bluuebunny/crossref_metadata_2025 huggingface dataset:
SIMandCCS52A1control root hair cell endoreplication and expansion
Authors: Li (李磊) Lei , Herburger Klaus , Vercauteren Ilse , Heyman Jefri , De Veylder Lieven
Published: October 2024

Arabidopsis thaliana(Arabidopsis) root hair cells undergo rapid cell elongation that is correlated with an increased DNA ploidy level through endoreplication. However, the contribution of endoreplication to hair cell growth is currently unclear. Here, we determined ploidy levels within the root hair cell file from the proximal meristem to the elongation zone and correlated them with cellular parameters. Our data show that cells in the basal meristem reach a 4C level prior to rapid elongation, whereas in the elongation zone a 16C level is reached prior to the onset of tip growth, suggesting that endoreplication is a prerequisite for rapid volume increase. Consistently, we show that mutants inSIAMESE(SIM) andCELL CYCLE SWITCH52 A1(CCS52A1), key endocycle regulators expressed in hair cells, display a decrease in cell volume and hair tip length. Interestingly, SIM and CCS52A1 affect cell width and length, respectively. In addition, CCS52A1 controls the growth rate of the root hair tip. Given the common association between cell expansion and cell wall modifications, we performed immunolabeling on wild-type and mutant roots, which revealed a reduced level of pectin methylesterification in the mutant backgrounds, suggesting that SIM and CCS52A1 may modulate root hair cell growth by affecting cell wall modifications.

The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (https://academic.oup.com/plphys/pages/General-Instructions) is Lieven De Veylder (lieven.deveylder@psb.vib-ugent.be).

ONE-SENTENCE SUMMARY

SIMandCCS52A1control Arabidopsis root hair cell volume by controlling endoreplication.
Predictive model for real-world performance of COVID-19 antigen tests based on laboratory evaluation
Authors: Bosch Miguel , Garcia Dawlyn , Rudtner Lindsey , Salcedo Nol , Colmenares Raul , Hoche Sina , Arocha Jose G , Hall Daniela , Moreno Adriana , Bosch Irene
Published: October 2024

Controlling spread of disease due to infectious agents require a quick response from public health sector. In the ongoing COVID-19 pandemic, the use of antigen tests has shown to be an excellent tool to inform authorities and mitigate the spread of the disease. In this communication we demonstrated how performance of an antigen test -- as a diagnosticin vitrodevice -- can be properly validated using quantitative laboratory experimentation and self-testing data from a clinical study. We also show how clinical performance of an antigen test can be predicted using mathematical modeling. The proposed appraisal methodology of antigen test performance under real-world conditions could be a useful tool to inform regulatory decision making. This approach allows to standardize, democratize, and speed up the process of validation, analysis, and comparison of antigen rapid tests, and thus to help developing effective public health response strategies.
Validation of the Comprehensive Online Sleep Monitoring Scale (COSMOS) in a Large Population Sample
Authors: Rida Laila , Ioannidis Konstantinos , Chamberlain Samuel R , Grant Jon E , Hellyer Peter , Giunchiglia Valentina , Trender William , Allebrandt Karla V , Shergill Sukhi , Williams Steven CR , Hampshire Adam
Published: October 2024

Researchers are increasingly studying cognitive and psychological constructs using automated online tools due to advantages in scalability, repeatability, accessibility and affordability. The online assessment of sleep presents a challenge, as the most popular instruments for reporting different aspects of sleep were originally designed to be deployed under supervised conditions by trained personnel. Here, we develop and validate the Comprehensive Online Sleep Monitoring Scale (COSMOS), a self-reported sleep scale optimised for online, independent administration. Using data from N = 5,815 adults, we show that COSMOS has good internal (Cronbach's alpha = 0.85) and convergent validity, via strong associations with established sleep scales. Poorer COSMOS sleep scores were found in participants diagnosed with psychological conditions, more frequent depression or anxiety symptoms, and higher compulsivity or neuroticism traits, demonstrating good construct validity. We propose COSMOS as a comprehensive and validated sleep assessment that is suitable for large-scale online transdiagnostic and mental health research.
Depolymerizing F-actin accelerates the exit from pluripotency to enhance stem cell-derived islet differentiation
Authors: Hogrebe Nathaniel J. , Schmidt Mason D. , Augsornworawat Punn , Gale Sarah E. , Shunkarova Mira , Millman Jeffrey R.
Published: October 2024

In this study, we demonstrate that cytoskeletal state at the onset of directed differentiation is critical for the specification of human pluripotent stem cells (hPSCs) to all three germ layers. In particular, a polymerized actin cytoskeleton facilitates directed ectoderm differentiation, while depolymerizing F-actin promotes mesendoderm lineages. Applying this concept to a stem cell-derived islet (SC-islet) differentiation protocol, we show that depolymerizing F-actin with latrunculin A (latA) during the first 24 hours of definitive endoderm formation facilitates rapid exit from pluripotency and alters Activin/Nodal, BMP, JNK-JUN, and WNT pathway signaling dynamics. These signaling changes influence downstream patterning of the gut tube, leading to improved pancreatic progenitor identity and decreased expression of markers associated with other endodermal lineages. Continued differentiation generates islets containing a higher percentage of β cells that exhibit improved maturation, insulin secretion, and ability to reverse hyperglycemia. Furthermore, this latA treatment reduces enterochromaffin cells in the final cell population and corrects differentiations from hPSC lines that otherwise fail to consistently produce pancreatic islets, highlighting the importance of cytoskeletal signaling at the onset of directed differentiation.
Evaluating signaling pathway inference from kinase-substrate interactions and phosphoproteomics data
Authors: Garrido-Rodriguez Martin , Potel Clement , Burtscher Mira Lea , Becher Isabelle , Rodriguez-Mier Pablo , Müller-Dott Sophia , Savitski Mikhail M , Saez-Rodriguez Julio
Published: October 2024

Cellular signaling plays a vital role in how cells communicate and adapt to both environmental and internal cues. At the molecular level, signaling is largely driven by phosphorylation cascades controlled by kinases. Because of this, kinase-driven signaling pathways are used as a conceptual framework to interpret molecular data across biological contexts. However, signaling pathways were created using limited throughput technologies. As knowledge of kinase-substrate interactions grows through novel computational and experimental approaches, and phosphoproteomic methods improve their coverage and accuracy, traditional signaling pathways need to be revisited. In this study, we critically assess context-specific signaling pathway reconstruction using phosphoproteomics and kinase-substrate networks. We first integrate literature, protein language models, and peptide array data to create a state-of-the-art kinase-substrate network. Focusing on epidermal growth factor (EGF), we conduct a meta-analysis of recent short-term response phosphoproteomics studies, which we complement with three own datasets, representing the most comprehensive characterization of the EGF response available to date. Using three alternative computational methods, we infer kinase-driven pathways, which we compare to multiple ground truth sets, including the canonical pathway, experimentally validated interactions, and correlation supported interactions. Our findings reveal that literature-curated networks, when combined with network propagation, yield the best recovery of ground truth interactions. We found that up to 90% of data-supported direct interactions are absent from current ground truth sets, indicating many unexplored, but data supported kinase interactions. Our results challenge traditional views on signaling pathways and illustrate how to develop new mechanistic hypotheses using phosphoproteomics and network methods.
A spatiotemporal atlas of human spermatogenesis based on single-cell transcriptomics and multiplex antibody imaging
Authors: Hikmet Feria , Méar Loren , Gustavsson Jonas , Miranda Gisele , Zhang Cheng , Katona Borbala , Schutten Rutger , Von Feilitzen Kalle , Forsberg Mattias , Stukenborg Jan-Bernd , Uhlén Mathias , Lindskog Cecilia
Published: October 2024

Human health depends on complex processes of intercellular interactions and single-cell type-specific functions. Dramatic improvements in single-cell RNA sequencing (scRNA-seq) have opened up the possibility to identify functional states of single cells. Still, spatial methods are crucial for under-standing transcript location in relation to tissue architecture. Here, we con-structed a large-scale mapping strategy for proteins based on scRNA-seq and fluorescent-based multiplex immunohistochemistry (mIHC). We focused on the spatiotemporal landscape of 12 distinct germ cell states in human testis and performed an in-depth characterization of ∼500 germ cell proteins. Quantitative spatial localization data based on a custom-built image analysis pipeline allowed us to cluster proteins according to expression, forming the basis for functional analysis. mRNA and protein expression dynamics showed multiple cases with low levels of co-expression, highlighting the necessity of studying protein levels in single-cell mapping projects. The pre-sented workflow holds promise for proteome-wide tissue studies in health and disease.
Continuous nucleolar ribosomal RNA synthesis in differentiating lens fiber cells until abrupt nuclear degradation required for ocular lens transparency
Authors: Rayêe Danielle , Meier U. Thomas , Eliscovich Carolina , Cvekl Aleš
Published: October 2024

Cellular differentiation requires highly coordinate action of all three transcriptional systems to produce rRNAs, mRNAs, and various “short” and “long” non-coding RNAs by RNA Polymerase I, II, and III systems, respectively. The RNA Polymerase I catalyzes transcription of about 400 copies of rDNA genes generating 18S, 5.8S, and 28S rRNA molecules from the individual primary transcript. Lens fiber cell differentiation is a unique process to study transcriptional mechanisms of individual crystallin genes as their very high transcriptional outputs are directly comparable only to globin genes in erythrocytes. Importantly, both terminally differentiated lens fiber cells and mammalian erythrocytes degrade their nuclei though by different mechanisms. In lens, generation of organelle-free zone (OFZ) includes degradation of mitochondria, endoplasmic reticulum, Golgi apparatus, and nuclei; nevertheless, very little is known about their nucleoli and rRNA transcription. Here, using RNA fluorescencein situhybridization (FISH) we evaluated nascent rRNA transcription during the entire process of lens fiber cell differentiation. The lens fiber cell nuclei undergo morphological changes prior their denucleation, including chromatin condensation; remarkably, the nascent rRNA transcription persists in all nuclei next to the OFZ. The changes in both nuclei and nucleoli shape and microarchitecture were evaluated by immunofluorescence to detect fibrillarin, nucleolin, UBF, and other nuclear proteins. These studies demonstrate for the first time that highly condensed lens fiber cell nuclei have the capacity to support rRNA transcription. Thus, “late” production of rRNA molecules and consequently the ribosomes contribute to the terminal translational mechanisms to produce maximal quantities of the crystallin proteins.
Performance of Handcrafted Radiomics versus Deep Learning for Prognosticating Head and Neck Squamous Cell Carcinoma – A Systematic Review with Critical Appraisal of Quantitative Imaging Studies
Authors: Gouthamchand Varsha , Fonseca Louise AF , Hoebers Frank JP , Fijten Rianne , Dekker Andre , Wee Leonard , Thomas T Hannah Mary
Published: October 2024

Head and neck squamous cell carcinoma (HNSCC) presents a complex clinical challenge due to its heterogeneous nature and diverse treatment responses. This systematic review critically appraises the performance of handcrafted radiomics (HC) and deep learning (DL) models in prognosticating outcomes in HNSCC patients treated with (chemo)-radiotherapy. A comprehensive literature search was conducted up to May 2023, identifying 23 eligible studies that met the inclusion criteria of methodological rigor and long-term outcome reporting. The review highlights the methodological variability and performance metrics of HC and DL models in predicting overall survival (OS), loco-regional recurrence (LRR) and distant metastasis (DM). While DL models demonstrated slightly superior performance metrics compared to HC models, the highest methodological quality was observed predominantly in studies using HC radiomics. The findings underscore the necessity for methodological improvements, including pre-registration of protocols and assessment of clinical utility, to enhance the reliability and applicability of radiomic-based prognostic models in clinical practice.
Echo-free quality factor of a multilayer axion haloscope
Authors: Hernández-Cabrera Juan F. , De Miguel Javier , Hernández-Suárez E. , Joven Enrique , Otani Chiko , Rubiño-Martín J. Alberto , Zioutas Konstantin ,   DALI Collaboration
Published: October 2024

We report a methodology to determine the quality factor (Q) of wavy dark matter detectors equipped with multilayered resonators, including Fabry-Pérot interferometers and the so-called dielectric haloscope. An anechoic chamber enables the observation of the resonance frequency and its amplitude for an unlimited series of layers for the first time, which is conveniently filtered. The frequency-normalized power enhancement measured in a Dark Photons and Axionlike Particles Interferometer (DALI) prototype is a few hundred per layer over a sweep bandwidth of a few dozen of megahertz. In light of this result, this scaled-down prototype is sensitive to axions saturating the local dark matter density with a coupling to photons between gaγγ≳10−12 and gaγγ≳few×10−14  GeV−1 at frequencies of several dozens of gigahertz once cooled down to the different working temperatures of the experiment and immersed in magnetic fields ranging from about 1 to 10 T; while the sensitivity of the full-scale DALI is projected at gaγγ≳few×10−15  GeV−1 over the entire 25–250  μeV range since Q≳104 is expected.

Published by the American Physical Society
2024
Black Holes with Electroweak Hair
Authors: Gervalle Romain , Volkov Mikhail S.
Published: October 2024

We construct static and axially symmetric magnetically charged hairy black holes in the gravity-coupled Weinberg-Salam theory. Large black holes merge with the Reissner-Nordström (RN) family, while the small ones are extremal and support a hair in the form of a ring-shaped electroweak condensate carrying superconducting W currents and up to 22% of the total magnetic charge. The extremal solutions are asymptotically RN with a mass below the total charge, M<|Q|, due to the negative Zeeman energy of the condensate interacting with the black hole magnetic field. Therefore, they cannot decay into RN black holes. As their charge increases, they show a phase transition when the horizon symmetry changes from spherical to oblate. At this point they have the mass typical for planetary size black holes of which ≈11% is stored in the hair. Being obtained within a well-tested theory, our solutions are expected to be physically relevant.

Published by the American Physical Society
2024
Renormalization-Group Evolution for the Three-Particle
B
-Meson Soft Function
Authors: Huang Yong-Kang , Ji Yao , Shen Yue-Long , Wang Chao , Wang Yu-Ming , Zhao Xue-Chen
Published: October 2024

We determine for the first time the renormalization-group equation for the three-particle B-meson soft function dictating the nonperturbative strong interaction dynamics of the long-distance penguin contributions to the double radiative B-meson decays. The distinctive feature of the ultraviolet renormalization of this fundamental soft function consists in the pattern of mixing positive into negative support for an arbitrary initial condition. The exact solution to this integrodifferential evolution equation is then derived with the Laplace transform technique, allowing for the model-independent extraction of the asymptotic behavior at large and small partonic momenta.

Published by the American Physical Society
2024
Cost of excursions until first crossing of the origin for random walk and Lévy flights: An exact general formula
Authors: Mori Francesco , Majumdar Satya N. , Vivo Pierpaolo
Published: October 2024

We consider a discrete-time random walk on a line starting at x0≥0 where a cost is incurred at each jump. We obtain an exact analytical formula for the distribution of the total cost of a trajectory until the process crosses the origin for the first time. The formula is valid for arbitrary jump distribution and cost function (heavy and light tailed alike), provided they are symmetric and continuous. We analyze the formula in different scaling regimes and find a high degree of universality with respect to the details of the jump distribution and the cost function. Applications are given to the motion of an active run-and-tumble particle in one dimension and extensions to multiple cost variables are considered. The analytical results are in perfect agreement with numerical simulations.

Published by the American Physical Society
2024
Capturing Long-Range Memory Structures with Tree-Geometry Process Tensors
Authors: Dowling Neil , Modi Kavan , Muñoz Roberto N. , Singh Sukhbinder , White Gregory A. L.
Published: October 2024

We introduce a class of quantum non-Markovian processes—dubbed process trees—that exhibit polynomially decaying temporal correlations and memory distributed across timescales. This class of processes is described by a tensor network with treelike geometry whose component tensors are (1) causality-preserving maps (superprocesses) and (2) locality-preserving temporal change-of-scale transformations. We show that the long-range correlations in this class of processes tends to originate almost entirely from memory effects and can accommodate genuinely quantum power-law correlations in time. Importantly, this class allows efficient computation of multitime correlation functions. To showcase the potential utility of this model-agnostic class for numerical simulation of physical models, we show how it can efficiently approximate the strong memory dynamics of the paradigmatic spin-boson model, in terms of arbitrary multitime features. In contrast to an equivalently costly matrix-product-operator representation, the ansatz produces a fiducial characterization of the relevant physics. Finally, leveraging 2D tensor-network renormalization-group methods, we detail an algorithm for deriving a process tree from an underlying Hamiltonian via the Feynmann-Vernon influence functional. Our work lays the foundation for the development of more efficient numerical techniques in the field of strongly interacting open quantum systems, as well as the theoretical development of a temporal renormalization-group scheme.

Published by the American Physical Society
2024
Synthesis, crystal structure and Hirshfeld surface analysis of (2-amino-1-methylbenzimidazole-κN
3)aquabis(4-oxopent-2-en-2-olato-κ2
O,O′)nickel(II) ethanol monosolvate
Authors: Siddikova Kyzlarkhan , Sardor Murodov , Tojiboyev Akmaljon , Kadirova Zukhra , Ashurov Jamshid , Daminova Shahlo
Published: October 2024

The molecule of the title compound, [Ni(C5H7O2)2(C8H9N3)(H2O)]·C2H5OH, has triclinic (P\overline{1}) symmetry. This compound is of interest for its antimicrobial properties. The asymmetric unit comprises two independent complex molecules, which are linked by N—H...O and O—H...O hydrogen bonds along [111]. Hirshfeld surface analysis indicates that 71.7% of intermolecular interactions come from H...H contacts, 17.7% from C...H/H...C contacts and 7.6% from O...H/H...O contacts, with the remaining contribution coming from N...H/H...N, C...N/N...C, C...C and O...O contacts.
Credit spread drivers and cross-country connectedness: a study of emerging economies in Asia
Authors: Kumar Mohit , Prasanna P. Krishna
Published: October 2024

Purpose

While the existing literature lacks a holistic approach to determining credit spreads and is limited to mostly developed countries, this study investigates credit spread determinants and their cross-country connectedness in the context of four emerging economies in Asia by incorporating bonds, market risk, macroeconomic and global factors.

Design/methodology/approach

This study utilizes principal component analysis for dimensionality reduction and variable representation. Furthermore, we employ the dynamic conditional correlation–generalized autoregressive conditional heteroskedasticity model to capture the cross-country credit spread connectedness between the variables.

Findings

The findings indicate that market volatilities are the most significant drivers of credit spreads, while global factors play a moderating role. Furthermore, the results provide compelling evidence of cross-country credit spread connectedness, with China as the primary transmitter and Malaysia as the primary receiver among the selected emerging economies.

Originality/value

This study addresses the limitations of previous research by extending the analysis beyond the commonly studied developed economies and focusing on emerging economies in Asia. It also employs a comprehensive approach to determine credit spread and explores cross-country credit spread connectedness in developing economies, thereby shedding light on financial risks and vulnerabilities within interconnected global financial systems.
Is job crafting beneficial for millennial employees? A moderated mediation model of affective organizational commitment, turnover intention and entrepreneurial leadership
Authors: Zainal Badri Siti Khadijah , Ngo Michelle She Min
Published: October 2024

Purpose

This paper presents a moderated mediation model of job crafting and turnover intention grounded in the affective events theory. It examines the mediating role of affective organisational commitment (AOC) and the moderating effect of entrepreneurial leadership (EL) on the link between millennials’ job crafting, AOC and, subsequently, turnover intention.

Design/methodology/approach

A sample of 352 millennials was analysed using structural equation modelling (SEM) and SPSS.

Findings

AOC mediated the relationship between two job crafting dimensions – increasing structural job resources and challenging job demands – and turnover intention among millennial workers. Moreover, EL enhances the relationship between these dimensions and AOC.

Originality/value

This paper offers insights into millennials’ work behaviour, highlighting the role of AOC in retention and the significance of EL in strengthening millennials’ emotional commitment, especially from those working in an SME context.
Serum interleukin‐10 level is increased and correlated positively with disease severity in patients with dipeptidyl peptidase‐4 inhibitor‐related bullous pemphigoid
Authors: Suzuki Shoya , Kamata Masahiro , Uchida Hideaki , Shimizu Teruo , Okada Yoshiki , Ito Makoto , Watanabe Ayu , Mizukawa Itsumi , Egawa Shota , Chijiwa Chika , Hiura Azusa , Fukaya Saki , Hayashi Kotaro , Fukuyasu Atsuko , Tanaka Takamitsu , Ishikawa Takeko , Tada Yayoi
Published: October 2024

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease with a linear deposit of autoantibodies at the epidermal basement membrane zone. It was reported that diabetes patients who took a dipeptidyl peptidase‐4 inhibitor (DPP4i), an oral antidiabetic drug, had an increased incidence of BP. However, data on DPP4i‐related BP are limited. In our study, we measured serum levels of various cytokines using LEGENDplex and assessed correlations of these serum levels with clinical severity and laboratory data. Serum samples obtained from BP patients who visited our hospital from June 2016 to February 2023 were collected in this study. Patients' background, characteristics, and clinical data were retrospectively collected from their charts. Serum samples from 27 patients with DPP4i‐unrelated BP, 17 patients with DPP4i‐related BP, and 13 healthy controls were analyzed. Patients with DPP4i‐related BP had lower score of Bullous Pemphigoid Disease Area Index (BPDAI)‐erythema/urticaria, lower number of circulating eosinophils, and lower titer of anti‐BP180 antibody than patients with DPP4i‐unrelated BP. The serum interleukin (IL)‐6 level was significantly higher in patients with DPP4i‐related BP than in healthy controls (P = 0.0037). The serum IL‐10 level was significantly higher in patients with DPP4i‐related BP than in patients with DPP4i‐unrelated BP and in healthy controls (P = 0.0006, P = 0.0448), and was positively correlated with the BPDAI‐blister/erosions score (r = 0.757, P = 0.001), BPDAI‐erythema/urticaria score (r = 0.616, P = 0.013), and BPDAI‐total score (r = 0.833, P < 0.001) in patients with DPP4i‐related BP. In conclusion, patients with DPP4i‐related BP had increased serum levels of IL‐6 and IL‐10 compared with healthy controls and positive correlations between the serum IL‐10 level and BPDAI scores reflecting clinical severity, indicating that the serum IL‐10 level is a potential objective biomarker of disease severity in patients with DPP4i‐related BP.
Diptera‐dominated generalist pollination systems in Eurya japonica and Eurya emarginata (Pentaphylacaceae)
Authors: Tatsuno Midzuho , Osawa Naoya
Published: October 2024

We investigated the flower visitors and floral traits of two dioecious shrub species Eurya japonica Thunb. (Pentaphylacaceae) and Eurya emarginata (Thunb.) Makino in temperate Kochi and subtropical Okinawa in Japan during the cool seasons. We demonstrated that the two Eurya species could be pollinated by a wide spectrum of flower visitors—mainly Diptera. The main pollinators were probably Chironomidae and Empididae for E. japonica in Kochi and Calliphoridae and Syrphidae for the remaining species–site combinations (i.e., E. emarginata in Kochi, E. japonica in Okinawa, and E. emarginata in Okinawa). We demonstrated that several dominant families of Dipteran visitors have the ability to pollinate the two Eurya species. Interestingly, floral traits (corolla diameter and nectar concentration) could not explain the difference in the assemblages. These results indicate that floral traits are not specifically adapted to their local pollinators. The fruit set rate was significantly lower for naturally pollinated flowers than for hand‐pollinated flowers, indicating pollen limitation in both Eurya species. However, there was no apparent difference in the number of seeds per fruit between naturally pollinated and hand‐pollinated flowers.
Can Australia Become a Green Iron Powerhouse?
Authors: Brooks Geoffrey , Jensen Paul H. , Petrie Stephen , Webster Elizabeth
Published: October 2024

As a country with an abundance of renewable resources, Australia has an opportunity to emerge as a global leader in the production of green iron rather than simply extracting and exporting iron ore around the world. While it makes sense to do so in the changing geopolitical environment, and to assist in achieving our commitments to dramatically reduce our carbon emissions, this paper sheds light on the complex technical and economic arguments for the creation of a green iron industry here in Australia. We argue that targeted government intervention coupled with industry commitment to transforming the sector could realistically result in the emergence of a nascent green iron industry in the medium term.
Variation in the social composition of the UK academic elite: The underlay of the two—or three—cultures?
Authors: Bukodi Erzsébet , Goldthorpe John H.
Published: October 2024

In this paper, we complement a previous study of the UK natural science elite, as represented by Fellows of the Royal Society, with a comparable study of the humanities and social sciences elites, as represented by Fellows of the British Academy. We seek to establish how far similarities and differences exist in the social composition of these three academic elites and in the routes that their members have followed into elite positions. We are also concerned with the consequences of the humanities and social sciences elites being brought together in the British Academy, in contrast with the situation in most other countries where elite natural and social scientists are located in the same academy. We pursue these issues in the context of C. P. Snow's discussion of the social underlay of the cultural disjunction that he saw between the natural sciences and the humanities, while also considering how the social sciences fit in. We find that there is support for Snow's position at the time of his writing. However, a notable development in more recent years is that the growing social sciences elite is moving in its social composition away from the humanities elite and closer to the natural science elite. This is primarily due to changes in the social origins and education of Fellows in those sections of the British Academy that are on the borderline between the social and the natural sciences. A widening difference thus arises with Fellows in the humanities sections most representative of Snow's ‘traditional culture’.
Sources and content of advice sought by parents/guardians prior to emergency department attendance
Authors: McNeil Scott , Goyal Nikita , Parr Mandy , Cheek John , Freed Gary , Meyer Alastair , West Adam , Craig Simon
Published: October 2024

Aim

To describe sources of advice and the recommendations given to parents/guardians prior to attending ED with their child.

Methods

This was a prospective observational study of patients presenting to two EDs of a multi‐centre Victorian Health service in June 2016. Data collection involved surveying all parents/guardians attending paediatric ED during a 1‐week period by trained research assistants. We determined the proportion of eligible respondents who sought advice before attending ED, the source of advice, and the type of advice provided.

Results

One thousand sixty‐nine patients presented to ED over the 1‐week period. There were 730 responses to the survey, of which 65% (477/730) had received a total of 620 recommendations prior to ED attendance. Seventy‐six per cent (362/477) had received advice from a single source, 19% (90/477) had received advice from 2 sources, and 5% (25/477) from 3 or more sources. The most common sources of advice were general practice consultations (49%), friends/family (13.5%), and NURSE‐ON‐CALL (11%). Fifty‐four per cent (335/620) of the recommendations were to attend ED immediately and 12% (77/620) were to attend if their child was getting worse.

Conclusions

Most parents and guardians sought advice from a single source prior to attending an ED. The most common source of advice was consultation with a general practitioner and the most common recommendation was to attend ED immediately, or if their child's condition worsened.
Delay discounting of rewards and losses, alcohol use, and the influence of socioeconomic factors: A cross‐sectional online study in frequent drinkers
Authors: Pinger Mathieu , Skirke Malin , Thome Janine , Sommer Wolfgang H. , Koppe Georgia , Kirsch Peter
Published: October 2024

Background

Delay discounting describes the devaluation of future outcomes over time and is a popular behavioral construct in addiction research. Prior studies show modest yet consistent associations between problematic alcohol use and delayed reward discounting (DRD). However, the potential confounding influence of socioeconomic status (SES, e.g., income and education) is rarely addressed. In this study, we aimed to investigate the robustness of DRD as a predictor of alcohol use after controlling for socioeconomic and demographic variables. Additionally, we aimed to test the association between delayed loss discounting (DLD) and alcohol use in a sufficiently large sample.

Methods

We collected data from 341 moderate‐to‐heavy‐drinking participants (27.92 ± 21.12 g alcohol/day, 43.48 ± 11.90 years old, 49.9% female, UK residents) in a cross‐sectional online study. DRD and DLD were measured using an intertemporal choice task. Questionnaires encompassed alcohol use (AUDIT, weekly alcohol consumption), education and income, subjective measures of past and present socioeconomic status, and impulsivity.

Results

DRD, but not DLD, was significantly associated with AUDIT scores (r = 0.15) and weekly alcohol consumption (r = 0.12). DRD remained a significant yet weak predictor of AUDIT scores when controlling for education and income, but not when controlling for education and age.

Conclusions

We replicated a small but robust association between alcohol use and DRD, but not DLD. This association appeared to be confounded by education and age, but not by income. We conclude that socioeconomic and demographic variables should systematically be accounted for in future studies investigating DRD and alcohol use.
Effectiveness of prophylactic central compartment neck dissection following Hemithyroidectomy in papillary thyroid cancer: a meta‐analysis
Authors: Zhao P. , Liang L.‐L. , Luo Y.‐B. , Liang Q.‐K. , Xiang B.‐D.
Published: October 2024

Introduction

In this study, we aimed to assess the effect of prophylactic central compartment neck dissection (pCCND) in conjunction with hemithyroidectomy (HT) for clinically low‐risk node‐negative (cN0) papillary thyroid carcinoma (PTC).

Methods

A thorough literature search was performed utilizing PubMed and EMBASE for articles published until October 2023. Subsequently, a meta‐analysis was performed on studies involving patients with cN0 PTC, with postoperative locoregional recurrence (LRR) and survival data, treated with HT + pCCND or HT. The study was registered with PROSPERO (CRD42024560962).

Results

We included seven studies in this meta‐analysis, including 2132 patients who met the inclusion criteria: six retrospective cohort studies and one randomized controlled trial. The HT + pCCND group consisted of 1090 cases, and the HT group had 1042 cases. The LRR rates after HT with or without pCCND were similar (3.58% vs. 4.51%; odds ratio (OR) = 0.65; 95% confidence interval (CI) = 0.41–1.03). Five of the seven studies provided prognostic and survival data, particularly the log hazard ratio (log HR) of disease‐free survival (DFS) between the two groups. There was also no significant difference in terms of DFS between the HT + pCCND and HT groups (OR = 0.67; 95% CI = 0.42–1.07).

Conclusions

There was no significant difference in LRR and DFS between the HT + pCCND and HT groups. pCCND did not demonstrate significant efficacy in improving oncological outcomes for low‐risk patients with cN0 PTC. Therefore, for patients with low‐risk cN0 PTC, thyroid surgeons should make reasonable and individualized decisions regarding the extent of surgical removal.
Explainability increases trust resilience in intelligent agents
Authors: Xu Min , Wang Yiwen
Published: October 2024

Even though artificial intelligence (AI)‐based systems typically outperform human decision‐makers, they are not immune to errors, leading users to lose trust in them and be less likely to use them again—a phenomenon known as algorithm aversion. The purpose of the present research was to investigate whether explainable AI (XAI) could function as a viable strategy to counter algorithm aversion. We conducted two experiments to examine how XAI influences users' willingness to continue using AI‐based systems when these systems exhibit errors. The results showed that, following the observation of algorithms erring, the inclination of users to delegate decisions to or follow advice from intelligent agents significantly decreased compared to the period before the errors were revealed. However, the explainability effectively mitigated this decline, with users in the XAI condition being more likely to continue utilizing intelligent agents for subsequent tasks after seeing algorithms erring than those in the non‐XAI condition. We further found that the explainability could reduce users' decision regret, and the decrease in decision regret mediated the relationship between the explainability and re‐use behaviour. These findings underscore the adaptive function of XAI in alleviating negative user experiences and maintaining user trust in the context of imperfect AI.
Decision regret and long‐term success rates after ventral buccal mucosa graft urethroplasty
Authors: Santiago Javier E. , Gross Michael D. , Accioly João Pedro , Voelzke Bryan B. , Breyer Benjamin N. , Khouri Roger K. , DeWitt‐Foy Molly E. , Angermeier Kenneth W. , Wood Hadley M.
Published: October 2024

Objectives

To characterise the long‐term success rate of ventral onlay buccal mucosa graft urethroplasty (vBMG) in the management of bulbar urethral stricture disease (USD), assess patient‐reported postoperative satisfaction and decision regret, and delineate clinical factors impacting patient‐reported metrics.

Subjects and Methods

Patients with prior vBMG for bulbar USD, performed at Cleveland Clinic between 2003 and 2022, were contacted and brief structured interviews were performed. Stricture recurrence and need for secondary procedures, baseline demographics, and patient‐reported outcome surveys were collected. The surveys included the Decision Regret Scale (DRS), the Urethral Stricture Symptom Impact Measure (USSIM) and the 10‐item Patient‐Reported Outcomes Measurement Information System Short Form, version 1.2 (PROMIS‐10). Descriptive, univariate and multivariable analyses were performed for clinical outcomes and survey responses.

Results

A total of 104 patients recorded responses. The median patient age was 49 years and the median follow‐up was 7.4 years at time of survey. The median graft length was 5 cm and 38% of patients underwent partial thickness augmented anastomotic urethroplasty. At time of follow‐up, 10 patients underwent a secondary procedure. Moderate to severe regret on the DRS was found in 12% of patients, and greater regret was associated with recurrence. The mean physical and mental health PROMIS‐10 Global Health T‐scores were 52 and 53. The mean total USSIM score was 56. A significant correlation was found between USSIM and DRS scores, with higher DRS score and recurrence negatively impacting USSIM score. USSIM scoring across all domains was significantly worse in the moderate to severe DRS group.

Conclusion

This study showed that vBMG for bulbar USD confers both high success rates and patient‐reported satisfaction at extended follow‐up, based on emerging and validated patient‐reported outcome measures.
Maximal point‐polyserial correlation for non‐normal random distributions
Authors: Barbiero Alessandro
Published: October 2024

We consider the problem of determining the maximum value of the point‐polyserial correlation between a random variable with an assigned continuous distribution and an ordinal random variable with categories, which are assigned the first natural values , and arbitrary probabilities . For different parametric distributions, we derive a closed‐form formula for the maximal point‐polyserial correlation as a function of the and of the distribution's parameters; we devise an algorithm for obtaining its maximum value numerically for any given . These maximum values and the features of the corresponding ‐point discrete random variables are discussed with respect to the underlying continuous distribution. Furthermore, we prove that if we do not assign the values of the ordinal random variable a priori but instead include them in the optimization problem, this latter approach is equivalent to the optimal quantization problem. In some circumstances, it leads to a significant increase in the maximum value of the point‐polyserial correlation. An application to real data exemplifies the main findings. A comparison between the discretization leading to the maximum point‐polyserial correlation and those obtained from optimal quantization and moment matching is sketched.
QM107, a novel CD148 (RTP Type J) activating peptide therapy for treating neovascular age‐related macular degeneration
Authors: Arokiasamy Samantha , Balderstone Michaela J. M. , Shaik Faheem , Cristante Enrico , Moseley Thomas C. , Madoo Akshay , Rizzi Matteo , Bainbridge James W. , Tsoyi Konstantin , Rosas Ivan O. , Whiteford James R. , De Rossi Giulia
Published: October 2024

Background and Purpose

Angiogenesis is a pathological component of neovascular age‐related macular degeneration. Current therapies, although successful, are prone to high levels of patient non‐response and a loss of efficacy over time, indicating the need to explore other therapeutic avenues. We have shown that an interaction between syndecan‐2 and the tyrosine phosphatase receptor CD148 (RTP Type J) results in the ablation of angiogenesis. Here we exploit this pathway to develop a peptide activator of CD148 as a therapy for neovascular age‐related macular degeneration.

Experimental Approach

We tested a peptide (QM107) derived from syndecan‐2 in a variety of angiogenesis models and a pre‐clinical model of neovascular age‐related macular degeneration. We assessed the toxicological and inflammatory profiles of QM107 and its stability in vitreous humour.

Key Results

QM107 inhibits angiogenesis in ex vivo sprouting assays and disrupts endothelial microcapillary formation via inhibition of cell migration. QM107 acts through CD148, leading to changes in GSK3A phosphorylation and β1 integrin activation. QM107 elicits a negligible inflammatory response and exhibits limited toxicity in cultured cells, and is stable in vitreous humour. Finally, we show proof of concept that QM107 blocks angiogenesis in vivo using a model of neovascular age‐related macular degeneration.

Conclusion and Implications

We have developed a CD148 activating peptide which shows promise in inhibiting angiogenesis in models of neovascular age‐related macular degeneration. This treatment could either represent an alternative or augment existing therapies, and owing to its distinct mode of action be used in patients who do not respond to existing treatments.
Slow dissociation kinetics of fentanyls and nitazenes correlates with reduced sensitivity to naloxone reversal at the μ‐opioid receptor
Authors: Alhosan Norah , Cavallo Damiana , Santiago Marina , Kelly Eamonn , Henderson Graeme
Published: October 2024

Background and Purpose

Fentanyls and nitazenes are μ‐opioid receptor agonists responsible for a large number of opioid overdose deaths. Here, we determined the potency, dissociation kinetics and antagonism by naloxone at the μ receptor of several fentanyl and nitazene analogues, compared to morphine and DAMGO.

Experimental Approach

In vitro assays of G protein activation and signalling and arrestin recruitment were performed. AtT20 cells expressing μ receptors were loaded with a membrane potential dye and changes in fluorescence used to determine agonist potency, dissociation kinetics and susceptibility to antagonism by naloxone. BRET experiments were undertaken in HEK293T cells expressing μ receptors to assess Gi protein activation and β‐arrestin 2 recruitment.

Key Results

The apparent rate of agonist dissociation from the μ receptor varied: morphine, DAMGO, alfentanil and fentanyl dissociated rapidly, whereas isotonitazene, etonitazene, ohmefentanyl and carfentanil dissociated slowly. Slowly dissociating agonists were more resistant to antagonism by naloxone. For carfentanil, the slow apparent rate of dissociation was not because of G protein receptor kinase‐mediated arrestin recruitment as its apparent rate of dissociation was not increased by inhibition of G protein‐coupled receptor kinases (GRKs) with Compound 101. The in vitro relative potencies of fentanyls and nitazenes compared to morphine were much lower than that previously observed in in vivo experiments.

Conclusions and Implications

With fentanyls and nitazenes that slowly dissociate from the μ receptor, antagonism by naloxone is pseudo‐competitive. In overdoses involving fentanyls and nitazenes, higher doses of naloxone may be required for reversal than those normally used to reverse heroin overdose.
A Data‐Driven Approach Identifies Subtypes of Caries From Dental Charting
Authors: Haworth Simon , Kastenbom Lisa , Persson Peter , Fries Niklas , Esberg Anders , Jönsson Daniel , Johansson Ingegerd
Published: October 2024

Objectives

The objectives were to: (i) assess the accuracy of dental data for adults obtained from the Swedish Quality Register on Caries and Periodontitis (SKaPa); (ii) explore whether Latent Class Analysis (LCA) can identify groups of people based on caries data; and (iii) characterise the dental, medical and behavioural characteristics of people in the LCA‐derived classes.

Methods

Caries data from the SKaPa register were compared with clinical data collected by five experienced dentists in a nested subgroup of the Malmö Offspring Study (MOS), namely the Malmö Offspring Dental Study (MODS) (n = 724) for validation. Dental data from SKaPa were then used to classify 61 984 adult participants of the Västerbotten Intervention Programme (VIP) into five classes using LCA and DMFS‐based quintile ranking, respectively. Dental status (including caries progression over 5 years), medical, anthropometric and behavioural characteristics were compared between the groups. Analyses were replicated in 2767 adults in the MOS.

Results

DMFS‐scores and number of teeth recorded within −2 to +2 years showed excellent agreement between the SKaPa and reference data with intra‐class correlations > 0.90. The five LCA classes differed in mean DMFS from 10.0 to 94.4. There were strong associations between LCA class and health, and health and behavioural measures respectively, including some associations that were not detected using DMFS‐ranked quintile groups. LCA class was associated with incremental change in DMFS, DFS, and number of teeth. The results in the MOS cohort were consistent with the results in the VIP cohort.

Conclusions

Dental data for adults from the SKaPa registry were considered accurate within 2 years of recording. The LCA approach can classify participants into caries subtypes based on dental charting. These groups differ in health and behavioural characteristics and future caries increment. The LCA approach may capture some information that is missing from DMFS‐ranked quintile groups, but is also heavily influenced by total DMFS, meaning that applying LCA in cumulative, highly age‐determined diseases, such as caries, is a challenge.