bluuebunny/crossref_metadata_2025 huggingface dataset:
Astrocytes in the rostral ventromedial medulla mediate the analgesic effect of electroacupuncture in a rodent model of chemotherapy-induced peripheral neuropathic pain
Authors: Chen Xuejiao , Mi Wenli , Gao Tianchi , Ding Fengfei , Wang Wei
Published: October 2024

Chemotherapy-induced peripheral neuropathic pain aggravates cancer survivors' life burden. Electroacupuncture (EA) has exhibited promising analgesic effects on neuropathic pain in previous studies. We investigated whether EA was effective in a paclitaxel-induced neuropathic pain mouse model. We further explored the functional role of astrocytes in the rostral ventromedial medulla (RVM), a well-established pain modulation center, in the process of neuropathic pain as well as the analgesic effect of EA. We found that paclitaxel induced mechanical allodynia, astrocytic calcium signaling, and neuronal activation in the RVM and spinal cord, which could be suppressed by EA treatment. Electroacupuncture effectively alleviated paclitaxel-induced mechanical allodynia, and the effect was attenuated by the chemogenetic activation of astrocytes in the RVM. In addition, inhibiting astrocytic calcium activity by using either IP3R2 knockout (IP3R2 KO) mice or microinjection of AAV-mediated hPMCA2 w/b into the RVM to reduce non–IP3R2-dependent Ca2+ signaling in astrocytes exhibited an analgesic effect on neuropathic pain, which mimicked the EA effect. The current study revealed the pivotal role of the RVM astrocytes in mediating the analgesic effects of EA on chemotherapy-induced peripheral neuropathic pain.
Widespread hyperexcitability of nociceptor somata outlasts enhanced avoidance behavior after incision injury
Authors: Bavencoffe Alexis , Lopez Elia R. , Johnson Kayla N. , Tian Jinbin , Gorgun Falih M. , Shen Breanna Q. , Domagala Drue M. , Zhu Michael X. , Dessauer Carmen W. , Walters Edgar T.
Published: October 2024

Nociceptors with somata in dorsal root ganglia (DRGs) readily switch from an electrically silent state to a hyperactive state of tonic, nonaccommodating, low-frequency, irregular discharge of action potentials (APs). Spontaneous activity (SA) during this state is present in vivo in rats months after spinal cord injury (SCI) and has been causally linked to SCI pain. Intrinsically generated SA and, more generally, ongoing activity (OA) are induced by various neuropathic conditions in rats, mice, and humans and are retained in nociceptor somata after dissociation and culturing, providing a powerful tool for investigating its mechanisms and functions. The present study shows that long-lasting hyperexcitability that can generate OA during modest depolarization in probable nociceptors dissociated from DRGs of male and female rats is induced by plantar incision injury. OA occurred when the soma was artificially depolarized to a level within the normal range of membrane potentials where large, transient depolarizing spontaneous fluctuations (DSFs) can approach AP threshold. This hyperexcitability persisted for at least 3 weeks, whereas behavioral indicators of affective pain—hind paw guarding and increased avoidance of a noxious substrate in an operant conflict test—persisted for 1 week or less. The most consistent electrophysiological alteration associated with OA was enhancement of DSFs. An unexpected discovery after plantar incisions was hyperexcitability in neurons from thoracic DRGs that innervate dermatomes distant from the injured tissue. Potential in vivo functions of widespread, low-frequency nociceptor OA consistent with these and other findings are to contribute to hyperalgesic priming and to drive anxiety-related hypervigilance.
Gaming the System? A Qualitative Exploration of Physician Assistant Learner Perceptions of Virtual Patient Education
Authors: Kanofsky Sharona , Hodwitz Kathryn , Tzakas Peter , Nyhof-Young Joyce M. , Walsh Catharine M.
Published: October 2024

Introduction

Virtual patients (VPs) are increasingly used in health professions education. How learners engage with VPs and the relationship between engagement and authenticity is not well understood. We explored learners' perceptions of VP education to gain an understanding of the characteristics promoting meaningful engagement in learning, including perceived authenticity.

Methods

Using a constructivist grounded theory approach, we conducted interviews and focus groups with 11 students from 2 Canadian Physician Assistant programs, where VP learning was implemented to supplement clinical education during the COVID-19 pandemic. We explored trainee perspectives on the use of VPs as an educational modality. Data were iteratively collected and descriptively analyzed thematically using a constant comparison approach until theoretical sufficiency was reached.

Results

We identified 3 groups of factors influencing these students' VP learning experiences: (1) technical factors related to the VP platform influenced the perceived authenticity of the patient interactions; (2) individual factors of learners' attitudes influenced their engagement and motivation; and (3) contextual factors related to the learning environment influenced the acceptability and perceived value of the learning experience. Overall, the psychological authenticity of the learning platform and students' motivation for self-directed learning were perceived as most important for students' learning experiences.

Conclusions

Implementing VP learning as a supplement to clinical education should be done with consideration of factors that enhance the psychological authenticity of the learning platform, promote learner engagement and accountability, and encourage acceptability of the learning modality through curricular placement and messaging.
Active Choice Nudge to Increase Screening for Primary Aldosteronism in At-Risk Patients
Authors: Passman Jesse E , Hwang Jasmine , Tang Justin , Fagen Madeline , Epps Mika , Peifer MaryAnne , Howell John T , Cohen Jordana B , Delgado M Kit , Wachtel Heather , Herman Daniel S
Published: October 2024

BACKGROUND:

Primary aldosteronism (PA) is the most common cause of secondary hypertension, yet screening remains startlingly infrequent. We describe (1) PA screening practices in a large, diverse health system, (2) the development of a computable phenotype for PA screening, and (3) the design and pilot deployment of an electronic health record (EHR)-based active choice nudge to recommend PA screening.

STUDY DESIGN:

A multidisciplinary team developed a multipronged intervention to improve PA screening informed by guidelines, expertise, and multivariable analyses of factors associated with screening. The intervention included EHR-based tools to automatically identify screen-eligible patients, an active choice nudge recommending screening for these patients, and screening result interpretation. The intervention was piloted across 2 primary care practices for 7 months. Screening frequencies were compared with clinics not receiving the intervention.

RESULTS:

The baseline frequency of screening of eligible patients within 1 year was 1.4%. Higher mean systolic blood pressure (odds ratio [OR] 1.4; p < 0.001), more antihypertensive medications (OR 1.3; p = 0.002), lower minimum serum potassium (OR 2.0; p = 0.001), specialist care (OR 3.0; p < 0.001), and Black race (OR 1.5; p = 0.001) were associated with a higher likelihood of screening. The refined computable phenotype identified a subcohort with a higher frequency of positive screening (8.6% vs 4.1%; p = 0.03). In a pilot study of an active choice nudge, a greater proportion of eligible patients were screened in the intervention clinics (16.4%) than in the nonintervention clinics (1.8%; p < 0.001).

CONCLUSIONS:

PA screening rates are low. This pilot study suggests an EHR-based nudge leveraging a precise computable phenotype can dramatically increase appropriate PA screening.
From lab to life: challenges and perspectives of fNIRS for haemodynamic-based neurofeedback in real-world environments
Authors: Klein Franziska , Kohl Simon H. , Lührs Michael , Mehler David M. A. , Sorger Bettina
Published: October 2024

Neurofeedback allows individuals to monitor and self-regulate their brain activity, potentially improving human brain function. Beyond the traditional electrophysiological approach using primarily electroencephalography, brain haemodynamics measured with functional magnetic resonance imaging (fMRI) and more recently, functional near-infrared spectroscopy (fNIRS) have been used (haemodynamic-based neurofeedback), particularly to improve the spatial specificity of neurofeedback. Over recent years, especially fNIRS has attracted great attention because it offers several advantages over fMRI such as increased user accessibility, cost-effectiveness and mobility—the latter being the most distinct feature of fNIRS. The next logical step would be to transfer haemodynamic-based neurofeedback protocols that have already been proven and validated by fMRI to mobile fNIRS. However, this undertaking is not always easy, especially since fNIRS novices may miss important fNIRS-specific methodological challenges. This review is aimed at researchers from different fields who seek to exploit the unique capabilities of fNIRS for neurofeedback. It carefully addresses fNIRS-specific challenges and offers suggestions for possible solutions. If the challenges raised are addressed and further developed, fNIRS could emerge as a useful neurofeedback technique with its own unique application potential—the targeted training of brain activity in real-world environments, thereby significantly expanding the scope and scalability of haemodynamic-based neurofeedback applications.

This article is part of the theme issue ‘Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation’.
Online self-evaluation of fMRI-based neurofeedback performance
Authors: Muñoz-Moldes Santiago , Tursic Anita , Lührs Michael , Eck Judith , Benitez Andonegui Amaia , Peters Judith , Cleeremans Axel , Goebel Rainer
Published: October 2024

This study explores the subjective evaluation of supplementary motor area (SMA) regulation performance in a real-time functional magnetic resonance imaging neurofeedback (fMRI-NF) task. In fMRI-NF, people learn how to self-regulate their brain activity by performing mental actions to achieve a certain target level (TL) of blood-oxygen-level-dependent (BOLD) activation. Here, we studied two types of self-evaluation: performance predictions and perceived confidence in the prediction judgement. Participants completed three sessions of SMA regulation in a 7 T fMRI scanner, performing a mental drawing task. During each trial, they modulated their imagery strategy to achieve one of two different levels of SMA activation and reported a performance prediction and their confidence in the prediction before receiving delayed BOLD-activation feedback. Results show that participants’ performance predictions improved with learning throughout the three sessions, and that these improvements were not driven exclusively by their knowledge of previous performance. Confidence reports on the other hand showed no change throughout training and did not correlate with better and worse predictions. In addition to shedding light on mechanisms of internal self-evaluation during neurofeedback training, these results also point to a dissociation between predictions of performance and confidence reports in the presence of feedback.

This article is part of the theme issue ‘Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation’.
APOEGenotype and Biological Age Impact Inter-Omic Associations Related to Bioenergetics
Authors: Ellis Dylan , Watanabe Kengo , Wilmanski Tomasz , Lustgarten Michael S. , Korat Andres V Ardisson , Glusman Gwênlyn , Hadlock Jennifer J. , Fiehn Oliver , Sebastiani Paola , Price Nathan D. , Hood Leroy , Magis Andrew T. , Evans Simon J. , Pflieger Lance , Lovejoy Jennifer C. , Gibbons Sean M. , Funk Cory C. , Baloni Priyanka , Rappaport Noa
Published: October 2024

Apolipoprotein E (APOE) modifies human aging; specifically, the ε2 and ε4 alleles are among the strongest genetic predictors of longevity and Alzheimer’s disease (AD) risk, respectively. However, detailed mechanisms for their influence on aging remain unclear. Herein, we analyzed inter-omic, context-dependent association patterns acrossAPOEgenotypes, sex, and health axes in 2,229 community-dwelling individuals to testAPOEgenotypes for variation in metabolites and metabolite-associations tied to a previously-validated metric of biological aging (BA) based on blood biomarkers. Our analysis, supported by validation in an independent cohort, identified topAPOE-associated plasma metabolites as diacylglycerols, which were increased in ε2-carriers and trended higher in ε4-carriers compared to ε3-homozygotes, despite the known opposing aging effects of the allele variants. ‘Omics association patterns of ε2-carriers and increased biological age were also counter-intuitively similar, displaying increased associations between insulin resistance markers and energy-generating pathway metabolites. These results provide an atlas ofAPOE-related ‘omic associations and support the involvement of bioenergetic pathways in mediating the impact ofAPOEon aging.
From Beeps to Streets: Unveiling Sensory Input and Relevance Across Auditory Contexts
Authors: Korte Silvia , Jaeger Manuela , Rosenkranz Marc , Bleichner Martin G.
Published: October 2024

This study investigates the neural basis of sound perception in everyday life using EEG data recorded in an office-like environment over 3.5 hours. We investigated how contextual factors such as personal relevance, task complexity and stimulus properties influence auditory processing in ecologically valid settings. By systematically increasing the complexity of acoustic scenes and tasks, we analysed changes in neural responses, particularly in the N100 and P300 components. Our results show that while the P300 is a stable marker of attention in both isolated sounds and complex soundscapes, the N100 is more sensitive to task complexity and environmental factors. This highlights the importance of context in shaping auditory perception. Furthermore, our results suggest that laboratory-based findings can be partially generalised to real-world settings, although task demands significantly influence neural markers. These findings provide new opportunities to study sound perception in naturalistic settings, without sacrificing the control typically afforded by laboratory studies.
Dietary patterns of adults in Italy: Results from the third Italian National Food Consumption Survey, INRAN-SCAI
Authors: Scarsi Nicolò , Pastorino Roberta , Savoia Cosimo , Raspolini Gian Marco , Pezzullo Angelo Maria , Boccia Stefania
Published: October 2024

Background & objective.

Diet is among the most significant modifiable risk factors for reducing the global burden of chronic diseases. This study aims to investigate the dietary patterns of adults in a large representative sample of the Italian population and to analyze these patterns according to sociodemographic characteristics.

Methods

Adult participants of the third Italian National Food Consumption Survey (INRAN- SCAI 2005-06) were included. A total of 878 food items were classified into 24 pre-defined food groups using the FoodEx2 classification system. Dietary patterns were identified through principal component analysis, and Z-scores were calculated to assess adherence to these patterns. Associations between sociodemographic characteristics, energy intake, and dietary adherence scores were investigated using linear regression models.

Results

Based on data from 2,831 subjects (median age 47, IQR 35-60), five principal components (PCs) were retained, explaining 35.6% of the overall variance. PC1 was indicative of a high-fat diet, PC2 suggested a western eating behavior, PC3 represented a health-conscious lifestyle, PC4 can be characterized as an Italian traditional diet, and PC5 represented an unhealthy dietary pattern. According to Z-scores, 42.4% of our study cohort showed high adherence to at least one of the dietary patterns. Less healthy dietary patterns were more prevalent among males and individuals from northern Italian regions.

Conclusions

Our results indicate a significant regional variation in terms of dietary pattern, mirroring the general trends of Italian eating habits of the last decades, characterized by a higher tendency towards a more westernized lifestyle. These findings underscore the importance of considering region-specific characteristics when designing future public health interventions and establishing national dietary guidelines.
ZNFX1 is a Novel Master Regulator in Epigenetically-induced Pathogen Mimicry and Inflammasome Signaling in Cancer
Authors: Stojanovic Lora , Abbotts Rachel , Tripathi Kaushlendra , Coon Collin M. , Rajendran Saranya , Farid Elnaz Abbasi , Hostetter Galen , Guarnieri Joseph W. , Wallace Douglas C. , Liu Sheng , Wan Jun , Calendo Gennaro , Marker Rebecca , Gohari Zahra , Inayatullah Mohammed M. A. , Tiwari Vijay K. , Kader Tanjina , Santagata Sandro , Drapkin Ronny , Kommoss Stefan , Pfisterer Jacobus , Konecny Gottfried E , Coopergard Ryan , Issa Jean-Pierre , Winterhoff Boris J. N. , Topper Michael J. , Sandusky George E. , Miller Kathy D. , Baylin Stephen B. , Nephew Kenneth P. , Rassool Feyruz V.
Published: October 2024

DNA methyltransferase and poly(ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon (IFN) genes (STING)-dependent pathogen mimicry response (PMR) in ovarian (OC) and other cancers. We now show that combining DNMTis and PARPis upregulates expression of a little-studied nucleic-acid sensor, NFX1-type zinc finger-containing 1 protein (ZNFX1). We demonstrate that ZNFX1 is a novel master regulator for PMR induction in mitochondria, serving as a gateway for STING-dependent PMR. In patient OC databases, high ZNFX1 expression levels correlate with advanced stage disease. ZNFX1 expression alone significantly correlates with an increase in overall survival in a phase 3 trial for therapy-resistant OC patients receiving bevacizumab in combination with chemotherapy. In correlative RNA-seq data, inflammasome signaling through ZNFX1 correlates with abnormal vasculogenesis. ZNFX1 controls PMR signaling through the mitochondria and may serve as a biomarker to facilitate offering personalized therapy in OC patients, highlighting the strong translational significance of our findings.

Significance statement

DNA methyltransferase and poly(ADP-ribose) polymerase inhibitors upregulate expression of a novel nucleic-acid sensor, ZNFX1 that serves as a mitochondrial gateway to STING-dependent interferon/inflammasome signaling with tumor suppressor properties in ovarian cancer.
Idiopathic Intracranial Hypertension and Cardiovascular Diseases Risk in the United Kingdom Women: An Obesity-Adjusted Risk Analysis Using Indirect Standardization
Authors: Azzam Ahmed Y. , Morsy Mahmoud M. , Ellabban Mohamed Hatem , Morsy Ahmed M. , Zahran Adham Adel , Nassar Mahmoud , Elsayed Omar S. , Elswedy Adam , Elamin Osman , Al Zomia Ahmed Saad , Abukhadijah Hana J. , Alotaibi Hammam A. , Atallah Oday , Azab Mohammed A. , Essibayi Muhammed Amir , Dmytriw Adam A. , Morsy Mohamed D. , Altschul David J.
Published: October 2024

Introduction

Idiopathic intracranial hypertension (IIH) is associated with increased cardiovascular disease (CVD) risk, but the relative contributions of obesity versus IIH-specific factors remain unclear. This study aims to disentangle the effects of obesity and IIH on stroke and CVD risk, building upon previous research suggesting a two-fold increased risk of cardiovascular events in women with IIH compared to BMI-matched controls.

Methods

We conducted an obesity-adjusted risk analysis using Indirect Standardization analysis based on Adderley et al. study which utilized data from a cohort of 2,760 women with IIH and 27,125 matched healthy controls from The Health Improvement Network (THIN) database. We employed innovative statistical models to adjust for the confounding effects of obesity, estimating the risk of ischemic stroke and cardiovascular disease attributable to IIH independent of obesity. Four distinct models were used to elucidate the complex interrelationships between IIH, obesity, and CVD risk.

Results

Our analysis revealed that IIH confers additional cardiovascular risk beyond that attributed to obesity alone. Risk ratios for various cardiovascular outcomes were consistently elevated across models comparing IIH patients to controls within the same obesity strata. A striking synergistic effect between IIH and obesity was observed, with the composite CVD risk reaching a risk ratio of 6.19 (95% CI: 4.58-8.36, p<0.001) in obese IIH patients compared to non-obese controls.

Conclusions

This study provides compelling evidence for a nuanced relationship between IIH, obesity, and cardiovascular risk. IIH appears to confer substantial cardiovascular risk independent of obesity, necessitating a paradigm shift in IIH management to encompass comprehensive cardiovascular risk mitigation. Further research is needed to elucidate the underlying mechanisms and develop targeted interventions for this unique patient population.
Molecular Specification of Claustro-Amygdalar and Paleocortical Neurons and Connectivity
Authors: Kaur Navjot , Kovner Rothem , Gulden Forrest O. , Pletikos Mihovil , Andrijevic David , Zhu Tianjia , Silbereis John , Ma Shaojie , Salla Nikkita , Martin Xabier de , Klarić Thomas S. , Liu Yuting , Shibata Akemi , Franjic Daniel , Cho Hyesun , Yuen Matthew , Chatterjee Ipsita , Burke Megan , Esakkimuthu Devippriya , Moser Markus , Santpere Gabriel , Mineur Yann S. , Pattabiraman Kartik , Picciotto Marina R. , Huang Hao , Sestan Nenad
Published: October 2024

The ventropallial excitatory neurons (ExNs) in the claustro-amygdalar complex and piriform cortex (PIR; part of paleocortex) form crucial reciprocal connections with the prefrontal cortex (PFC), integrating cognitive and sensory information that result in adaptive behaviors. Early-life disruptions in these circuits are linked to neuropsychiatric disorders, highlighting the importance of understanding their development. Our study uncovers that transcription factors SOX4, SOX11, and TFAP2D play a pivotal role in the development, identity, and PFC connectivity of these neurons. Using mouse models, we demonstrate that the absence of transcription factors SOX4 and SOX11 in post-mitotic ExNs dramatically reduces the size of the basolateral amygdala complex (BLC), claustrum, and PIR. SOX4 and SOX11 control BLC formation through direct regulation ofTfap2dexpression. Cross-species analyses, including humans, identified conservedTfap2dexpression in developing ExNs of BLC, claustrum, paleocortex including PIR, and the associated transitional areas of the frontal, insular and temporal cortex. While the loss and haploinsufficiency ofTfap2dyield similar alterations in learned threat behaviors, differences emerge in the manifestation ofTfap2ddosage, particularly in terms of changes observed in BLC size and the connectivity pattern between the BLC and PFC. This underscores the significance ofTfap2ddosage in orchestrating developmental shifts in BLC-PFC connectivity and behavioral modifications reminiscent of symptoms of neuropsychiatric disorders. Together, these findings reveal key elements of a conserved gene regulatory network that shapes the development and function of crucial ventropallial ExNs and their PFC connectivity and offer insights into their evolution and alterations in neuropsychiatric disorders.
Ca2+-dependent vesicular and non-vesicular lipid transfer controls hypoosmotic plasma membrane expansion
Authors: Mu Baicong , Rutkowski David M. , Grenci Gianluca , Vavylonis Dimitrios , Zhang Dan
Published: October 2024

Robust coordination of surface and volume changes is critical for cell integrity. Few studies have elucidated the plasma membrane (PM) remodeling events during cell surface and volume alteration, especially regarding PM sensing and its subsequent rearrangements. Here, using fission yeast protoplasts, we reveal a Ca2+-dependent mechanism for membrane addition that ensures PM integrity and allows its expansion during acute hypoosmotic cell swelling. We show that MscS-like mechanosensitive channels activated by PM tension control extracellular Ca2+influx, which triggers direct lipid transfer at endoplasmic reticulum (ER)-PM contact sites by conserved extended-synaptotagmins and accelerates exocytosis, enabling PM expansion necessary for osmotic equilibrium. Defects in any of these key events result in rapid protoplast rupture upon severe hypotonic shock. Our numerical simulations of hypoosmotic expansion further propose a cellular strategy that combines instantaneous non-vesicular lipid transfer with bulk exocytic membrane delivery to maintain PM integrity for dramatic cell surface/volume adaptation.
Intrinsic Diversity In Primary Cilia Revealed Through Spatial Proteomics
Authors: Hansen Jan N. , Sun Huangqingbo , Kahnert Konstantin , Westenius Eini , Johannesson Alexandra , Tzavlaki Kalliopi , Winsnes Casper , Pohjanen Emmie , Fall Jenny , Navarro Frederic Ballllosera , Bäckström Anna , Lindskog Cecilia , Johansson Fredric , von Feilitzen Kalle , Vega Angelica Delgado , Uhlén Mathias , Casals Anna Martinez , Mahdessian Diana , Lindstrand Anna , Axelsson Ulrika , Lundberg Emma
Published: October 2024

Primary cilia are a critical organelle found on most human cells, and their dysfunction is linked to hereditary ciliopathies with diverse symptoms. Despite their significance, the specific roles of cilia in different cell types remain poorly understood due to limitations in analyzing ciliary protein composition. We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia. Our analysis identified the subciliary locations of 654 proteins across three cell lines, examining 110,844 individual cilia. We found that 67% of the ciliary proteome is cell-type specific, and 78% exhibited dynamically varied localization patterns, indicating that protein trafficking is crucial for ciliary function. Our findings portray cilia as dynamic sensors tuning their proteome to effectively sense the environment and compute cellular responses. We identified 71 novel cilia proteins and linked a genetic variant inCREB3to typical ciliopathy phenotypes. This open, spatial cilia atlas advances research on cilia and ciliopathies.
Prion propagation is controlled by a hierarchical network involving the nuclear Tfap2c and hnRNP K factors and the cytosolic mTORC1 complex
Authors: Sellitto Stefano , Caredio Davide , Bimbati Matteo , Mariutti Giovanni , Cerisoli Martina , Frick Lukas , Bouris Vangelis , Morales Carlos Omar Oueslati , Vena Dalila Laura , Neupane Sandesh , Baroni Federico , Ging Kathi , Yin Jiang-An , De Cecco Elena , Armani Andrea , Aguzzi Adriano
Published: October 2024

Heterogeneous Nuclear Ribonucleoprotein K (hnRNP K) is a limiting factor for prion propagation. However, little is known about the function of hnRNP K except that it is essential to cell survival. Here, we performed a synthetic-viability CRISPR ablation screen to identify epistatic interactors ofHNRNPK. We found that deletion of Transcription Factor AP-2γ (TFAP2C) suppressed the death of hnRNP K-depleted LN-229 and U-251 MG cells, whereas its overexpression hypersensitized cells to hnRNP K loss.HNRNPKablation decreased cellular ATP, downregulated genes related to lipid and glucose metabolism, and enhanced autophagy. Co-occurrent deletion ofTFAP2Creversed these effects, restoring transcriptional balance and alleviating energy deficiency. We linkedHNRNPKandTFAP2Cinteraction to mTOR signaling, observing thatHNRNPKablation inhibited mTORC1 activity through downregulation of mTOR and Rptor, whileTFAP2Coverexpression enhanced mTORC1 downstream functions. In prion-infected cells,TFAP2Cactivation reduced prion levels and countered the increased prion propagation caused byHNRNPKsuppression. Short-term pharmacological inhibition of mTOR also elevated prion levels and partially mimicked the effects ofHNRNPKsilencing. Our study identifiesTFAP2Cas a genetic interactor ofHNRNPK, implicates their roles in mTOR metabolic regulation, and establishes a causative link between these activities and prion propagation.
Analyzing super-enhancer temporal dynamics reveals potential critical enhancers and their gene regulatory networks underlying skeletal muscle development
Authors: Zhang Song , Wang Chao , Qin Shenghua , Chen Choulin , Bao Yongzhou , Zhang Yuanyuan , Xu Lingna , Liu Qingyou , Zhao Yunxiang , Li Kui , Tang Zhonglin , Liu Yuwen
Published: October 2024

Super-enhancers (SEs) govern the expression of genes defining cell identity. However, the dynamic landscape of SEs and their critical constituent enhancers involved in skeletal muscle development remains unclear. In this study, using pig as a model, we employed cleavage under targets and tagmentation (CUT&Tag) to profile the enhancer-associated histone modification marker H3K27ac in skeletal muscle across two prenatal and three postnatal stages, and investigated how SEs influence skeletal muscle development. We identify three SE families with distinct temporal dynamics: continuous (Con, 397), transient (TS, 434), and de novo (DN, 756). These SE families are associated with different temporal gene expression trajectories, biological functions, and DNA methylation levels. Notably, several lines of evidence suggest a potential prominent role of Con SEs in regulating porcine muscle development and meat traits. To pinpoint keycis-regulatory units in Con SEs, we developed an integrative approach that leverages information from eRNA annotation, genome-wide association study (GWAS) signals, and high-throughput capture self-transcribing active regulatory region sequencing (STARR-seq) experiments. Within Con SEs, we identify 20 candidate critical enhancers with meat and carcass-associated DNA variations that affect enhancer activity, and infer their upstream transcription factors and downstream target genes. As a proof of concept, we experimentally validate the role of one such enhancer and its potential target gene during myogenesis. Our findings reveal the dynamic regulatory features of SEs in skeletal muscle development and provide a general integrative framework for identifying critical enhancers underlying the formation of complex traits.
Inferring ancestry with the hierarchical soft clustering approach tangleGen
Authors: Burger Klara Elisabeth , Klepper Solveig , von Luxburg Ulrike , Baumdicker Franz
Published: October 2024

Understanding the genetic ancestry of populations is central to numerous scientific and societal fields. It contributes to a better understanding of human evolutionary history, advances personalized medicine, aids in forensic identification, and allows individuals to connect to their genealogical roots. Existing methods, such as ADMIXTURE, have significantly improved our ability to infer ancestries. However, these methods typically work with a fixed number of independent ancestral populations. As a result, they provide insight into genetic admixture, but do not include a hierarchical interpretation. In particular, the intricate ancestral population structures remain difficult to unravel. Alternative methods with a consistent inheritance structure, such as hierarchical clustering, may offer benefits in terms of interpreting the inferred ancestries. Here, we present tangleGen, a soft clustering tool that transfers the hierarchical machine learning framework Tangles, which leverages graph theoretical concepts, to the field of population genetics. The hierarchical perspective of tangleGen on the composition and structure of populations improves the interpretability of the inferred ancestral relationships. Moreover, tangleGen adds a new layer of explainability, as it allows identifying the single-nucleotide polymorphisms that are responsible for the clustering structure. We demonstrate the capabilities and benefits of tangleGen for the inference of ancestral relationships, using both simulated data and data from the 1000 Genomes Project.
Coexistence of anomalous Hall effect and weak magnetization in a nominally collinear antiferromagnet MnTe
Authors: Kluczyk K. P. , Gas K. , Grzybowski M. J. , Skupiński P. , Borysiewicz M. A. , Fąs T. , Suffczyński J. , Domagala J. Z. , Grasza K. , Mycielski A. , Baj M. , Ahn K. H. , Výborný K. , Sawicki M. , Gryglas-Borysiewicz M.
Published: October 2024

In various material systems, an antiferromagnetic phase was found to coexist with a weak ferromagneticlike signal, while symmetry-based theoretical predictions indicate a possibility of a nonzero anomalous Hall effect (AHE) even in the absence of sample magnetization. This is the case of nominally collinear antiferromagnets, in particular, hexagonal MnTe, where the AHE and no detectable magnetization have been recently reported. To clarify the role of magnetization, we present a study of bulk MnTe samples, combining experiment and theory. We demonstrate that the existence of the AHE in the hexagonal MnTe is accompanied by the presence of a weak but detectable ferromagneticlike signal, vanishing at the Néel temperature. In contrast to thin layer samples, we find that the AHE hysteresis loop shows an opposite sign and Barkhausen-like jumps. We introduce a macrospin model involving the Dzyaloshinskii–Moriya type interaction, which explains the existence of a nonzero magnetic moment in the absence of external field and reproduces well hysteretic behavior of the AHE. Using analysis of Néel-vector-dependent Berry curvature, we show that the intrinsic AHE in hexagonal MnTe can be nonzero even when the magnetization vanishes and, also, that it changes sign depending on the Fermi energy position.

Published by the American Physical Society
2024
Searching for long-lived light neutralinos and axionlike particles at the SHiNESS experiment
Authors: Wang Zeren Simon , Zhang Yu , Liu Wei
Published: October 2024

Recently, Soleti [] proposed a new experiment called SHiNESS at the upcoming European Spallation Source (ESS) facility, making use of the 2-GeV proton beam there impinging on a fixed target, in order to search for hidden sterile neutrinos that could lie in different mass ranges and arise with distinct signatures. Such signatures include excesses in electron-positron pairs that may originate from displaced decays of long-lived particles (LLPs). At the ESS, the dominant sources of such LLPs are decays at rest of π+ mesons and μ+ leptons. We choose to investigate theoretical scenarios of long-lived light neutralinos in the R-parity-violating supersymmetry and long-lived weak-violating electrophilic axionlike particles, as these LLPs can be produced from decays of π+ and μ+. Since the π+’s and μ+’s decay at rest at the ESS, we compute the spectra of the therefrom produced LLPs and thus estimate the expected sensitivity reach of SHiNESS to the LLPs in these two scenarios. Our calculation shows that in multiple relevant benchmark scenarios, SHiNESS can probe large parameter regions of these models beyond the existing bounds, in just a couple of years of data-collection time.

Published by the American Physical Society
2024
Is doublet-triplet splitting necessary?
Authors: Doršner Ilja , Saad Shaikh
Published: October 2024

We demonstrate that it is not necessary to substantially break the mass degeneracy between the Standard Model Higgs boson doublet and the corresponding scalar leptoquark, where these two fields comprise a single five-dimensional SU(5) representation. More precisely, we show that the experimental data on partial proton decay lifetimes cannot place any meaningful bound on the mass of the scalar leptoquark, also known as the color triplet, if one includes effects of higher-dimensional operators. We use the Georgi-Glashow model for our demonstration and point out that the complete suppression of proton decay via the scalar leptoquark mediation is not in conflict with the partial suppression of the gauge mediated two-body proton decay signatures. Finally, we derive a proper limit on the cutoff scale of the aforementioned higher-dimensional operators and outline how this scenario could be tested.

Published by the American Physical Society
2024
Generation of ultrarelativistic vortex leptons with large orbital angular momenta
Authors: Ababekri Mamutjan , Zhou Jun-Lin , Guo Ren-Tong , Ren Yong-Zheng , Kou Yu-Han , Zhao Qian , Li Zhong-Peng , Li Jian-Xing
Published: October 2024

We put forward a novel method for generating ultrarelativistic vortex positrons and electrons with intrinsic orbital angular momenta (OAM) through nonlinear Breit-Wheeler (NBW) scattering of vortex γ photons. A complete angular momentum-resolved scattering theory has been formulated, introducing angular momenta of laser photons and vortex particles into the conventional NBW scattering framework. We find that vortex positron (electron) can be produced when the outgoing electron (positron) is generated along the collision axis. By unveiling the angular momentum transfer mechanism, we clarify that the OAM of the γ photon and the large angular momenta due to multiple laser photons are entirely transferred to the generated vortex leptons. Furthermore, the cone opening angle and superposition state of the vortex γ photon can be determined via the angular distribution of created pairs in NBW processes.

Published by the American Physical Society
2024
Thermodynamic Approach to Quantifying Incompatible Instruments
Authors: Hsieh Chung-Yun , Chen Shin-Liang
Published: October 2024

We consider a thermodynamic framework to quantify instrument incompatibility via a resource theory thermodynamic constraints. We use the minimal needed to erase incompatibility’s signature to measure incompatibility. Unexpectedly, this time value is equivalent to incompatibility advantage in a work extraction task. Hence, both thermalization time and extractable work can directly quantify instrument incompatibility. Finally, we show that incompatibility signatures must vanish in non-Markovian thermalization.

Published by the American Physical Society
2024
Person-centered and qualitative approaches to network analysis in physics education research
Authors: Traxler Adrienne L. , Amaral Camila Mani Dias do , Henderson Charles , LaForge Evan , Hatcher Chase , Swirtz Madison , Barthelemy Ramón
Published: October 2024

Network analysis has become a well-recognized methodology in physics education research (PER), with study topics including student performance and persistence, faculty change, and the structure of conceptual networks. The social network analysis side of this work has focused on quantitative analysis of whole-network cases, such as the structure of networks in single classrooms. Egocentric or personal network approaches are largely unexplored, and qualitative methods are underdeveloped. In this paper, we outline theoretical and practical differences between two major network paradigms—whole-network and egocentric—and introduce theoretical frameworks and methodological considerations for egocentric studies. We also describe qualitative and mixed-methods approaches that are currently missing from the PER literature. We identify areas where these additional network methods may be of particular interest to physics education researchers and end by discussing example cases and implications for new PER studies.

Published by the American Physical Society
2024
Declaration of free sugars from fruits on food labels: a scoping review
Authors: Padovan Marina , Ares Gaston , Scapin Tailane , Kraemer Mariana Vieira dos Santos , Chaddad Maria Cecília Cury , Fernandes Ana Carolina , Bernardo Greyce Luci , Uggioni Paula Lazzarin , Pettigrew Simone , Proença Rossana Pacheco da Costa
Published: October 2024

Purpose

The World Health Organization recommends limiting the intake of free sugars, which can be added to packaged foods and may appear on labels under different terms. The aim of this research was to analyse the evidence related to the declaration of free sugars from fruits on packaged food labels.

Design/methodology/approach

A scoping review was conducted following the recommendations of the Joanna Briggs Institute (JBI).

Findings

Ten eligible studies, conducted in seven countries, were included in this review. The percentage of packaged foods in which free sugars were identified ranged from 52.5 to 86.5%. In three studies, terms related to sugars were identified inductively by reading the entire ingredient list, whereas in the other studies sugars were identified by searching for a list of predefined terms. Studies differed in the definition of sugars and the terms used to identify them. Nine studies included fruit sugars within the terms used to identify free sugars. However, they lacked consistency in the types of fruit sugars considered and did not discuss their agreement with the adopted definitions of sugars.

Originality/value

As far as can be ascertained, this is the first review that addresses the declaration of free sugars from fruits on packaged food labels. Overall, there is a scarcity of literature focused on identifying and discussing the range of free sugars from fruits declared on food labels.
Statistical monitoring applied to data science in classification: continuous validation in predictive models
Authors: Bueno Carlos Renato , Sordan Juliano Endrigo , Oprime Pedro Carlos , Vicentin Damaris Chieregato , Condé Giovanni Cláudio Pinto
Published: October 2024

Purpose

This study aims to analyze the performance of quality indices to continuously validate a predictive model focused on the control chart classification.

Design/methodology/approach

The research method used analytical statistical methods to propose a classification model. The project science research concepts were integrated with the statistical process monitoring (SPM) concepts using the modeling methods applied in the data science (DS) area. For the integration development, SPM Phases I and II were associated, generating models with a structured data analysis process, creating a continuous validation approach.

Findings

Validation was performed by simulation and analytical techniques applied to the Cohen’s Kappa index, supported by voluntary comparisons in the Matthews correlation coefficient (MCC) and the Youden index, generating prescriptive criteria for the classification. Kappa-based control charts performed well for m = 5 sample amounts and n = 500 sizes when Pe is less than 0.8. The simulations also showed that Kappa control requires fewer samples than the other indices studied.

Originality/value

The main contributions of this study to both theory and practitioners is summarized as follows: (1) it proposes DS and SPM integration; (2) it develops a tool for continuous predictive classification models validation; (3) it compares different indices for model quality, indicating their advantages and disadvantages; (4) it defines sampling criteria and procedure for SPM application considering the technique’s Phases I and II and (5) the validated approach serves as a basis for various analyses, enabling an objective comparison among all alternative designs.
Influence of employee job crafting in Chinese manufacturing enterprises on safety innovation performance: a moderated mediation model
Authors: Yang Jiaoping , Qi Ziru , Zhu Jianhua
Published: October 2024

Purpose

The purpose of this paper is to explore the influence of employees’ job crafting on safety innovation performance through psychological empowerment and the moderation effects of employees’ mindfulness traits and job complexity on such impact.

Design/methodology/approach

This study conducted structure equation modeling to analyze data collected from 1,566 employees in 96 manufacturing enterprises in northern and central China.

Findings

Results showed that employees’ job crafting has a positive effect on safety innovation performance, partially through psychological empowerment, and that effect was moderated by employee mindfulness traits and job complexity.

Practical implications

Manufacturing enterprises should seek to promote employees’ job crafting behavior in the workplace, improve employees’ psychological empowerment and pay attention to mindfulness training for enterprise managers and employees, so as to reduce the probability of unsafe behavior.

Originality/value

This study reveals the underlying influence mechanism of employees’ job crafting on safety innovation performance using the self-determination theory and suggests that psychological empowerment is critical in determining how employees’ job crafting influences safety innovation performance. Furthermore, both employees’ mindfulness traits and job complexity positively moderate the above mediation.
A comprehensive framework for examining the influence of tower crane safe operations on sustainable practices in modular integrated construction
Authors: Ali Ali Hassan , Zayed Tarek , Abdulai Sulemana Fatoama , Wang Roy Dong
Published: October 2024

Purpose

This study aims to explore the tower crane safety factors (TCSFs) that influence tower crane safe operations (TCSOs) in modular integrated construction (MiC). It evaluates how the adoption of these factors contributes to achieving TCSOs and promoting sustainable practices (SPs) within MiC.

Design/methodology/approach

To achieve this aim, the study employed a systematic search to ensure a comprehensive collection of variables. Additionally, it conducted a questionnaire survey involving professionals and utilized a brainstorming technique to categorize the different variables. Finally, partial least squares structural equation modeling (PLS-SEM) was employed to test the relationship between TCSOs and SPs.

Findings

The results of measurement models indicated strong convergent and discriminant validity, with each observed variable correlating well with its latent variable. Moreover, a significant positive correlation between TCSOs and SPs was evidenced by a path coefficient (β = 0.755) and ap-value of <0.05. Lastly, the structural model revealed that the independent variables strongly influence the dependent variable (i.e. SPs) by 57%, underscoring safety's pivotal role in advancing sustainability within MiC projects. These findings provide empirical evidence that improving tower crane safety can directly enhance sustainable practices, offering a dual benefit of increased safety and sustainability for the construction sector.

Originality/value

This study makes a unique and previously undiscovered contribution to the field by identifying the TCSFs in MiC and employing a novel approach by utilizing PLS-SEM to create a unique mathematical model. It offers valuable insights into the relationship between TCSFs, TCSOs and SPs, thus contributing to methodological advancements within Safety Science and providing a foundation for future research and practical implementation in the construction industry.