bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel dominant and recessive variants in human ROBO1 cause distinct neurodevelopmental defects through different mechanisms
Authors: Huang Yan , Ma Mengqi , Mao Xiao , Pehlivan Davut , Kanca Oguz , Un-Candan Feride , Shu Li , Akay Gulsen , Mitani Tadahiro , Lu Shenzhao , Candan Sukru , Wang Hua , Xiao Bo , Lupski James R , Bellen Hugo J 
Published: March 2022

Abstract
The Roundabout (Robo) receptors, located on growth cones of neurons, induce axon repulsion in response to the extracellular ligand Slit. The Robo family of proteins controls midline crossing of commissural neurons during development in flies. Mono- and bi-allelic variants in human ROBO1 (HGNC: 10249) have been associated with incomplete penetrance and variable expressivity for a breath of phenotypes, including neurodevelopmental defects such as strabismus, pituitary defects, intellectual impairment, as well as defects in heart and kidney. Here, we report two novel ROBO1 variants associated with very distinct phenotypes. A homozygous missense p.S1522L variant in three affected siblings with nystagmus; and a monoallelic de novo p.D422G variant in a proband who presented with early-onset epileptic encephalopathy. We modeled these variants in Drosophila and first generated a null allele by inserting a CRIMIC T2A-GAL4 in an intron. Flies that lack robo1 exhibit reduced viability but have very severe midline crossing defects in the central nervous system. The fly wild-type cDNA driven by T2A-Gal4 partially rescues both defects. Overexpression of the human reference ROBO1 with T2A-GAL4 is toxic and reduces viability, whereas the recessive p.S1522L variant is less toxic, suggesting that it is a partial loss-of-function allele. In contrast, the dominant variant in fly robo1 (p.D413G) affects protein localization, impairs axonal guidance activity and induces mild phototransduction defects, suggesting that it is a neomorphic allele. In summary, our studies expand the phenotypic spectrum associated with ROBO1 variant alleles.
Device-measured sedentary time in Norwegian children and adolescents in the era of ubiquitous internet access: secular changes between 2005, 2011 and 2018
Authors: Dalene Knut Eirik , Kolle Elin , Steene-Johannessen Jostein , Hansen Bjørge H , Ekelund Ulf , Grydeland May , Anderssen Sigmund Alfred , Tarp Jakob 
Published: March 2022

Abstract

Background
Access to screen-based media has been revolutionized during the past two decades. How this has affected sedentary time (ST) accumulation in children is poorly understood.

Methods
This study, based on the Physical Activity among Norwegian Children Study (PANCS), uses accelerometer data from population-based samples of 9- and 15-year-olds, collected in 2005 (n = 1722), 2011 (n = 1587) and 2018 (n = 1859). Secular changes between surveys were analysed using random-effects linear regression models adjusted for survey-specific factors. Data on ST were collected using hip-worn ActiGraphs and ST was defined using a threshold equivalent to &lt;100 counts/min. Sedentary bouts were grouped by duration: &lt;1, 1–5, 5–15, 15–30 and ≥30 min.

Results
Between 2005 and 2018, ST increased by 29 min/day in 9-year-old boys (95% CI: 19, 39; P &lt;0.001), by 21 min/day in 15-year-old boys (95% CI: 8, 34; P = 0.002) and by 22 min/day in 15-year-old girls (95% CI: 10, 35; P &lt;0.001), but not in 9-year-old girls at 6 min/day (95% CI: -3, 16; P = 0.191). All age-sex groups accumulated less ST in bouts lasting &lt;5 min and more ST in longer bouts, particularly in 5–15-min bouts. Adolescent girls also increased ST accumulation in 15–30-min and ≥30-min bouts. Changes were largely mirrored before, during and after school on weekdays and during weekend days.

Conclusions
Coinciding with the introduction of smartphones, tablets and near-universal internet access, total daily ST and ST accumulated in prolonged sedentary bouts increased between 2005 and 2018 in children and adolescents.
Measuring Religious Non-Affiliation in China: A Comparison of Major National Surveys in China
Authors: Zhang Chan , Brenner Philip S , He Lirui 
Published: March 2022

Abstract
Measuring the rate of religious non-affiliation is a difficult task in China, one of the least religious countries in the world, and elsewhere. This study evaluates the trend of religious non-affiliation in China using 22 surveys spanning three decades. We found that two surveys asking beliefs in a mix of gods and religions yielded dramatically lower estimates of non-affiliation compared to the others that measured affiliation explicitly. Among the latter, using a filter question (a yes/no question for religious affiliation) increased the reports of non-affiliation but allowing multiple choices and putting “no religion” toward the end of the lists of response options moderately decreased the reports of non-affiliation. After accounting for question design and demographic differences across the surveys, the decline in religious non-affiliation is reduced and becomes not significant during more recent years.
On the Degree of Curves with Prescribed Multiplicities and Bounded Negativity
Authors: Galindo Carlos , Monserrat Francisco , Moreno-Ávila Carlos-Jesús , Pérez-Callejo Elvira 
Published: March 2022

Abstract
We provide a lower bound on the degree of curves of the projective plane $\mathbb {P}^2$ passing through the centers of a divisorial valuation $\nu $ of $\mathbb {P}^2$ with prescribed multiplicities, and an upper bound for the Seshadri-type constant of $\nu $, $\hat {\mu }(\nu )$, constant that is crucial in the Nagata-type valuative conjecture. We also give some results related to the bounded negativity conjecture concerning those rational surfaces having the projective plane as a relatively minimal model.
Effectiveness of Pneumococcal Conjugate Vaccination Against Virus-Associated Lower Respiratory Tract Infection Among Adults: A Case-Control Study
Authors: Lewnard Joseph A , Bruxvoort Katia J , Hong Vennis X , Grant Lindsay R , Jódar Luis , Cané Alejandro , Gessner Bradford D , Tartof Sara Y 
Published: March 2022

Abstract

Background
Interactions of Streptococcus pneumoniae with viruses feature in the pathogenesis of numerous respiratory illnesses.

Methods
We undertook a case-control study among adults at Kaiser Permanente Southern California between 2015 and 2019. Case patients had diagnoses of lower respiratory tract infection (LRTI; including pneumonia or nonpneumonia LRTI diagnoses), with viral infections detected by multiplex polymerase chain reaction testing. Controls without LRTI diagnoses were matched to case patients by demographic and clinical attributes. We measured vaccine effectiveness (VE) for 13-valent (PCV13) against virus-associated LRTI by determining the adjusted odds ratio for PCV13 receipt, comparing case patients and controls.

Results
Primary analyses included 13 856 case patients with virus-associated LRTI and 227 887 matched controls. Receipt of PCV13 was associated with a VE of 24.9% (95% confidence interval, 18.4%–30.9%) against virus-associated pneumonia and 21.5% (10.9%–30.9%) against other (nonpneumonia) virus-associated LRTIs. We estimated VEs of 26.8% (95% confidence interval, 19.9%–33.1%) and 18.6% (9.3%–27.0%) against all virus-associated LRTI episodes diagnosed in inpatient and outpatient settings, respectively. We identified statistically significant protection against LRTI episodes associated with influenza A and B viruses, endemic human coronaviruses, parainfluenza viruses, human metapneumovirus, and enteroviruses but not respiratory syncytial virus or adenoviruses.

Conclusions
Among adults, PCV13 conferred moderate protection against virus-associated LRTI. The impacts of pneumococcal conjugate vaccines may be mediated, in part, by effects on polymicrobial interactions between pneumococci and respiratory viruses.
Differential Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Profiles After Allergic Reactions to Messenger RNA Coronavirus Disease 2019 Vaccine
Authors: Maron Jenny S , Conroy Michelle , Naranbai Vivek , Samarakoon Upeka , Motazedi Tina , Farmer Jocelyn R , Freeman Esther , Banerji Aleena , Bartsch Yannic C , Gregory David J , Poznansky Mark C , Alter Galit , Blumenthal Kimberly G 
Published: March 2022

Abstract
Allergic symptoms after messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines occur in up to 2% of recipients. Compared to nonallergic controls (n = 18), individuals with immediate allergic reactions to mRNA COVID-19 vaccines (n = 8) mounted lower immunoglobulin G1 (IgG1) to multiple antigenic targets in severe acute respiratory syndrome coronavirus 2 spike following vaccination, with significantly lower IgG1 to full-length spike (P = .04). Individuals with immediate allergic reactions to mRNA COVID-19 vaccines bound Fcγ receptors similarly to nonallergic controls. Although there was a trend toward an overall reduction in opsonophagocytic function in individuals with immediate allergic reactions compared to nonallergic controls, allergic patients produced functional antibodies exhibiting a high ratio of opsonophagocytic function to IgG1 titer.
A qualitative study exploring patient shadowing as a method to improve patient-centred care: 10 principles for a new gold standard
Authors: Goodrich Joanna , Ridge Damien , Cartwright Tina 
Published: March 2022

Abstract

Background
In recent years, there has been an increased emphasis on patient experience as a dimension of quality in healthcare and subsequently a drive to understand care from the patient’s perspective. Patient shadowing is an approach that has been used in service improvement projects, but its potential as a quality improvement (QI) method has not been studied in practical and replicable detail.

Objective
This new research aimed to produce clear guidance on patient shadowing for future Quality Improvement projects.

Methods
Qualitative interviews were conducted with 20 clinical and non-clinical participants of a national QI programme in UK, which focused on improving the experience of patients at the end of life. All participants had shadowed patients. Data were analysed using a thematic analysis.

Results
There were two broad themes: (i) The process of shadowing: how participants went about shadowing, adopting different approaches and making judgements about the care they observed and any challenges they had encountered. (ii) The impact of shadowing: on the engagement and motivation of those who shadowed and in terms of service changes to benefit patients and their families.

Conclusion
The findings led to a new set of ‘gold standard’ principles to benefit both staff and patients where shadowing is used as a QI method. These, together with new guidance, will ensure that shadowing is conducted as a team exercise, that all those involved are more robustly prepared and supported and that its purpose as a method to improve patient experience will be better understood.
vp1524, a Vibrio parahaemolyticus NAD
+-dependent deacetylase, regulates host response during infection by induction of host histone deacetylation
Authors: Mishra Pragyan , Beura Shibangini , Sikder Sweta , Dhal Ajit Kumar , Vasudevan Madavan , Roy Manjima , Rakshit Joydeep , Budhwar Roli , Kundu Tapas K , Modak Rahul 
Published: March 2022

Abstract
Gram-negative intracellular pathogen Vibrio parahaemolyticus manifests its infection through a series of effector proteins released into the host via the type III secretion system. Most of these effector proteins alter signalling pathways of the host to facilitate survival and proliferation of bacteria inside host cells. Here, we report V. parahaemolyticus (serotype O3:K6) infection-induced histone deacetylation in host intestinal epithelial cells, particularly deacetylation of H3K9, H3K56, H3K18 and H4K16 residues. We found a putative NAD+-dependent deacetylase, vp1524 (vpCobB) of V. parahaemolyticus, was overexpressed during infection. Biochemical assays revealed that Vp1524 is a functional NAD+-dependent Sir2 family deacetylase in vitro, which was capable of deacetylating acetylated histones. Furthermore, we observed that vp1524 is expressed and localized to the nuclear periphery of the host cells during infection. Consequently, Vp1524 translocated to nuclear compartments of transfected cells, deacetylated histones, specifically causing deacetylation of those residues (K56, K16, K18) associated with V. parahaemolyticus infection. This infection induced deacetylation resulted in transcriptional repression of several host genes involved in epigenetic regulation, immune response, autophagy etc. Thus, our study shows that a V. parahaemolyticus lysine deacetylase Vp1524 is secreted inside the host cells during infection, modulating host gene expression through histone deacetylation.
Stereotactic ablative radiotherapy for pulmonary oligometastases from primary hepatocellular carcinoma: a multicenter and retrospective analysis (KROG 17-08)
Authors: Jo In Young , Park Hee Chul , Kim Eun Seog , Yeo Seung-Gu , Kim Myungsoo , Seong Jinsil , Kim Jun Won , Kim Tae Hyun , Yoon Won Sup , Jeong Bae Kwon , Kim Sung Hwan , Lee Jong Hoon 
Published: March 2022

Abstract

Objective
Hypofractionated radiotherapy has recently been applied to treat pulmonary metastases of hepatocellular carcinoma. However, there is no definite evidence on its safety and efficacy. We evaluate the clinical outcomes of hypofractionated radiotherapy for oligo pulmonary metastases of hepatocellular carcinoma in the multicenter and retrospective study.

Methods
From March 2011 to February 2018, 58 patients with fewer than five pulmonary metastases of hepatocellular carcinoma who underwent hypofractionated radiotherapy in nine tertiary university hospitals were analyzed retrospectively. The primary endpoint was the local control rate. The secondary endpoints were overall survival, progression-free survival, prognostic factors affecting the treatment outcomes and treatment-related side effects.

Results
The local tumor response rate including complete and partial response was 77.6% at 3 months after hypofractionated radiotherapy. The median survival and progression-free survival times were 20.9 and 5.3 months, respectively. The 1-year overall survival and progression-free survival rates were 65.5 and 22.4%, respectively. The good treatment response after hypofractionated radiotherapy (P = 0.001), the absence of intrahepatic tumor (P = 0.004) and Child-Pugh class A (P = 0.010) were revealed as significant prognostic factors for overall survival in the multivariate analysis. A progression-free interval of &lt;6 months (P = 0.009) was a negative prognostic factor for overall survival in the multivariate analysis. Of 58 patients, five (8.6%) had grade 2 or higher radiation pneumonitis after hypofractionated radiotherapy.

Conclusions
The favorable local control rate and acceptable toxicity indicate the clinical usefulness of hypofractionated radiotherapy for hepatocellular carcinoma patients who have less than five pulmonary metastases.
Application of the Principle of Unity in the Legal Settlement of Sovereignty Disputes over Islands and Other Maritime Features
Authors: Kong Lingjie , Liu Congcong 
Published: March 2022

Abstract
The legal principle of ‘unity’ has been frequently invoked by States to claim sovereignty of islands and other insular features. It has been used by the adjudicators in diverse ways and with differing results. With a view to clarifying the legal paradigm of the principle of ‘unity’, this article undertakes an analysis of the relevant jurisprudence in this field. This leads to the identification of three typologies of ‘unity’ claims—‘dependency’, ‘natural unity’ and ‘collective approach’. Each of these is examined in further detail, with some key findings and observations. Importantly, the principle of unity can never be the root of title to contested territories where existing titles can be established. Instead, the unity principle operates in specific ways, with a series of conditions: absence of established title, presumed existence of identical title and broad agreement between the parties. The article concludes by observing the need for continued research on this topic.
Galactic chemical evolution of the solar neighbourhood, solar twins, and exoplanet indicators
Authors: Cowley Charles R , Yüce Kutluay 
Published: March 2022

ABSTRACT
Galactic chemical evolution (GCE), solar analogues or twins, and peculiarities of the solar composition with respect to the twins are inextricably related. We examine GCE parameters from the literature and present newly derived values using a quadratic fit that gives zero for a Solar age (i.e. 4.6 Gyr). We show how the GCE parameters may be used not only to ‘correct’ abundances to the solar age, but to predict average relative elemental abundances as a function of age. We address the question of whether the solar abundances are depleted in refractories and enhanced in volatiles and find that the answer is sensitive to the selection of a representative standard. The best quality data sets do not support the notion that the Sun is depleted in refractories or enhanced in volatiles. A simple model allows us to estimate the amount of refractory-rich material missing from the Sun or alternately added to the average solar twin. The model gives between zero and 1.4 earth masses.
Local variations of the stellar velocity ellipsoid – II. The effect of the bar in the inner regions of Auriga galaxies
Authors: Walo-Martín Daniel , Pinna Francesca , Grand Robert J J , Pérez Isabel , Falcón-Barroso Jesús , Fragkoudi Francesca , Martig Marie 
Published: March 2022

ABSTRACT
Theoretical works have shown that off-plane motions of bars can heat stars in the vertical direction during buckling but is not clear how do they affect the rest of components of the stellar velocity ellipsoid (SVE). We study the 2D spatial distribution of the vertical, σz, azimuthal, σϕ, and radial, σr velocity dispersions in the inner regions of Auriga galaxies, a set of high-resolution magneto-hydrodynamical cosmological zoom-in simulations, to unveil the influence of the bar on the stellar kinematics. σz and σϕ maps exhibit non-axisymmetric features that closely match the bar light distribution with low-σ regions along the bar major axis and high values in the perpendicular direction. On the other hand, σr velocity dispersion maps present more axisymmetric distributions. We show that isophotal profile differences best capture the impact of the bar on the three SVE components providing strong correlations with bar morphology proxies although there is no relation with individual σ. Time evolution analysis shows that these differences are a consequence of the bar formation and that they tightly coevolve with the strength of the bar. We discuss the presence of different behaviours of σz and its connection with observations. This work helps us understand the intrinsic σ distribution and motivates the use of isophotal profiles as a mean to quantify the effect of bars.
Extracting photometric redshift from galaxy flux and image data using neural networks in the CSST survey
Authors: Zhou Xingchen , Gong Yan , Meng Xian-Min , Cao Ye , Chen Xuelei , Chen Zhu , Du Wei , Fu Liping , Luo Zhijian 
Published: March 2022

ABSTRACT
The accuracy of galaxy photometric redshift (photo-z) can significantly affect the analysis of weak gravitational lensing measurements, especially for future high-precision surveys. In this work, we try to extract photo-z information from both galaxy flux and image data expected to be obtained by China Space Station Telescope (CSST) using neural networks. We generate mock galaxy images based on the observational images from the Advanced Camera for Surveys of Hubble Space Telescope (HST-ACS) and COSMOS catalogues, considering the CSST instrumental effects. Galaxy flux data are then measured directly from these images by aperture photometry. The multilayer perceptron (MLP) and convolutional neural network (CNN) are constructed to predict photo-z from fluxes and images, respectively. We also propose to use an efficient hybrid network, which combines the MLP and CNN, by employing the transfer learning techniques to investigate the improvement of the result with both flux and image data included. We find that the photo-z accuracy and outlier fraction can achieve σNMAD = 0.023 and $\eta = 1.43{{\ \rm per\ cent}}$ for the MLP using flux data only, and σNMAD = 0.025 and $\eta = 1.21{{\ \rm per\ cent}}$ for the CNN using image data only. The result can be further improved in high efficiency as σNMAD = 0.020 and $\eta = 0.90{{\ \rm per\ cent}}$ for the hybrid transfer network. These approaches result in similar galaxy median and mean redshifts 0.8 and 0.9, respectively, for the redshift range from 0 to 4. This indicates that our networks can effectively and properly extract photo-z information from the CSST galaxy flux and image data.
The satchel pipeline: a general tool for data classified through citizen science
Authors: Safron E J , Boyajian T S , Eisner N 
Published: March 2022

ABSTRACT
Citizen science is a powerful analysis tool, capable of processing large amounts of data in a very short time. To bridge the gap between classification data products from web-based citizen science platforms to statistically robust signal significance scores, we present the Search Algorithm for Transits in the Citizen science Hunt for Exoplanets in Light curves (satchel) pipeline. This open source, customizable pipeline was constructed to identify and assign significance estimates to one-dimensional features marked by volunteers. We describe the functional capabilities of the satchel pipeline through application to features in photometric time-series data from the Kepler Space Telescope, classified by volunteers as part of the Planet Hunters citizen science project hosted on the Zooniverse platform. We evaluate the satchel pipeline’s overall performance based on recovery of known signals (both simulations and signals corresponding to official Kepler Objects of Interest) and relative contamination by spurious features. We find that, for a range of pipeline hyperparameters and with a reasonable score cutoff, satchel is able to recover volunteer identifications of over 98 per cent of signals from simulations corresponding to exoplanets &gt;2 R⊕ in radius and about 85 per cent of signals corresponding to the same size range of KOIs. satchel is transparently adaptable to other citizen science classification data sets and available on GitHub.
Production efficiencies of sound waves in the intracluster medium driven by AGN jets
Authors: Wang Shiang-Chih , Yang H-Y Karen 
Published: March 2022

ABSTRACT
Feedback from active galactic nuclei (AGNs) is believed to be the most promising solution to the cooling flow problem in cool-core clusters. Dissipation of sound waves is considered as one of the possible heating mechanisms; however, its relative contribution to heating remains unclear. To estimate the energy budget for heating, we perform 3D hydrodynamic simulations of AGN jet injections in a Perseus-like cluster and quantify the amount of energy stored in the forms of weak shocks and waves. We find that, for a single jet injection with typical parameters in cool-core clusters, ${\sim}9{{\ \rm per\ cent}}$ of the total jet energy is stored in compressional waves (including both shocks and waves). However, due to the destructive effects among randomly phased waves as well as the dissipation of shock energies, in our simulations including self-regulated AGN feedback, no more than $3{{\ \rm per\ cent}}$ of the total injected energy goes into compressional waves. We further separate the energy contribution from shocks and waves and find that, for a single outburst, the shocks can only contribute to ${\sim}20{-}30{{\ \rm per\ cent}}$ of the total compressional energy in the inner radii and quickly dissipate away. In the self-regulated case where shocks are repeatedly generated, shocks completely dominate over sound waves in the inner region and can still provide ${\sim}40{-}50{{\ \rm per\ cent}}$ of the total compressional energy at outer radii. Our results suggest that the production of sound waves is not as efficient as what was previously found, and thus sound wave dissipation may be a subdominant source of heating in cool-core clusters.