bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTIn 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

AbstractCellular 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

SummaryHuman 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

ABSTRACTCellular 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

AbstractHead 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
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
Credit spread drivers and cross-country connectedness: a study of emerging economies in Asia
Authors: Kumar Mohit , Prasanna P. Krishna 
Published: October 2024

PurposeWhile 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/approachThis 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.FindingsThe 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/valueThis 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

PurposeThis 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/approachA sample of 352 millennials was analysed using structural equation modelling (SEM) and SPSS.FindingsAOC 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/valueThis 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

AbstractBullous 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

AbstractWe 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

AbstractAs 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

AbstractIn 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

AbstractAimTo describe sources of advice and the recommendations given to parents/guardians prior to attending ED with their child.MethodsThis 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.ResultsOne 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.ConclusionsMost 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.