bluuebunny/crossref_metadata_2025_split huggingface dataset:
Grid cells anticipate the animal’s future movement
Authors: Csordás Dóra Éva , Nagele Johannes , Stemmler Martin , Herz Andreas V. M. 
Published: December 2024

AbstractGrid cells in the rodent medial entorhinal cortex preferentially fire spikes when the animal is within certain regions of space. When experimental data are averaged over time, spatial firing fields become apparent. If these firing fields represented only the current position of the animal, a grid cell’s firing should not depend on whether the animal is running into or out of a firing field. Yet many grid cells are sensitive to the animal’s direction of motion relative to the firing-field center. Such apparent egocentric "inbound-outbound tuning" could be a sign of prospective encoding of future position, but it is unclear whether grid cells code ahead in space or in time. To investigate this question, we decided to undo the inbound-outbound modulation by shifting all spikes within a given firing field by a fixed distance in space or in time. For grid-cell data recorded in mice, optimizing in space requires a forward shift of around 2.5 cm, whereas optimizing in time yielded a forward shift of about 170 ms. In either case the firing-field sizes decrease. Minimizing just the field size yields somewhat smaller shifts (roughly 1.8 cm and around 115 ms ahead). Jointly optimizing along the temporal and spatial dimension reveals a continuum of flat inbound-outbound tuning curves and a shallow minimum for field sizes, located at about 2.3 cm and 35 ms. These findings call into question a purely spatial or purely temporal interpretation of grid-cell firing fields and inbound-outbound tuning.
Genetic Causes of Sudden Cardiac Arrest in the Community
Authors: Kransdorf Evan P. , Mathias Marco , Nakamura Kotoka , Tyrer Jonathan , Pharaoh Paul D. , Chugh Harpriya , Reinier Kyndaron , Akdemir Zeynep , Boerwinkle Eric , Yu Bing , Chugh Sumeet S. 
Published: December 2024

AbstractBackgroundAnnually 300,000 Americans experience sudden cardiac arrest (SCA). Studies in referral SCA cohorts have observed rare variants in genes associated with arrhythmia and cardiomyopathy. We sought to: (1) establish the population prevalence of rare disease-causing variants in a set of candidate genes and (2) confirm the association of disease-causing variants in these genes with SCA in two prospective population-based studies.MethodsSCA patients (n=3264) were accrued from the Oregon Sudden Unexpected Death Study and the PREdiction of Sudden death in mulTi-ethnic cOmmunities (PRESTO) study and compared to control patients (n=13713) from the Atherosclerosis Risk in Communities (ARIC) study. Whole genome sequencing was performed. Disease-causing (likely pathogenic or pathogenic) variants in candidate genes associated with arrhythmia/cardiomyopathy were identified using updated American College of Medical Genetics and Genomics criteria. Gene- collapsing case-control analysis was performed using the conditional logistic regression-sequence kernel association test.ResultsWe identified 300 disease-causing variants, the majority of which were in cardiomyopathy genes (71%). There were 136 patients (4.2%) in the SCA group and 351 patients (2.6%) in the control group with one or more disease-causing variants (OR 1.66, 95% confidence interval 1.33-2.07, p<0.001). We identified 13 genes associated with an increased risk of SCA, nine associated with cardiomyopathy (BAG3, DSC2, DSG2, FLNC, LMNA, MYBPC3, TNNI3, TNNT2, TTN) and four with arrhythmia (CACNA1C, CASQ2, KCNH2, KCNQ1).ConclusionsDisease-causing variants in cardiomyopathy genes were the predominant genetic cause of SCA. These findings inform which genes to include in genetic screening for SCA.
Modulation of the JAK2-STAT3 pathway promotes expansion and maturation of human iPSCs-derived myogenic progenitor cells
Authors: Caputo Luca , Stamenkovic Cedomir , Tierney Matthew T. , Falzarano Maria Sofia , Bassel-Duby Rhonda , Ferlini Alessandra , Olson Eric N. , Puri Pier Lorenzo , Sacco Alessandra 
Published: December 2024

SummaryGeneration ofin vitroinduced pluripotent cells (hiPSCs)-derived skeletal muscle progenitor cells (SMPCs) holds great promise for regenerative medicine for skeletal muscle wasting diseases, as for example Duchenne Muscular Dystrophy (DMD). Multiple approaches, involving ectopic expression of key regulatory myogenic genes or small molecules cocktails, have been described by different groups to obtain SMPC towards cell-transplantationin vivoas a therapeutic approach to skeletal muscle diseases. However, hiPSCs-derived SMPC generated using transgene-free protocols are usually obtained in a low amount and resemble a more embryonal/fetal stage of differentiation. Here we demonstrate that modulation of the JAK2/STAT3 signaling pathway during anin vitroskeletal muscle differentiation protocol, increases the yield ofPAX7+andCD54+SMPCs and drive them to a post- natal maturation stage, in both human ES and patient-derived iPSCs. Importantly, upon removal of the inhibition from the cultures, the obtained SMPCs are able to differentiate into multinucleated myotubesin vitro.These findings reveal that modulation of the JAK2/STAT3 signaling pathway is a potential therapeutic avenue to generate SMPCsin vitrowith increase potential for cell-therapy approaches.
“Imaging Translation in Early Embryo Development”
Authors: Bensidoun Pierre , Verbrugghe Morgane , Lagha Mounia 
Published: December 2024

AbstractThe ultimate output of gene expression is to ensure that proteins are synthesized at the right levels, locations, and timings. Recently different imaging-based methods have been developed to visualize the translation of single mRNA molecules. These methods rely on signal amplification with the introduction of an array of a short peptide sequence (a tag such as SunTag), recognized by a genetically encodable single-chain antibody (a detector such as scFv). In this chapter, we discuss such methods to image and quantify translation dynamics in the earlyDrosophilaembryo and provide examples based on atwist-32XSunTagreporter. We outline a step-by-step protocol to light-up translation in living embryos. We also detail a combinatorial strategy in fixed samples (smFISH-IF), allowing to distinguish single mRNA molecules engaged in translation.
The impact of sex differences on perceived pain intensity in pain protocol standardization
Authors: Wragan Max , O’Connor Niamh , Ashe Hannah , O’Flaherty Ruairi , Witney Alice G. 
Published: December 2024

AbstractBackgroundSex differences have been widely demonstrated in both acute and chronic pain. Sex differences may have wider impact on research design and analysis than already established. This study addresses an important methodological aspect with regards to how sex differences could influence the design of standardized experimental pain protocols used to characterize an individuals’ pain response.MethodsThis study addresses sex differences of perceived pain at tonic heat pain threshold (HPT). Participants used a computerized visual analogue scale (CoVAS) to continually rated subjective pain intensity during tonic HPT. Metrics (Mean, Standard Deviation, Maximum) were extracted from the CoVAS to characterize perceived pain.ResultsFemale participants rated pain intensity at HPT significantly lower than male participants across all extracted metrics used to characterize the coVAS rating. The effect of sex on the mean and standard deviation of pain intensity ratings at HPT was medium, while the effect size of sex on the maximum pain intensity rating at HPT was large.ConclusionThe significant sex differences in perceived pain intensity at HPT indicates that methods of standardization to a specific pain intensity merit sex-specific consideration. Additionally, these observed sex differences underscore the necessity for sex specific design across both pre-clinical and clinical studies of pain.
A new class of natural anthelmintics targeting lipid metabolism
Authors: Zahreddine Fahs Hala , Refai Fathima S. , Gopinadhan Suma , Moussa Yasmine , Gan Hin Hark , Hunashal Yamanappa , Battaglia Gennaro , Cipriani Patricia G. , Ciancia Claire , Rahiman Nabil , Kremb Stephan , Xie Xin , Pearson Yanthe E. , Butterfoss Glenn L. , Maizels Rick M. , Esposito Gennaro , Page Antony P. , Gunsalus Kristin C. , Piano Fabio 
Published: December 2024

AbstractParasitic helminths are a major global health threat, infecting nearly one-fifth of the human population and causing significant losses in livestock and crops. Resistance to the few anthelmintic drugs is increasing. Here, we report a set of avocado fatty alcohols/acetates (AFAs) that exhibit nematocidal activity against four veterinary parasitic nematode species:Brugia pahangi,Teladorsagia circumcinctaandHeligmosomoides polygyrus, as well as a multidrug resistant strain (UGA) ofHaemonchus contortus.AFA shows significant efficacy inH. polygyrusinfected mice. InC. elegans, AFA exposure affects all developmental stages, causing paralysis, impaired mitochondrial respiration, increased reactive oxygen species production and mitochondrial damage. In embryos, AFAs penetrate the eggshell and induce rapid developmental arrest. Genetic and biochemical tests reveal that AFAs inhibit POD-2, encoding an acetyl CoA carboxylase, the rate-limiting enzyme in lipid biosynthesis. These results uncover a new anthelmintic class affecting lipid metabolism.
Nonuple atg8 mutant provides genetic evidence for functional specialization of ATG8 isoforms inArabidopsis thaliana
Authors: Del Chiaro Alessia , Grujic Nenad , Zhao Jierui , Papareddy Ranjith Kumar , Gao Peng , Ma Juncai , Lofke Christian , Bhattacharya Anuradha , Gruetzner Ramona , Bourguet Pierre , Berger Frédéric , Kang Byung-Ho , Marillonnet Sylvestre , Dagdas Yasin 
Published: December 2024

AbstractAutophagy sustains cellular health by recycling damaged or excess components through autophagosomes. It is mediated by conserved ATG proteins, which coordinate autophagosome biogenesis and selective cargo degradation. Among these, the ubiquitin-like ATG8 protein plays a central role by linking cargo to the growing autophagosomes through interacting with selective autophagy receptors. Unlike most ATG proteins, the ATG8 gene family is significantly expanded in vascular plants, but its functional specialization remains poorly understood. Using transcriptional and translational reporters inArabidopsis thaliana, we revealed that ATG8 isoforms are differentially expressed across tissues and form distinct autophagosomes within the same cell. To explore ATG8 specialization, we generated the nonupleΔatg8mutant lacking all nine ATG8 isoforms. The mutant displayed hypersensitivity to carbon and nitrogen starvation, coupled with defects in bulk and selective autophagy as shown by biochemical and ultrastructural analyses. Complementation experiments demonstrated that ATG8A could rescue both carbon and nitrogen starvation phenotypes, whereas ATG8H could only complement carbon starvation. Proximity labeling proteomics further identified isoform-specific interactors under nitrogen starvation, underscoring their functional divergence. These findings provide genetic evidence for functional specialization of ATG8 isoforms in plants and lay the foundation for investigating their roles in diverse cell types and stress conditions.
In-flight testing of the integrated mission management system
Authors: Grzybowski Piotr , Ziółkowski Kamil 
Published: December 2024

Purpose
The purpose of this paper is to present research on the flight demonstration of avionics technology for CS-23 commuter category aircraft. The Integrated Mission Management System (IMMS) is designed to reduce pilot workload by aggregating hazard information from multiple domains (airspace, traffic, weather and terrain) and automatically prefiltering this data to display only hazards relevant to the flight plan, from origin to destination. This paper details the design of the IMMS, along with the process of the integration on aircraft and flight demonstration results.

Design/methodology/approach
The IMMS integrates several technologies, including the Advanced Weather Awareness System, Tactical Separation System, Compact Computing Platform and Flight Reconfiguration System. Hazards are consolidated in a Unified Hazard Database (UHD) and assigned severity levels, providing automated hazard filtering and path planning.

Findings
Simulations and flight tests demonstrated that the IMMS effectively reduces the information displayed to pilots in real-time without loss of critical safety data. Feedbacks from test pilots on IMMS usage, as well as suggestions for improving the multi-source Graphical User Interface, are also discussed.

Research limitations/implications
Limitations of the UHD were identified, offering insights into potential expansions to support more efficient automatic flight planning. The technology was validated through extensive laboratory testing and real-world flight trials, achieving Technology Readiness Level 5. This validation demonstrated how the severity of hazards can be linked to their transparency level on the display, with the aim of reducing information overload.

Practical implications
The IMMS shows potential to be ground-breaking system in the CS-23 aircraft category, autonomously supporting route planning and flight execution while adapting to in-flight weather changes and ensuring tactical separation from other aircraft. It also shows that multi-domain hazard information can be processed on limited on-board avionics systems.

Originality/value
This study highlights the importance of Hardware-In-The-Loop testing in verifying new technologies and mitigating risks related to software reliability, flight demonstrations and system integration.
Health system responsiveness from perspective of people with disabilities in west of Iran: a quantitative study
Authors: Piroozi Bakhtiar , Shokri Azad , Safari Hossein , Mohammadi Bolbanabad Amjad , Hematpour Siroos , Rahimi Ramyar , Adabi Jalil , Mahmodpour Jamal 
Published: December 2024

PurposeResponsiveness is one of the key components of good governance and one of the ultimate goals of health systems. The purpose of this study was to investigate the importance and level of health system responsiveness (HSR) from the perspective of people with disabilities in Iran.Design/methodology/approachThis cross-sectional study was carried out using multi-stage sampling in Kurdistan province in 2020. Of 1,067 participants, 889 and 520 had used outpatient and inpatient services, respectively. HSR questionnaire developed by World Health Organization was completed.FindingsThe dimensions of prompt attention (97%) and social support (81%) were the most and the least important dimensions for the respondents, respectively. In general, 43.6% of the respondents reported a “poor” status for HSR.Research limitations/implicationsDesigning targeted interventions to increase the level of health system responsiveness, especially with a focus on dimensions that are important to respondents but have weak performance, such as communication, confidentiality and autonomy, is suggested based on the findings of this study.Originality/valueThis is the first study performed on HSR from the perspective of people with disabilities in Iran. The findings of this study could be of interest to health policy makers to understand and improve healthcare experiences for marginalized populations globally.
Polysaccharides from fermented garlic attenuate high‐fat diet‐induced obesity in mice through gut microbes
Authors: Liu Qi , Li Ya‐Qian , Xu Wen‐Man , Fan Si‐Yao , Huang Yu , Lu Shi‐Rui , Kang Xue‐Ping , Zhang Yang , Ji Wenxiu , Dong Wei‐Wei 
Published: December 2024

AbstractThe weight loss and lipid‐lowering effects of fermented garlic polysaccharides (BGP) in obese mice were analyzed by detecting the intestinal flora and short‐chain fatty acids. An obesity model was established by feeding mice a high‐fat diet (HFD) for 8 weeks. After euthanasia, biochemical index testing and hematoxylin and eosin staining were performed. Spearman analysis was used to assess the relationship between the 16S rRNA sequencing results and the fatty acid content in mouse feces. Compared with the obese model mice, the BGP group had significantly reduced body weight and serum triglycerides, total cholesterol, low‐density lipoprotein cholesterol, malondialdehyde, and free fatty acids in the serum. Moreover, BGP reversed HFD‐induced gut microbiota dysbiosis, as indicated by the elevated populations of Paraclostridium, Lachnospiraceae_UCG_006, Enterorhabdus, and Lachnospiraceae‐NK4A136. BGP also significantly increased the contents of acetic, propionic, butyric, and valeric acids. These results indicate that BGP may serve as a potential prebiotic agent that modulates particular bacteria in the gut and their byproducts that play a crucial role in preventing diseases associated with obesity.
Co‐encapsulation of vitamins B6 and B12 using zein/gum arabic nanocarriers for enhanced stability, bioaccessibility, and oral bioavailability
Authors: Karoshi Vijaykumar Ramesh , Nallamuthu Ilaiyaraja , Anand Tamatam 
Published: December 2024

AbstractThe present study aimed to fabricate a co‐deliver system using zein/gum arabic (GA) polymers for enhanced stability and bioavailability of vitamins (B6 and B12). The anti‐solvent evaporation method was used for the preparation of PC–ZG NPs (pyridoxine–cyanocobalamin zein–GA nanoparticles). The process conditions were statistically optimized using the design of Box–Behnken. The optimized conditions produced small‐sized particles (∼170 nm) with high zeta potential (−31 mV) and efficient encapsulation for pyridoxine (61.6%) and cyanocobalamin (56.3%). Scanning electron microscopy, x‐ray diffractometry, and Thermogravimetric analysis results confirmed that the developed formulation had a roughly spherical shape and an amorphous character with better thermal stability compared to free‐forms of the vitamins. The results of the storage study showed no significant changes in nanoparticle size at 4, 25, and 37°C over a 90‐day period. However, a slight variation in retention of the vitamins was observed during the initial period. The bioaccessibility of both the vitamins from PC–ZG NPs ranged between 56% and 62% post 6 h simulated digestion. In Caco‐2 cells, the cellular uptake of vitamins was higher from nanoforms compared to the free‐forms. Further, oral administration of PC–ZG NPs in rats exhibited 4.8‐ and 2.2‐fold increases in relative bioavailability of vitamins B6 and B12, respectively. A significant reduction of plasma homocysteine level (p ˂ 0.05) in the treated group was also observed. Together, these results suggest that the developed nanoformulation has improved physicochemical properties with enhanced bioavailability and, hence, could be used as an effective delivery system for the vitamins in food and nutraceutical products.
Impact of concomitant aortic valve replacement in patients with mild‐to‐moderate aortic valve regurgitation undergoing left ventricular assist device implantation: EUROMACS analysis
Authors: Gliozzi Gregorio , Nersesian Gaik , Gallone Guglielmo , Schoenrath Felix , Netuka Ivan , Zimpfer Daniel , de By Theo M. M. H. , Faerber Gloria , Spitaleri Antonio , Vendramin Igor , Gummert Jan , Falk Volkmar , Meyns Bart , Rinaldi Mauro , Potapov Evgenij , Loforte Antonio 
Published: December 2024

AbstractIntroductionLeft ventricular assist device (LVAD) therapy may lead to an aortic regurgitation, limiting left ventricular unloading and causing adverse events. Whether concomitant aortic valve replacement may improve outcomes in patients with preoperative mild‐to‐moderate aortic regurgitation remains unclear.MethodsA retrospective propensity score‐matched analysis of adult patients with preoperative mild‐to‐moderate aortic regurgitation undergoing durable LVAD implantation between 01/01/2011 and 30/11/2021 was performed. Patients undergoing concomitant valve surgery other than biological aortic valve replacement were excluded, resulting in 77 with concomitant biological aortic valve replacement and 385 without.ResultsFollowing 1:1 propensity score matching, two groups of 55 patients with and without biological aortic valve replacement were obtained, (mean age 59 ± 11 years, 92% male, 59.1% HeartWare). Aortic regurgitation was mild in 72.7% and 76.4% and moderate in 27.3% and 23.6% in non‐replacement and replacement cohorts respectively. The 30‐day survival was 89.1% vs. 85.5% (p = 0.59), 1‐year survival 69.1% vs. 56.4% (p = 0.19), and 2‐year survival 61.8% vs. 47.3% (p = 0.10) in the non‐replacement and replacement groups, respectively. After a mean follow‐up of 1.2 years, non‐replacement patients had a higher incidence of pump thrombosis (11 [20%] vs. 3 [5.5%], p = 0.022) and fewer major bleedings (2 [3.6%] vs. 11 [20%], p = 0.008).ConclusionCompared with those treated conservatively, patients with mild‐to‐moderate aortic regurgitation undergoing concomitant aortic valve replacement during LVAD implantation have a similar survival up to 2 years on support. Patients with concomitant valve replacement had a higher risk of bleeding complications but fewer pump thromboses.
Elastoplastic Crack Initiation Behavior of Unsaturated Rock Fractures (Cavities) With Asymmetric Hole‐Edge Cracks Under Gas‐Ice Pressure
Authors: Chen Wenhua , Xiang Tian 
Published: December 2024

ABSTRACTCurrent research on frost heave‐induced cracking in fractures of rock masses in cold regions typically assumes that fractures are fully saturated. However, in actual engineering practice, rock mass fractures are often in an unsaturated state. Upon freezing, the fracture surfaces are subjected to a complex combination of gas pressure, freezing pressure, and ice friction forces. This study investigates the crack initiation mechanisms of unsaturated rock fractures with asymmetric edge cracks under gas‐ice pressure conditions. Assuming a small yield range, we derive the calculation formulas for gas pressure after freezing, stress intensity factor, crack initiation angle, and crack initiation stress based on the complex variable function and elastic‐plastic crack mechanics theory. Additionally, an improved phase‐field model is proposed for calculating dynamic crack propagation in mixed‐mode I‐II fractures, with key parameters analyzed and discussed. The results demonstrate that: By comparing the analytical solutions with numerical calculations, the validity of the proposed model is verified. During the freezing process, dynamic crack propagation in unsaturated fractures will exhibit bifurcation. At higher water saturation levels, crack propagation shows a pattern of initial bifurcation followed by subsequent merging.