bluuebunny/crossref_metadata_2025 huggingface dataset:
Head kinematics associated with off field head injury assessment (HIA1) events in a season of English elite-level club men’s and women’s rugby union matches
Authors: Allan David , Tooby James , Starling Lindsay , Tucker Ross , Falvey Éanna , Salmon Danielle , Brown James , Hudson Sam , Stokes Keith , Jones Ben , Kemp Simon , O’Halloran Patrick , Cross Matt , Bussey Melanie , Tierney Gregory
Published: October 2024

Objectives

To investigate head kinematic variables in elite men’s and women’s rugby union and their ability to predict player removal for an off-field (HIA1) head injury assessment.

Methods

Instrumented Mouthguard (iMG) data were collected for 250 men and 132 women from 1,865 and 807 player-matches, respectively, and synchronised to video-coded match footage. Head peak resultant linear acceleration (PLA), peak resultant angular acceleration (PAA) and peak change in angular velocity (dPAV) were extracted from each head acceleration event (HAE). HAEs were linked to documented HIA1 events, with ten logistical regression models for men and women, using a random subset of non-case HAEs, calculated to identify kinematic variables associated with HIA1 events. Receiver operating characteristic curves (ROC) were used to describe thresholds for HIA1 removal.

Results

Increases in PLA, and dPAV were significantly associated with an increasing likelihood of HIA1 removal in the men’s game, with an OR ranging from 1.05-1.12 and 1.13-1.18, respectively. The optimal values to maximise for both sensitivity and specificity for detecting an HIA1 were 1.96krad.s-2, 24.29g, and 14.75rad.s-1for PAA, PLA, and dPAV respectively. Only one model had any significant variable associated with increasing the likelihood of a HIA1 removal in the women’s game – PAA with an OR of 8.51 (1.23-58.66). The optimal values for sensitivity and specificity for women were 2.01krad.s-2, 25.98g, and 15.38rad.s-1for PAA, PLA, and dPAV respectively.

Conclusion

PLA and dPAV were predictive of men’s HIA1 events. Further HIA1 data are needed to understand the role of head kinematic variables in the women’s game. The calculated spectrum of sensitivity and specificity of iMG alerts for HIA1 removals in men and women present a starting point for further discussion about using iMGs as an additional trigger in the existing HIA process.

Key Points

Concussion is the most common injury in rugby union. Current on-field suspected concussion detection methods rely on visually identifying an athlete exhibiting concussion signs, reporting symptoms or identifying clinical features in real time or upon video review of the event.

Increases in peak linear acceleration (PLA) and changes in Peak Angular Velocity (dPAV) were predictive of men’s Head Injury Assessment 1 (HIA1) events, and Peak Angular Acceleration (PAA) was predictive of women’s HIA1 events; however, further HIA1 data are needed to fully understand the role of head kinematic variables within the women’s game.

The findings contributed to the evidence that informed the 2024 World Rugby policy change to include instrumented mouthguards (iMG) measurements as a trigger for the HIA1 removal process in the elite adult game.
The Spc105Knl1/Kre28Zwintcomplex promotes mitotic error correction by outer kinetochore recruitment of the Ipl1Aurora Bkinase
Authors: Dudziak Alexander , Schmidt Jasmin , Hamm Frederik , Tendulkar Sharvari , Jänen Karolin , Vetter Ingrid R. , Singh Sylvia , Fischböck Josef , Herzog Franz , Westermann Stefan
Published: October 2024

Kinetochores link chromosomes to dynamic microtubules of the mitotic spindle. To ensure equal chromosome segregation, sister chromatids must attach to microtubules from opposing spindle poles, a configuration referred to as biorientation. To avoid chromosome missegregation the conserved kinase Aurora B phosphorylates outer kinetochore proteins on attachments lacking tension, allowing re-establishment of new connections until biorientation is achieved. While Aurora B localizes to the centromere and inner kinetochore as part of the chromosomal passenger complex (CPC), the underlying recruitment pathways can be eliminated without fully disrupting biorientation. It therefore remains unclear how the kinase operates during error correction and whether additional mechanisms may facilitate tension-dependent phosphorylation of substrate proteins.

In this study, we identify the conserved KMN subcomplex Spc105Knl1/Kre28Zwintas an outer kinetochore receptor of the Aurora kinase Ipl1 inSaccharomyces cerevisiae. We show that mutations in the helical bundle domain of Spc105/Kre28 cause defective mitotic error correction, closely resembling the effects ofipl1orsli15mutants. In biochemical experiments we show that Ipl1/Sli15 directly associates with the KMN network via the Spc105/Kre28 subcomplex and that binding is inhibited by Ipl1 autophosphorylation. The phenotype of thekre28mutant cells can be efficiently suppressed by artificial recruitment of Ipl1, demonstrating the importance of Ipl1 docking to the outer kinetochore. These results have important implications for the mechanism of tension-dependent error correction during chromosome biorientation.
Miniature: Unsupervised glimpses into multiplexed tissue imaging datasets as thumbnails for data portals
Authors: Taylor Adam J
Published: October 2024

Multiplexed tissue imaging can illuminate complex spatial protein expression patterns in healthy and diseased specimens. Large-scale atlas programs such as Human Tumor Atlas Network and are relying heavily on highly-multiplexed approaches including CyCIF and CODEX to image up to 100 antigens. Such high dimensionality allows a deep understanding of cellular diversity and spatial structure, but can provide a challenge for image visualization and exploration. One challenge for data portals and visualization tools is the generation of an informative and pleasing image preview that captures the full heterogeneity of the image, rather than relying on a multi-channel overlay that may be restricted to 4-6 channels. We describeMiniature, a tool to automatically generate informative image thumbnails from multiplexed tissue images in an unsupervised and scalable manner.Miniatureaims to aid researchers in understanding tissue heterogeneity and identifying potential pathological features without extensive manual intervention.Miniatureuses a choice of unsupervised dimensionality reduction methods including uniform manifold embedding and projection (UMAP), t-distributed stochastic neighbor Embedding (t-SNE), and principal Component analysis (PCA) to reduce on-tissue pixels from a low-resolution, high dimensional image to two or three dimensions. Pixels are then color encoded by their coordinate in low dimensional space using a choice of color maps. We show that perceptually distinct regions inMiniaturethumbnails reflect known pathological features seen in both the source multiplexed tissue image and H&E imaging of the same sample. We evaluateMiniatureparameters for dimensionality reduction and pixel color encoding to recommend default configurations that maximize perceptual trustworthiness to both the low-dimensional embedding and high-dimensional image and provide high Mantel correlation between the perceived color difference (delta E 2000) and distance in high- and low-dimensional space. By simulating color vision deficiency, we show thatMiniaturethumbnails are accessible to all. We demonstrate thatMiniaturethumbnails are suitable for a wide range of multiplexed tissue imaging modalities and show their application in the Human Tumor Atlas Network Data Portal.
Computing the Human Interactome
Authors: Zhang Jing , Humphreys Ian R. , Pei Jimin , Kim Jinuk , Choi Chulwon , Yuan Rongqing , Durham Jesse , Liu Siqi , Choi Hee-Jung , Baek Minkyung , Baker David , Cong Qian
Published: October 2024

Protein-protein interactions (PPI) are essential for biological function. Recent advances in coevolutionary analysis and Deep Learning (DL) based protein structure prediction have enabled comprehensive PPI identification in bacterial and yeast proteomes, but these approaches have limited success to date for the more complex human proteome. Here, we overcome this challenge by 1) enhancing the coevolutionary signals with 7-fold deeper multiple sequence alignments harvested from 30 petabytes of unassembled genomic data, and 2) developing a new DL network trained on augmented datasets of domain-domain interactions from 200 million predicted protein structures. These advancements allow us to systematically screen through 200 million human protein pairs and predict 18,316 PPIs with an expected precision of 90%, among which 5,578 are novel predictions. 3D models of these predicted PPIs nearly triple the number of human PPIs with accurate structural information, providing numerous insights into protein function and mechanisms of human diseases.
PfPPM2 signalling regulates asexual division and sexual conversion of human malaria parasitePlasmodium falciparum
Authors: Rawat Akanksha , Antil Neelam , Meenakshi  , Deshmukh Bhagyashree , Rai Akhila Balakrishna , Kumar Narendra , Prasad T.S. Keshava , Karmodiya Krishanpal , Sharma Pushkar
Published: October 2024

Malaria parasite transits through distinct developmental stages during its life cycle in the human and mosquito host, which includes unique asynchronous division in the erythrocytes. The switch from its asexual stage to sexual forms, which is critical for disease transmission, is intricately regulated but signalling pathways involved in this process have remained unknown. In the present study, we report a novel signalling pathway involving Protein Phosphatase PfPPM2, which regulates asexual division of the parasite as well as its conversion to sexual forms. Phosphoproteomics revealed that PfPPM2 may regulate the phosphorylation of key proteins involved in chromatin remodelling and protein translation. One of the key PfPPM2-targets that emerged from these studies was Heterochromatin Protein 1 (HP1), a regulator of heritable gene silencing which contributes to both mitotic proliferation as well as sexual commitment of the parasite. We demonstrate that PfPPM2 promotes sexual conversion by regulating the interaction between HP1, H3K9me3 and chromatin and it achieves this by dephosphorylating S33 of HP1. Regulation of HP1 and Histone H3 by PfPPM2 may also contribute to division. In addition, PfPPM2 also regulates protein synthesis in the parasite by repressing the phosphorylation of initiation factor eIF2α, which is likely to contribute to parasite division and possibly sexual differentiation.
Age-related increases in PDE11A4 protein expression trigger liquid:liquid phase separation (LLPS) of the enzyme that can be reversed by PDE11A4 small molecules inhibitors
Authors: Amurrio E , Patel J , Danaher M , Goodwin M , Kargbo P , Lin S , Hoffman CS , Ul Mahmood S , Rotella DP , Kelly MP
Published: October 2024

PDE11A is a little-studied phosphodiesterase sub-family that breaks down cAMP/cGMP, with the PDE11A4 isoform being enriched in the memory-related brain region called the hippocampus. Age-related increases in PDE11A expression occur in human and rodent hippocampus and cause age-related cognitive decline of social memories. Interestingly, the age-related increase in PDE11A4 protein ectopically accumulates in spherical clusters that group together in the brain to form linear filamentous patterns termed “ghost axons.” The biophysical/physiochemical mechanisms underlying this age-related clustering of PDE11A4 are not yet known. As such, we determine here if age-related clustering of PDE11A4 may reflect liquid:liquid phase separation (LLPS), and if PDE11A inhibitors being developed for age-related cognitive decline can reverse this biomolecular condensation. We found that human and mouse PDE11A4 exhibit several LLPS-promoting sequence features including intrinsically disordered regions, non-covalent pi-pi interactions, and prion-like domains, with multiple bioinformatic tools predicting PDE11A4 undergoes LLPS. Consistent with these predictions, age-related PDE11A4 clusters were non-membrane bound spherical droplets that progressively fuse over time in a concentration-dependent manner. 5 different PDE11 inhibitors (tadalafil, BC11-38, SMQ-02-57, SMQ-03-30 and SMQ-03-20) across 3 scaffolds reversed PDE11A4 LLPS (a.k.a. remixing) in hippocampal HT22 cells, with PDE11A4 droplets reforming (a.k.a. de-mixing) following a 5-hour washout of low but not high concentrations of these compounds. Strikingly, a single oral administration of 30 mg/kg SMQ-03-20 substantially reduced the presence of PDE11A4 ghost axon in the aged mouse brain. Thus, PDE11A4 exhibits 4 defining criteria of LLPS, and PDE11A small molecule inhibitors reverse this age-related phenotype bothin vitroandin vivo.
Diverse calcium dynamics underlie place field formation in hippocampal CA1 pyramidal cells
Authors: Sumegi Mate , Olah Gaspar , Lukacs Istvan Paul , Blazsek Martin , Makara Judit K. , Nusser Zoltan
Published: October 2024

Every explored environment is represented in the hippocampus by the activity of distinct populations of pyramidal cells (PCs) that typically fire at specific locations called their place fields (PFs). PFs are constantly born even in familiar surroundings (during representational drift), and many rapidly emerge when the animal explores a new or altered environment (during global or partial remapping). Behavioral time scale synaptic plasticity (BTSP), a plasticity mechanism based on prolonged somatic bursts induced by dendritic Ca2+plateau potentials, was recently proposed as the main cellular mechanism underlying new PF formations (PFF), but it is unknown whether burst-associated large somatic [Ca2+] transients are necessary and/or sufficient for PFF. To address this issue, here we performedin vivotwo-photon [Ca2+] imaging of hippocampal CA1 PCs in head-restrained mice to investigate somatic [Ca2+] dynamics underlying PFFs in familiar and novel virtual environments. Our results demonstrate that although many PFs are formed by BTSP-like events, PFs also frequently emerge with initial [Ca2+] dynamics that do not match any of the characteristics of BTSP. BTSP and non-BTSP-like new PFFs occur spontaneously in familiar environments, during neuronal representational switches and instantaneously in new environments. Our data also reveal that solitary [Ca2+] transients that exceed in amplitude those evoking BTSP-like PFFs frequently occur without inducing PFs, demonstrating that large [Ca2+] transientsper seare not sufficient for PFF.
The role of cytochrome c in mitochondrial metabolism of human oocytes
Authors: Surmacki Jakub Maciej , Abramczyk Halina , Sobkiewicz Bogna , Walczak-Jędrzejowska Renata , Słowikowska-Hilczer Jolanta , Marchlewska Katarzyna
Published: October 2024

We investigated the biochemical composition of specific organelles in human oocyte cells at various maturation stages (GV, immature MI, MII with the first polar body, MII with giant polar body, and vacuoles) using Raman imaging. The structures analyzed included the nucleus, zona pellucida, perivitelline space, polar body, mitochondria, and cytoplasm. Raman imaging combined with chemometric classification via Cluster Analysis facilitated a comprehensive biochemical analysis of the proteomic, lipidomic, and DNA profiles of the human oocyte. Our findings indicate that cytochromecis a crucial protein in oocyte mitochondria, essential for both cellular respiration (via oxidative phosphorylation) and apoptosis. Effective oocyte cell functioning requires cytochromecin its redox-balanced forms: reduced and oxidized. The oxidized form of cytochromecplays a pivotal role in the electron transport chain, enabling proper electron shuttling between complex III, cytochromec, and complex IV. This process ensures controlled oxidative phosphorylation and ATP production, which are vital for most steps in oocyte maturation.

Background

In spite of progress in the identification of the fertile/infertile human oocytes in the recent decades, our understanding of molecular mechanisms occurring in the female reproductive cells did not make significant progress.

Objective

The present study aimed to develop our knowledge on mitochondrial metabolism in oocyte cells.

Results

Biochemical human oocyte analysis of proteomic-lipidomic-DNA profile by using Raman imaging combined with chemometric classification method of Cluster Analysis has been obtained. Our results show that cytochromecis a key protein in oocyte mitochondria that is needed to maintain life (respiration via oxidative phosphorylation) and cell death (apoptosis).

Materials and Methods

In this experimental study, the nine fresh human native live oocytes from six donors collected in Salve Medica, Lodz, Poland have been investigated. The fingerprint and high-frequency region were evaluated by using Raman spectroscopy and imaging from 400 to 3500 cm-1. The principal component analysis method was used to visualize the difference in the Raman spectra of oocytes at different stage of maturation. The study was approved by the Bioethical Committee of the Medical University in Lodz, Poland (No RNN/83/23/KE). Written informed consent was obtained from all patients who voluntarily participated in the study. All procedures were conducted in accordance with the guidelines of the Declaration of Helsinki (2013).

Abstract Figure
Evolutionary origins and innovations sculpting the mammalian PRPS enzyme complex
Authors: Karki Bibek R. , Macmillan Austin C. , Vicente-Muñoz Sara , Greis Kenneth D. , Romick Lindsey E. , Cunningham J. Tom
Published: October 2024

The phosphoribosyl pyrophosphate synthetase (PRPS) enzyme conducts a chokepoint reaction connecting central carbon metabolism and nucleotide production pathways, making it essential for life1,2. Here, we show that the presence of multiple PRPS-encoding genes is a hallmark trait of eukaryotes, and we trace the evolutionary origins and define the individual functions of each of the five mammalian PRPS homologs – three isozymes (one testis-restricted)3,4and two non-enzymatic associated proteins (APs)5,6– which we demonstrate operate together as a large molecular weight complex capable of attaining a heterogeneous array of functional multimeric configurations. Employing a repertoire of isogenic fibroblast clones in all viable individual or combinatorial assembly states, we define preferential interactions between subunits, and we show that cells lacking PRPS2, PRPSAP1, and PRPSAP2 render PRPS1 into aberrant homo-oligomeric assemblies with diminished metabolic flux and impaired proliferative capacity. We demonstrate how numerous evolutionary innovations in the duplicated genes have created specialized roles for individual complex members and identify translational control mechanisms that enable fine-tuned regulation of PRPS assembly and activity, which provide clues into the positive and negative selective pressures that facilitate metabolic flexibility and tissue specialization in advanced lifeforms. Collectively, our study demonstrates how evolution has transformed a single PRPS gene into a multimeric complex endowed with functional and regulatory features that govern cellular biochemistry.
A molecular representation system with a common reference frame for natural products pathway discovery and structural diversity tasks
Authors: Babineau Nicole , Nguyen Le Thanh Dien , Mathieu Davis , McCue Clint , Schlecht Nicholas , Abrahamson Taylor , Hamberger Björn , Busta Lucas
Published: October 2024

Researchers have uncovered hundreds of thousands of natural products, many of which contribute to medicine, materials, and agriculture. However, missing knowledge of the biosynthetic pathways to these products hinders their expanded use. Nucleotide sequencing is key in pathway elucidation efforts, and analyses of natural products’ molecular structures, though seldom discussed explicitly, also play an important role by suggesting hypothetical pathways for testing. Structural analyses are also important in drug discovery, where many molecular representation systems – methods of representing molecular structures in a computer-friendly format – have been developed. Unfortunately, pathway elucidation investigations seldom use these representation systems. This gap is likely because those systems are primarily built to document molecular connectivity and topology, rather than the absolute positions of bonds and atoms in a common reference frame, the latter of which enables chemical structures to be connected with potential underlying biosynthetic steps. Here, we present a unique molecular representation system built around a common reference frame. We tested this system using triterpenoid structures as a case study and explored the system’s applications in biosynthesis and structural diversity tasks. The common reference frame system can identify structural regions of high or low variability on the scale of atoms and bonds and enable hierarchical clustering that is closely connected to underlying biosynthesis. Combined with phylogenetic distribution information, the system illuminates distinct sources of structural variability, such as different enzyme families operating in the same pathway. These characteristics outline the potential of common reference frame molecular representation systems to support large-scale pathway elucidation efforts.

Significance Statement

Studying natural products and their biosynthetic pathways aids in identifying, characterizing, and developing new therapeutics, materials, and biotechnologies. Analyzing chemical structures is key to understanding biosynthesis and such analyses enhance pathway elucidation efforts, but few molecular representation systems have been designed with biosynthesis in mind. This study developed a new molecular representation system using a common reference frame, identifying corresponding atoms and bonds across many chemical structures. This system revealed hotspots and dimensions of variation in chemical structures, distinct overall structural groups, and parallels between molecules’ structural features and underlying biosynthesis. More widespread use of common reference frame molecular representation systems could hasten pathway elucidation efforts.
High-coverage nanopore sequencing of samples from the 1000 Genomes Project to build a comprehensive catalog of human genetic variation
Authors: Gustafson Jonas A. , Gibson Sophia B. , Damaraju Nikhita , Zalusky Miranda P.G. , Hoekzema Kendra , Twesigomwe David , Yang Lei , Snead Anthony A. , Richmond Phillip A. , De Coster Wouter , Olson Nathan D. , Guarracino Andrea , Li Qiuhui , Miller Angela L. , Goffena Joy , Anderson Zachary B. , Storz Sophie H.R. , Ward Sydney A. , Sinha Maisha , Gonzaga-Jauregui Claudia , Clarke Wayne E. , Basile Anna O. , Corvelo André , Reeves Catherine , Helland Adrienne , Musunuri Rajeeva Lochan , Revsine Mahler , Patterson Karynne E. , Paschal Cate R. , Zakarian Christina , Goodwin Sara , Jensen Tanner D. , Robb Esther ,   The 1000 Genomes ONT Sequencing Consortium,   University of Washington Center for Rare Disease Research (UW-CRDR),   Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium, McCombie William Richard , Sedlazeck Fritz J. , Zook Justin M. , Montgomery Stephen B. , Garrison Erik , Kolmogorov Mikhail , Schatz Michael C. , McLaughlin Richard N. , Dashnow Harriet , Zody Michael C. , Loose Matt , Jain Miten , Eichler Evan E. , Miller Danny E.
Published: October 2024

Fewer than half of individuals with a suspected Mendelian or monogenic condition receive a precise molecular diagnosis after comprehensive clinical genetic testing. Improvements in data quality and costs have heightened interest in using long-read sequencing (LRS) to streamline clinical genomic testing, but the absence of control data sets for variant filtering and prioritization has made tertiary analysis of LRS data challenging. To address this, the 1000 Genomes Project (1KGP) Oxford Nanopore Technologies Sequencing Consortium aims to generate LRS data from at least 800 of the 1KGP samples. Our goal is to use LRS to identify a broader spectrum of variation so we may improve our understanding of normal patterns of human variation. Here, we present data from analysis of the first 100 samples, representing all 5 superpopulations and 19 subpopulations. These samples, sequenced to an average depth of coverage of 37× and sequence read N50 of 54 kbp, have high concordance with previous studies for identifying single nucleotide and indel variants outside of homopolymer regions. Using multiple structural variant (SV) callers, we identify an average of 24,543 high-confidence SVs per genome, including shared and private SVs likely to disrupt gene function as well as pathogenic expansions within disease-associated repeats that were not detected using short reads. Evaluation of methylation signatures revealed expected patterns at known imprinted loci, samples with skewed X-inactivation patterns, and novel differentially methylated regions. All raw sequencing data, processed data, and summary statistics are publicly available, providing a valuable resource for the clinical genetics community to discover pathogenic SVs.
Probing the nature of the anticharmed-strange pentaquark states: Mass spectra, decays, and magnetic moments
Authors: Liu Xuejie , Tan Yue , Chen Xiaoyun , Chen Dianyong , Huang Hongxia , Ping Jialun
Published: October 2024

Within the framework of the quark delocalization color screening model, a systematic investigation of the anticharmed-strange pentaquark system is performed using the resonance group method. The currently estimations predict three bound states with estimated masses to be 2886 MeV, 3039 MeV, and 3153 MeV, respectively. Additionally, three resonance states are identified in various scattering phase shifts processes. Among them, two resonance states ΣD¯ and Σ*D¯* with quantum number 12(12−) are detected in channels ND¯s* and ND¯, and ΣD¯* and ΛD¯, with masses and decay widths of (MR=3053–3055  MeV, Ttotal=13.0–13.4  MeV) and (MR=3389–3390  MeV, Ttotal=10.4  MeV), respectively. In the ΛD¯* and ΣD¯* channels, a resonance state with quantum number 12(32−) is discovered, with its mass and decay width being 3250–3252 MeV and 4.4,MeV, respectively. These predicted pentaquark states have c¯snnn quark compositions, allowing them to be recognized as genuine pentaquark states. To validate these predictions, it is expected that upcoming experiments will further explore the predicted resonance and bound states in these possible decay channels.

Published by the American Physical Society
2024
Self-interacting scalar dark matter around binary black holes
Authors: Aurrekoetxea Josu C. , Marsden James , Clough Katy , Ferreira Pedro G.
Published: October 2024

Gravitational waves can provide crucial insights about the environments in which black holes live. In this work, we use numerical relativity simulations to study the behavior of self-interacting scalar (wavelike) dark matter clouds accreting onto isolated and binary black holes. We find that repulsive self-interactions smoothen the “spike” of an isolated black hole and saturate the density. Attractive self-interactions enhance the growth and result in more cuspy profiles, but can become unstable and undergo explosions akin to the superradiant bosenova that reduce the local cloud density. We quantify the impact of self-interactions on an equal-mass black hole merger by computing the dephasing of the gravitational-wave signal for a range of couplings. We find that repulsive self-interactions saturate the density of the cloud, thereby reducing the dephasing. For attractive self-interactions, the dephasing may be larger, but if these interactions dominate prior to the merger, the dark matter can undergo bosenova during the inspiral phase, disrupting the cloud and subsequently reducing the dephasing.

Published by the American Physical Society
2024
Policy recommendations on supporting employee financial participation
Authors: Lowitzsch Jens
Published: October 2024

Purpose

From the first PEPPER report in 1991 until this PEPPER V Report the EU has not only expanded from 12 Members States to currently 27 but also faced complex and urgent challenges. Both the financial crisis of 2008/09 and the coronavirus disease 2019 (COVID-19) pandemic 2020/21 have left their marks on “Social Europe”. Although the overall dynamic of employee financial participation (EFP) across the EU 27 is positive, EFP is declining in terms of its share of household income in the light of the concentration of capital ownership and of capital income. Along with the issue of distributive justice, other challenges, such as business succession in small and medium enterprises (SMEs) that have been on the agenda for decades, and new ones like the extension of EFP to social enterprises, are calling for action.

Design/methodology/approach

From the comparison of the countries, the cluster analysis and the background of the importance of legal framework and fiscal incentives, two general principles can be derived: (1) establishing EFP schemes through legislation is of primary importance as countries that provide a stable and transparent regulatory framework for EFP also show a wider implementation of EFP practices; (2) when properly designed, fiscal incentives promote the spread of EFP effectively as both countries with a long tradition of tax incentives for EFP (e.g. UK, France) and those with a more recent development (e.g. Austria) confirm.

Findings

It is against this background that the following policy recommendations should be read. Tax incentives should (and in most countries they actually do) target those taxes, which constitute the heaviest burden in the national taxation system. (1) Tax incentives should be provided for both employees and the employer company. (2) Even substantial tax incentives may prove inefficient when the pre-conditions for eligibility are too restrictive, complex or inflexible. (3) Some forms of tax incentives are more suitable for certain types of plans, e.g. deferred taxation for employee share ownership (ESO), capital gains tax in lieu of personal income tax for dividends and sale of shares, or tax exemptions for matching contributions for European Employee Stock Ownership Plans (ESOPs).

Originality/value

In light of this need for SME action and the great potential for introducing ESO in this enterprise segment, from our recommendations we emphasise in particular: Alleviating the evaluation problem in unlisted SMEs through debt-to-equity-swaps. ESO may initially take the form of an employee loan to the company, creating corporate debt, which is subsequently converted into company shares. Facilitating share transfers in privately held limited liability companies (LLCs) by ending the requisite for notarial certification (Italy and France) or limiting it to the identity of seller and buyer. ESO in SMEs via intermediary entities, e.g. trusts, foundations, LLCs or other special purpose vehicle (SPVs) to hold and administer employee shares (AT, IE, UK, HU, FR, SI, USA).
Children and the Gender Earnings Gap: Evidence for Australia*
Authors: Bahar Elif , Bradshaw Natasha , Deutscher Nathan , Montaigne Maxine
Published: October 2024

We estimate the impact of children on the gender earnings gap in Australia using an event study approach. We show that the arrival of children has a large and persistent impact on the gender earnings gap, reducing female annual earnings by 53 per cent, on average, in the first 5 years of parenthood. We attribute the gap in earnings to lower participation rates and reduced working hours among mothers, including a shift to part‐time work. Although the decline in earnings for women is similar regardless of their breadwinner status prior to children, women with greater access to workplace flexibility are more likely to remain employed after having children.
Preoperative markers for identifying CT ≤2 cm solid nodules of lung adenocarcinoma based on image deep learning
Authors: Gao Zhen , Liu Shang , Li Xiao , Xu Lin , Xiao Han , Guo Ji‐chao , Yu Yue , Li Meng , Ren Wan‐gang , Peng Zhong‐min
Published: October 2024

Background

The solid pattern is a highly malignant subtype of lung adenocarcinoma. In the current era of transitioning from lobectomy to sublobar resection for the surgical treatment of small lung cancers, preoperative identification of this subtype is highly important for patient surgical approach selection and long‐term prognosis.

Methods

A total of 1489 patients with clinical stage IA1‐2 primary lung adenocarcinoma were enrolled. Based on patient clinical characteristics and lung imaging features obtained via deep learning, highly correlated diagnostic factors were identified through LASSO regression and decision tree analysis. Subsequently, a logistic model and nomogram were constructed. A restricted cubic spline (RCS) was used to calculate the optimal inflection point of quantitative data and the differences between the groups.

Results

The three‐dimensional proportion of solid component (PSC), sex, and smoking status was identified as being highly correlated diagnostic factors for solid predominant adenocarcinoma. The logistic model had good prediction efficiency, and the area under the ROC curve was 0.85. Decision curve analysis demonstrated that the application of diagnostic factors can improve patient outcomes. RCS analysis indicated that the proportion of solid adenocarcinomas increased by 4.6 times when the PSC was ≥72%. A PSC of 72% is a good cutoff point.

Conclusion

The preoperative diagnosis of solid‐pattern adenocarcinoma can be confirmed by typical imaging features and clinical characteristics, assisting the thoracic surgeon in developing a more precise surgical plan.
From pin money to side hustle: Rural and regional women's side businesses in Australia 1900–2023
Authors: Prowse Louise
Published: October 2024

In the last 15 years, mainstream use of the term ‘side hustle’ has boomed. But the act of having a side hustle is not new; the term's novelty obscures a long‐established pattern of ‘sideline earning’ by Australian rural women, and indeed around the world. Through the lens of environmental, labour and gender history, and using interviews, digital media, diaries, court records, newspaper and magazine articles and other archival records, this research explores how Australian rural women have engaged in and relied on the practice of sideline earning as an economic necessity, long before it entered the mainstream economy and consciousness.
Prenatal detection of placenta accreta spectrum using a sonographic checklist
Authors: Bartels Helena C. , Walsh Jennifer M. , Carroll Stephen , Downey Paul , O'Brien Donal J. , McAuliffe Fionnuala M. , C'Connor Clare , Thompson Claire , Donnelly Jennifer , Brennan Donal J. , Corcoran Siobhan M.
Published: October 2024

Introduction

The European Working Group for Abnormally Invasive Placenta proposed a checklist of ultrasound features for the antenatal detection of placenta accreta spectrum (PAS). This study aims to assess the performance of the checklist in identifying histopathologically confirmed PAS cases in a cohort with a high pre‐test probability of PAS, and identify if particular features are associated with PAS.

Material and Methods

This is a prospective multi‐site cohort study conducted between 2018 and 2023. Consecutive patients who underwent ultrasound assessment for suspicion of PAS were included, and the sonographic checklist was completed at the time of ultrasound. Cases were defined as PAS where they had intraoperative findings as described by the International Federation of Gynecology and Obstetrics (FIGO) grading, and histopathological findings for hysterectomy and myometrial resection cases. All non‐PAS cases in this study had placenta previa and at least one prior cesarean delivery.

Results

Seventy‐eight participants met inclusion criteria, of whom 63 (80.7%) were diagnosed with PAS. Cesarean hysterectomy was performed in 49 cases (62.8%). Overall, third‐trimester ultrasound performed at a median gestational age of 32 weeks (IQR 30–34 weeks) had a sensitivity of 0.84 (95% CI 0.73 to 0.92) and specificity of 0.73 (95% CI 0.45 to 0.92) for detecting PAS, with a positive and negative likelihood ratio of 3.15 (95% CI 1.35 to 7.35) and 0.22 (95% CI 0.11 to 0.41), respectively. Features most associated with PAS were abnormal placental lacunae (Odds Ratio [OR] 5.40 [95% CI 1.61 to 18.03] and myometrial thinning OR 6.87 [95% CI 1.93 to 24.4]). While many of the ultrasound features seen in PAS were also present in cases of placenta previa with prior Cesarean section, the median (IQR) number of features present in PAS cases was significantly higher than in the non‐PAS placenta previa group (six features [3–8] vs. two features [0–3] p = 0.001). No case of non‐PAS placenta previa had more than five features present.

Conclusions

The use of a standardized sonographic checklist had a high sensitivity and good specificity for the detection of PAS in this prospective cohort of well‐classified PAS cases.
The efficacy of expanded non‐invasive prenatal testing (NIPT) in a high‐risk twin pregnancies cohort
Authors: Meng Meng , Chen Jianping , Yang Yingjun , Zhang Yun , Zou Gang , Zhou Fenhe , Wei Xing , Ge Yuchun , Zhou Jia , Sun Luming
Published: October 2024

Introduction

Our objective was to evaluate the efficacy of expanded non‐invasive prenatal testing (NIPT) that includes both trisomies and copy number variants (CNVs) in high‐risk twin pregnancies.

Material and Methods

A prospective, double‐blinded cohort study was conducted, enrolling 73 high‐risk twin pregnancies characterized by increased risk of genetic disorders due to factors such as increased nuchal translucency, structural anomalies, fetal growth restriction, and other factors associated with chromosomal abnormality. Participants underwent invasive karyotyping and chromosomal microarray analysis, alongside separate expanded NIPT for research purposes. The sensitivity, specificity, positive predictive value, and negative predictive value of expanded NIPT were calculated.

Results

The cohort included 24 monochorionic and 49 dichorionic twin pregnancies. The median cell‐free fetal DNA concentration in expanded NIPT was 16.7% (range 3.86%–49.1%), with a test failure rate of 1.4% (1/73). High‐risk findings for trisomy 21/13/18 were identified in five cases (6.8%), Turner syndrome in one case (1.4%), and CNVs indicative of high risk for clinically significant microdeletion/microduplication syndromes (MMS) in ten cases (13.7%). Of these, 56 cases (76.7%) tested NIPT negative, revealing one false‐negative for 45, X and five false‐negatives for CNVs. Expanded NIPT achieved a detection rate of 100% (5/5) for trisomy 21/13/18 with a false‐positive rate of 0% (0/5), a detection rate of 33.3% (1/3) for sex chromosome abnormalities with a false‐positive rate of 0% (0/3), and a detection rate of 66.7% (4/6) for MMS with a false‐positive rate of 3.0% (2/67). The positive predictive values for trisomy T21/13/18, sex chromosome abnormalities, and known MMS were 100% (5/5), 100% (1/1), and 66.7% (4/6) in the expanded NIPT, respectively.

Conclusions

The expanded NIPT demonstrated high detection rates for common trisomies and moderate detection rates for prenatal MMS in high‐risk twin pregnancies. Further studies with large sample sizes in low‐risk populations are needed.
COVID‐19 pandemic impact on gynecologic cancer treatment pathways in a Finnish tertiary center
Authors: Pikkujämsä Hanna , Luukkaala Tiina , Nyberg Reita H. , Louvanto Karolina
Published: October 2024

Introduction

COVID‐19 and new guidelines during the pandemic affected the gynecologic cancer treatment pathways, resulting in recorded delays and modifications in the treatment protocols. The aim of this study was to determine the impact of the COVID‐19 pandemic in one of the major gynecologic cancer care centers in Finland, Tampere University Hospital.

Material and Methods

Our retrospective register study included 909 patients that were new gynecologic cancer cases (uterine, cervical, vulvar, vaginal, or ovarian) referred to the Tampere University Hospital Gynecologic Oncology Outpatient Clinic between March 17th, 2018, and March 15th, 2022. The patients were divided into two separate groups depending on their time of referral: time before COVID (March 17th, 2018, to March 15th, 2020), and during COVID (March 16th, 2020, to March 15th, 2022). These groups were compared in terms of patient characteristics, different cancer types and stages, symptoms, and treatment methods.

Results

During the COVID‐19 pandemic, patients generally suffered from cancer symptoms longer (p < 0.003) and were more likely to be overweight (p = 0.035). The improved multidisciplinary team meeting gave the patients a faster route to their first intervention during COVID (p < 0.05). An insignificant shift toward nonsurgical first interventions and non‐curative intent was seen during COVID, but the multidisciplinary team treatment plans were mostly implemented accordingly on both eras. No decrease was seen in the number of new gynecologic cancer cases, and the one‐year overall survival remained the same in both groups.

Conclusions

Overall, the COVID‐19 pandemic did not significantly alter treatment pathways in gynecologic cancer care at Tampere University Hospital. The number of new patients and given treatments remained relatively stable. During COVID, access from referral to cancer treatment was significantly accelerated, which is likely confounded by changes to the multidisciplinary team protocol made in early 2021.
Habitualness, reward and external constraints: Exploring the underlying influences of daily water intake using the Situated Assessment Method2
Authors: Rodger Amy , Barsalou Lawrence W. , Papies Esther K.
Published: October 2024

Understanding what facilitates and hinders water drinking is crucial to inform interventions for preventing underhydration. Using the Situated Assessment Method2, we extended previous research by examining what influences water drinking in daily life. We studied 213 UK adults, assessing 13 potential predictors (e.g. thirst, availability of other drinks) of their typical water intake across 10 everyday situations (e.g. during work, dinner). Participants then reported their actual water intake in these situations over three alternating days during a 1‐week follow‐up. We evaluated the variability of water intake and its influences across individuals and situations and the prospective relationship between these influences and water intake. The 13 identified predictors explained substantial proportions of variation in water intake. Factors like habitualness (e.g. subjective effort), self‐relevance (e.g. health consciousness) and immediate feedback (e.g. taste) were positively associated with water intake. However, the influence of these factors varied significantly across individuals and situations. Our results suggest that various interrelated predictors facilitate and hinder water drinking behaviour, emphasising the importance of using comprehensive behaviour theories to inform research in this domain. They also align with growing evidence that reward may regulate habitual behaviour.
Timely Follow‐Up After a First Diagnosis of Cirrhosis is Associated With Reduced Mortality but No Impact on Rehospitalisations: A Population‐Based Cohort of 8852 Patients
Authors: Schechter Max S. , Widman Linnea , Wester Axel , Shang Ying , Stål Per , Fortune Brett , Hagström Hannes
Published: October 2024

Background and Aims

Timely transition of care amongst patients with a first diagnosis of cirrhosis in a hospital to an outpatient visit is important. We evaluated rates of outpatient follow‐up after a first diagnosis of cirrhosis during an inpatient setting, and its association with subsequent rates of rehospitalisation and mortality.

Methods

We conducted a population‐based cohort study identifying all hospitalised patients in Sweden diagnosed with cirrhosis between 2002 and 2020 from the Swedish National Patient Register. The primary outcome was any outpatient visit related to cirrhosis within 90 days after hospital discharge. Secondary outcomes were rates of rehospitalisation and mortality within 1 year of discharge in patients receiving outpatient follow‐up within 90 days or not. Cox regression was used for all analyses, and incidence rates per 1000 person‐years were calculated for mortality and rehospitalisation.

Results

Of 8852 patients, 3759 (42%) had outpatient follow‐up within 90 days of discharge. Patients who received follow‐up within 90 days of discharge were younger, had a higher level of education and were more likely to have liver decompensation or hepatocellular carcinoma compared to those without timely follow‐up. We found that follow‐up within 90 days was associated with lower rates of all‐cause mortality within 1 year (aHR = 0.86, 95%CI = 0.78–0.96) but with no significant impact on rehospitalisations (aHR = 0.97, 95%CI = 0.91–1.03).

Conclusions

In Sweden, 42% of hospitalised patients with newly diagnosed cirrhosis receive outpatient follow‐up within 90 days of their hospital discharge. These patients may experience lower mortality but no change in rehospitalisations within 1 year.
Chemistry/structural biology of psychedelic drugs and their receptor(s)
Authors: Gumpper Ryan H. , Nichols David E.
Published: October 2024

This brief review highlights some of the structure–activity relationships of classic serotonergic psychedelics. In particular, we discuss structural features of three chemotypes: phenethylamines, ergolines and certain tryptamines, which possess psychedelic activity in humans. Where they are known, we point out the underlying molecular mechanisms utilized by each of the three chemotypes of psychedelic molecules. With a focus on the 5‐HT2A receptor subtype, a G‐protein coupled receptor known to be the primary target of psychedelics, we refer to several X‐ray and cryoEM structures, with a variety of ligands bound, to illustrate the underlying atomistic basis for some of the known pharmacological observations of psychedelic drug actions.
Association between statin use and dry eye disease in patients with hyperlipidemia: A population‐based retrospective cohort study
Authors: Wang Yong‐Wei , Liu Sian‐De , Lin Guan‐Ling , Huang Evelyn‐Jou‐Chen , Keller Joseph Jordan , Wang Li‐Hsuan
Published: October 2024

Higher serum cholesterol levels have been associated with an increased risk of dry eye disease (DED). The relationship between statin (HMG‐CoA reductase inhibitor) use and DED in patients with hyperlipidemia remains unclear. To investigate the association between statin use and the risk of DED in patients with hyperlipidemia, we conducted a population‐based retrospective cohort study utilizing data from Taiwan's Longitudinal Generation Tracking Database. Patients were categorized into statin users and nonusers, with a 5‐year follow‐up period. The study identified patients with newly diagnosed hyperlipidemia, excluding those with prior DED diagnoses. Matching and adjustments for covariates resulted in 41,931 individuals in each group. Patients receiving statin therapy were compared with those unexposed. Cumulative exposure doses were also evaluated to assess dose–response relationships. The primary outcome was the incidence of DED diagnosed during the follow‐up period. Cox proportional hazards regression models estimated the risk of DED, and conditional logistic regression analyzed the dose–response effect of statin exposure. Among 41,931 matched pairs, statin users exhibited a slightly increased risk of developing DED compared with nonusers (adjusted hazard ratio, 1.06; 95% CI, 1.02–1.11; p < 0.01). However, no dose–response relationship was observed between statin exposure and DED risk. Statin use among patients with hyperlipidemia is associated with a marginally higher risk of DED. These findings underscore the importance of regular eye examinations in this patient population to facilitate early detection and management of DED.
1112. Pittosporum beecheyi Tuyama
Authors: Utteridge Timothy M. A. , Yamanaka Masumi , Komaki Yoshiteru , Kawakita Atsushi
Published: October 2024

Pittosporum beecheyi Tuyama, endemic to the Ogasawara (Bonin) Islands is described and illustrated; the species is known only from the Hahajima Island group. Key characters for the recognition of this species include the hairy ovary, the solitary flowers with curved pedicels, and the pendulous globose fruits that dehisce into three valves.