bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual A2A/A2B Adenosine Receptor Antagonist M1069 Counteracts Immunosuppressive Mechanisms of Adenosine and Reduces Tumor Growth In Vivo
Authors: Schiemann Kai , Belousova Natalya , Matevossian Armine , Nallaparaju Kalyan C. , Kradjian Giorgio , Pandya Meghana , Chen Zhouxiang , Aral Esengul , Krauel Eva-Maria , Petrova Elissaveta , Boesler Carsten , Kitzing Thomas , Lecomte Marc , Wagner Christian , Blayo Anne Laure , Schann Stephan , Huck Bayard , Moisan Jacques , Zaynagetdinov Rinat 
Published: August 2024

Abstract
While A2A adenosine receptor (AR) was considered as a major contributor to adenosine-mediated immunosuppression, A2B, having the lowest affinity to adenosine, has also emerged as a potential contributor to tumor promotion. Therefore, in adenosine-rich tumor microenvironment (TME), where A2B could be complementary and/or compensatory to A2A, simultaneous targeting of A2A and A2B ARs can provide higher potential for cancer immunotherapy. We developed M1069—a highly selective dual antagonist of the A2A and A2B AR. In assays with primary human and murine immune cells, M1069 rescued IL2 production from T cells (A2A dependent) and inhibited VEGF production by myeloid cells (A2B dependent) in adenosine-high settings. M1069 also demonstrated superior suppression of the secretion of protumorigenic cytokines CXCL1, CXCL5, and rescue of IL12 secretion from adenosine-differentiated dendritic cells compared to an A2A-selective antagonist (A2Ai). In a one-way mixed lymphocyte reaction (MLR) assay, adenosine-differentiated human and murine dendritic cells treated with M1069 demonstrated superior T-cell stimulatory activity compared to dendritic cells differentiated in presence of A2Ai. In vivo, M1069 decreased tumor growth as a monotherapy and enhanced antitumor activity of bintrafusp alfa (BA) or cisplatin in syngeneic adenosinehi/CD73hi 4T1 breast tumor model, but not in the CD73 knockout 4T1 tumor model or in adenosinelow/CD73low MC38 murine colon carcinoma model. In summary, our dual A2A/A2B AR antagonist M1069 may counteract immune-suppressive mechanisms of high concentrations of adenosine in vitro and in vivo and enhance the antitumor activity of other agents, including BA and cisplatin.
Differentiating Left Ventricular Remodeling in Aortic Stenosis From Systemic Hypertension
Authors: Mahmod Masliza , Chan Kenneth , Fernandes Joao F. , Ariga Rina , Raman Betty , Zacur Ernesto , Law Ho-fon Royce , Rigolli Marzia , Francis Jane M. , Dass Sairia , O’Gallagher Kevin , Myerson Saul G. , Karamitsos Theodoros D. , Neubauer Stefan , Lamata Pablo 
Published: August 2024

BACKGROUND:
Left ventricular (LV) hypertrophy occurs in both aortic stenosis (AS) and systemic hypertension (HTN) in response to wall stress. However, differentiation of hypertrophy due to these 2 etiologies is lacking. The aim was to study the 3-dimensional geometric remodeling pattern in severe AS pre- and postsurgical aortic valve replacement and to compare with HTN and healthy controls.

METHODS:
Ninety-one subjects (36 severe AS, 19 HTN, and 36 healthy controls) underwent cine cardiac magnetic resonance. Cardiac magnetic resonance was repeated 8 months post-aortic valve replacement (n=18). Principal component analysis was performed on the 3-dimensional meshes reconstructed from 109 cardiac magnetic resonance scans of 91 subjects at end-diastole. Principal component analysis modes were compared across experimental groups together with conventional metrics of shape, strain, and scar.

RESULTS:

A unique AS signature was identified by wall thickness linked to a LV left-right axis shift and a decrease in short-axis eccentricity. HTN was uniquely linked to increased septal thickness. Combining these 3 features had good discriminative ability between AS and HTN (area under the curve, 0.792). The LV left-right axis shift was not reversible post-aortic valve replacement, did not associate with strain, age, or sex, and was predictive of postoperative LV mass regression (R
2
=0.339,
P
=0.014).

CONCLUSIONS:
Unique remodeling signatures might differentiate the etiology of LV hypertrophy. Preliminary findings suggest that LV axis shift is characteristic in AS, is not reversible post-aortic valve replacement, predicts mass regression, and may be interpreted to be an adaptive mechanism.
Predictive and Diagnostic Value of the Angiogenic Proteins in Patients With Chronic Kidney Disease
Authors: Melamed Nir , Kingdom John C. , Fu Lei , Yip Paul M. , Arruda-Caycho Isabel , Hui Dini , Hladunewich Michelle A. 
Published: August 2024

BACKGROUND:
Our objective was to investigate the predictive and diagnostic accuracy of the angiogenic proteins sFlt-1 (soluble fms–like tyrosine kinase-1) and PlGF (placental growth factor) for preterm preeclampsia and explore the relationship between renal function and these proteins.

METHODS:
We completed a blinded, prospective, longitudinal, observational study of patients with chronic kidney disease followed at a tertiary center (2018–2023). Serum samples were obtained at 3 time points along gestation (planned sampling): 12–16, 18–22, and 28–32 weeks. In addition, samples were obtained whenever preeclampsia was suspected (indicated sampling). sFlt-1 and PlGF levels remained concealed until the study ended. The primary outcome was preterm preeclampsia. The planned and indicated samples were used to estimate the predictive and diagnostic accuracy of the angiogenic proteins, respectively.

RESULTS:
Of the 97 participants, 21 (21.6%) experienced preterm preeclampsia. In asymptomatic patients with chronic kidney disease, the angiogenic proteins were predictive of preterm preeclampsia only when sampled in the third trimester, in which case the sFlt-1/PlGF ratio (false positive rate of 37% for a detection rate of 80%) was more predictive than either sFlt-1 or PlGF in isolation. In patients with suspected preeclampsia, the diagnostic accuracy of the sFlt-1/PlGF ratio (false positive rate of 26% for a detection rate of 80%) was higher than that of sFlt-1 and PlGF in isolation. Diminished renal function was associated with increased levels of PlGF.

CONCLUSIONS:
sFlt-1 and PlGF can effectively predict and improve the diagnostic accuracy for preterm preeclampsia among patients with chronic kidney disease. The optimal sFlt-1/PlGF ratio cutoff to rule out preeclampsia may need to be lower in patients with impaired renal function.
A novel, robust, and portable platform for magnetoencephalography using optically-pumped magnetometers
Authors: Schofield Holly , Hill Ryan M. , Feys Odile , Holmes Niall , Osborne James , Doyle Cody , Bobela David , Corvilain Pierre , Wens Vincent , Rier Lukas , Bowtell Richard , Ferez Maxime , Mullinger Karen J. , Coleman Sebastian , Rhodes Natalie , Rea Molly , Tanner Zoe , Boto Elena , de Tiège Xavier , Shah Vishal , Brookes Matthew J. 
Published: August 2024

Abstract
Magnetoencephalography (MEG) measures brain function via assessment of magnetic fields generated by neural currents. Conventional MEG uses superconducting sensors, which place significant limitations on performance, practicality, and deployment; however, the field has been revolutionised in recent years by the introduction of optically-pumped magnetometers (OPMs). OPMs enable measurement of the MEG signal without cryogenics, and consequently the conception of “OPM-MEG” systems which ostensibly allow increased sensitivity and resolution, lifespan compliance, free subject movement, and lower cost. However, OPM-MEG is in its infancy with existing limitations on both sensor and system design. Here, we report a new OPM-MEG design with miniaturised and integrated electronic control, a high level of portability, and improved sensor dynamic range. We show that this system produces equivalent measures compared with an established OPM-MEG instrument; specifically, when measuring task-induced beta-band, gamma-band, and evoked neuro-electrical responses, source localisations from the two systems were comparable and temporal correlation of measured brain responses was &gt;0.7 at the individual level and &gt;0.9 for groups. Using an electromagnetic phantom, we demonstrate improved dynamic range by running the system in background fields up to 8 nT. We show that the system is effective in gathering data during free movement (including a sitting-to-standing paradigm) and that it is compatible with simultaneous electroencephalography (EEG). Finally, we demonstrate portability by moving the system between two laboratories. Overall, our new system is shown to be a significant step forward for OPM-MEG and offers an attractive platform for next generation functional medical imaging.
Lumbosacral spinal cord functional connectivity at rest: From feasibility to reliability
Authors: Ricchi Ilaria , Kinany Nawal , Van De Ville Dimitri 
Published: August 2024

Abstract
In the past decade, exploration of spontaneous blood-oxygen-level-dependent (BOLD) signal fluctuations has expanded beyond the brain to include the spinal cord. While most studies have predominantly focused on the cervical region, the lumbosacral segments play a crucial role in motor control and sensory processing of the lower limbs. Addressing this gap, the aims of the current study were twofold: first, confirming the presence and nature of organized spontaneous BOLD signals in the human lumbosacral spinal cord; second, systematically assessing the impact of various denoising strategies on signal quality and functional connectivity (FC) patterns. Given the susceptibility of spinal cord functional magnetic resonance imaging (fMRI) to noise, this step is pivotal to ensure the robustness of intrinsic FC. Our findings uncovered bilateral FC between the ventral and dorsal horns. Importantly, these patterns were consistently observed across denoising methods and demonstrating fair to excellent split-half temporal stability. Importantly, the evaluation of diverse denoising strategies highlighted the efficacy of physiological noise modeling (PNM)-based pipelines in cleaning the signal while preserving the strength of connectivity estimates. Together, our results provide evidence of robust FC patterns in the lumbosacral spinal cord, thereby paving the way for future studies probing caudal spinal activity.
Mind Melds: Verbal Labels Induce Greater Representational Alignment
Authors: Suffill Ellise , van Paridon Jeroen , Lupyan Gary 
Published: August 2024

Abstract
What determines whether two people represent something in a similar way? We examined the role of verbal labels in promoting representational alignment. Across two experiments, three groups of participants sorted novel shapes from two visually dissimilar categories. Prior to sorting, participants in two of the groups were pre-exposed to the shapes using a simple visual matching task designed to reinforce the visual category structure. In one of these groups, participants additionally heard one of two nonsense category labels accompanying the shapes. Exposure to these redundant labels led people to represent the shapes in a more categorical way, which led to greater alignment between sorters. We found this effect of label-induced alignment despite the two categories being highly visually distinct and despite participants in both pre-exposure conditions receiving identical visual experience with the shapes. Experiment 2 replicated this basic result using more even more stringent testing conditions. The results hint at the possibly extensive role that labels may play in aligning people’s mental representations.
Post-rut aggression in caribou: limited evidence for interference competition but strong evidence for male harassment
Authors: Webber Quinn M.R. , Vander Wal Eric 
Published: August 2024

Abstract
Social competition for resources is widespread among animals. Females of many species compete for foraging resources through interference competition, which is a behavioural interaction between animals that reduces an individual’s access to shared resources. In addition to competition from other females, females also often face harassment from males during and after the breeding season. The female competition hypothesis predicts that female-initiated aggression associated with foraging competition increases as a function of group size, but we expected this effect to be more pronounced in higher quality foraging habitat. The male harassment hypothesis predicts that male harassment of females should also increase as a function of group size as well as a function of the ratio of males to other group members. Here, we tested the female competition and male harassment hypotheses for caribou (Rangifer tarandus) within the context of variation in the social environment (i.e., group size and sex ratio) and the physical environment (i.e., variation in habitat quality). We conducted focal observations of caribou on Fogo Island, Newfoundland, over three years and quantified aggressive social interactions in different habitat types to test our hypotheses. Specifically, we took advantage of natural variation in caribou behaviour in our system and observed caribou foraging in an enhanced habitat (i.e., recreational sports complex field) and natural habitat (i.e., lichen barrens). We found limited support for the female competition hypothesis, possibly because of females’ propensity to increase foraging rates in enhanced habitats. By contrast, we found strong support for the male harassment hypothesis, where males increase the frequency of harassment as group size increased. Our results suggest costs of grouping for female caribou in the post-rut time period may be related to the presence of males potentially seeking mating opportunities.
Designing of nematode egg parasitic fungus, Purpureocillium lilacinum, nanoemulsion for management of Meloidogyne incognita infection in tomato
Authors: Nagachandrabose Seenivasan , Sivathanu Logaraj , Pon Sathya Moorthy , Kalimuthu Raja , Somasundaram Prabhu , Subramanian K.S. 
Published: August 2024

Summary
Purpureocillium lilacinum is a potent biocontrol agent against Meloidogyne spp. and various other plant-parasitic nematodes in crops. However, existing commercial formulations of P. lilacinum suffer from drawbacks like short shelf life and inconsistent performance in different environmental conditions. To address these issues, a new nano-formulation of P. lilacinum was developed and tested against Meloidogyne incognita infecting tomatoes. Initially, edible oil-based emulsions were prepared using probe ultrasonication, with 40 formulations screened and 14 selected for further testing. Seven of these emulsions remained stable at room temperature (28 ± 4°C) for 8 weeks, with stability assessed based on particle size, zeta potential, and particle shape using particle size analysis and transmission electron microscopy (TEM). Among these, NE 8 (comprising 10 ml of 1% carboxyl methyl cellulose (CMC), 1.25 ml of Tween 80 and 5 ml of sunflower oil) exhibited superior characteristics, with an average particle size of 226.6 nm, a zeta potential of −54.80 mV, and a spherical morphology under TEM examination. The P. lilacinum nanoemulsion formulation was produced by homogenising NE 8 emulsion and spores at a 1:1 ratio, ensuring efficient spore dispersion and encapsulation without loss of viability. In vitro tests demonstrated 100% immobility of M. incognita second-stage juveniles (J2) and 100% parasitism of eggs at a concentration of 5.0 ml l−1. Under glasshouse conditions, soil drenching with the nano-formulation at concentrations ranging from 0.5 to 5.0 ml l−1 resulted in enhanced tomato growth and significant suppression of M. incognita populations in soil and roots, with increased egg mass parasitism. Bio-safety tests confirmed that P. lilacinum nano-formulation at concentrations of 0.25 ml l−1 and 5.0 ml l−1 had no harmful effects on the earthworm Eudrilus eugeniae.
Factors Affecting Health Care Utilization Associations Among Young Adolescents With Persistent or Recurrent Pain
Authors: Ahn Rachel Elise , Senger-Carpenter Thea , Voepel-Lewis Terri 
Published: August 2024

Background: It is unclear how family factors affect health care utilization among youth with persistent or recurrent pain, despite potential relevance to interventions targeting treatment barriers. Objective: We aimed to examine health care utilization among young adolescents with persistent or recurrent pain and family factor influences toward higher health care utilization. Methods: We analyzed longitudinal data from the Adolescent Brain Cognitive Development Study and coded pain as none, infrequent (present 1-2 years), or persistent/recurrent pain (present 3-4 years). Higher health care utilization was coded as nonroutine or emergency department visit at ≥2 years. Parent-reported education, pain status, family income, and insurance status were recorded. Logistic regression examined the contributions of the child’s pain and family factors toward higher health care utilization. Results: Among 5960 youth, 1908 (32%) had persistent/recurrent pain and 2199 (37%) had infrequent pain. Youth with persistent/recurrent pain were more likely to have higher health care utilization compared to those without pain (adjusted odds ratio [OR]: 2.39) or those with infrequent pain (OR: 1.79). Higher health care utilization was associated with parents’ pain (adjusted OR: 1.22) and higher education (adjusted OR: 1.44), and family income below the poverty line (adjusted OR: 1.26), controlling for child characteristics and pain status. Conclusion: Findings show how youths’ persistent/recurrent pain, parental, and family socioeconomic factors affect health care utilization among young adolescents, emphasizing a need for family-centered care and economic policies.
NXPH4 mediated by m5C contributes to the malignant characteristics of colorectal cancer via inhibiting HIF1A degradation
Authors: Yang Lei , Shi Jiawen , Zhong Mingyang , Sun Pingping , Zhang Xiaojing , Lian Zhengyi , Yin Hang , Xu Lijun , He Guyin , Xu Haiyan , Wu Han , Wang Ziheng , Miao Kai , Huang Jianfei 
Published: August 2024

Abstract
Objective
Colorectal cancer (CRC) is a form of malignancy that exhibits a comparatively elevated occurrence and fatality rate. Given the relatively slower progress in diagnostic and therapeutic approaches for CRC, there is a need to investigate more accurate and efficient biomarkers.

Methods
Core regulatory genes were screened using the TCGA database, and the expression of neurexophilin 4 (NXPH4) and its prognostic implications were validated using tissue microarray staining. The assessment of NXPH4 functions involved a range of experiments, including cellular, organoid, and murine models. Furthermore, a regulatory network between m5C, NXPH4, and HIF1A was established through several in vitro experiments.

Results
The overexpression of NXPH4 is associated with unfavorable prognoses in patients with CRC and hepatocellular carcinoma. Additionally, it facilitates the progression of malignant tumors both in laboratory settings and in living organisms of colorectal carcinoma. Our research also reveals that NXPH4 mRNA can avoid degradation through RNautophagy, relying on an m5C-dependent mechanism. Moreover, NXPH4 amplifies the HIF signaling pathway and stabilizes HIF1A by competitively binding to PHD4.

Conclusions
NXPH4, regulated by m5C, promotes malignant tumor progression and regulates the HIF pathway. Consequently, targeting NXPH4 through molecular therapies could potentially serve as an efficacious therapeutic strategy for the management of CRC exhibiting elevated NXPH4 expression.

Graphical abstract
Modeling relaxation experiments with a mechanistic model of gene expression
Authors: Estavoyer Maxime , Dufeu Marion , Ranson Grégoire , Lefort Sylvain , Voeltzel Thibault , Maguer-Satta Véronique , Gandrillon Olivier , Lepoutre Thomas 
Published: August 2024

Abstract
Background
In the present work, we aimed at modeling a relaxation experiment which consists in selecting a subfraction of a cell population and observing the speed at which the entire initial distribution for a given marker is reconstituted.

Methods
For this we first proposed a modification of a previously published mechanistic two-state model of gene expression to which we added a state-dependent proliferation term. This results in a system of two partial differential equations. Under the assumption of a linear dependence of the proliferation rate with respect to the marker level, we could derive the asymptotic profile of the solutions of this model.

Results
In order to confront our model with experimental data, we generated a relaxation experiment of the CD34 antigen on the surface of TF1-BA cells, starting either from the highest or the lowest CD34 expression levels. We observed in both cases that after approximately 25 days the distribution of CD34 returns to its initial stationary state. Numerical simulations, based on parameter values estimated from the dataset, have shown that the model solutions closely align with the experimental data from the relaxation experiments.

Conclusion
Altogether our results strongly support the notion that cells should be seen and modeled as probabilistic dynamical systems.
Impact of the medical fitness model on long term health outcomes in older adults
Authors: Brar Ranveer , Katz Alan , Ferguson Thomas , Whitlock Reid , Di Nella Michelle , Bohm Clara , Rigatto Claudio , Komenda Paul , Boreskie Sue , Solmundson Carrie , Kosowan Leanne , Tangri Navdeep 
Published: August 2024

Abstract
Background
Physical inactivity is common among older adults and is associated with poor health outcomes. Medical fitness facilities provide a medically focused approach to physical fitness and can improve physical activity in their communities. This study aimed to assess the relationship between membership in the medical fitness model and all-cause mortality, health care utilization, and major adverse cardiac events in older adults.

Methods
A propensity weighted retrospective cohort study linked individuals that attended medical fitness facilities to provincial health administrative databases. Older adults who had at least 1 year of health coverage from their index date between January 1st, 2005 to December 31st 2015 were included. Controls were assigned a pseudo-index date at random based on the frequency distribution of index dates in members. Members were stratified into low frequency attenders (< 1 Weekly Visits) and regular frequency attenders (> 1 Weekly Visits). Time to event models estimated the hazard ratios (HRs) for risk of all-cause mortality and major adverse cardiac event. Negative binomial models estimated the risk ratios (RRs) for risk of hospitalizations, outpatient primary care visits and emergency department visits.

Results
Among 3,029 older adult members and 91,734 controls, members had a 45% lower risk of all-cause mortality (HR: 0.55, 95% CI: 0.50 – 0.61), 20% lower risk of hospitalizations (RR: 0.80, 95% CI: 0.75 – 0.84), and a 27% (HR: 0.72, 95% CI: 0.66 – 0.77), lower risk of a major adverse cardiovascular event. A dose–response effect with larger risk reductions was associated with more frequent attendance as regular frequency attenders were 4% more likely to visit a general practitioner for a routine healthcare visit (RR: 1.04, 95% CI: 1.01 – 1.07), but 23% less likely to visit the emergency department (RR: 0.87, 95% CI: 0.82 – 0.92).

Conclusions
Membership at a medical fitness facility was associated with a decreased risk of mortality, health care utilization and cardiovascular events. The medical fitness model may be an alternative approach for public health strategies to promote positive health behaviors in older adult populations.