 Hz), whereas infragranular layer stimulation of PV neurons better entrained the LFP at delta (δ: 2–5 Hz) and theta (θ: 6–10 Hz) frequencies. At the level of neuronal action potential activity, we observed that supragranular neurons better followed the imposed PV stimulation rhythm than their infragranular counterparts at most frequencies when the stimulation was delivered in their respective layer. Moreover, the neuronal entrainment evoked by local stimulation could propagate across layers, though with a lesser impact when the stimulation occurs in deep layers, suggesting a direction-specific laminar propagation. These results establish a layer-based framework for oscillations to entrain the primary somatosensory cortex in awake conditions.
Simultaneous Determination of Montelukast Sodium and Loratadine by Eco-Friendly Densitometry and Spectrophotometric Methods
Authors: Mahmoud Shimaa A , El-Kosasy Amira M , Fouad Fatma A
Published: April 2023

Recently, the aim of analytical community is to reduce the usage of hazardous chemicals; so eco-friendly, rapid, selective and cost-effective methods were developed for simultaneous determination of montelukast sodium (MKT) and loratadine (LRT). The first method was based on chromatographic separation performed on precoated silica gel 60 GF254 plates with ethyl acetate–ethanol 9: 1 (v/v) as the mobile phase. The developed plates were scanned and quantified at 260 nm. The method gives linear correlation over concentration ranges of 0.3–3.6 μg/spot and 0.2–4.0 μg/spot for MKT and LRT, respectively. It was also successfully applied to analysis of both drugs in their pharmaceutical preparation and human plasma. The other methods are UV-spectrophotometric methods based on smart spectra manipulating to zero order spectrum of each drug. These methods are named response correlation (RC), a-centering and ratio derivative methods. RC and a-centering methods were dependent on the presence of an isosbestic point between the overlapped spectra of both drugs. While ratio derivative method based on manipulation of the ratio spectra of both drugs. The two drugs obey Beer–Lambert law over the concentration ranges of 3.0–30.0 μg/mL in the three spectrophotometric methods. Moreover, the greenness of the developed methods is assessed using suitable analytical Eco-Scale and Green Analytical Procedure Index.
Ecofriendly Chromatographic Assay of Metformin Combinations; Content Uniformity Tests and Toxicity Profiling
Authors: Emam Aml A , Abdelaleem Eglal A , Magdy Fatma , Gouda Ahmed M , Abdallah Fatma F
Published: April 2023

Accurate, sensitive and green HPTLC chromatographic method was proposed for simultaneous determination of metformin, glipizide and sitagliptin in the presence of metformin potential toxic impurities melamine and cyanoguanidine. The separation was completed on silica gel HPTLC F254 plates using a mixture of ethyl acetate: methanol: ammonia: formic acid (7: 2: 0.2: 0.2, by volume) as a developing system with UV scanning for the developed bands at 235 nm. The Rf values for metformin, glipizide, sitagliptin, melamine and cyanoguanidine were 0.17, 0.84, 0.67, 0.47 and 0.75, respectively. Linear responses were observed in the ranges of 0.2–3, 0.07–1.5, 1.5–5, 0.8–4 and 0.4–2 μg/band with correlation coefficients of 0.9999, 0.9998, 0.9997, 0.9996 and 0.9998 for metformin, glipizide, sitagliptin, melamine and cyanoguanidine, respectively. The proposed method was validated as per ICH criteria with respect to linearity, accuracy, precision, specificity and robustness. The validated method was successfully applied for determination of the studied drugs in Janumet® and Engilor® tablets; also, the results were statistically compared to those obtained by the reported spectrophotometric method and no significant difference was found between them. This method permitted the accurate simultaneous determination of the studied drugs, indicating its ability to be used for routine quality control assays of these drugs.
Effects of ageing on aortic hemodynamics measured by 4D-flow MRI: a case series
Authors: Juffermans Joe F , Westenberg Jos J M , van den Boogaard Pieter J , Lamb Hildo J
Published: April 2023

Background

It has been demonstrated that the rate of aortic dilatation is influenced by alteration of aortic hemodynamics, such as normalized flow displacement (FDN) and wall shear stress (WSS). However, the effects of ageing on aortic hemodynamics have not yet been described.

Case summary

4D-Flow MRI derived aorta hemodynamics were derived in the ascending aorta of a patient with ascending aortic aneurysm (mean ± standard deviation: 46 ± 1 mm) and a healthy volunteer (aortic diameter 30 ± 1 mm) with long-term follow-up of ten and eight years, respectively. At all timepoints, compared to the healthy volunteer, the patient demonstrated higher magnitudes of FDN (7% ± 1% vs. 3% ± 1%) and WSS angle (36° ± 3° vs. 24° ± 6°), and lower WSS magnitude (565 ± 100 mPa vs. 910 ± 115 mPa), axial WSS (426 ± 71 mPa vs. 800 ± 108 mPa) and circumferential WSS (297 ± 64 mPa vs. 340 ± 85 mPa). The patient and healthy volunteer demonstrated different aortic dilatation rates (regression slope ± standard error: 0.2 ± 0.1 vs. 0.1 ± 0.2 mm per year) and trends in FDN (0.1% ± 0.1% vs. 0.1% ± 0.2% per year), WSS magnitude (22 ± 9 vs. 35 ± 13 mPa per year), axial WSS (19 ± 4 vs. 37 ± 7 mPa per year), circumferential WSS (9 ± 8 vs. 5 ± 15 mPa per year), and WSS angle (-0.5° ± 0.4° vs. -0.8° ± 1.0° per year).

Discussion

Aortic hemodynamic parameters are marginally affected by ageing and the aortic diameter in this case series. Since aortic hemodynamic parameters have been associated with aortic dilation by previous studies, the outcomes of the two subjects suggest that the aortic dilatation rate will remain constant while individuals are ageing and dilating.
Fulminant myocarditis in a young woman with mixed connective tissue disease: a case report
Authors: Hamana Tomoyo , Kawamori Hiroyuki , Satomi-Kobayashi Seimi , Yamamoto Yuzuru , Ikeda Yoshihiko , Hirata Ken-ichi
Published: April 2023

Background

Although cardiac involvement is relatively common in mixed connective tissue disease (MCTD), few reports on MCTD-associated fulminant myocarditis are available.

Case summary

A 22-year-old woman diagnosed with MCTD was admitted to our institution for cold-like symptoms and chest pain. Echocardiography revealed that the left ventricular ejection fraction (LVEF) had rapidly decreased from 50 to 20%. Because endomyocardial biopsy revealed no significant lymphocytic infiltration, immunosuppressant drugs were not started initially; however, steroid pulse therapy (methylprednisolone, one1000 mg/day) was initiated due to prolonged symptoms and unimproved haemodynamics. Despite strong immunosuppressant therapy, the LVEF did not improve, and severe mitral regurgitation appeared. Three days after steroid pulse therapy initiation, she experienced a sudden cardiac arrest; thus, venoarterial extracorporeal membrane oxygenation (VA-ECMO) and intra-aortic balloon pumping (IABP) were initiated. Subsequent immunosuppressant therapy was continued with prednisolone (100 mg/day) and intravenous cyclophosphamide (1000 mg). Six days after steroid therapy initiation, the LVEF improved to 40% and then recovered to near-normal levels. After successful weaning off of VA-ECMO and IABP, she was discharged. Thereafter, a detailed histopathological examination revealed multi-focal signs of ischaemic micro-circulatory injury and diffuse HLA-DR in the vascular endothelium, suggesting an autoimmune inflammatory response.

Discussion

We report a rare case of fulminant myocarditis in a patient with MCTD who recovered with immunosuppressive treatment. Despite the absence of significant lymphocytic infiltration findings on histopathological examination, patients with MCTD may experience a dramatic clinical course. Although it is unclear whether myocarditis is triggered by viral infections, certain autoimmune mechanisms may lead to its development.
A longitudinal study of facial asymmetry in a normal birth cohort up to 6 years of age and the predisposing factors
Authors: Launonen Anniina M , Vuollo Ville , Aarnivala Henri , Heikkinen Tuomo , Pirttiniemi Pertti , Valkama A Marita , Harila Virpi
Published: April 2023

Objectives

This prospective, population-based cohort study aimed to investigate the development of facial asymmetry up to 6 years of age using a three-dimensional (3D) soft tissue imaging method in a normal population. In addition, the study sought to identify potential predisposing factors to facial asymmetry.

Methods

A total of 102 newborns were enrolled in the study at birth. 3D stereophotogrammetric images of the head and face were analysed at the ages of 12 months (T1), 3 years (T2), and 6 years (T3). The surface-based analysis involved the calculation of the average distance (mm) and the symmetry percentage (%) between the original and mirrored surfaces. For landmark-based analysis, the distance of facial landmarks to the facial midline was examined.

Results

The final analysis included 70 (68.6%) subjects. Surface-based analysis showed a significant improvement of facial symmetry from T1 to T3 in all facial areas. Landmark-based analysis showed that upper facial landmarks were located, on average, slightly on the left and lower facial landmarks slightly on the right in relation to the facial midline (P < 0.001).

Limitations

The size of the study population was limited. Facial posture may affect the reliability of the results, especially in younger children.

Conclusion

Facial asymmetry is detectable in early childhood and tends to reduce with age in young children. The lower face deviates slightly to the right, and the upper face to the left in relation to the facial midline. Possible predisposing factors for facial asymmetry at the age of 6 years include deformational plagiocephaly, sleeping position, and previous facial asymmetry.
Prevention of white spot lesions with fluoride varnish during orthodontic treatment with fixed appliances: a systematic review
Authors: Sonesson Mikael , Twetman Svante
Published: April 2023

Background

Fluoride varnish (FV) is an established technology for primary and secondary caries prevention.

Objective

The aim of this review was to evaluate the preventive effect of FV on development of white spot lesions (WSL) when regularly applied during orthodontic treatment with fixed appliances.

Search methods

We searched PubMed, Scopus and Google Scholar up to October 2022 using predetermined keywords.

Selection criteria

We included randomized controlled trials of a duration of minimum 12 months and at least quarterly FV applications.

Data collection and analysis

Based on abstracts, we retrieved full-text papers, extracted key outcome data, and assessed risk of bias. Primary outcome was prevalence of WSLs on subject level after debonding. We conducted a narrative synthesis and pooled comparable outcome data in a random effects model.

Results

We included seven studies covering 666 patients and assessed four publications with low or moderate risk of bias and three with high. The prevalence of WSLs at debonding varied between 12 and 55%. All studies presented results in favour for the FV intervention, one reached statistical significance on subject level. Five studies provided data for a meta-analysis. The pooled risk ratio was 0.64 [95% CI: 0.42, 0.98], indicating a statistically significant preventive effect. Certainty of evidence was graded as very low after reducing for risk of bias, inconsistency and imprecision.

Limitations

We pooled data on subject level and did not consider lesion severity on tooth level.

Conclusions and implications

Even if the certainty of evidence was very low, it was shown that FV can prevent development of WSL when regularly applied during orthodontic treatment. Larger investigations reporting a core outcome set are required to increase the certainty of evidence.

Registration

PROSPERO database (CRD42022370062).
Consumer preferences for beef quality grades on imported and domestic beef
Authors: Gao Shijun , Grebitus Carola , DeLong Karen
Published: April 2023

The Chinese government has recently introduced an updated beef quality-grade system. We implemented a shelf-simulation choice experiment and estimated random parameter logit models with error components to analyse Chinese consumer willingness to pay for domestic and imported beef flank labelled with the new quality grades and other relevant beef labels. Results indicated that Chinese consumers were willing to pay more for Premium quality domestic beef compared to ungraded beef, while Regular quality beef was discounted by consumers, particularly for imported beef. The results suggest that foreign beef producers could compete more closely with domestic beef if it was labelled as Premium quality.
Evaluation of the short-term outcomes of robotic-assisted radical resection for perihilar cholangiocarcinoma: a propensity-scored matching analysis
Authors: Huang Xi-Tai , Xie Jin-Zhao , Cai Jian-Peng , Chen Wei , Chen Liu-Hua , Liang Li-Jian , Yin Xiao-Yu
Published: April 2023

Background

The application of robotic-assisted radical resection in perihilar cholangiocarcinoma (pCCA) remains poorly defined. This study aimed to evaluate the safety and efficacy of robotic-assisted radical resection for pCCA in our institute.

Methods

Between July 2017 and July 2022, pCCA patients undergoing robotic-assisted and open radical resection at First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were included. The short-term outcomes were compared by using propensity-scored matching (PSM) analysis.

Results

Eighty-six pCCA patients were enrolled. After PSM at a ratio of 1:2, 10 and 20 patients were assigned to the robotic-assisted and open groups, respectively. There were no significant disparities in the clinicopathological features between the two groups. The robotic-assisted group had significantly longer operation time (median: 548 vs 353 min, P = 0.004) and larger total number of lymph nodes examined (median: 11 vs 5, P = 0.010) than the open group. The robotic-assisted group tended to have a lower intraoperative blood loss (median: 125 vs 350 mL, P = 0.067), blood transfusion rates (30.0% vs 70.0%, P = 0.056), and post-operative overall morbidities (30.0% vs 70.0%, P = 0.056) than the open group, even though the differences were not statistically significant. There were no significant differences in the negative resection margin, post-operative major morbidities, or post-operative length-of-stay between the robotic-assisted and open groups (all P > 0.05).

Conclusions

Robotic-assisted radical resection of pCCA may get a larger total number of lymph nodes examined than open surgery. Provided robotic-assisted surgery may be a feasible and safe technique for selected pCCA patients.
Ultrasound-guided fine-needle aspiration/biopsy-based pancreatic organoids establishment: an alternative model for basic and preclinical research
Authors: Chen Sheng , Wang Min , Liu Lei , Wang Guodong , Wang Lei , Zhong Changqing , Gao Chao , Wu Wei , Li Lianyong
Published: April 2023

Pancreatic ductal adenocarcinoma (PDAC), as one of the malignant cancers with the worst prognosis, is becoming the most urgent clinical problem. Due to the lack of early diagnosis and curable therapeutic methods, it is critical to exploit proper models that can capture the overall attributes of the primary tumor. Recently, organoid technology has emerged and flourished as a powerful tool to enable long-term culture of pancreatic tissues, including PDAC. As accumulating studies suggest, organoids can retain morphological, genetic, and behavioral traits, and have tremendous value in predicting the therapeutic response to conventional chemotherapy drugs or newfangled agents. Herein, this review comprehensively summarizes the tissue source including human fetal and adult pancreatic tissue to generate a pancreatic organoid as well as current organoids cultivate system. As PDAC organoids can be established from a small number of samples derived from endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB), we also review the literature to date on EUS-FNA/FNB-based organoid constitution and its implementation in inquiring tumor behavior and evaluating therapeutic responses. By enabling the alignment of basic and clinical research platforms, the application of organoids would open up new avenues for drug discovery and maximally benefit translational medicine in the near future.
A gene-level test for directional selection on gene expression
Authors: Colbran Laura L , Ramos-Almodovar Fabian C , Mathieson Iain
Published: April 2023

Most variants identified in human genome-wide association studies and scans for selection are noncoding. Interpretation of their effects and the way in which they contribute to phenotypic variation and adaptation in human populations is therefore limited by our understanding of gene regulation and the difficulty of confidently linking noncoding variants to genes. To overcome this, we developed a gene-wise test for population-specific selection based on combinations of regulatory variants. Specifically, we use the QX statistic to test for polygenic selection on cis-regulatory variants based on whether the variance across populations in the predicted expression of a particular gene is higher than expected under neutrality. We then applied this approach to human data, testing for selection on 17,388 protein-coding genes in 26 populations from the Thousand Genomes Project. We identified 45 genes with significant evidence (FDR<0.1) for selection, including FADS1, KHK, SULT1A2, ITGAM, and several genes in the HLA region. We further confirm that these signals correspond to plausible population-level differences in predicted expression. While the small number of significant genes (0.2%) is consistent with most cis-regulatory variation evolving under genetic drift or stabilizing selection, it remains possible that there are effects not captured in this study. Our gene-level QX score is independent of standard genomic tests for selection, and may therefore be useful in combination with traditional selection scans to specifically identify selection on regulatory variation. Overall, our results demonstrate the utility of combining population-level genomic data with functional data to understand the evolution of gene expression.
Genetic and genomic analyses of Drosophila melanogaster models of chromatin modification disorders
Authors: MacPherson Rebecca A , Shankar Vijay , Anholt Robert R H , Mackay Trudy F C
Published: April 2023

Switch/sucrose nonfermentable (SWI/SNF)-related intellectual disability disorders (SSRIDDs) and Cornelia de Lange syndrome are rare syndromic neurodevelopmental disorders with overlapping clinical phenotypes. SSRIDDs are associated with the BAF (Brahma-Related Gene-1 associated factor) complex, whereas CdLS is a disorder of chromatin modification associated with the cohesin complex. Here, we used RNA interference in Drosophila melanogaster to reduce the expression of six genes (brm, osa, Snr1, SMC1, SMC3, vtd) orthologous to human genes associated with SSRIDDs and CdLS. These fly models exhibit changes in sleep, activity, startle behavior (a proxy for sensorimotor integration), and brain morphology. Whole genome RNA sequencing identified 9,657 differentially expressed genes (FDR < 0.05), 156 of which are differentially expressed in both sexes in SSRIDD- and CdLS-specific analyses, including Bap60, which is orthologous to SMARCD1, an SSRIDD-associated BAF component. k-means clustering reveals genes co-regulated within and across SSRIDD and CdLS fly models. RNAi-mediated reduction of expression of six genes co-regulated with focal genes brm, osa, and/or Snr1 recapitulated changes in the behavior of the focal genes. Based on the assumption that fundamental biological processes are evolutionarily conserved, Drosophila models can be used to understand underlying molecular effects of variants in chromatin-modification pathways and may aid in the discovery of drugs that ameliorate deleterious phenotypic effects.
European Patent Enforcement and the UPC: Status Quo and Perspectives ‒ Conference in Luxembourg, 24 and 25 November 2022
Authors: Kapischke Justus
Published: April 2023

The Unified Patent Court (the UPC) will soon open its doors to litigants and harmonise what used to be diverse domestic concepts of patent law. Its jurisprudence will undoubtedly be influenced by the various national practices. To shed light on what the future may look like, practitioners and academics met in Luxembourg to discuss the status quo and perspectives of European patent enforcement. The conference featured panels on important topics in patent enforcement followed by in-depth discussions between the panellists and the audience.
QTL detection and candidate gene analysis of grape white rot resistance by interspecific grape (Vitis vinifera L. × Vitis davidii Foex.) crossing
Authors: Li Peng , Tan Xibei , Liu Ruitao , Rahman Faiz Ur , Jiang Jianfu , Sun Lei , Fan Xiucai , Liu Jihong , Liu Chonghuai , Zhang Ying
Published: April 2023

Grape white rot, a devastating disease of grapevines caused by Coniella diplodiella (Speg.) Sacc., leads to significant yield losses in grape. Breeding grape cultivars resistant to white rot is essential to reduce the regular use of chemical treatments. In recent years, Chinese grape species have gained more attention for grape breeding due to their high tolerance to various biotic and abiotic factors along with changing climatic conditions. In this study, we employed whole-genome resequencing (WGR) to genotype the parents of ‘Manicure Finger’ (Vitis vinifera, female) and ‘0940’ (Vitis davidii, male), along with 101 F1 mapping population individuals, thereby constructing a linkage genetic map. The linkage map contained 9337 single-nucleotide polymorphism (SNP) markers with an average marker distance of 0.3 cM. After 3 years of phenotypic evaluation of the progeny for white rot resistance, we confirmed one stable quantitative trait locus (QTL) for white rot resistance on chromosome 3, explaining up to 17.9% of the phenotypic variation. For this locus, we used RNA-seq to detect candidate gene expression and identified PR1 as a candidate gene involved in white rot resistance. Finally, we demonstrated that recombinant PR1 protein could inhibit the growth of C. diplodiella and that overexpression of PR1 in susceptible V. vinifera increased grape resistance to the pathogen.
On Composition of Torsors
Authors: Florence Mathieu , Izquierdo Diego , Lucchini Arteche Giancarlo
Published: April 2023

Let $K$ be a field, let $X$ be a connected smooth $K$-scheme, and let $G,H$ be two smooth connected $K$-group schemes. Given $Y \to X$ a $G$-torsor and $Z \to Y$ an $H$-torsor, we study whether one can find an extension $E$ of $G$ by $H$ so that the composite $Z \to X$ is an $E$-torsor. We give both positive and negative results, depending on the nature of the groups $G$ and $H$.
Leader Turnover, Regime Type, and Growth Volatility
Authors: Doces John A , Lupton Danielle L
Published: April 2023

How do leaders influence national-level economic outcomes? We address this question by considering how leadership turnover influences volatility in economic growth. In doing so, we theorize that leaders from mixed regimes will reduce economic volatility due to domestic political incentives to create stable economic outcomes. Furthermore, we decompose the influence of leaders in non-democratic regimes and argue that leaders in party-based authoritarian regimes will also reduce economic volatility. To test our hypotheses, we focus on the effect of leadership turnover due to natural leader death to control for issues of endogeneity. We find that leaders in mixed regimes reduce volatility more than leaders in autocratic and democratic regimes and that leaders in party-based authoritarian regimes reduce volatility more than those in military or monarchy-based regimes. We conclude by explaining the implications of our findings for the study of leaders in international politics and their impact on economic growth and development.
Exogenous fibrolytic enzymes promoted energy and nitrogen utilization and decreased CH4 emission per unit dry matter intake of tan sheep grazed a typical steppe by enhancing nutrient digestibility on China loess plateau
Authors: Shi Hairen , Guo Pei , Zhou Jieyan , Wang Zhen , He Meiyue , Shi Liyuan , Huang Xiaojuan , Guo Penghui , Guo Zhaoxia , Zhang Yuwen , Hou Fujiang
Published: April 2023

Exogenous fibrolytic enzyme (EFE) products in ruminant nutrition may be an important alternative to meet the increased demands for animal products in the future with reduced environmental impacts. This study aimed to evaluate the dose–response of EFE supplementation on the nutrient digestibility, nitrogen and energy utilization, and methane (CH4) emissions of Tan sheep grazed in summer and winter. A total of 20 Tan wether sheep with an initial body weight of 23.17 ± 0.24 kg were used in a randomized complete block design and categorized into two groups. Animals fed orally with 1 g of EFE (10,000 U/g) mixed with 30 mL of water using a drencher constituted the EFE group. For experimental accuracy, the control (CON) group was orally administered with 30 mL of normal saline daily before grazing. The following results were obtained: EFE in the diet increased dry matter intake (DMI) (P < 0.05), average daily gain (ADG) (P < 0.05), and digestibility (P < 0.05) compared with CON in summer and winter. DMI increased but ADG and digestibility decreased in winter compared with those in summer. Sheep fed with the EFE diet increased the concentrations of rumen ammonia nitrogen (P < 0.05) and total volatile fatty acids (P > 0.05), but reduced pH (P > 0.05), compared with CON in summer and winter. EFE increased nitrogen (N) intake, digestible N, retained N, and retained N/digestible N (P < 0.05) but reduced fecal N/N intake, urinary N/N intake, and excretion N/N intake in summer and winter (P < 0.05), compared with CON. Retained N/N intake was reduced and excretion N/N intake increased in winter relative to those in summer. In winter, gross energy (GE), manure E/GE, CH4 emissions, CH4/DMI, and CH4/GE increased but digestion energy and metabolic energy decreased compared with those in summer. Sheep fed with the EFE diet had a greater GE intake than those fed with the CON diet (P < 0.05) but had lesser CH4/DMI and CH4E/GE (P < 0.05) than those fed with the CON diet in both summer and winter. In conclusion, EFE supplementation increased DMI, apparent digestibility, and N deposition rate. These effects were beneficial for animal production. The CH4 emission per unit DMI of grazing Tan sheep was lesser and conducive for augmenting the environmental benefits.
Apoha for Beginners
Authors: Taber John
Published: April 2023

This study proposes, as an entryway into the complex debate about ‘exclusion’ (apoha) in Indian philosophy, that the main idea underlying Dignāga’s theory of apoha is that the relation between a word and its meaning—all the individuals that it can refer to—is established more by noticing what it is not used for than what it is used for. The Mīmāṃsā philosopher Kumārila raises a number of objections based on his construal of an apoha as a ‘non-existence’ (abhāva), but he also zeroes in on the problem of how, if apohas are known only by language and inference, they could ever be known at all. In this connection, he criticises Dignāga’s idea that the meaning of a word is learned by noticing that it is not used for things other than its usual referent. It seems, then, that much of what Dharmakīrti is doing in his discussion of apoha is to provide, in response to Kumārila, an account of how perceptual experiences of distinct particulars that have the same effects naturally give rise to an ascertainment of their exclusion from other entities, which can then be assigned as the meaning of an expression.