bluuebunny/crossref_metadata_2025 huggingface dataset:
Between Presentation and Hearing
Authors: French Derek
Published: October 2021

The chapter discusses the various processes between presentation and hearing of a winding-up petition. A winding-up petition must be served in accordance with the Insolvency Rules 2016 (IR 2016). Service is the responsibility of the petitioner and will not be undertaken by the court. If service of a petition to wind up a registered company is not to be on the company’s solicitor, the petition must be served at the company’s registered office, if it has one. Other methods of service at the registered office are not permitted. A winding-up order made on a petition that has not been served is fundamentally defective and will normally be set aside. The court can properly refuse to set aside the order only if there is no prejudice to the company or a third party. If an order is made and service is affected under the order, a sealed copy of the order must accompany the certificate of service. The present rules make wider provision for service than previous rules did.
Company Subject to Another Insolvency Procedure
Authors: French Derek
Published: October 2021

This chapter sets out who can apply for a winding-up order and when a winding-up order can be made where a company is already subject to an insolvency procedure. This chapter discusses the insolvency procedures under the law of England and Wales, other parts of the United Kingdom and outside the UK. A supervisor of a company voluntary arrangement (CVA) approved under IA 1986, part 1, may petition for the compulsory winding up of the company, and the court may appoint the supervisor to be liquidator of the company. IA 1986, part 1, is applied with modifications to building societies by the Building Societies Act 1986. When a company is in administration, no petition for it to be wound up may be presented without the administrator’s consent or the court’s permission, unless it is presented for the purpose of proceedings under the default rules of a recognized body in a financial market.
Zeta revisited
Authors: Hoover David L
Published: October 2021

It has been claimed that traditional interpretations of Zeta based on graphs with bisector lines (Craig and Kinney, 2009, Shakespeare, Computers, and the Mystery of Authorship. Cambridge: Cambridge University Press.) are unsound, that validation with a held-out segments is inadequate, that counting types rather than tokens is suspect, and that the relationship between stronger Zeta scores and shorter word n-grams is an artifact of the method rather than a research finding (Rizvi, 2019a, The interpretation of zeta test results. Digital Scholarship in the Humanities, 34(2): 401–18). All of these claims are unsound. The separation of base and counter segments in a Zeta analysis is in fact an important research finding, the traditional interpretation of Zeta results based on a bisector line remain sound, and validation with a held-out segments is an appropriate method. Zeta’s reliance on consistency rather than frequency is not a bug but valuable feature that provides an important complementary method to those based on frequency. The results of extensive testing on corpora of prose, poetry, and drama show that increasing word n-gram length (but not character n-gram length) is often negatively correlated with classification accuracy. Higher Zeta scores are often correlated with better results, though the results vary a great deal depending on the corpus, the classification method, and the type and length of n-gram. Most importantly, these results show that Zeta gives strong results that are competitive with methods like Cosine Delta and Support Vector Machine on these classification tasks.
Stability and change in attitudes towards homosexuality among immigrant-origin adolescents in Norway
Authors: Sterri Erika Braanen
Published: October 2021

This article explores attitudes about the acceptability of homosexuality among immigrant-origin adolescents in Norway. Using a sample of students enrolled in upper secondary school, and comparing the data from the World Value Survey, I discuss the extent to which attitudes towards homosexuality among immigrant-origin youth are predominantly static or subject to change as a result of exposure to Norwegian society. Despite substantial differences between native- and immigrant-origin youth, and between different groups according to regional origin and religious affiliation, I find clear indications of changes in attitudes across all groups in the direction of higher level of tolerance. Immigrant-origin youth in Norway consider themselves more tolerant than their parents; have more positive attitudes towards homosexuality than adolescents residing in their countries of origin have; and family length of residence correlates positively with acceptance of homosexuality. Exposure in the form of school contexts where native-origin adolescents make up a larger proportion of the student body is also positively correlated with more positive attitudes towards homosexuality among immigrant-origin youth, but only at the highest level of native density.
SN 2018hfm: a low-energy Type II supernova with prominent signatures of circumstellar interaction and dust formation
Authors: Zhang Xinghan , Wang Xiaofeng , Sai Hanna , Niculescu-Duvaz Maria , Filippenko Alexei V , Zheng WeiKang , Brink T G , Lin Han , Zhang Jicheng , Cai Yongzhi , Mo Jun , Zhang Jujia , Baron E , DerKacy J M , Huang F , Zhang T-M
Published: October 2021

We present multiband optical photometric and spectroscopic observations of an unusual Type II supernova, SN 2018hfm, which exploded in the nearby (d ≈ 34.67 Mpc) dwarf galaxy PGC 1297331 with a very low star formation rate (0.0270 M⊙ yr−1) and a subsolar metallicity environment (∼0.5 Z⊙). The V-band light curve of SN 2018hfm reaches a peak with value of −18.69 ± 0.64 mag, followed by a fast decline (4.42 ± 0.13 mag (100 d)−1). After about 50 d, it is found to experience a large flux drop (∼3.0 mag in V), and then enters into an unusually faint tail, which indicates a relatively small amount of 56Ni synthesized during the explosion. From the bolometric light curve, SN 2018hfm is estimated to have low ejecta mass (∼1.3 M⊙) and low explosion energy (∼1050 erg) compared with typical SNe II. The photospheric spectra of SN 2018hfm are similar to those of other SNe II, with P Cygni profiles of the Balmer series and metal lines, while at late phases the spectra are characterized by box-like profiles of H α emission, suggesting significant interaction between the SN ejecta and circumstellar matter. These box-like emission features are found to show increasing asymmetry with time, with the red-side component becoming gradually weaker, indicating that dust is continuously formed in the ejecta. Based on the dust-estimation tool damocles, we find that the dust increases from ∼10−6 M⊙ to 10−4–10−3 M⊙ between +66.7 d and +389.4 d after explosion.
The large-scale monopole of the power spectrum in a Euclid-like survey: wide-angle effects, lensing, and the ‘finger of the observer’
Authors: Elkhashab Mohamed Yousry , Porciani Cristiano , Bertacca Daniele
Published: October 2021

Radial redshift-space distortions due to peculiar velocities and other light-cone effects shape the maps we build of the Universe. We address the open question of their impact onto the monopole moment of the galaxy power spectrum, P0(k). Specifically, we use an upgraded numerical implementation of the liger method to generate 140 mock galaxy density fields for a full Euclid-like survey and we measure P0(k) in each of them utilizing a standard estimator. We compare the spectra obtained by turning on and off different effects. Our results show that wide-angle effects due to radial peculiar velocities generate excess power above the level expected within the plane–parallel approximation. They are detectable with a signal-to-noise ratio of 2.7 for $k\lt 0.02\, h$ Mpc−1. Weak-lensing magnification also produces additional power on large scales which, if the current favourite model for the luminosity function of Hα emitters turns out to be realistic, can only be detected with a signal-to-noise ratio of 1.3 at best. Finally, we demonstrate that measuring P0(k) in the standard of rest of the observer generates an additive component reflecting the kinematic dipole overdensity caused by the peculiar velocity. This component is characterized by a damped oscillatory pattern on large scales. We show that this ‘finger of the observer’ effect is detectable in some redshift bins and suggest that its measurement could possibly open new research directions in connection with the determination of the cosmological parameters, the properties of the galaxy population under study, and the dipole itself.
A measurement of the Ly β forest power spectrum and its cross with the Ly α forest in X-Shooter XQ-100
Authors: Wilson Bayu , Iršič Vid , McQuinn Matthew
Published: October 2021

The Ly α forest is the large-scale structure probe for which we appear to have modelling control to the highest wavenumbers. This makes the Ly α forest of great interest for constraining the warmness/fuzziness of dark matter and the timing of reionization processes. However, the standard statistic, the Ly α forest power spectrum, is unable to strongly constrain the intergalactic medium (IGM) temperature–density relation, and this inability further limits how well other high-wavenumber-sensitive parameters can be constrained. With the aim of breaking these degeneracies, we measure the power spectrum of the Ly β forest and its cross-correlation with the coeval Ly α forest using the 100 spectra of z = 3.5–4.5 quasars in the VLT/X-Shooter XQ-100 Legacy Survey, motivated by the Ly β transition’s smaller absorption cross-section that makes it sensitive to somewhat higher densities relative to the Ly α transition. Our inferences from this measurement for the IGM temperature–density relation appear to latch consistently on to the recent tight lower redshift Ly α forest constraints. The z = 3.4–4.7 trends we find using the Ly α–Ly β cross-correlation show a flattening of the slope of the temperature–density relation with decreasing redshift. This is the trend anticipated from ongoing He ii reionization and there being sufficient time to reach the asymptotic temperature–density slope after hydrogen reionization completes. Furthermore, our measurements provide a consistency check on IGM models that explain the Ly α forest, with the cross-correlation being immune to systematics that are uncorrelated between the two forests, such as metal line contamination.
From blue cloud to red sequence: evidence of morphological transition prior to star formation quenching
Authors: Sampaio V M , de Carvalho R R , Ferreras I , Aragón-Salamanca A , Parker L C
Published: October 2021

We present a study of a sample of 254 clusters from the SDSS-DR7 Yang Catalogue and an auxiliary sample of field galaxies to perform a detailed investigation on how galaxy quenching depends on both environment and galaxy stellar mass. Our samples are restricted to 0.03 ≤ z ≤ 0.1 and we only consider clusters with log (Mhalo/M⊙) ≥ 14. Comparing properties of field and cluster galaxies in the blue cloud, green valley, and red sequence, we find evidence that field galaxies in the red sequence hosted star formation events $\rm 2.1 \pm 0.7$ Gyr ago, on average, more recently than galaxies in cluster environments. Dissecting the star formation rate versus stellar mass diagram we show how morphology rapidly changes after reaching the green valley region, while the star formation rate keeps decreasing. In addition, we use the relation between location in the projected phase space and infall time to explore the time delay between morphological and specific star formation rate variations. We estimate that the transition from late- to early-type morphology happens in Δtinf ∼ 1 Gyr, whereas the quenching of star formation takes ∼3 Gyr. The time-scale we estimate for morphological transitions is similar to the expected for the delayed-then-rapid quenching model. Therefore, we suggest that the delay phase is characterized mostly by morphological transition, which then contributes morphological quenching as an additional ingredient in galaxy evolution.
Comparison of the mass distributions of short-period exoplanets detected by transit and RV methods
Authors: Yakovlev Oleg Ya , Ananyeva V I , Ivanova A E , Tavrov A V
Published: October 2021

We analyse the causes of a discrepancy between the earlier obtained samples of the mass distributions of exoplanets detected by the transit method and the radial velocity (RV) one and corrected for some observational selection effects. It is found that this discrepancy can be removed by introducing the following restrictions into the procedures forming the samples: (i) to consider, among transit exoplanets, only those which masses were determined by the RV method (i.e. excluding the transit time variation method); (ii) to take into account exoplanets with orbital periods P ∈ [1, 100] days and masses M ∈ [0.02, 13]MJ (Jupiter masses). In addition, we compare here the distributions by projective masses (which is Msin i, where i is the orbital inclination of an exoplanet). For this, the mass distribution of transit exoplanets is transformed into the projective mass distribution. Due to these three changes in the procedure, the obtained RV and transit distributions exhibit a similar behaviour in an interval of M ∈ [0.02, Mmid]MJ and coincide at M ∈ [Mmid, 13]MJ, where Mmid ≈ 0.17MJ.
ECO: the Evidence and Conclusion Ontology, an update for 2022
Authors: Nadendla Suvarna , Jackson Rebecca , Munro James , Quaglia Federica , Mészáros Bálint , Olley Dustin , Hobbs Elizabeth T , Goralski Stephen M , Chibucos Marcus , Mungall Christopher John , Tosatto Silvio C E , Erill Ivan , Giglio Michelle G
Published: October 2021

The Evidence and Conclusion Ontology (ECO) is a community resource that provides an ontology of terms used to capture the type of evidence that supports biomedical annotations and assertions. Consistent capture of evidence information with ECO allows tracking of annotation provenance, establishment of quality control measures, and evidence-based data mining. ECO is in use by dozens of data repositories and resources with both specific and general areas of focus. ECO is continually being expanded and enhanced in response to user requests as well as our aim to adhere to community best-practices for ontology development. The ECO support team engages in multiple collaborations with other ontologies and annotating groups. Here we report on recent updates to the ECO ontology itself as well as associated resources that are available through this project. ECO project products are freely available for download from the project website (https://evidenceontology.org/) and GitHub (https://github.com/evidenceontology/evidenceontology). ECO is released into the public domain under a CC0 1.0 Universal license.
HumanNet v3: an improved database of human gene networks for disease research
Authors: Kim Chan Yeong , Baek Seungbyn , Cha Junha , Yang Sunmo , Kim Eiru , Marcotte Edward M , Hart Traver , Lee Insuk
Published: October 2021

Network medicine has proven useful for dissecting genetic organization of complex human diseases. We have previously published HumanNet, an integrated network of human genes for disease studies. Since the release of the last version of HumanNet, many large-scale protein–protein interaction datasets have accumulated in public depositories. Additionally, the numbers of research papers and functional annotations for gene–phenotype associations have increased significantly. Therefore, updating HumanNet is a timely task for further improvement of network-based research into diseases. Here, we present HumanNet v3 (https://www.inetbio.org/humannet/, covering 99.8% of human protein coding genes) constructed by means of the expanded data with improved network inference algorithms. HumanNet v3 supports a three-tier model: HumanNet-PI (a protein–protein physical interaction network), HumanNet-FN (a functional gene network), and HumanNet-XC (a functional network extended by co-citation). Users can select a suitable tier of HumanNet for their study purpose. We showed that on disease gene predictions, HumanNet v3 outperforms both the previous HumanNet version and other integrated human gene networks. Furthermore, we demonstrated that HumanNet provides a feasible approach for selecting host genes likely to be associated with COVID-19.
Ensembl 2022
Authors: Cunningham Fiona , Allen James E , Allen Jamie , Alvarez-Jarreta Jorge , Amode M Ridwan , Armean Irina M , Austine-Orimoloye Olanrewaju , Azov Andrey G , Barnes If , Bennett Ruth , Berry Andrew , Bhai Jyothish , Bignell Alexandra , Billis Konstantinos , Boddu Sanjay , Brooks Lucy , Charkhchi Mehrnaz , Cummins Carla , Da Rin Fioretto Luca , Davidson Claire , Dodiya Kamalkumar , Donaldson Sarah , El Houdaigui Bilal , El Naboulsi Tamara , Fatima Reham , Giron Carlos Garcia , Genez Thiago , Martinez Jose Gonzalez , Guijarro-Clarke Cristina , Gymer Arthur , Hardy Matthew , Hollis Zoe , Hourlier Thibaut , Hunt Toby , Juettemann Thomas , Kaikala Vinay , Kay Mike , Lavidas Ilias , Le Tuan , Lemos Diana , Marugán José Carlos , Mohanan Shamika , Mushtaq Aleena , Naven Marc , Ogeh Denye N , Parker Anne , Parton Andrew , Perry Malcolm , Piližota Ivana , Prosovetskaia Irina , Sakthivel Manoj Pandian , Salam Ahamed Imran Abdul , Schmitt Bianca M , Schuilenburg Helen , Sheppard Dan , Pérez-Silva José G , Stark William , Steed Emily , Sutinen Kyösti , Sukumaran Ranjit , Sumathipala Dulika , Suner Marie-Marthe , Szpak Michal , Thormann Anja , Tricomi Francesca Floriana , Urbina-Gómez David , Veidenberg Andres , Walsh Thomas A , Walts Brandon , Willhoft Natalie , Winterbottom Andrea , Wass Elizabeth , Chakiachvili Marc , Flint Bethany , Frankish Adam , Giorgetti Stefano , Haggerty Leanne , Hunt Sarah E , IIsley Garth R , Loveland Jane E , Martin Fergal J , Moore Benjamin , Mudge Jonathan M , Muffato Matthieu , Perry Emily , Ruffier Magali , Tate John , Thybert David , Trevanion Stephen J , Dyer Sarah , Harrison Peter W , Howe Kevin L , Yates Andrew D , Zerbino Daniel R , Flicek Paul
Published: October 2021

Ensembl (https://www.ensembl.org) is unique in its flexible infrastructure for access to genomic data and annotation. It has been designed to efficiently deliver annotation at scale for all eukaryotic life, and it also provides deep comprehensive annotation for key species. Genomes representing a greater diversity of species are increasingly being sequenced. In response, we have focussed our recent efforts on expediting the annotation of new assemblies. Here, we report the release of the greatest annual number of newly annotated genomes in the history of Ensembl via our dedicated Ensembl Rapid Release platform (http://rapid.ensembl.org). We have also developed a new method to generate comparative analyses at scale for these assemblies and, for the first time, we have annotated non-vertebrate eukaryotes. Meanwhile, we continually improve, extend and update the annotation for our high-value reference vertebrate genomes and report the details here. We have a range of specific software tools for specific tasks, such as the Ensembl Variant Effect Predictor (VEP) and the newly developed interface for the Variant Recoder. All Ensembl data, software and tools are freely available for download and are accessible programmatically.
The European Nucleotide Archive in 2021
Authors: Cummins Carla , Ahamed Alisha , Aslam Raheela , Burgin Josephine , Devraj Rajkumar , Edbali Ossama , Gupta Dipayan , Harrison Peter W , Haseeb Muhammad , Holt Sam , Ibrahim Talal , Ivanov Eugene , Jayathilaka Suran , Kadhirvelu Vishnukumar , Kay Simon , Kumar Manish , Lathi Ankur , Leinonen Rasko , Madeira Fabio , Madhusoodanan Nandana , Mansurova Milena , O’Cathail Colman , Pearce Matt , Pesant Stéphane , Rahman Nadim , Rajan Jeena , Rinck Gabriele , Selvakumar Sandeep , Sokolov Alexey , Suman Swati , Thorne Ross , Totoo Prabhat , Vijayaraja Senthilnathan , Waheed Zahra , Zyoud Ahmad , Lopez Rodrigo , Burdett Tony , Cochrane Guy
Published: October 2021

The European Nucleotide Archive (ENA, https://www.ebi.ac.uk/ena), maintained at the European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI) provides freely accessible services, both for deposition of, and access to, open nucleotide sequencing data. Open scientific data are of paramount importance to the scientific community and contribute daily to the acceleration of scientific advance. Here, we outline the major updates to ENA’s services and infrastructure that have been delivered over the past year.
SPICA: Swiss portal for immune cell analysis
Authors: Andreatta Massimo , David Fabrice P A , Iseli Christian , Guex Nicolas , Carmona Santiago J
Published: October 2021

Single-cell transcriptomics allows the study of immune cell heterogeneity at an unprecedented level of resolution. The Swiss portal for immune cell analysis (SPICA) is a web resource dedicated to the exploration and analysis of single-cell RNA-seq data of immune cells. In contrast to other single-cell databases, SPICA hosts curated, cell type-specific reference atlases that describe immune cell states at high resolution, and published single-cell datasets analysed in the context of these atlases. Additionally, users can privately analyse their own data in the context of existing atlases and contribute to the SPICA database. SPICA is available at https://spica.unil.ch.
RNA chaperone activatesSalmonellavirulence program during infection
Authors: Choi Jeongjoon , Salvail Hubert , Groisman Eduardo A
Published: October 2021

Organisms often harbor seemingly redundant proteins. In the bacterium Salmonella enterica serovar Typhimurium (S. Typhimurium), the RNA chaperones CspC and CspE appear to play redundant virulence roles because a mutant lacking both chaperones is attenuated, whereas mutants lacking only one exhibit wild-type virulence. We now report that CspC—but not CspE—is necessary to activate the master virulence regulator PhoP when S. Typhimurium experiences mildly acidic pH, such as inside macrophages. This CspC-dependent PhoP activation is specific to mildly acidic pH because a cspC mutant behaves like wild-type S. Typhimurium under other PhoP-activating conditions. Moreover, it is mediated by ugtL, a virulence gene required for PhoP activation inside macrophages. Purified CspC promotes ugtL translation by disrupting a secondary structure in the ugtL mRNA that occludes ugtL’s ribosome binding site. Our findings demonstrate that proteins that are seemingly redundant actually confer distinct and critical functions to the lifestyle of an organism.
Priority index: database of genetic targets in immune-mediated disease
Authors: Fang Hai , Knight Julian C
Published: October 2021

We describe a comprehensive and unique database ‘Priority index’ (Pi; http://pi.well.ox.ac.uk) of prioritized genes encoding potential therapeutic targets that encompasses all major immune-mediated diseases. We provide targets at the gene level, each receiving a 5-star rating supported by: genomic evidence arising from disease genome-wide associations and functional immunogenomics, annotation evidence using ontologies restricted to genes with genomic evidence, and network evidence from protein interactions. Target genes often act together in related molecular pathways. The underlying Pi approach is unique in identifying a network of highly rated genes that mediate pathway crosstalk. In the Pi website, disease-centric pages are specially designed to enable the users to browse a complete list of prioritized genes and also a manageable list of nodal genes at the pathway crosstalk level; both switchable by clicks. Moreover, target genes are cross-referenced and supported using additional information, particularly regarding tractability, including druggable pockets viewed in 3D within protein structures. Target genes highly rated across diseases suggest drug repurposing opportunity, while genes in a particular disease reveal disease-specific targeting potential. To facilitate the ease of such utility, cross-disease comparisons involving multiple diseases are also supported. This facility, together with the faceted search, enhances integrative mining of the Pi resource to accelerate early-stage therapeutic target identification and validation leveraging human genetics.
Differential cerebrovascular risks in glioblastoma and meningioma patients: a population-based matched cohort study in Wales (United Kingdom)
Authors: Poon Michael T C , Jin Kai , Brennan Paul M , Figueroa Jonine , Sudlow Cathie
Published: October 2021

Aims

There is limited evidence on cerebrovascular risks in glioblastoma and meningioma patients. We aimed to compare cerebrovascular risks of these patients with the general population.

Method

We used population-based routine healthcare and administrative data linkage in this matched cohort study. Cases were adult glioblastoma and meningioma patients diagnosed in Wales 2000-2014 identified in the cancer registry. Controls from cancer-free general population were matched to cases (5:1 ratio) on age (±5 years), sex and GP practice. Factors included in multivariable models were age, sex, index of multiple deprivation, hypertension, diabetes, high cholesterol, history of cardiovascular disease, and medications for cardiovascular diseases. Outcomes were fatal and non-fatal haemorrhagic and ischaemic stroke. We used flexible parametric models adjusting for confounders to calculate the hazard ratios (HR).

Results

Final analytic population was 16,921 participants, of which 1,340 had glioblastoma and 1,498 had meningioma. The median follow-up time was 0.5 year for glioblastoma patients, 4.9 years for meningioma patients, and 6.6 years for controls. The number of haemorrhage and ischaemic stroke was 154 and 374 in the glioblastoma matched cohort, respectively, and 180 and 569 in the meningioma matched cohort, respectively. The adjusted HRs for haemorrhagic and ischaemic stroke were 3.74 (95%CI 1.87-6.57) and 5.62 (95%CI 2.56-10.42) in glioblastoma patients, respectively, and were 2.42 (95%CI 1.58-3.52) and 1.86 (95%CI 1.54-2.23) in meningioma patients compared with their controls.

Conclusion

Glioblastoma and meningioma patients had higher cerebrovascular risks; these risks were even higher for glioblastoma patients. Further assessment of these potentially modifiable risks may improve survivorship.
Brain tumour related epilepsy with co-existing non epileptic attacks: Characteristics of a clinically challenging cohort
Authors: Samarasekera Shanika , Liang Di
Published: October 2021

Aims

The co-existence of non-epileptic attacks (NEAD) in patients with brain tumour related epilepsy (BTRE) is poorly described. Non epileptic attacks (NEAD) co-occur in up to 30% of patients with epilepsy PWE. Adverse life events are associated with development of NEAD; their co-occurrence in those with BTRE is potentially un-surprising.

We sought to characterise the evolution of symptoms in this cohort.

Method

Clinical trajectories of patients with BTRE and co-existing NEAD were characterised. The diagnosis of NEAD was based on the epilepsy specialist’s observation of attacks and /or capture of attacks on video. Some patients had additional video EEG correlate.

Patients had been referred because of persisting symptoms in spite of escalating antiepileptic therapy.

Results

Of eight patients, six were initially misdiagnosed with escalating seizures. One patient developed NEAD de novo following tumour biopsy, the remaining patients developed NEAD following onset of BTRE. Onset of NEAD was not temporally linked with the diagnosis of a brain tumour. In five patients, NEAD onset occurred when seizures were controlled (< 1 seizure/ month). All patients reported fear of developing uncontrolled seizures as being associated with their symptoms and identified their NEAD as more disabling than their epilepsy.

Patients were eventually managed with polytherapy -two found adjunctive clobazam helpful and four were offered antidepressant/ anxiolytic medication. Behavourial strategies including mindfulness were also discussed. At time of last follow up, seven patients had on-going NEAD symptoms in spite of good seizure control.

Conclusion

NEAD can co-occur with BTRE and should be considered in those with rapidly escalating symptoms in spite of antiepileptic therapy and radiologically stable lesions. Both making the diagnosis of NEAD and providing ongoing support is challenging. These patients require a multidisciplinary approach with support from allied specialties including neuropsychiatry and neuropsychology.
Characterizing immune cell subsets of tumour infiltrating lymphocytes (TILs) in brain metastases
Authors: Kalita-de Croft Priyakshi , Chittoory Haarika , Simpson Peter , Lakhani Sunil
Published: October 2021

Aims

The heterogeneity of TILs are not well characterized in brain metastasis. To address this, we performed a targeted analysis of immune cell subsets in brain metastasis tissues.

Method

We performed multiplex immunofluorescence (mIF) on a limited cohort of brain metastases arising from breast cancers (n=20). Using RNA-interference validated antibodies, we quantitated the subsets of immune cells in formalin-fixed paraffin embedded whole sections. The panel of proteins analyzed included PanCK, CD8, CD4, Vista and Iba1 and an average of 15000 cells per sample were analysed. We also analysed an independent publicly available cohort at the RNA level to corroborate our findings.

Results

We found that increased density of tils (high>30%; low <30%) correlated with survival and they were two distinct phenotypes. The tumours with low tils had significantly higher expression of the immune-checkpoint molecule Vista in tumour cells (p<0.01) as well as in their microenvironment (p<0.001). Contrastingly, the brain metastatic tumours with high tils displayed higher expression of microglia. Low tils-tumours display CD8+ T-cells that exclusively co-express Vista (p<0.01) compared to high tils group where CD8+ T-cells significantly co-express Iba1 (p<0.05). Interestingly no definite phenotypes were observed in CD4+ T-cells. These results were also found in an independent cohort where Vista was a highly ranked gene within the CD8+ T-cell population.

Conclusion

Variety of immune escape routes may be involved in brain metastasis. This may be executed by increasing the expression of T-cell inhibitory molecule Vista or by increased activated microglia which may release immunosuppressive cytokines. Further studies are required to provide mechanistic insights into these phenomena.
Ependymomas: surgeon case volume and patient outcomes
Authors: Sun Rosa , Slator Naomi , Kay Andrew
Published: October 2021

Aims

Ependymomas (tumours arising from ependymal cells) are rare in the adult population and therefore there is limited class 1 evidence on the treatment and management of these patients. We present our experience from a large single center. We address whether management should be undertaken by sub-specialised surgeons with high volume experience.

Method

Retrospective comparative study.

Results

High volume surgeons operated on larger volume (16.14 mm3, 8.31mm3, p=0.10) and more complex tumours (multi-centric cases p=0.10). We find a non-significant improvement in complication rate (p=0.77), extent of gross total resection (70.8% against 65.7%) and a positive change in performance status for high volume surgeons (p=0.84). Length of hospital stay is significantly prolonged when complications occur (14.2 and 48.4 days, p<0.05).

Conclusion

Surgeons who have higher case load of ependymomas operate on more complex tumours. In addition, our results indicate there is a technical advantage of high volume surgeons compared to low volume surgeons, which translates into improved clinical outcomes for patients. We show that this has a significant impact on length of hospital stay, as well as the associated economical implications. For rare tumours such as ependymomas, super-specialisation and referral to surgeons with higher case volume will likely improve patient outcomes.

We call for a multi-centre, prospective studies to combine data in demonstrating statistical significance (power calculation for complication rate, N=150, p=0.05).
Does dietary fat affect advanced glycation end products and their receptors? A systematic review of clinical trials
Authors: Mendes Nélia P , Ribeiro Priscila V M , Alfenas Rita C G
Published: October 2021

Context

Dietary fat seems to affect advanced glycation end products (AGEs) and their receptors. This systematic review assesses studies that evaluated the effect of dietary fat on markers of glycation.

Objective

The aim of this systematic review was to analyze the effect of dietary fat on markers of glycation and to explore the mechanisms involved.

Data Sources

This study was conducted according to PRISMA guidelines. PubMed, Cochrane, and Scopus databases were searched, using descriptors related to dietary fat, AGEs, and the receptors for AGEs.

Study Selection

Studies were selected independently by the 3 authors. Divergent decisions were resolved by consensus. All studies that evaluated the effects of the quantity and quality of dietary fat on circulating concentrations of AGEs and their receptors in adults and elderly adults with or without chronic diseases were included. Initially, 9 studies met the selection criteria.

Data Extraction

Three authors performed data extraction independently. Six studies were included.

Results

Consumption of a Mediterranean diet rich in monounsaturated fatty acids (MUFAs) and low in dietary AGEs reduced serum concentrations of AGEs, reduced expression of the receptor for AGE (RAGE), and increased expression of the AGE receptor 1 (AGER1) when compared with consumption of a Western diet rich in saturated fatty acids and dietary AGEs. Supplementation with omega-3 polyunsaturated fatty acids (PUFAs) resulted in decreased concentrations of fluorescent AGEs and decreased expression of RAGE as well as increased expression of AGER1.

Conclusions

Increased consumption of MUFAs and omega-3 PUFAs and reduced consumption of saturated fatty acids seem to be effective strategies to beneficially affect glycation markers, which in turn may prevent and control chronic diseases.

Systematic Review Registration

PROSPERO registration number CRD42021220489.
A Chimeric TGA Repressor Slows Down Fruit Maturation and Ripening in Tomato
Authors: Lemaire-Chamley Martine , Koutouan Claude , Jorly Joana , Assali Julien , Yoshida Takuya , Nogueira Marilise , Tohge Takayuki , Ferrand Carine , Peres Lázaro E P , Asamizu Erika , Ezura Hiroshi , Fraser Paul D , Hajirezaei Mohammad-Reza , Fernie Alisdair R , Rothan Christophe
Published: October 2021

The bZIP transcription factor (TF) SlTGA2.2 was previously highlighted as a possible hub in a network regulating fruit growth and transition to ripening (maturation phase). It belongs to a clade of TFs well known for their involvement in the regulation of the salicylic acid–dependent systemic acquired resistance. To investigate if this TGA TF plays a role in tomato fruit growth and maturation, we took advantage of the fruit-specific SlPPC2 promoter (PPC2pro) to target the expression of a SlTGA2.2-SRDX chimeric repressor in a developmental window restricted to early fruit growth and maturation. Here, we show that this SlTGA2.2-SRDX repressor alters early fruit development and metabolism, including chloroplast number and structure, considerably extends the time necessary to reach the mature green stage and slows down fruit ripening. RNA sequencing and plant hormone analyses reveal that PPC2pro:SlTGA2.2-SRDX fruits are maintained in an immature stage as long as PPC2pro is active, through early modifications of plant hormonal signaling and down-regulation of MADS-RIN and NAC-NOR ripening regulators. Once PPC2pro becomes inactive and therefore SlTGA2.2-SRDX expression is reduced, ripening can proceed, albeit at a slower pace than normal. Altogether, this work emphasizes the developmental continuum between fruit growth, maturation and ripening and provides a useful tool to alter and study the molecular bases of tomato fruit transition to ripening.
Single-cell transcriptomics sheds light on the identity and metabolism of developing leaf cells
Authors: Tenorio Berrío Rubén , Verstaen Kevin , Vandamme Niels , Pevernagie Julie , Achon Ignacio , Van Duyse Julie , Van Isterdael Gert , Saeys Yvan , De Veylder Lieven , Inzé Dirk , Dubois Marieke
Published: October 2021

As the main photosynthetic instruments of vascular plants, leaves are crucial and complex plant organs. A strict organization of leaf mesophyll and epidermal cell layers orchestrates photosynthesis and gas exchange. In addition, water and nutrients for leaf growth are transported through the vascular tissue. To establish the single-cell transcriptomic landscape of these different leaf tissues, we performed high-throughput transcriptome sequencing of individual cells isolated from young leaves of Arabidopsis (Arabidopsis thaliana) seedlings grown in two different environmental conditions. The detection of approximately 19,000 different transcripts in over 1,800 high-quality leaf cells revealed 14 cell populations composing the young, differentiating leaf. Besides the cell populations comprising the core leaf tissues, we identified subpopulations with a distinct identity or metabolic activity. In addition, we proposed cell-type-specific markers for each of these populations. Finally, an intuitive web tool allows for browsing the presented dataset. Our data present insights on how the different cell populations constituting a developing leaf are connected via developmental, metabolic, or stress-related trajectories.
The Born rule and logical inference in quantum mechanics
Authors: Ichikawa Tsubasa
Published: October 2021

Logical inference leads to one of the major interpretations of probability theory called logical interpretation, in which the probability is seen as a measure of the plausibility of a logical statement under incomplete information. Assuming that our usual inference procedure is working rationally for every set of logical propositions represented in terms of commuting projectors on a given Hilbert space, we extend the logical interpretation to quantum mechanics and derive the Born rule. Our result implies that, from epistemological viewpoints, we can regard quantum mechanics as a natural extension of classical probability theory.
A Bessel δ-Method and Hybrid Bounds for GL2
Authors: Fan Yilan , Sun Qingfeng
Published: October 2021

Let g be a primitive holomorphic or Maass newform for $\Gamma_0(D)$. In this paper, by studying the Bessel integrals associated with g, we prove an asymptotic Bessel δ-identity associated with g. Among other applications, we prove the following hybrid subconvexity bound $$\begin{eqnarray*} L\left(1/2+it,g\otimes \chi\right)\ll_{g,\varepsilon} (q(1+|t|))^{\varepsilon}q^{3/8}(1+|t|)^{1/3} \end{eqnarray*}$$ for any ε > 0, where $\chi \bmod q$ is a primitive Dirichlet character with q prime and $(q, D)=1$. This improves the previous known result.
Histopathology, salivary flow and ultrasonography of the parotid gland: three complementary measurements in primary Sjögren’s syndrome
Authors: Mossel Esther , van Ginkel Martha S , Haacke Erlin A , Arends Suzanne , Liefers Silvia C , Delli Konstantina , van Nimwegen Jolien F , Stel Alja J , Spijkervet Fred K L , Vissink Arjan , van der Vegt Bert , Kroese Frans G M , Bootsma Hendrika
Published: October 2021

Objective

The involvement of salivary glands in primary SS (pSS) can be assessed in different ways: histopathology, salivary flow and ultrasonography. To understand the relative value of these different approaches, it is crucial to understand the relationship between them. As we routinely perform these three modalities in the parotid gland for disease evaluation, our aim was to investigate the construct validity between these modalities in one and the same gland.

Methods

Consecutive sicca patients underwent a multidisciplinary diagnostic workup including parotid gland biopsy, collection of parotid gland–specific saliva and parotid gland ultrasonography. Patients who were classified as pSS according to the ACR-EULAR criteria were included. Construct validity was assessed using Spearman’s correlation coefficients.

Results

The 41 included pSS patients completed a full workup within a mean time interval of 2.6 months. Correlations between histopathological features and stimulated parotid salivary flow were fair (ρ = −0.123 for focus score and ρ = −0.259 for percentage of CD45+ infiltrate). Likewise, poor correlations were observed between stimulated parotid salivary flow and parotid ultrasonography (ρ = −0.196). Moderate to good associations were found between the histopathological items focus score and the percentage of CD45+ infiltrate, with parotid US scores (total US score: ρ = 0.510 and ρ = 0.560; highest for homogeneity: ρ = 0.574 and ρ = 0.633).

Conclusion

Although pSS-associated ultrasonographic findings did correlate with histopathological features, the three modalities that evaluate salivary gland involvement assess different (or at best partly related) constructs. Therefore histopathology, salivary flow and ultrasonography are complementary measurements and cannot directly replace each other in the workup of pSS.
Litchi chinensis inspired nanoformulations: a synergy guided approach for unraveling promising cytotoxic attributes of metal and nonmetal conjugates
Authors: Hussain Amina , Safdar Naila , Ain Noor-ul , Abbasi Rashda , Yasmin Azra
Published: October 2021

In present study, diverse Litchi chinensis-mediated nanostructures in combination with 5-fluorouracil drug were fabricated viz. Au, Se, Ag, Ag–Se, Ag–Au, 5-FU Ag–Se and 5-FU Ag–Au with subsequent characterization and scrutinization of their anticarcinogenic capabilities. UV–Visible spectroscopic analysis confirmed the state transition for each precursor salt. XRD and transmission electron microscopy analysis revealed spherical/quasispherical nanostructures with monoclinic crystalline organization ranged between 18 nm and 38 nm. FTIR analysis revealed fabricated nanoparticles to be capped with various phytoconstituents. DLS and Zeta potential analysis of unloaded and drug-loaded bielemental nanoparticles (BNPs) showed comparatively large hydrodynamic particle size distribution and sufficient stability of nanoparticles. BNPs showed promising lethality concentrations for brine shrimp (LC50 < 2 μg/ml) and antitumor (LC50 < 10 μg/ml) assessments. These findings were in positive correlation with the antioxidant inhibitory concentrations IC50 (74.2–180.1 μg/ml) of the tested entities. Ag–Se and Ag–Au were loaded with 5-FU (loading efficiency of 47% ± 1.14 and 25% ± 0.32, respectively) in light of their promising cytotoxic actions. All nanostructures showed profound hemocompatibility with maximum hemolytic activity as low as 2.4%. Highly significant difference (P < 0.01) was observed in antineoplastic potentials of unloaded and 5-FU loaded BNPs against HepG2 and HT144, with most substantial IC50 for 5-FU Ag–Au (8.95 ± 2.86 μg/ml). 5-FU Ag–Au was identified as a significant inducer of DNA fragmentation with maximum relative tail moment (HepG2: 3.45 ± 0.21) among all treatments.
Diversity of Botryosphaeriaceae and Diaporthe Species Associated with Postharvest Apple Fruit Decay in Serbia
Authors: Vučković Nina , Vico Ivana , Duduk Bojan , Duduk Nataša
Published: October 2021

Family Botryosphaeriaceae and the genus Diaporthe (family Diaporthaceae) represent diverse groups of plant pathogens, which include causal agents of leaf spot, shoot blight, branch and stem cankers, dieback, and pre- and postharvest apple fruit decay. Apple fruit with symptoms of light to dark brown decay were collected during and after harvest from 2016 to 2018. Thirty selected isolates, on which pathogenicity was confirmed, were identified and characterized based on multilocus phylogeny and morphology. Five species from the family Botryosphaeriaceae and two from the genus Diaporthe (fam. Diaporthaceae) were discovered. The most commonly isolated was Diplodia seriata followed by Botryosphaeria dothidea. In this work, Diaporthe rudis is described as a new postharvest pathogen of apple fruit. Diplodia bulgarica, Diplodia sapinea, Neofusicoccum yunnanense, and Diaporthe eres are initially described as postharvest apple and D. sapinea as postharvest quince and medlar fruit pathogens in Serbia. Because species of the family Botryosphaeriaceae and the genus Diaporthe are known to cause other diseases on their hosts, have an endophytic nature, and have a wide host range, findings from this study imply that they may become a new challenge for successful fruit production.
Are split liver grafts a suitable option in high-risk liver transplant recipients?
Authors: Lau Ngee-Soon , Liu Ken , McCaughan Geoffrey , Crawford Michael , Pulitano Carlo
Published: October 2021

Purpose of review

To assess the outcomes of split liver transplantation (SLT) in adults and children and evaluate its role in high-risk recipients with a high model for end-stage liver disease (MELD) score, an urgent indication or requiring retransplantation.

Recent findings

Split liver grafts in general have equivalent long-term survival outcomes to whole grafts despite an increase in biliary complications. Recent success and technical advances have encouraged use of these grafts in high-risk recipients. Split liver grafts can be used successfully in recipients with a high MELD score if there is adequate weight-matching. There are mixed results in urgent indication recipients and for retransplantation such that use in this group of patients remains controversial.

SLT addresses donor shortages by facilitating the transplant of two recipients from the same donor liver. By using careful donor and recipient selection criteria, SLT can achieve equivalent long-term outcomes to whole grafts. These grafts have been used successfully in recipients with a high MELD score, but should be used selectively in urgent indication recipients and for retransplantation.
Post-COVID-19 Syndrome
Authors: Pierce Janet D. , Shen Qiuhua , Cintron Samantha A. , Hiebert John B.
Published: October 2021

Background

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many individuals have reported persistent symptoms and/or complications lasting beyond 4 weeks, which is now called post-COVID-19 syndrome. SARS-CoV-2 is a respiratory coronavirus that causes COVID-19, and injury to the lungs is expected; however, there is often damage to numerous other cells and organs, leading to an array of symptoms. These long-term symptoms occur in patients with mild to severe COVID-19; currently, there is limited literature on the potential pathophysiological mechanisms of this syndrome.

Objectives

The purpose of this integrative review is to summarize and evaluate post-COVID-19 syndrome from a biological perspective.

Methods

An integrative review was conducted using Whittemore and Knafl’s methodology for literature published through August 30, 2021. The PubMed, CINAHL, and Web of Science databases were searched for articles published as of August 30, 2021, using combinations of the following key words: post-COVID-19 syndrome, post-SARS-CoV-2, long COVID-19, long COVID-19 syndrome, and pathophysiology of post-COVID-19. Data were analyzed using the constant comparison method.

Results

The search generated 27,929 articles. After removing duplicates and screening abstracts and full-text reviews, we retained 68 articles and examined 54 specific articles related to the pathophysiology of post-COVID-19 syndrome. The findings from our review indicated that there were four pathophysiological categories involved: virus-specific pathophysiological variations, oxidative stress, immunologic abnormalities, and inflammatory damage.

Discussion

Although studies examining the pathophysiology of post-COVID-19 syndrome are still relatively few, there is growing evidence that this is a complex and multifactorial syndrome involving virus-specific pathophysiological variations that affect many mechanisms but specifically oxidative stress, immune function, and inflammation. Further research is needed to elucidate the pathophysiology, pathogenesis, and longer term consequences involved in post-COVID-19 syndrome.