bluuebunny/crossref_metadata_2025 huggingface dataset:
Stable White Matter Structure in the First Three Years after Psychosis Onset
Authors: Van Dyken Peter C. , Yang Kun , Faria Andreia V. , Sawa Akira , MacKinley Michael , Khan Ali R. , Palaniyappan Lena
Published: August 2024

Background

White matter alterations observed using diffusion weighted imaging have become a hallmark of chronic schizophrenia, but it is unclear when these changes arise over the course of the disease. Nearly all studies thus far have been cross-sectional, so despite their large sample sizes, they cannot determine if changes accumulate as a degenerative process, or if patients with pre-existing white matter damage are predisposed to more chronic forms of schizophrenia.

Methods

We examined 160 scans comprising two years of annual follow-up data from n=42 controls and n=28 schizophrenia patients recruited in the first two years since their diagnosis, totalling two to three scans per subject. We additionally examined six-month follow-up data obtained from an ultra-high field (7 Tesla) scanner (n=68 scans; n=19 first-episode schizophrenia patients; n=15 controls) as a validation dataset. A longitudinal model was used to compare the trajectory of diffusion tenor parameters between patients and controls. Positive and negative symptom scores were correlated with diffusion parameters using ROI- and clustering-based approaches.

Results

We failed to observe any longitudinal differences in any diffusion tensor imaging parameters between patients and controls in either dataset. We did, however, observe consistent associations between white matter alterations and negative symptoms in both datasets.

Conclusions

White matter does not appear susceptible to schizophrenia-linked degeneration in the early stages of disease, but pre-existing pathology may be linked to disease severity.
Genetic ancestry-specific meQTLs control immune function regulation in a breast cancer cohort of African and European patients
Authors: Founta Kyriaki , Chambwe Nyasha
Published: August 2024

We explored the impact of genetic ancestry on DNA methylation (DNAm) in African and European ancestry breast cancer patients. Analyzing data from 578 subjects in The Cancer Genome Atlas (TCGA) cohort, we identified 757 differentially methylated sites associated with genetic ancestry (aDMS). Methylation quantitative trait loci (meQTL) mapping showed that the majority of aDMS are regulated by multiple SNPs differentially prevalent by ancestry. Notably, expression quantitative methylation (eQTM) mapping linked 95% of aDMS to local gene expression, indicating potential impact on gene regulation.

Furthermore, 72% of ancestry eQTMs were regulated by meQTLs, underscoring the genetic regulation of DNAm variation affecting the transcriptome. Immune response regulation, particularly involving HLA genes, was the most enriched process among ancestry eQTMs. Additionally, 31% of differentially expressed genes between groups defined by genetic ancestry were under ancestry eQTM control. These findings highlight the gene regulatory potential of ancestry-associated DNAm and its importance in population-specific analyses.
Single-cell X-chromosome inactivation analysis links biased chimerism to differential gene expression and epigenetic erosion
Authors: Henning Robert H. , Rust Thomas M. , Dijksterhuis Kasper , Eggen Bart J.L. , Guryev Victor
Published: August 2024

Female cells randomly inactivate one X-chromosome, resulting in cellular mosaicism. Determining the bias in X-chromosomal inactivation (XCI) at single cell level may be relevant for understanding diseases prevalent in females. Here, we introduce a computational method that determines XCI profiles at single-cell level using solely sc/snRNA-Seq data. XCI analysis of skin cells from hybrid mice validates our approach and reveals biased inactivation of X-chromosomes among cell types. In human lung and brain cells, XCI status can be determined in 33.8% and 23.6% of cells. Among the patients, cells with opposite inactivation patterns differently express members of specific gene families and pathways. Alzheimer’s disease patients show reversal of XCI in cortical microglia and regional increase in biallelic expression denoting epigenetic erosion. We provide a robust utility to explore the degree and impact of XCI in single cell expression data.
Inferring in vivo murine cerebrospinal fluid flow using artificial intelligence velocimetry with moving boundaries and uncertainty quantification
Authors: Toscano Juan Diego , Wu Chenxi , Ladrón-de-Guevara Antonio , Du Ting , Nedergaard Maiken , Kelley Douglas H. , Karniadakis George Em , Boster Kimberly A. S.
Published: August 2024

Cerebrospinal fluid (CSF) flow is crucial for clearing metabolic waste from the brain, a process whose dysregulation is linked to neurodegenerative diseases like Alzheimer’s. Traditional approaches like particle tracking velocimetry (PTV) are limited by their reliance on single-plane two-dimensional measurements, which fail to capture the complex dynamics of CSF flow fully. To overcome these limitations, we employ Artificial Intelligence Velocimetry (AIV) to reconstruct three-dimensional velocities, infer pressure and wall shear stress, and quantify flow rates. Given the experimental nature of the data and inherent variability in biological systems, robust uncertainty quantification (UQ) is essential. Towards this end, we have modified the baseline AIV architecture to address aleatoric uncertainty caused by noisy experimental data, enhancing our measurement refinement capabilities. We also implement UQ for the model and epistemic uncertainties arising from the governing equations and network representation. Toward this end, we test multiple governing laws, representation models, and initializations. Our approach not only advances the accuracy of CSF flow quantification but also can be adapted to other applications that use physics-informed machine learning to reconstruct fields from experimental data, providing a versatile tool for inverse problems.
Impaired S-nitrosylation of Cx43 prevents arrhythmogenicity and myocardial injury upon cardiac stress in Duchenne Muscular Dystrophy
Authors: Muñoz Manuel F. , Quan Jonathan J. , Nguyen Thao T. , Nuno Janet , Sheehy Adrian , Burboa Pia C. , Gaete Pablo S. , Lillo Mauricio A. , Contreras Jorge E.
Published: August 2024

Connexin-43 (Cx43) plays a critical role in the propagation of action potentials and cardiac contractility. In healthy cardiomyocytes, Cx43 is mainly located at the intercalated disk; however, Cx43 remodeling is observed in cardiac pathologies and is linked with arrhythmogenesis and sudden cardiac death. Using a mouse model of Duchenne muscular dystrophy (DMD), we previously demonstrated that Cx43 localizes to the lateral side of dystrophic cardiomyocytes, forming undocked hemichannels. β-adrenergic signaling-induced cardiac stress promotes S-nitrosylation and the opening of undocked Cx43 hemichannels leading to disrupted cardiac membrane excitability and deadly arrhythmogenic behaviors. To establish the direct role of S-nitrosylated Cx43 in DMD cardiomyopathy, we generated knockin DMDmdxmice with reduced levels of S-nitrosylated Cx43, by replacing cysteine 271 with a serine in one Cx43 of the unique site for S-nitrosylation of Cx43 (DMDmdx:C271S+/-). Immunofluorescence analysis revealed that cardiac Cx43 lateralization in DMDmdx:C271S+/-mice was similar to DMDmdxmice, indicating that the genetic modification did not prevent Cx43 remodeling. Upon isoproterenol treatment, DMDmdxmice displayed a higher incidence of arrhythmogenic events when compared to DMDmdx:C271S+/-mice, which more closely resemble wild-type mice. Optical mapping imaging in isolated hearts showed that DMDmdxmice displayed aberrant Ca2+signaling and prolonged action potentials, which is restored in DMDmdx:C271S+/-mice. Isoproterenol treatment evoked severe myocardial injury in DMDmdxmice, which was significantly attenuated in DMDmdx:C271S+/-mice. Notably, DMDmdxmice treated with Gap19, a Cx43 hemichannel blocker, exhibited cardioprotection against myocardial injury. We concluded that S-nitrosylation of Cx43 proteins is a fundamental NO-mediated mechanism involved in arrhythmias and myocardial injury in DMDmdx, occurring through the opening of hemichannels following β-adrenergic stress.
Phospho-regulated tuning of viscoelastic properties balances centrosome growth and strength
Authors: Amato Matthew , Hwang June Ho , Rios Manolo U. , Familiari Nicole E. , Rosen Michael K. , Woodruff Jeffrey B.
Published: August 2024

Centrosomes nucleate microtubule asters and comprise centrioles surrounded by pericentriolar material (PCM). In preparation for mitosis, the PCM scaffold grows dramatically while resisting microtubule pulling forces. How PCM achieves dynamic growth while maintaining mechanical strength is unclear. Here we probed the dynamic and material properties of theC. elegansPCM scaffold. Single-embryo extrusion experiments revealed that the protein SPD-5 forms distinct but co-existing dynamic and stable scaffolds within PCM. The stable scaffold grew in preparation for mitosis, then disappeared at anaphase onset. SPD-5 mutants that lacked PLK-1 phosphorylation at four key sites (4A) could not build the stable scaffold, whereas phospho-mimetic SPD-5(4E) could. Expression of SPD-5(4A) impaired PCM assembly, but this phenotype was partially rescued by eliminating microtubule pulling forces, indicating material weakness. SPD-5(4A) expression also resulted in chromosome segregation defects, revealing the importance of PCM strength for development. Unexpectedly, expression of SPD-5(4E) prevented full-scale PCM growth and caused embryonic lethality.In vitro, PLK-1-induced phosphorylation increased the viscoelastic moduli of minimal SPD-5 scaffolds, which increased their solidity. This caused faster initial growth that then plateaued, in effect setting an upper limit to SPD-5 scaffold size. Thus, PCM scaffold assembly and strength are optimized through phospho-regulated equilibrium of dynamic and stable scaffold components. Our results further reveal kinase-driven kinetic arrest as a potential mechanism of centrosome size scaling.

SIGNIFICANCE STATEMENT

To build and position the mitotic spindle, centrosomes must grow large enough to nucleate many hundreds of microtubules and resist their pulling forces. How centrosomes simultaneously achieve dynamic growth and tensile strength is unknown. Here, we show that centrosomes behave as phosphorylation-tunable hydrogels with both liquid-like and solid-like properties, which contribute to dynamics and material strength, respectively. Phospho-null or phospho-mimicking mutations in the scaffold protein SPD-5 dysregulate the balance of liquid- and sold-like behaviors within the centrosome, impairing function and embryo viability in both cases. Our results showcase how meso-scale material properties contribute to the function of a membrane-less organelle and how they are finely tuned by chemical modifications.
Energy filtering enables macromolecular MicroED data at sub-atomic resolution
Authors: Clabbers Max T.B. , Hattne Johan , Martynowycz Michael W. , Gonen Tamir
Published: August 2024

High resolution information is important for accurate structure modelling. However, this level of detail is typically difficult to attain in macromolecular crystallography because the diffracted intensities rapidly fade with increasing resolution. The problem cannot be circumvented by increasing the fluence as this leads to detrimental radiation damage. Previously, we demonstrated that high quality MicroED data can be obtained at low flux conditions using electron counting with direct electron detectors. The improved sensitivity and accuracy of these detectors essentially eliminate the read-out noise, such that the measurement of faint high-resolution reflections is limited by other sources of noise. Inelastic scattering is a major contributor of such noise, increasing background counts and broadening diffraction spots. Here, we demonstrate that a substantial improvement in signal-to-noise ratio can be achieved using an energy filter to largely remove the inelastically scattered electrons. This strategy resulted in sub-atomic resolution MicroED data from proteinase K crystals, enabling accurate structure modelling and the visualization of detailed features. Interestingly, filtering out the noise revealed diffuse scattering phenomena that can hold additional structural information. Our findings suggest that combining energy filtering and electron counting can provide more accurate measurements at higher resolution, providing better insights into protein function and facilitating more precise model refinement.
SU(2)
principal chiral model with tensor renormalization group on a cubic lattice
Authors: Akiyama Shinichiro , Jha Raghav G. , Unmuth-Yockey Judah
Published: August 2024

We study the continuous phase transition and thermodynamic observables in the three-dimensional Euclidean SU(2) principal chiral field model with the triad tensor renormalization group and the anisotropic tensor renormalization group methods. Using these methods, we find results that are consistent with previous Monte Carlo estimates and the predicted renormalization group scaling of the magnetization close to criticality. These results bring us one step closer to studying finite-density quantum chromodynamics in four dimensions using tensor network methods.

Published by the American Physical Society
2024
Seeing beauty in the quark-gluon plasma with energy correlators
Authors: Andres Carlota , Dominguez Fabio , Holguin Jack , Marquet Cyrille , Moult Ian
Published: August 2024

Heavy quarks created in heavy-ion collisions serve as an excellent probe of the produced quark-gluon plasma (QGP). The radiation pattern of jets formed from heavy quarks as they traverse the QGP exhibits a particularly interesting structure due to the interplay of two competing effects: the suppression of small-angle radiation, also known as the “dead-cone” effect, and the enhancement of emitted gluons by medium-induced radiation. In this , we propose a new observable, based on the energy correlator approach to jet substructure, which will allow us to disentangle the two scales associated to these two phenomena and to determine under which conditions the dead cone is filled by medium-induced radiation. Combined with the forthcoming high-statistics measurements of heavy-flavor jets, this work provides a novel tool to unravel the dynamics of the QGP.

Published by the American Physical Society
2024
Exploring the Temperature and Composition Dependence of the Ionic Transport in Solid-State Battery Composites
Authors: Rudel Yannik , Kraft Marvin A. , Ketter Lukas , Zeier Wolfgang G.
Published: August 2024

Solid-state electrolytes offer a promising avenue for energy storage in the context of lithium-based batteries, not only from an energy density perspective, but also by eliminating issues such as freezing of the liquid electrolyte at low temperatures and the performance limitations associated with that. In solid-state batteries, solid electrolytes are not only used in separators but are also needed in composite electrodes. However, the transport properties of solid-state battery composites are often investigated at room temperature, while the temperature dependence of effective ion transport as a function of volume fraction remains underexplored. Therefore, this work investigates the effective ionic transport in composites of multiple sulfide-based solid electrolytes with Si/C as the active material, as a function of composition and temperature. Analyzing impedance spectra with a transmission line model, this work reveals changes in activation barrier and with that the temperature dependence of ion transport upon varying the volume ratios. This finding emphasizes the importance of considering the activation energy in solid-state battery design to tailor battery performance to the temperature range of application.

Published by the American Physical Society
2024
Assessing the impact of dynamic capabilities, resilience and strategic alignment on startup competitiveness in Iran
Authors: Taghavy Arezoo , Hazari Narges , Hooshmand Chaijani Milad
Published: August 2024

Purpose

In uncertain and emerging conditions, businesses must adopt new strategies to compete and survive the changing and unstable environment. This research seeks to investigate the role of dynamic capabilities in the competitiveness of startups, emphasizing resilience and strategic alignment.

Design/methodology/approach

Isfahan Scientific and Research Town has always been a pioneer in the field of science and technology in Iran and is known as the most extensive technology and knowledge-based complex in Iran. The sample size of 300 companies active in the startup field was selected using a simple random sampling method. Questionnaires were collected from the managers of technological startup companies in Isfahan, and the SEM model was used to analyze the data.

Findings

This research shows that dynamic capabilities in terms of coordination, flexibility and integration significantly impact competitiveness. Resilience and strategic alignment also increase the organization’s performance and strengthen the organization in gaining a more competitive advantage in the industry.

Originality/value

Finally, dynamic capabilities indirectly affect competitiveness through resilience and strategic alignment. This shows a need for strategic alignment and resilience to change advantage shape in dynamic conditions.
Turning crisis into opportunity: the emergence of cyber risk takaful in the digital world
Authors: Memon Ubedullah , Waseem Muhammad , Zain ul Abidin Muhammad , Junejo Zeeshan , Ali Masroor
Published: August 2024

Learning outcomes

After reading this case study, students will be able to understand the impact of cyber threats on businesses; explore the intersection of innovation and ethical considerations; understand the proactive role of entrepreneurs in identifying gaps in traditional industries, such as insurance, and innovating solutions that align with local dynamics; and learn to formulate strategies addressing cultural factors, market gaps and challenges.

Case overview/synopsis

The case study follows Hasnain, a prosperous entrepreneur in Pakistan, who was surprised by the news of a cyberattack on Bank Islami. This event, coupled with a personal data breach in his family’s business, triggered Hasnain’s willingness and interest to address the growing threat of cyber risks and attacks. As the progenitor of a digital solutions startup, he identified a gap in the insurance industry’s replication to cyber threats and envisioned the desideratum for a Sharia-compliant cyber-insurance product withal called cyber risk takaful. The case study explores Hasnain’s journey as he contemplated the challenges of introducing cyber risk takaful – a Sharia-compliant insurance solution for businesses and individuals. Apperceiving the low vigilance and perceived costs associated with cyber insurance, Hasnain faced the dilemma of surmounting these barriers in a country where the penetration of insurance, in general, is already minimal. The story raises critical questions: How can Hasnain efficaciously introduce cyber risk takaful to a market reluctant to embrace cyber insurance? What business strategies should he use to engender vigilance and acceptance of this innovative insurance solution? Will businesses and individuals embrace the concept of cyber risk takaful and recognize its paramount in forfending their digital assets?

Complexity academic level

This case study is designed to meet the educational needs of both undergraduate and postgraduate students, particularly those enrolled in business administration programs. This case study is tailored for students in the final year of BBA and the first year of MBA programs. It is also well-suited for executive education programs that focus on strategic decision-making in the context of emerging market challenges, such as entrepreneurship and corporate strategy. The case study is particularly relevant for courses centered on entrepreneurship, business strategy, strategic management and corporate strategy.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS11: Entrepreneurship.
Micro-credentials through the eyes of employers: benefits, challenges and enablers of effectiveness
Authors: Thi Ngoc Ha Nguyen , Van Dyke Nina , Spittle Michael , Watt Anthony , Smallridge Andrew
Published: August 2024

Purpose

This study explores the perceptions of Australian employers regarding the benefits and challenges of micro-credentials within higher education and enablers of their effectiveness.

Design/methodology/approach

A qualitative approach that included 11 semi-structured interviews with employers affiliated with an Australian university was used. A deductive thematic approach was employed to analyse the data.

Findings

Micro-credentials were generally seen to be beneficial for an array of people, including employees, employers, customers and communities – stakeholders in all environmental layers of micro-credentials’ ecological system. Findings also indicated that both challenges of micro-credentials and enablers of their effectiveness depended heavily on attributes of learners, employers and higher education providers. The conclusion is that, based on the evidence of this study, micro-credentials within higher education are worth trialling.

Originality/value

Although research interest in micro-credentials is growing, few empirical studies have investigated micro-credentials’ benefits, challenges and enablers of effectiveness, especially from the perspective of employers. The study carries practical and policy implications for those involved with micro-credential research and development.
Information sharing in a green supply chain: a bane or a boon?
Authors: Quadir Abdul , Raj Alok , Agrawal Anupam
Published: August 2024

Purpose

The purpose of this paper is to investigate the impact of demand information sharing on products’ greening levels with downstream competition. Specifically, this study examine two types of green products, “development-intensive” (DI) and “marginal-cost intensive” (MI), in a two-echelon supply chain where the manufacturer produces substitutable products, and competing retailers operate in a market with uncertain demand.

Design/methodology/approach

The authors adopt the manufacturer-led Stackelberg game-theoretic framework and consider a multistage game. This study consider how retailers receive private signals about uncertain demand and decide whether to share this information with the manufacturer, who then decides whether to acquire this information at a certain given cost. This paper considers backward induction and Bayesian Nash equilibrium to solve the model.

Findings

The authors find that in the absence of competition, information sharing is the only equilibrium and improves the greening level under DI, whereas no-information sharing is the only equilibrium and improves the greening level under MI, an increase in downstream competition drives higher investment in greening efforts by the manufacturer in both DI and MI and the manufacturer needs to offer a payment to the retailers to obtain demand information under both simultaneous and sequential contract schemes.

Originality/value

This paper contributes to the literature by examining how the nature of products (margin intensive green product or development intensive green product) influences green supply chain decisions under information asymmetry and downstream competition.
Farmers’ willingness to adopt digital application tools in Ogun State, Nigeria
Authors: Abioye Daniel Oyewale , Popoola Olufemi , Akande Adebowale , Fadare David Abimbola , Omitoyin Siyanbola Adewumi , Yinusa Babatunde , Kolade Olayinka Oladayo
Published: August 2024

Purpose

The agricultural sector has experienced a transformative impact through the adoption of digital technologies, particularly mobile applications designed for farmers. This study investigates the factors influencing smallholder farmers' willingness to adopt digital application tools in Ogun State, Nigeria, focusing on the IITA herbicide calculator and Akilimo mobile applications.

Design/methodology/approach

Data were gathered from 572 smallholder farmers participating in the Zero Hunger project. This research contributes to the limited empirical evidence in Nigeria concerning farmers' willingness to adopt digital application tools. The study analyzes the effects of education, training, access to internet services, smartphone ownership, willingness to use paid applications, awareness of application tools and the cost of digital tools on farmers' willingness to adopt. Gender differentials in willingness to adopt were also explored.

Findings

The results indicate positive and statistically significant effects of education, training, internet access, smartphone ownership, willingness to use paid applications, awareness of application tools and the cost of digital tools on farmers' willingness to adopt. However, female farmers exhibited a lower willingness to adopt digital application tools.

Practical implications

Policymakers are urged to create supportive policies promoting basic formal education and provide effective extension services to enhance farmers' training. Additionally, efforts should be made to reduce the cost of digital applications and improve internet accessibility in rural areas. Encouraging female farmers to adopt advanced agricultural technologies is essential. Stakeholders are advised to raise awareness of digital application tools to expedite the adoption of agricultural technologies in the country.

Social implications

This study will be helpful for the government to determine the state’s readiness for digital agriculture, it will help technology developers and agricultural technology startups to understand the factors determining farmers willingness to adopt digital application tools.

Originality/value

This study offers insights into the readiness of Ogun State, Nigeria, for digital agriculture. It provides valuable information for technology developers and agricultural startups to understand the determinants of farmers' willingness to adopt digital application tools, contributing to the advancement of the agricultural technology landscape.
Cross‐correlation reflection waveform inversion based on a weighted norm of the time‐shift obtained by dynamic image warping
Authors: Qu Yingming , Dong Shihao , Zhong Tianmiao , Ren Yi , Li Zizheng , Xing Boshen , Li Yifan
Published: August 2024

The computational efficiency of cross‐correlation reflection waveform inversion can be improved by utilizing the outcomes of reverse time migration instead of the least‐squares reverse time migration results in each iteration. However, the inversion effect of cross‐correlation reflection waveform inversion needs to be optimized as the inversion results may not be optimal. The conventional cross‐correlation operator tends to produce interference values that can compromise the precision of time‐shift estimations. Moreover, the time shift obtained through dynamic image warping can exhibit spiky disturbances, making it difficult to determine accurate time‐shift values. These challenges can cause the inversion process to converge to a local minimum, thereby affecting the quality of the inversion results. To address these limitations, this paper proposes a new approach called cross‐correlation reflection waveform inversion based on dynamic image warping. The proposed method integrates a weighted norm derived from dynamic image warping to effectively regulate the time‐shift values throughout the inversion process. The effectiveness of the proposed cross‐correlation reflection waveform inversion based on the dynamic image warping method is validated through simulations using a simple two‐layer model and a resampled Sigsbee 2A model. A comparative analysis is performed to evaluate the performance of cross‐correlation reflection waveform inversion based on dynamic image warping in mitigating cross‐correlation interference, demonstrating its superior capability compared to the conventional cross‐correlation reflection waveform inversion method.
Depositional Environment and Origin of Inertinite‐rich Coal in the Ordos Basin
Authors: SHI Qingmin , ZHAO Jun , JI Ruijun , XUE Weifeng , HAN Bo , CAI Yue , LI Chunhao , CUI Shidong
Published: August 2024

Inertinite‐rich coal is widely distributed in the Ordos Basin, represented by the No. 2 coal seam of the Middle Jurassic Yan'an Formation. This paper combined coal petrology and geochemistry to analyze the origin of inertinite, changes in the coal‐forming environment and control characteristics of wildfire. Research has shown that there are two forms of inertinite sources in the study area. Alongside typical fusinization, wildfire events also play a substantial role in inertinite formation. There are significant fluctuations in the coal‐forming environment of samples at different depths. Coal samples were formed in dry forest swamp with low water levels and strong oxidation, which have a high inertinite content, and the samples formed in wet forest swamp and limnic showed low inertinite content. Conversely, the inertinite content of different origins does not fully correspond to the depositional environment characterized by dryness and oxidation. Nonpyrogenic inertinites were significantly influenced by climatic conditions, while pyrofusinite was not entirely controlled by climatic conditions but rather directly impacted by wildfire events. The high oxygen level was the main factor causing widespread wildfire events. Overall, the combination of wildfire activity and oxidation generates a high content of inertinite in the Middle Jurassic coal of the Ordos Basin.
Psychosis metabolic risk calculator (PsyMetRiC) in early psychosis: External validation study in Finland
Authors: Keinänen Jaakko , Eskelinen Saana , From Tiina , Laurikainen Heikki , Hietala Jarmo , Murray Graham K. , Suvisaari Jaana , Perry Benjamin I.
Published: August 2024

Introduction

Accurate detection of cardiometabolic risk in early psychosis is crucial to reducing somatic morbidity and mortality in people with psychotic disorders. We conducted an external validation of the psychosis metabolic risk calculator (PsyMetRiC), a cardiometabolic risk prediction tool developed in the UK and tailored for young people with psychosis. We compared the predictive accuracy and clinical usefulness of PsyMetRiC and a general population‐based risk prediction tool for type 2 diabetes, the Finnish Diabetes Risk Score (FINDRISC).

Methods

We included first‐episode psychosis and ultra‐high‐risk for psychosis patients without metabolic syndrome aged 18–35 years from the Helsinki Early Psychosis and Turku Early Psychosis Study cohorts. We tested two versions of PsyMetRiC: the full model including age, sex, ethnicity, body‐mass index, smoking status, prescription of metabolically‐active antipsychotic medication, high‐density lipoprotein, and triglyceride concentrations, and the partial‐model excluding biochemical predictors, and the simplified FINDRISC including BMI, sex, systolic blood pressure, and fasting glucose. Discrimination, calibration, and decision curve analyses were used to assess the predictive performance and clinical usefulness of both PsyMetRiC and FINDRISC. We performed a site‐specific re‐calibration of PsyMetRiC (PsyMetRiC‐Fi).

Results

The study sample consisted of 278 individuals (all White European ethnicity, 58.6% male, mean age 24.8 years, 37.8% smoking, mean BMI 23.5). Discrimination was marginally better in the PsyMetRiC full model (C = 0.72, 95% CI, 0.59–0.82) compared with partial model (C = 0.70, 95% CI 0.59–0.80) or FINDRISC (C = 0.63, 95% CI 0.54–0.71). Calibration plots displayed evidence of minor miscalibration for PsyMetRiC, which corrected following recalibration. Miscalibration was more pronounced for FINDRISC. Decision curve analysis showed that PsyMetRiC offers likely clinical usefulness in improving cardiometabolic risk management in early psychosis compared with giving everyone or no one an intervention.

Conclusion

PsyMetRiC has utility in predicting cardiometabolic risk in Finnish patients with early psychosis. It has better discriminatory accuracy and offers more accurate risk prediction compared to other available strategies.
The production of terra sigillata in Arezzo, Central Italy: an archaeometric investigation
Authors: Mascaro Maria Emanuela , Cantisani Emma , Ricci Marilena , Pallecchi Pasquino , Vilucchi Silvia , Dalconi Maria Chiara , Maritan Lara
Published: August 2024

This work deals with the archaeometric investigation on 25 fragments of terra sigillata (red‐coated ceramic ware and moulds) found in the city of Arezzo, Tuscany (central Italy), and attributed to several important workshops from the first century BCE to the second century CE. Optical and spectroscopic techniques were used to analyse both the ceramic bodies and the red slips. All the potsherds showed a very fine‐grained ceramic body, sharing similar mineralogical compositions, mainly consisting in quartz, plagioclase, pyroxene, hematite, K‐feldspars, and illite/muscovite. The mineralogical data suggest that both the red‐coated wares and the moulds were produced using the same calcareous‐illitic clay and fired under oxidising conditions at temperatures between 850°C and 1000°C. A K‐rich illitic clay with a Fe content around 10–15% (in wt%) was used to elaborate the slips. Al‐substituted hematite was found in red slips by micro‐Raman spectroscopy. Comparison of the chemical data with terra sigillata from other important production areas in Italy and from other regions of the Meditteranean Sea, allowed to define that the studied samples, locally produced in Arezzo, differ systematically from all others, although they show similarities with nearby Pisan productions as well as those Puteolan.
Digital workflow for graft harvest and positioning in deficient anterior mandibles versus conventional technique: Randomized controlled trial
Authors: Sakr Mohamed Ibrahim , Hanafy Mahmoud , Gibaly Amr , Mounir Mohamed
Published: August 2024

Background

The cortical shell technique is frequently associated with technical drawbacks, such as the lack of anatomical guidance during shell harvest and graft. This study aims to assess the horizontal bone gain and accuracy of a digitalized protocol that incorporates two interlocking patient‐specific stackable guides (PSSGs) to control the shell harvest, positioning, and fixation.

Patients and Methods

Twenty patients with deficient anterior mandibles were randomly allocated; 10 patients received freehand symphyseal shell harvest and fixation (the control group), whereas the other 10 received fully guided harvest and graft (study group) using (PSSGs), the first aided an accurate shell harvest, whereas the second conveyed shell fixation. The interposition gap among both groups was loaded with an equal mix of xenogeneic and autogenous particulates. The mean radiographic bone gain among both groups was calibrated 6 months postoperatively, and the accuracy of the digital plan was assessed by superimposing and comparing the virtually planned horizontal bone dimensions with the immediate postoperative actual bone dimensions.

Results

The mean 6‐month postoperative horizontal bone gain value of the study group was recorded as (4.97 ± 0.73) mm versus (4.45 ± 0.61) mm for the control group, with a statistically insignificant mean gain difference of (0.52) mm, (p = 0.101). The mean virtual preplanned horizontal bone gain was recorded (5.4 ± 0.6) versus (5.4 ± 0.6) for the immediate postoperative actual bone gain, which was also statistically insignificant (p = 0.9).

Conclusion

The (PSSGs) provided a precise method for graft harvest, position, and fixation, resulting in satisfactory alveolar ridge dimensions with intimate accuracy.
Use of fusion imaging in safe, rapid, and accurate placement of percutaneous right ventricular assist device in the management of acute post‐surgical right ventricular failure
Authors: Alkhawam Mustafa , Chen Weihan , Mahmood Abdullah , Ebrahimi Ali J. , Nanda Navin C. , Ahmed Mustafa I.
Published: August 2024

Fusion imaging (FI) technology using EchoNavigator that integrates live transesophageal echocardiogram and overlays on real‐time fluoroscopy. We present our experience placing a right ventricular (RV) support device, a ProtekDuo, in our patient with post‐operative RV failure using FI to guide the implantation.
Maternal immune activation exerts long‐term effects on activity and sleep in male offspring mice
Authors: ElGrawani Waleed , Mueller Flavia S. , Schalbetter Sina M. , Brown Steven A. , Weber‐Stadlbauer Ulrike , Tarokh Leila
Published: August 2024

Exposure to infectious or non‐infectious immune activation during early development is a serious risk factor for long‐term behavioural dysfunctions. Mouse models of maternal immune activation (MIA) have increasingly been used to address neuronal and behavioural dysfunctions in response to prenatal infections. One commonly employed MIA model involves administering poly(I:C) (polyriboinosinic‐polyribocytdilic acid), a synthetic analogue of double‐stranded RNA, during gestation, which robustly induces an acute viral‐like inflammatory response. Using electroencephalography (EEG) and infrared (IR) activity recordings, we explored alterations in sleep/wake, circadian and locomotor activity patterns on the adult male offspring of poly(I:C)‐treated mothers. Our findings demonstrate that these offspring displayed reduced home cage activity during the (subjective) night under both light/dark or constant darkness conditions. In line with this finding, these mice exhibited an increase in non‐rapid eye movement (NREM) sleep duration as well as an increase in sleep spindles density. Following sleep deprivation, poly(I:C)‐exposed offspring extended NREM sleep duration and prolonged NREM sleep bouts during the dark phase as compared with non‐exposed mice. Additionally, these mice exhibited a significant alteration in NREM sleep EEG spectral power under heightened sleep pressure. Together, our study highlights the lasting effects of infection and/or immune activation during pregnancy on circadian activity and sleep/wake patterns in the offspring.
The posterior intralaminar thalamic nucleus promotes nose‐to‐nose contacts leading to prosocial reception in the sequence of mouse social interaction
Authors: Arakawa Hiroyuki , Tokashiki Mana
Published: August 2024

Efficient social interaction is essential for an adaptive life and consists of sequential processes of multisensory events with social counterparts. Social touch/contact is a unique component that promotes a sequence of social behaviours initiated by detection and approach to assess a social stimulus and subsequent touch/contact interaction to form prosocial relationships. We hypothesized that the thalamic sensory relay circuit from the posterior intralaminar nucleus of the thalamus (pIL) to the paraventricular nucleus of the hypothalamus (PVN) and the medial amygdala (MeA) plays a key role in the social contact‐mediated sequence of events. We found that neurons in the pIL along with the PVN and MeA were activated by social encounters and that pIL activity was more abundant in a direct physical encounter, whereas MeA activity was dominant in an indirect through grid encounter. Chemogenetic inhibition of pIL neurons selectively decreased the investigatory approach and sniffing of a same‐sex, but not an opposite‐sex, stimulus mouse in an indirect encounter situation and decreased the facial/snout contact ratio in a direct encounter setting. Furthermore, chemogenetic pIL inhibition had no impact on anxiety‐like behaviours or body coordinative motor behaviours, but it impaired whisker‐related and plantar touch tactile sense. We propose that the pIL circuit can relay social tactile sensations and mediate the sequence of nonsexual prosocial interactions through an investigatory approach to tactile contact and thus plays a significant role in establishing prosocial relationships in mouse models.
Preoperative cognitive profile predictive of cognitive decline after subthalamic deep brain stimulation in Parkinson's disease
Authors: Mana Josef , Bezdicek Ondrej , Růžička Filip , Lasica Andrej , Šmídová Anna , Klempířová Olga , Nikolai Tomáš , Uhrová Tereza , Růžička Evžen , Urgošík Dušan , Jech Robert
Published: August 2024

Cognitive decline represents a severe non‐motor symptom of Parkinson's disease (PD) that can significantly reduce the benefits of subthalamic deep brain stimulation (STN DBS). Here, we aimed to describe post‐surgery cognitive decline and identify pre‐surgery cognitive profile associated with faster decline in STN DBS‐treated PD patients. A retrospective observational study of 126 PD patients treated by STN DBS combined with oral dopaminergic therapy followed for 3.54 years on average (SD = 2.32) with repeated assessments of cognition was conducted. Pre‐surgery cognitive profile was obtained via a comprehensive neuropsychological examination and data analysed using exploratory factor analysis and Bayesian generalized linear mixed models. On the whole, we observed a mild annual cognitive decline of 0.90 points from a total of 144 points in the Mattis Dementia Rating Scale (95% posterior probability interval [−1.19, −0.62]) with high inter‐individual variability. However, true score changes did not reach previously reported reliable change cut‐offs. Executive deficit was the only pre‐surgery cognitive variable to reliably predict the rate of post‐surgery cognitive decline. On the other hand, exploratory analysis of electrode localization did not yield any statistically clear results. Overall, our data and models imply mild gradual average annual post‐surgery cognitive decline with high inter‐individual variability in STN DBS‐treated PD patients. Nonetheless, patients with worse long‐term cognitive prognosis can be reliably identified via pre‐surgery examination of executive functions. To further increase the utility of our results, we demonstrate how our models can help with disentangling true score changes from measurement error in future studies of post‐surgery cognitive changes.
Utilizing an acute hyperthermia‐induced seizure test and pharmacokinetic studies to establish optimal dosing regimens in a mouse model of Dravet syndrome
Authors: Mensah Jeffrey A. , Johnson Kristina , Freeman Tia , Reilly Christopher A. , Rower Joseph E. , Metcalf Cameron S. , Wilcox Karen S.
Published: August 2024

Objective

The current standard of care for Dravet syndrome (DS) includes polytherapy after inadequate seizure control with one or more monotherapy approaches. Treatment guidelines are often based on expert opinions, and finding an optimal balance between seizure control and adverse drug effects can be challenging. This study utilizes the efficacy and pharmacokinetic assessment of a second‐line treatment regimen that combines clobazam and sodium valproate with an add‐on drug as a proof‐of‐principle approach to establish an effective therapeutic regimen in a DS mouse model.

Methods

We evaluated the efficacy of add‐on therapies stiripentol, cannabidiol, lorcaserin, or fenfluramine added to clobazam and sodium valproate against hyperthermia‐induced seizures in Scn1aA1783V/WT mice. Clobazam, N‐desmethyl clobazam (an active metabolite of clobazam), sodium valproate, stiripentol, and cannabidiol concentrations were quantified in plasma and brain using liquid chromatography–tandem mass spectrometry for the combinations deemed effective against hyperthermia‐induced seizures. The concentration data were used to calculate pharmacokinetic parameters via noncompartmental analysis in Phoenix WinNonLin.

Results

Higher doses of stiripentol or cannabidiol, in combination with clobazam and sodium valproate, were effective against hyperthermia‐induced seizures in Scn1aA1783V/WT mice. In Scn1aWT/WT mice, brain clobazam and N‐desmethyl clobazam concentrations were higher in the triple‐drug combinations than in the clobazam monotherapy. Stiripentol and cannabidiol brain concentrations were greater in the triple‐drug therapy than when given alone.

Significance

A polypharmacy strategy may be a practical preclinical approach to identifying efficacious compounds for DS. The drug–drug interactions between compounds used in this study may explain the potentiated efficacy of some polytherapies.
CADICA: A new dataset for coronary artery disease detection by using invasive coronary angiography
Authors: Jiménez‐Partinen Ariadna , Molina‐Cabello Miguel A. , Thurnhofer‐Hemsi Karl , Palomo Esteban J. , Rodríguez‐Capitán Jorge , Molina‐Ramos Ana I. , Jiménez‐Navarro Manuel
Published: August 2024

Coronary artery disease (CAD) remains the leading cause of death globally and invasive coronary angiography (ICA) is considered the gold standard of anatomical imaging evaluation when CAD is suspected. However, risk evaluation based on ICA has several limitations, such as visual assessment of stenosis severity, which has significant interobserver variability. This motivates to development of a lesion classification system that can support specialists in their clinical procedures. Although deep learning classification methods are well‐developed in other areas of medical imaging, ICA image classification is still at an early stage. One of the most important reasons is the lack of available and high‐quality open‐access datasets. In this paper, we reported a new annotated ICA images dataset, CADICA, to provide the research community with a comprehensive and rigorous dataset of coronary angiography consisting of a set of acquired patient videos and associated disease‐related metadata. This dataset can be used by clinicians to train their skills in angiographic assessment of CAD severity, by computer scientists to create computer‐aided diagnostic systems to help in such assessment, and to validate existing methods for CAD detection. In addition, baseline classification methods are proposed and analysed, validating the functionality of CADICA with deep learning‐based methods and giving the scientific community a starting point to improve CAD detection.
Multi‐stage stochastic frontier analysis for simple networks
Authors: Johnes Geraint , Tsionas Mike , Izzeldin Marwan
Published: August 2024

We develop a method for modelling multi‐stage production using stochastic frontier analysis. This approach is suitable for the analysis of costs or output where intermediate outputs become inputs into a subsequent stage of the production process, either within an organisation or in the form of a supply chain. Our focus is on higher education institutions in England, and the purpose is to assess the performance of our novel methods using Markov Chain Monte Carlo methods. Without taking into full account of the complexity of the ‘network’, key decisions cannot be made regarding intake quality, student/staff ratios, per‐student spending or academic reputation (the last of which involves costly decisions in terms of academic openings and the profile of candidates desired for any given university).