bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex disparities of human neuromuscular decline in older humans
Authors: Guo Yuxiao , Jones Eleanor J. , Smart Thomas F. , Altheyab Abdulmajeed , Gamage Nishadi , Stashuk Daniel W. , Piasecki Jessica , Phillips Bethan E. , Atherton Philip J. , Piasecki Mathew 
Published: June 2024

AbstractFemales typically live longer than males but, paradoxically, spend a greater number of later years in poorer health. The neuromuscular system is a critical component of the progression to frailty, and motor unit (MU) characteristics differ by sex in healthy young individuals and may adapt to ageing in a sex‐specific manner due to divergent hormonal profiles. The purpose of this study was to investigate sex differences in vastus lateralis (VL) MU structure and function in early to late elderly humans. Intramuscular electromyography signals from 50 healthy older adults (M/F: 26/24) were collected from VL during standardized submaximal contractions and decomposed to quantify MU characteristics. Muscle size and neuromuscular performance were also measured. Females had higher MU firing rate (FR) than males (P = 0.025), with no difference in MU structure or neuromuscular junction transmission (NMJ) instability. All MU characteristics increased from low‐ to mid‐level contractions (P < 0.05) without sex × level interactions. Females had smaller cross‐sectional area of VL, lower strength and poorer force steadiness (P < 0.05). From early to late elderly, both sexes showed decreased neuromuscular function (P < 0.05) without sex‐specific patterns. Higher VL MUFRs at normalized contraction levels previously observed in young are also apparent in old individuals, with no sex‐based difference of estimates of MU structure or NMJ transmission instability. From early to late elderly, the deterioration of neuromuscular function and MU characteristics did not differ between sexes, yet function was consistently greater in males. These parallel trajectories underscore the lower initial level for older females and may offer insights into identifying critical intervention periods.
imageKey points
Females generally exhibit an extended lifespan when compared to males, yet this is accompanied by a poorer healthspan and higher rates of frailty.
In healthy young people, motor unit firing rate (MUFR) at normalized contraction intensities is widely reported to be higher in females than in age‐matched males.
Here we show in 50 people that older females have higher MUFR than older males with little difference in other MU parameters. The trajectory of decline from early to late elderly does not differ between sexes, yet function is consistently lower in females.
These findings highlight distinguishable sex disparities in some MU characteristics and neuromuscular function, and suggest early interventions are needed for females to prevent functional deterioration to reduce the ageing health–sex paradox.
Numerical Investigation of the Impact of the Rectangular Nozzle Aspect Ratio on Liquid Jet in Crossflow
Authors: Shao Meng , He Zhixia , Wang Qian 
Published: June 2024

Abstract
High-fidelity simulation is conducted to investigate liquid jet in crossflow, specifically regarding the rectangular nozzle. The influence of aspect ratio (AR) of nozzles on the atomization characteristics of liquid column in the process of primary breakup is explored by the analysis of the flow structure of crossflow and liquid column. The aspect ratio is ranging from 1 to 8. The results indicate that as the increase of aspect ratio, the disturbance of crossflow to the liquid on the sides is weakened. While the thickness of liquid column also gradually decreases, which enables smaller disturbances to promote droplet shedding. Therefore, surface breakup first weakens and then strengthens. In the column breakup process, the increase of aspect ratio causes crossflow to become the main factor affecting column breakup, and the influence of air pressure gradually weakens. This indicates a shift in the mechanism of surface instability from “Rayleigh–Taylor” (R–T) instability to “Kelvin–Helmholtz” (K–H) instability.
Antagonism of epidermal growth factor receptor signaling favors hepatitis E virus life cycle
Authors: Woytinek Kathrin , Glitscher Mirco , Hildt Eberhard 
Published: June 2024

ABSTRACT

Hepatitis E virus (HEV) poses a global threat, which currently remains understudied in terms of host interactions. Epidermal growth factor receptor (EGFR) plays multifaceted roles in viral pathogenesis, impacting host-cell entry, viral replication, and host-defense modulation. On the one hand, EGFR signaling emerged as a major driver in innate immunity; on the other hand, a crosstalk between HEV and EGFR requires deeper analysis. We therefore aimed to dissect the receptor’s involvement in the HEV life cycle. In persistently HEV-infected cells, the EGFR amount is decreased alongside with enhanced receptor internalization. As compared with the control ligand-induced EGFR, activation revealed an early receptor internalization and degradation in HEV-replicating cells, resulting in a notable EGFR signaling delay. Interestingly, inhibition or silencing of EGFR increased viral replication, extracellular and intracellular viral transcripts, and released infectious particles. The pro-viral impact of EGFR inhibition was attributed to (i) impaired expression of interferon-stimulated genes, (ii) activation of the autophagosomal system, (iii) virus-induced inhibition of lysosomal acidification, and (iv) a decrease of the cellular cholesterol level.

IMPORTANCE
This study identifies epidermal growth factor receptor (EGFR) as a novel host factor affecting hepatitis E virus (HEV): EGFR downregulation promotes viral replication, release, and evasion from the innate immune response. The discovery that EGFR inhibition favors viral spread is particularly concerning for HEV patients undergoing EGFR inhibitor treatment.
Bacterial cell volume regulation and the importance of cyclic di-AMP
Authors: Foster Alexander J. , van den Noort Marco , Poolman Bert 
Published: June 2024

SUMMARY
Nucleotide-derived second messengers are present in all domains of life. In prokaryotes, most of their functionality is associated with general lifestyle and metabolic adaptations, often in response to environmental fluctuations of physical parameters. In the last two decades, cyclic di-AMP has emerged as an important signaling nucleotide in many prokaryotic lineages, including Firmicutes, Actinobacteria, and Cyanobacteria. Its importance is highlighted by the fact that both the lack and overproduction of cyclic di-AMP affect viability of prokaryotes that utilize cyclic di-AMP, and that it generates a strong innate immune response in eukaryotes. In bacteria that produce the second messenger, most molecular targets of cyclic di-AMP are associated with cell volume control. Besides, other evidence links the second messenger to cell wall remodeling, DNA damage repair, sporulation, central metabolism, and the regulation of glycogen turnover. In this review, we take a biochemical, quantitative approach to address the main cellular processes that are directly regulated by cyclic di-AMP and show that these processes are very connected and require regulation of a similar set of proteins to which cyclic di-AMP binds. Altogether, we argue that cyclic di-AMP is a master regulator of cell volume and that other cellular processes can be connected with cyclic di-AMP through this core function. We further highlight important directions in which the cyclic di-AMP field has to develop to gain a full understanding of the cyclic di-AMP signaling network and why some processes are regulated, while others are not.
An ancillary care policy in a vaccine trial conducted in a resource-constrained setting: evaluation and policy recommendations
Authors: Lemey Gwen , Larivière Ynke , Osang'ir Bernard Isekah , Zola Trésor , Kimbulu Primo , Milolo Solange , Danoff Engbu , Tchuma Yves , Maketa Vivi , Mitashi Patrick , Ravinetto Raffaella , Van Damme Pierre , Van geertruyden Jean-Pierre , Muhindo-Mavoko Hypolite 
Published: June 2024

IntroductionClear guidelines to implement ancillary care (AC) in clinical trials conducted in resource-constrained settings are lacking. Here, we evaluate an AC policy developed for a vaccine trial in the Democratic Republic of the Congo and formulate policy recommendations.MethodsTo evaluate the AC policy, we performed a longitudinal cohort study, nested in an open-label, single-centre, randomised Ebola vaccine trial conducted among healthcare personnel. Participants’ demographic information, residence distance to the study site and details on the financial and/or medical support provided for any (serious) adverse events ((S)AE) were combined and analysed. To assess the feasibility of the AC policy, an expenditure analysis of the costs related to AC support outcomes was performed.ResultsEnrolment in this evaluation study started on 29 November 2021. The study lasted 11 months and included 655 participants from the Ebola vaccine trial. In total, 393 participants used the AC policy, mostly for AE management (703 AE and 94 SAE) via medication provided by the study pharmacy (75.3%). Men had a 35.2% (95% CI 4.0% to 56.6%) lower likelihood of reporting AE compared with women. Likewise, this was 32.3% lower (95% CI 5.8% to 51.4%) for facility-based compared with community-based healthcare providers. The daily AE reporting was 78.8% lower during the passive vs the active trial stage, and 97.4% lower during unscheduled vs scheduled visits (p<0.001). Participants living further than 10 km from the trial site more frequently reported the travel distance as a reason for not using the policy (p<0.04). In practice, only 1.1% of the operational trial budget was used for AC policy support.ConclusionThe trial design, study population and local health system impacted the use of the AC policy. Nonetheless, the AC policy implementation in this remote and resource-constrained setting was feasible, had negligible budgetary implications and contributed to participants’ healthcare options and well-being.
Herpes zoster vaccine and the risk of stroke: a population-based cohort study using linked data from the Clinical Practice Research Datalink
Authors: Richardson Kathryn , Loke Yoon Kong , McDonald Helen I , Parretti Helen Mary , Marra Fawziah 
Published: June 2024

BackgroundStudies report herpes zoster associated with short-term stroke risk, but it is unclear whether herpes zoster vaccine reduces stroke risk.MethodsWe performed cohort studies using Clinical Practice Research Datalink Aurum linked to hospital admission, mortality and deprivation data. We included 678 110 adults aged 70–80 years receiving a live attenuated herpes zoster vaccination between 1 September 2013 and 31 December 2019. We conducted three comparisons to a historical unvaccinated cohort, an active comparator and a self-controlled case series (SCCS). The historical cohort comprised 678 110 matched unvaccinated adults between 2007 and 2012. The active comparator comprised 653 373 adults receiving an influenza vaccination between 2013 and 2019 meeting herpes zoster vaccine eligibility. Cox regression was used to estimate HRs for stroke in the subsequent 5 years adjusted for measured confounders, in the vaccinated compared with comparator cohorts. Secondary outcomes included stroke/transient ischaemic attack and myocardial infarction. The SCCS included incident strokes 12 months before or after herpes zoster vaccination to address healthy vaccinee bias.ResultsWe recorded 16 281 and 30 430 incident strokes among vaccinated and unvaccinated historical patients, over a median of 2.7 and 5.0 years follow-up, respectively. The adjusted HR for stroke for herpes zoster vaccination compared with unvaccinated historical patients was 0.84 (95% CI 0.82 to 0.86) and to influenza-vaccinated patients was 0.88 (0.85 to 0.89). However, stroke incidence rates were lower in the herpes zoster-vaccinated group prevaccination compared with both comparator cohorts. The SCCS found no association between herpes zoster vaccination and stroke 30–119 days later.ConclusionsDespite our cohort study, with extensive confounder adjustment and an influenza vaccination active comparator, finding herpes zoster vaccination associated with 12%–16% reduced stroke rates, additional analyses suggested this was largely explained by healthy vaccinee bias. Our study illustrates the importance of robust sensitivity analyses and testing the suitability of causal inference tools for observational vaccine studies.
Search for baryon junctions in photonuclear processes and isobar collisions at RHIC
Authors: Lewis Nicole , Lv Wendi , Ross Mason Alexander , Tsang Chun Yuen , Brandenburg James Daniel , Lin Zi-Wei , Ma Rongrong , Tang Zebo , Tribedy Prithwish , Xu Zhangbu 
Published: June 2024

AbstractDuring the early development of quantum chromodynamics, it was proposed that baryon number could be carried by a non-perturbative Y-shaped topology of gluon fields, called the gluon junction, rather than by the valence quarks as in the QCD standard model. A puzzling feature of ultra-relativistic nucleus-nucleus collisions is the apparent substantial baryon excess in the mid-rapidity region that could not be adequately accounted for in most conventional models of quark and diquark transport. The transport of baryonic gluon junctions is predicted to lead to a characteristic exponential distribution of net-baryon density with rapidity and could resolve the puzzle. In this context we point out that the rapidity density of net-baryons near mid-rapidity indeed follows an exponential distribution with a slope of $$-0.61\pm 0.03$$

-
0.61
±
0.03

as a function of beam rapidity in the existing global data from A+A collisions at AGS, SPS and RHIC energies. To further test if quarks or gluon junctions carry the baryon quantum number, we propose to study the absolute magnitude of the baryon vs. charge stopping in isobar collisions at RHIC. We also argue that semi-inclusive photon-induced processes ($$\gamma +p$$

γ
+
p

/A) at RHIC kinematics provide an opportunity to search for the signatures of the baryon junction and to shed light onto the mechanisms of observed baryon excess in the mid-rapidity region in ultra-relativistic nucleus-nucleus collisions. Such measurements can be further validated in A+A collisions at the LHC and $$e+p$$

e
+
p

/A collisions at the EIC.
From pole parameters to line shapes and branching ratios
Authors: Heuser L. A. , Chanturia G. , Guo F.-K. , Hanhart C. , Hoferichter M. , Kubis B. 
Published: June 2024

AbstractResonances are uniquely characterized by their complex pole locations and the corresponding residues. In practice, however, resonances are typically identified experimentally as structures in invariant mass distributions, with branching fractions of resonances determined as ratios of count rates. To make contact between these quantities it is necessary to connect line shapes and resonance parameters. In this work we propose such a connection and illustrate the formalism with detailed studies of the $$\rho (770)$$

ρ
(
770
)

and $$f_0(500)$$

f
0

(
500
)

resonances. Based on the line shapes inferred from the resonance parameters along these lines, expressions for partial widths and branching ratios are derived and compared to other approaches in the literature.
$$M_W$$ in string derived Z$$^\prime $$ models
Authors: Faraggi Alon E. , Goodsell Mark D. 
Published: June 2024

AbstractWe introduce a phenomenological model for a string-derived $$Z^\prime $$

Z
′

scenario, and study its predictions for the mass of the W boson. In the process, we compare it to collider constraints for both pair-produced particles, Higgs boson properties, and $$Z^\prime $$

Z
′

searches. We also describe the implementation of new tools in the scanning code BSMArt.
The Dependence on Temperature of the Mn4+ Emission Intensity and Lifetime in Na2SiF6
Authors: Beers W. W. , Brik M. G. , Ma C.-G. , Cohen W. E. , Srivastava A. M. 
Published: June 2024

We have measured the dependence of the Mn4+ lifetime and intensity on temperature of commercial Na2SiF6:Mn4+ phosphor. The data are fitted to existing physical models to extract the activation energy for thermal quenching. The parameters of our fitting are compared with those reported for laboratory synthesized Na2SiF6:Mn4+ and commercial K2SiF6:Mn4+ phosphors that is sold under the trade name, TriGain®. This comparative analysis sheds light on the mechanism of thermal quenching of the Mn4+ ion luminescence in M2SiF6 (M = K, Na) compounds. We show that the activation energy and the onset temperature of thermal quenching for the 2E→4T2→4A2 crossover process is correlated with the energy of the 4T2 level and argue that this is a robust electronic structure-property relationship in fluoride hosts with low defect density. The study provides, therefore, an understanding of the factors responsible for non-radiative relaxation processes, which is fundamental to the understanding of phosphor quantum efficiency and performance.
Reflections and Roadmaps: Career Development beyond the FDA-AACR Oncology Educational Fellowship
Authors: Patel Timil , Chen Chris , Al Hadidi Samer , Kadry Yasmin , Sridhara Rajeshwari , Purcell Erin , Wisch Laura , Retzlaff Jon , Foti Margaret , Pazdur Richard , Kluetz Paul , Gao Jennifer 
Published: June 2024

Abstract
In 2020, the FDA’s Oncology Center of Excellence, in collaboration with the American Association for Cancer Research, launched a novel educational partnership known as the FDA-AACR Oncology Educational Fellowship. This year-long program is aimed for hematology/oncology fellows, scientists, and early-career investigators, offering an in-depth exploration of the regulatory review process by blending didactic learning with practical cases discussing oncology drug approvals. The fellowship has been met with enthusiastic feedback, with participants lauding its role in demystifying the regulatory landscape and enhancing their professional careers. This article reflects on the experiences of four alumni, showcasing the program’s transformative impact across diverse oncology career paths in government, academia, and industry.
Abstract B011: Detecting pairwise and higher-order antagonistic epistatic effects among somatic cancer genotypes to discover synthetic lethality
Authors: Alfaro-Murillo Jorge A. , Dasari Krishna , Townsend Jeffrey P 
Published: June 2024

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR013) of the Conference Program/Proceedings.
Citation Format: Jorge A. Alfaro-Murillo, Krishna Dasari, Jeffrey P Townsend. Detecting pairwise and higher-order antagonistic epistatic effects among somatic cancer genotypes to discover synthetic lethality [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B011.
Abstract B014: Unveiling the future: Exploring cutting-edge technologies for synthetic lethality discovery
Authors: David Peter Oloche 
Published: June 2024

Abstract
Synthetic lethality discovery is an emerging field of research that aims to reshape the landscape of cancer treatment, offering new hope and possibilities for patients faced with challenging diagnoses. In this article, we explored the cutting-edge technologies shaping the future of synthetic lathality research. Artificial intelligence and machine learning are not just buzzwords but indispensable tools that are shaping the field of precision medicine and personalized cancer treatment. By leveraging the power of computational tools, scientists can accelerate the identification of synthetic lethal interactions and pave the way for the development of more effective targeted cancer therapies. Through case studies, researchers can uncover the functional genomics of complex diseases and identify novel drug targets for cancer therapy. The integration of multi-omics approaches not only enhances the depth of analysis but also offers a more nuanced understanding of the molecular mechanisms driving synthetic lethal interactions, paving the way to unlock novel therapeutics and personalized treatment strategies. In addition, the integration of high-throughput screening techniques, such as CRISPR-Cas9 gene editing, opens up new avenues for identifying new drug targets and therapeutic strategies, ultimately paving a new era where personalized and targeted therapies redefine the way we approach cancer care, ushering in a novel era of precision and efficacy in medicine.
Citation Format: Peter Oloche David. Unveiling the future: Exploring cutting-edge technologies for synthetic lethality discovery [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B014.
Abstract B022: TEAD inhibition overcomes YAP/TAZ-driven resistance to RAS(ON) inhibitors
Authors: Vemulapalli Vidyasiri , Dinh Phuong , Ayala Mariela Moreno , Zhang Zheng , Labrecque Mark , Aronchik Ida , Jiang Jingjing , Singh Mallika , Quintana Elsa , Weller Caroline , Wildes David 
Published: June 2024

Abstract
Acquired resistance poses a significant challenge to the long-term efficacy of RAS inhibitors in clinical settings (Awad et al, 2021). Genome-wide CRISPR screening efforts, conducted by us and others in the field, have identified key components of the Hippo pathway as major mediators of resistance to RAS inhibitors (Mukhopadhyay et al., 2023, Edwards et al., 2023). Specifically, the oncogenic transcriptional co-regulators YAP and TAZ, which require binding to the TEAD transcription factors to elicit their activity, have emerged as pivotal players in resistance mechanisms to MAPK pathway targeted therapies. In this work, we demonstrate that YAP overexpression is a driver of resistance to RAS(ON) multi-selective and RAS(ON) G12C-selective inhibitors. The YAP transcriptional signature is elevated in cells with acquired resistance to RAS(ON) inhibitors, and combination with TEAD inhibitors enhances their sensitivity to RAS(ON) inhibition. Notably, phosphoproteomics and imaging studies revealed that the YAP cytoplasmic retention mark is reduced upon treatment of cancer cells with RAS(ON) multi-selective inhibitor, leading to the translocation of YAP to the nucleus and its subsequent activation. Furthermore, a pan-TEAD inhibitor exhibits a high degree of synergy with RAS(ON) inhibitors in a panel of KRAS mutant cell lines in vitro. We are currently investigating the combination of RAS(ON) and TEAD inhibitors in vivo. Our studies support further investigation of combination strategies using RAS(ON) and TEAD inhibitors to mitigate the emergence of persister cells and overcome resistance to monotherapy.
Citation Format: Vidyasiri Vemulapalli, Phuong Dinh, Mariela Moreno Ayala, Zheng Zhang, Mark Labrecque, Ida Aronchik, Jingjing Jiang, Mallika Singh, Elsa Quintana, Caroline Weller, David Wildes. TEAD inhibition overcomes YAP/TAZ-driven resistance to RAS(ON) inhibitors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B022.