bluuebunny/crossref_metadata_2025_split huggingface dataset:
GRSF1 antagonizes age-associated hypercoagulability via modulation of fibrinogen mRNA stability
Authors: Liu Doudou , Xu Chenzhong , Gong Ze , Zhao Yijie , Fang Zhiqiang , Rao Xiaoli , Chen Qingyu , Li Guodong , Kong Wei , Chen Jun 
Published: November 2023

AbstractAge-associated hypercoagulability is accompanied by the increase of plasma levels of some coagulation factors including fibrinogen which may contribute to the increased risk of cardiovascular, cerebrovascular, and thrombotic diseases in elderly people. However, the underlying mechanism of increased plasma fibrinogen concentration during aging is still elusive. GRSF1 belongs to the heterogeneous nuclear ribonucleoproteins F/H (hnRNP F/H) subfamily. Here, we report that GRSF1 attenuates hypercoagulability via negative modulation of fibrinogen expression. We demonstrated that GRSF1 negatively regulated fibrinogen expression at both mRNA and protein levels. GRSF1 directly interacted with the coding region (CDS) of FGA, FGB, and FGG mRNAs, and decreased their stability thus mitigating fibrinogen expression. We further identified that only a few G-tracts within the Fib C domain of FGA, FGB, and FGG CDS and the qRRM2 domain of GRSF1 were required for their interaction. Moreover, we confirmed hypercoagulability and the decrease of GRSF1 expression level during mice aging. Functionally, GRSF1 overexpression in old mice liver decreased fibrinogen plasma level, reduced hypercoagulability, and mitigated blood coagulation activity, whereas GRSF1 knockdown in young mice liver increased fibrinogen plasma level and promoted blood coagulation activity. Collectively, our findings unveil a novel posttranscriptional regulation of fibrinogen by GRSF1 and uncover a critical role of GRSF1 in regulating blood coagulation activity.
Fetal biometry and amniotic fluid volume assessment end-to-end automation using Deep Learning
Authors: Slimani Saad , Hounka Salaheddine , Mahmoudi Abdelhak , Rehah Taha , Laoudiyi Dalal , Saadi Hanane , Bouziyane Amal , Lamrissi Amine , Jalal Mohamed , Bouhya Said , Akiki Mustapha , Bouyakhf Youssef , Badaoui Bouabid , Radgui Amina , Mhlanga Musa , Bouyakhf El Houssine 
Published: November 2023

AbstractFetal biometry and amniotic fluid volume assessments are two essential yet repetitive tasks in fetal ultrasound screening scans, aiding in the detection of potentially life-threatening conditions. However, these assessment methods can occasionally yield unreliable results. Advances in deep learning have opened up new avenues for automated measurements in fetal ultrasound, demonstrating human-level performance in various fetal ultrasound tasks. Nevertheless, the majority of these studies are retrospective in silico studies, with a limited number including African patients in their datasets. In this study we developed and prospectively assessed the performance of deep learning models for end-to-end automation of fetal biometry and amniotic fluid volume measurements. These models were trained using a newly constructed database of 172,293 de-identified Moroccan fetal ultrasound images, supplemented with publicly available datasets. the models were then tested on prospectively acquired video clips from 172 pregnant people forming a consecutive series gathered at four healthcare centers in Morocco. Our results demonstrate that the 95% limits of agreement between the models and practitioners for the studied measurements were narrower than the reported intra- and inter-observer variability among expert human sonographers for all the parameters under study. This means that these models could be deployed in clinical conditions, to alleviate time-consuming, repetitive tasks, and make fetal ultrasound more accessible in limited-resource environments.
Non-reciprocity across scales in active mixtures
Authors: Dinelli Alberto , O’Byrne Jérémy , Curatolo Agnese , Zhao Yongfeng , Sollich Peter , Tailleur Julien 
Published: November 2023

AbstractIn active matter, particles typically experience mediated interactions, which are not constrained by Newton’s third law and are therefore generically non-reciprocal. Non-reciprocity leads to a rich set of emerging behaviors that are hard to account for starting from the microscopic scale, due to the absence of a generic theoretical framework out of equilibrium. Here we consider bacterial mixtures that interact via mediated, non-reciprocal interactions (NRI) like quorum-sensing and chemotaxis. By explicitly relating microscopic and macroscopic dynamics, we show that, under conditions that we derive explicitly, non-reciprocity may fade upon coarse-graining, leading to large-scale equilibrium descriptions. In turn, this allows us to account quantitatively, and without fitting parameters, for the rich behaviors observed in microscopic simulations including phase separation, demixing, and multi-phase coexistence. We also derive the condition under which non-reciprocity survives coarse-graining, leading to a wealth of dynamical patterns. Again, our analytical approach allows us to predict the phase diagram of the system starting from its microscopic description. All in all, our work demonstrates that the fate of non-reciprocity across scales is a subtle and important question.
Quantitative assessment of the universal thermopower in the Hubbard model
Authors: Wang Wen O. , Ding Jixun K. , Huang Edwin W. , Moritz Brian , Devereaux Thomas P. 
Published: November 2023

AbstractAs primarily an electronic observable, the room-temperature thermopower S in cuprates provides possibilities for a quantitative assessment of the Hubbard model. Using determinant quantum Monte Carlo, we demonstrate agreement between Hubbard model calculations and experimentally measured room-temperature S across multiple cuprate families, both qualitatively in terms of the doping dependence and quantitatively in terms of magnitude. We observe an upturn in S with decreasing temperatures, which possesses a slope comparable to that observed experimentally in cuprates. From our calculations, the doping at which S changes sign occurs in close proximity to a vanishing temperature dependence of the chemical potential at fixed density. Our results emphasize the importance of interaction effects in the systematic assessment of the thermopower S in cuprates.
Wnt activation disturbs cell competition and causes diffuse invasion of transformed cells through NF-κB-MMP21 pathway
Authors: Nakai Kazuki , Lin Hancheng , Yamano Shotaro , Tanaka Shinya , Kitamoto Sho , Saitoh Hitoshi , Sakuma Kenta , Kurauchi Junpei , Akter Eilma , Konno Masamitsu , Ishibashi Kojiro , Kamata Ryo , Ohashi Akihiro , Koseki Jun , Takahashi Hirotaka , Yokoyama Hideshi , Shiraki Yukihiro , Enomoto Atsushi , Abe Sohei , Hayakawa Yoku , Ushiku Tetsuo , Mutoh Michihiro , Fujita Yasuyuki , Kon Shunsuke 
Published: November 2023

AbstractNormal epithelial cells exert their competitive advantage over RasV12-transformed cells and eliminate them into the apical lumen via cell competition. However, the internal or external factors that compromise cell competition and provoke carcinogenesis remain elusive. In this study, we examine the effect of sequential accumulation of gene mutations, mimicking multi-sequential carcinogenesis on RasV12-induced cell competition in intestinal epithelial tissues. Consequently, we find that the directionality of RasV12-cell extrusion in Wnt-activated epithelia is reversed, and transformed cells are delaminated into the basal lamina via non-cell autonomous MMP21 upregulation. Subsequently, diffusively infiltrating, transformed cells develop into highly invasive carcinomas. The elevated production of MMP21 is elicited partly through NF-κB signaling, blockage of which restores apical elimination of RasV12 cells. We further demonstrate that the NF-κB-MMP21 axis is significantly bolstered in early colorectal carcinoma in humans. Collectively, this study shows that cells with high mutational burdens exploit cell competition for their benefit by behaving as unfit cells, endowing them with an invasion advantage.
Lipofuscin-like autofluorescence within microglia and its impact on studying microglial engulfment
Authors: Stillman Jacob M. , Mendes Lopes Francisco , Lin Jing-Ping , Hu Kevin , Reich Daniel S. , Schafer Dorothy P. 
Published: November 2023

AbstractEngulfment of cellular material and proteins is a key function for microglia, a resident macrophage of the central nervous system (CNS). Among the techniques used to measure microglial engulfment, confocal light microscopy has been used the most extensively. Here, we show that autofluorescence (AF) likely due to lipofuscin (lipo-AF) and typically associated with aging, can also be detected within microglial lysosomes in the young mouse brain by light microscopy. This lipo-AF signal accumulates first within microglia and it occurs earliest in white versus gray matter. Importantly, in gray matter, lipo-AF signal can confound the interpretation of antibody-labeled synaptic material within microglia in young adult mice. We further show that there is an age-dependent accumulation of lipo-AF inside and outside of microglia, which is not affected by amyloid plaques. We finally implement a robust and cost-effective strategy to quench AF in mouse, marmoset, and human brain tissue.
To investigate the mechanism of Yiwei Decoction in the treatment of premature ovarian insufficiency-related osteoporosis using transcriptomics, network pharmacology and molecular docking techniques
Authors: Fan Weisen , Meng Yan , Zhang Jing , Li Muzhen , Zhang Yingjie , Qu Xintian , Xiu Xin 
Published: November 2023

AbstractTo investigate the molecular mechanism of Yiwei Decoction (YWD) in preventing Premature ovarian insufficiency (POI)-related osteoporosis from the hypothalamic perspective , and to screen for the key active and acting molecules in YWD. Cyclophosphamide was used to create the POI rat model. Groups A, B, and C were established. The Model + YWD group was group A, the model control group was group B, and the normal control group was group C. ELISA was used to determine serum GnRH and FSH levels after gavage. The transcription levels of mRNAs in each group's hypothalamus tissues were examined using RNA-seq sequencing technology. The GSEA method was used to enrich pathways based on the gene expression levels of each group. The TCM–active ingredient–target–disease network map was created using differentially expressed mRNAs (DEmRNAs) and network pharmacology. The molecular docking method was employed to investigate the affinity of the active ingredient with key targets. GnRH and FSH levels in POI rats' serum were reduced by YWD. Between groups A and B, there were 638 DEmRNAs (P < 0.05) and 55 high-significance DEmRNAs (P-adjust < 0.01). The MAPK, Hedgehog, Calcium, and B cell receptor pathways are primarily enriched in DEmRNAs from Group A and Group B. The GSEA pathway enrichment analysis indicates that YWD may regulate Long-term potentiation, Amphetamine addiction, and the Renin-angiotensin system and play a role in preventing osteoporosis. The Chinese herbal medicine (CHM)—Active ingredient-Target-disease network map includes 137 targets, 4 CHMs, and 22 active ingredients. The result of docking indicated that Stigmasterol, interacts well with the core proteins ALB, VCL and KAT5. Following the screening, we identified the targets, active components, and key pathways associated with YWD osteoporosis prevention. Most of these key targets and pathways are associated with osteoporosis, but further experimental validation is required.
Lithic usewear confirms the function of Wilamaya Patjxa projectile points
Authors: Smallwood Ashley , Haas Randall , Jennings Thomas 
Published: November 2023

AbstractApproximately 9000 years ago at the Andean highland site of Wilamaya Patjxa, forager communities interred female and male individuals with projectile points, suggesting that large-mammal hunting may have been a gender neutral activity among that community. We report a lithic usewear analysis, which confirms that the ostensible projectile points were indeed used as projectile points. The data further reveal evidence of cutting and hide scraping consistent with animal processing activities. A new radiocarbon date shows that the female and male individuals were contemporaries, or nearly so, sometime between 9.0 and 8.7 cal. ka. These findings support a model of early subsistence practices in which both female and male individuals at Wilamaya Patjxa hunted large mammals.
Nordic hamstring exercises in functional knee rehabilitation after anterior cruciate ligament reconstruction: a prospective, randomised, controlled study
Authors: Chen JiaWei , Wu TianYu , Guo Ying 
Published: November 2023

AbstractTo study the effect of using Nordic hamstring exercise method on muscle strength and knee joint stability of patients after ACL reconstruction. 60 patients admitted to our hospital for ACL reconstruction were randomly divided into a test group (n = 30, applying Nordic hamstring exercise) and a control group (n = 30, applying conventional rehabilitation training methods), and the difference in the circumference of the thighs of the patients in the two groups was analysed after training, and the peak torque (PT), total torque (PT), and flexion and extension strength were measured by using the Biodex system3 Multi-joint Isokinetic Testing System at knee joints with an angular velocity of 60°/s and 120°/s. The peak torque (PT), total work (TW), and average peak torque (AVG PT) were measured by extension and flexion strength at angular velocity, and the Lysholm Knee Score was used to assess the knee function of 60 patients. There was no difference in the difference in thigh circumference between the two groups before surgery (P > 0.05); the difference in thigh circumference between the patients in the test group at 12 and 24 weeks after surgery was (− 0.35 ± 0.22) cm and (0.12 ± 0.03) cm, respectively, which were higher than those in the control group, (− 0.51 ± 0.15) cm and (− 0.41 ± 0.34) cm (P < 0.05). At the 12th and 24th postoperative weeks, the popliteal muscle strength of both groups was improved compared with that before surgery; among them, by comparing the popliteal peak moments with different angular velocities, the ratio of popliteal peak moment on the affected side/peak moment on the healthy side of the popliteal muscle of the experimental group was significantly higher than that of the control group, and the difference was significant (P < 0.05), but there was still a gap compared with that of the healthy side. The Lachmen test and the anterior drawer test were negative in the test and control groups at the 24th postoperative week of review, and the anterior tibial shift was < 5 mm in the KT-1000 test, and the difference in the anterior shift was < 3 mm compared with the healthy side, and there was no significant difference between the two groups. By Nordic hamstring exercise can make patients after knee ACL reconstruction reduce patient pain, accelerate the recovery of knee function, improve the swelling of the lower limb, reach the level of flexor strength of the healthy side within 24 weeks, and can increase the stability of the knee joint.
Humor appreciation can be predicted with machine learning techniques
Authors: Rosenbusch Hannes , Visser Thomas 
Published: November 2023

AbstractHumor research is supposed to predict whether something is funny. According to its theories and observations, amusement should be predictable based on a wide variety of variables. We test the practical value of humor appreciation research in terms of prediction accuracy. We find that machine learning methods (boosted decision trees) can indeed predict humor appreciation with an accuracy close to its theoretical ceiling. However, individual demographic and psychological variables, while replicating previous statistical findings, offer only negligible gains in accuracy. Successful predictions require previous ratings by the same rater, unless highly specific interactions between rater and joke content can be assessed. We discuss implications for humor research, and offer advice for practitioners designing content recommendations engines or entertainment platforms, as well as other research fields aiming to review their practical usefulness.
In vitro modelling of local gene therapy with IL-15/IL-15Rα and a PD-L1 antagonist in melanoma reveals an interplay between NK cells and CD4+ T cells
Authors: Awad Robin Maximilian , De Vlaeminck Yannick , Meeus Fien , Ertveldt Thomas , Zeven Katty , Ceuppens Hannelore , Goyvaerts Cleo , Verdonck Magali , Salguero Gustavo , Raes Geert , Devoogdt Nick , Breckpot Karine 
Published: November 2023

AbstractBlockade of the immune checkpoint axis consisting of programmed death-1 (PD-1) and its ligand PD-L1 alleviates the functional inhibition of tumor-infiltrating lymphoid cells yet weakly induces their expansion. Exogenous cytokines could further expand lymphoid cells and thus synergize with αPD-L1 therapy. However, systemic delivery of most cytokines causes severe toxicity due to unspecific expansion of immune cells in the periphery. Here, we modelled local delivery of cytokines and αPD-L1 therapeutics to immune cell-containing in vitro melanoma tumors. Three-dimensional tumor models consisting of 624-MEL cells were co-cultured with human peripheral blood lymphoid cells (PBLs) in presence of the cytokines IL-2, IL-7, IL-15, IL-21 and IFN-γ. To model local gene therapy, melanoma tumors were modified with lentiviral vectors encoding IL-15 fused to IL-15Rα (IL-15/IL-15Rα) and K2-Fc, a fusion of a human PD-L1 specific single domain antibody to immunoglobulin (Ig)G1 Fc. To evaluate the interplay between PBL fractions, NK cells, CD4+ T cells or CD8+ T cells were depleted. Tumor cell killing was followed up using real time imaging and immune cell expansion and activation was evaluated with flow cytometry. Among the tested cytokines, IL-15 was the most potent cytokine in stimulating tumor cell killing and expanding both natural killer (NK) cells and CD8+ T cells. Gene-based delivery of IL-15/IL-15Rα to tumor cells, shows expansion of NK cells, activation of NK cells, CD4+ and CD8+ T cells, and killing of tumor spheroids. Both NK cells and CD8+ T cells are necessary for tumor cell killing and CD4+ T-cell activation was reduced without NK cells. Co-delivery of K2-Fc improved tumor cell killing coinciding with increased activation of NK cells, which was independent of bystander T cells. CD4+ or CD8+ T cells were not affected by the co-delivery of K2-Fc even though NK-cell activation impacted CD4+ T-cell activation. This study demonstrates that gene-based delivery of IL-15/IL-15Rα to tumor cells effectively mediates anti-tumor activity and sensitizes the tumor microenvironment for therapy with αPD-L1 therapeutics mainly by impacting NK cells. These findings warrant further investigation of gene-based IL-15 and K2-Fc delivery in vivo.
Evidence of diverse animal exploitation during the Middle Paleolithic at Ghar-e Boof (southern Zagros)
Authors: Mata-González Mario , Starkovich Britt M. , Zeidi Mohsen , Conard Nicholas J. 
Published: November 2023

AbstractAlthough Middle Paleolithic (MP) hominin diets consisted mainly of ungulates, increasing evidence demonstrates that hominins at least occasionally consumed tortoises, birds, leporids, fish, and carnivores. Until now, the MP zooarchaeological record in the Zagros Mountains has been almost exclusively restricted to ungulates. The narrow range of hominin prey may reflect socioeconomic decisions and/or environmental constraints, but could also result from a research bias favoring the study of large prey, since archaeologists have undertaken no systematic taphonomic analyses of small game or carnivores in the region. Here, we report on the first comprehensive taphonomic analysis of an MP faunal assemblage from Ghar-e Boof (∼ 81–45 kyr), a Late Pleistocene site in the southern Zagros of Iran. Anthropogenic bone surface modifications point to hominins as the main agent of accumulation. Hominins preyed primarily on ungulates, particularly wild goat. However, we also found evidence for MP hominin exploitation of carnivores and tortoises at the site. Although small game represents only a minor portion of the diet, our results suggest that the hunting behavior of MP hominins in the Zagros was more diverse than previously thought, similar to what we find elsewhere in Eurasia.
Long-term association of ultra-short heart rate variability with cardiovascular events
Authors: Orini Michele , van Duijvenboden Stefan , Young William J. , Ramírez Julia , Jones Aled R. , Hughes Alun D. , Tinker Andrew , Munroe Patricia B. , Lambiase Pier D. 
Published: November 2023

AbstractHeart rate variability (HRV) is a cardiac autonomic marker with predictive value in cardiac patients. Ultra-short HRV (usHRV) can be measured at scale using standard and wearable ECGs, but its association with cardiovascular events in the general population is undetermined. We aimed to validate usHRV measured using ≤ 15-s ECGs (using RMSSD, SDSD and PHF indices) and investigate its association with atrial fibrillation, major adverse cardiac events, stroke and mortality in individuals without cardiovascular disease. In the National Survey for Health and Development (n = 1337 participants), agreement between 15-s and 6-min HRV, assessed with correlation analysis and Bland–Altman plots, was very good for RMSSD and SDSD and good for PHF. In the UK Biobank (n = 51,628 participants, 64% male, median age 58), after a median follow-up of 11.5 (11.4–11.7) years, incidence of outcomes ranged between 1.7% and 4.3%. Non-linear Cox regression analysis showed that reduced usHRV from 15-, 10- and 5-s ECGs was associated with all outcomes. Individuals with low usHRV (< 20th percentile) had hazard ratios for outcomes between 1.16 and 1.29, p < 0.05, with respect to the reference group. In conclusion, usHRV from ≤ 15-s ECGs correlates with standard short-term HRV and predicts increased risk of cardiovascular events in a large population-representative cohort.
Investigating the role of aae-miR-34-5p in the regulation of juvenile hormone biosynthesis genes in the mosquito Aedes aegypti
Authors: Hussain Mazhar , Qi Zhi , Hedges Lauren M. , Nouzova Marcela , Noriega Fernando G. , Asgari Sassan 
Published: November 2023

AbstractJuvenile hormone (JH) controls the development and reproduction of insects. Therefore, a tight regulation of the expression of JH biosynthetic enzymes is critical. microRNAs (miRNAs) play significant roles in the post-transcriptional regulation of gene expression by interacting with complementary sequences in target genes. Previously, we reported that several miRNAs were differentially expressed during three developmental stages of Aedes aegypti mosquitoes with different JH levels (no JH, high JH, and low JH). One of these miRNAs was aae-miR-34-5p. In this study, we identified the presence of potential target sequences of aae-miR-34-5p in the transcripts of some genes encoding JH biosynthetic enzymes. We analysed the developmental expression patterns of aae-miR-34-5p and the predicted target genes involved in JH biogenesis. Increases in miRNA abundance were followed, with a delay, by decreases in transcript levels of target genes. Application of an inhibitor and a mimic of aae-miR-34-5p led respectively to increased and decreased levels of thiolase transcripts, which is one of the early genes of JH biosynthesis. Female adult mosquitoes injected with an aae-miR-34-5p inhibitor exhibited significantly increased transcript levels of three genes encoding JH biosynthetic enzymes, acetoacetyl-CoA thiolase (thiolase), farnesyl diphosphate phosphatase, and farnesal dehydrogenase. Overall, our results suggest a potential role of miRNAs in JH production by directly targeting genes involved in its biosynthesis.