bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Io's Sulfur Isotope Cycle to Understand the History of Tidal Heating
Authors: Hughes Ery C. , de Kleer Katherine , Eiler John , Nimmo Francis , Mandt Kathleen , Hofmann Amy E. 
Published: April 2024

AbstractStable isotope fractionation of sulfur offers a window into Io's tidal heating history, which is difficult to constrain because Io's dynamic atmosphere and high resurfacing rates leave it with a young surface. We constructed a numerical model to describe the fluxes in Io's sulfur cycle using literature constraints on rates and isotopic fractionations of relevant processes. Combining our numerical model with measurements of the 34S/32S ratio in Io's atmosphere, we constrain the rates for the processes that move sulfur between reservoirs and model the evolution of sulfur isotopes over time. Gravitational stratification of SO2 in the upper atmosphere, leading to a decrease in 34S/32S with increasing altitude, is the main cause of sulfur isotopic fractionation associated with loss to space. Efficient recycling of the atmospheric escape residue into the interior is required to explain the 34S/32S enrichment magnitude measured in the modern atmosphere. We hypothesize this recycling occurs by SO2 surface frost burial and SO2 reaction with crustal rocks, which founder into the mantle and/or mix with mantle‐derived magmas as they ascend. Therefore, we predict that magmatic SO2 plumes vented from the mantle to the atmosphere will have lower 34S/32S than the ambient atmosphere, yet are still significantly enriched compared to solar‐system average sulfur. Observations of atmospheric variations in 34S/32S with time and/or location could reveal the average mantle melting rate and hence whether the current tidal heating rate is anomalous compared to Io's long‐term average. Our modeling suggests that tides have heated Io for >1.6 Gyr if Io today is representative of past Io.
The predictive value of MRI scores for neurodevelopmental outcome in infants with neonatal encephalopathy
Authors: Andorka Csilla , Barta Hajnalka , Sesztak Timea , Nyilas Nora , Kovacs Kata , Dunai Ludovika , Rudas Gabor , Jermendy Agnes , Szabo Miklos , Szakmar Eniko 
Published: April 2024

Abstract

Background
MRI scoring systems are utilized to quantify brain injury and predict outcome in infants with neonatal encephalopathy (NE). Our aim was to evaluate the predictive accuracy of total scores, white matter (WM) and grey matter (GM) subscores of Barkovich and Weeke scoring systems for neurodevelopmental outcome at 2 years of age in infants receiving therapeutic hypothermia for NE.

Methods
Data of 162 infants were analyzed in this retrospective cohort study. DeLong tests were used to compare areas under the curve of corresponding items of the two scoring systems. LASSO logistic regression was carried out to evaluate the association between MRI scores and adverse composite (death or severe disabilities), motor and cognitive outcomes (Bayley developmental index <70).

Results
Weeke scores predicted each outcome measure with greater accuracy than the corresponding items of Barkovich system (DeLong tests p < 0.03). Total scores, GM and cerebellum involvement were associated with increased odds for adverse outcomes, in contrast to WM injury, after adjustment to 5’ Apgar score, first postnatal lactate and aEEG normalization within 48 h.

Conclusion
A more detailed scoring system had better predictive value for adverse outcome. GM injury graded on both scoring systems was an independent predictor of each outcome measure.

Impact statements

A more detailed MRI scoring system had a better predictive value for motor, cognitive and composite outcomes.

While hypoxic-ischemic brain injuries in the deep grey matter and cerebellum were predictive of adverse outcome, white matter injury including cortical involvement was not associated with any of the outcome measures at 2 years of age.

Structured MRI evaluation based on validated scores may aid future clinical research, as well as inform parents and caregivers to optimize care beyond the neonatal period.
Drug repurposing for cancer therapy
Authors: Xia Ying , Sun Ming , Huang Hai , Jin Wei-Lin 
Published: April 2024

AbstractCancer, a complex and multifactorial disease, presents a significant challenge to global health. Despite significant advances in surgical, radiotherapeutic and immunological approaches, which have improved cancer treatment outcomes, drug therapy continues to serve as a key therapeutic strategy. However, the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects, and thus there remains a critical need to develop novel cancer therapeutics. One promising strategy that has received widespread attention in recent years is drug repurposing: the identification of new applications for existing, clinically approved drugs. Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective, proven to be safe, and can significantly expedite the drug development process due to their already established safety profiles. In light of this, the present review offers a comprehensive overview of the various methods employed in drug repurposing, specifically focusing on the repurposing of drugs to treat cancer. We describe the antitumor properties of candidate drugs, and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment. In addition, we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery. We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen. To conclude, we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.
Pure rotation in the temporomandibular joint during jaw opening? A digital motion analysis
Authors: Jász Bálint , Balogh Tamás , Ambrus Szilvia , Schmidt Péter , Bányai Gréta Lilla , Körmendi Szandra , Jász Máté 
Published: April 2024

Abstract
Objective
In the temporomandibular joint two separate movements of rotation and translation occur in two articular spaces during mouth opening. Over the years, the approach has changed considerably, but it is still subject to controversy as to which of these movement is involved in the initial stage of mouth opening. In the present study, the extent of rotation and translation was investigated in the first 5 mm of mouth opening.

Materials and methods
The study was carried out on 46 volunteers. Anamnesis was taken and patients were examined. For the investigation, an ultrasonic digital motion analyser (KaVo Arcus Digma 2) was applied. The measurements were made after calibration to an arbitrary axis. Each participant performed three open-close movements in succession, starting from maximum intercuspal position.

Results
Data were statistically processed using cubic spline interpolation. Linear regression was then used. The resulting line is significantly (p < 0.0001) different from the horizontal that represents only rotational movement.

Conclusion
The results show that during mouth opening from maximum intercuspal position, translation is present continuously in addition to rotation. Therefore, it might be time to re-evaluate the principle of a pure rotational approach.
The role of CXCL2-mediated crosstalk between tumor cells and macrophages in Fusobacterium nucleatum-promoted oral squamous cell carcinoma progression
Authors: Nie Fujiao , Zhang Jie , Tian Haoyang , Zhao Jingjing , Gong Pizhang , Wang Huiru , Wang Suli , Yang Pishan , Yang Chengzhe 
Published: April 2024

AbstractDysbiosis of the oral microbiota is related to chronic inflammation and carcinogenesis. Fusobacterium nucleatum (Fn), a significant component of the oral microbiota, can perturb the immune system and form an inflammatory microenvironment for promoting the occurrence and progression of oral squamous cell carcinoma (OSCC). However, the underlying mechanisms remain elusive. Here, we investigated the impacts of Fn on OSCC cells and the crosstalk between OSCC cells and macrophages. 16 s rDNA sequencing and fluorescence in situ hybridization verified that Fn was notably enriched in clinical OSCC tissues compared to paracancerous tissues. The conditioned medium co-culture model validated that Fn and macrophages exhibited tumor-promoting properties by facilitating OSCC cell proliferation, migration, and invasion. Besides, Fn and OSCC cells can recruit macrophages and facilitate their M2 polarization. This crosstalk between OSCC cells and macrophages was further enhanced by Fn, thereby amplifying this positive feedback loop between them. The production of CXCL2 in response to Fn stimulation was a significant mediator. Suppression of CXCL2 in OSCC cells weakened Fn’s promoting effects on OSCC cell proliferation, migration, macrophage recruitment, and M2 polarization. Conversely, knocking down CXCL2 in macrophages reversed the Fn-induced feedback effect of macrophages on the highly invasive phenotype of OSCC cells. Mechanistically, Fn activated the NF-κB pathway in both OSCC cells and macrophages, leading to the upregulation of CXCL2 expression. In addition, the SCC7 subcutaneous tumor-bearing model in C3H mice also substantiated Fn’s ability to enhance tumor progression by facilitating cell proliferation, activating NF-κB signaling, up-regulating CXCL2 expression, and inducing M2 macrophage infiltration. However, these effects were reversed by the CXCL2-CXCR2 inhibitor SB225002. In summary, this study suggests that Fn contributes to OSCC progression by promoting tumor cell proliferation, macrophage recruitment, and M2 polarization. Simultaneously, the enhanced CXCL2-mediated crosstalk between OSCC cells and macrophages plays a vital role in the pro-cancer effect of Fn.
Cancer-associated fibroblasts secrete FGF5 to inhibit ferroptosis to decrease cisplatin sensitivity in nasopharyngeal carcinoma through binding to FGFR2
Authors: Liu Feng , Tang Ling , Liu Huai , Chen Yanzhu , Xiao Tengfei , Gu Wangning , Yang Hongmin , Wang Hui , Chen Pan 
Published: April 2024

AbstractCisplatin (DDP)-based chemoradiotherapy is one of the standard treatments for nasopharyngeal carcinoma (NPC). However, the sensitivity and side effects of DDP to patients remain major obstacles for NPC treatment. This research aimed to study DDP sensitivity regulated by cancer-associated fibroblasts (CAFs) through modulating ferroptosis. We demonstrated that DDP triggered ferroptosis in NPC cells, and it inhibited tumor growth via inducing ferroptosis in xenograft model. CAFs secreted high level of FGF5, thus inhibiting DDP-induced ferroptosis in NPC cells. Mechanistically, FGF5 secreted by CAFs directly bound to FGFR2 in NPC cells, leading to the activation of Keap1/Nrf2/HO-1 signaling. Rescued experiments indicated that FGFR2 overexpression inhibited DDP-induced ferroptosis, and CAFs protected against DDP-induced ferroptosis via FGF5/FGFR2 axis in NPC cells. In vivo data further showed the protective effects of FGF5 on DDP-triggered ferroptosis in NPC xenograft model. In conclusion, CAFs inhibited ferroptosis to decrease DDP sensitivity in NPC through secreting FGF5 and activating downstream FGFR2/Nrf2 signaling. The therapeutic strategy targeting FGF5/FGFR2 axis from CAFs might augment DDP sensitivity, thus decreasing the side effects of DDP in NPC treatment.
Speed of environmental change frames relative ecological risk in climate change and climate intervention scenarios
Authors: Hueholt Daniel M. , Barnes Elizabeth A. , Hurrell James W. , Morrison Ariel L. 
Published: April 2024

AbstractStratospheric aerosol injection is a potential method of climate intervention to reduce climate risk as decarbonization efforts continue. However, possible ecosystem impacts from the strategic design of hypothetical intervention scenarios are poorly understood. Two recent Earth system model simulations depict policy-relevant stratospheric aerosol injection scenarios with similar global temperature targets, but a 10-year delay in intervention deployment. Here we show this delay leads to distinct ecological risk profiles through climate speeds, which describe the rate of movement of thermal conditions. On a planetary scale, climate speeds in the simulation where the intervention maintains temperature are not statistically distinguishable from preindustrial conditions. In contrast, rapid temperature reduction following delayed deployment produces climate speeds over land beyond either a preindustrial baseline or no-intervention climate change with present policy. The area exposed to threshold climate speeds places different scenarios in context to their relative ecological risks. Our results support discussion of tradeoffs and timescales in future scenario design and decision-making.
Iron alloys of volatile elements in the deep Earth’s interior
Authors: Tian Yifan , Zhang Peiyu , Zhang Wei , Feng Xiaolei , Redfern Simon A. T. , Liu Hanyu 
Published: April 2024

AbstractInvestigations into the compositional model of the Earth, particularly the atypical concentrations of volatile elements within the silicate portion of the early Earth, have attracted significant interest due to their pivotal role in elucidating the planet’s evolution and dynamics. To understand the behavior of such volatile elements, an established ‘volatility trend’ has been used to explain the observed depletion of certain volatile elements. However, elements such as Se and Br remain notably over-depleted in the silicate Earth. Here we show the results from first-principles simulations that explore the potential for these elements to integrate into hcp-Fe through the formation of substitutional alloys, long presumed to be predominant constituents of the Earth’s core. Based on our findings, the thermodynamic stability of these alloys suggests that these volatile elements might indeed be partially sequestered within the Earth’s core. We suggest potential reservoirs for volatile elements within the deep Earth, augmenting our understanding of the deep Earth’s composition.
CD20/MS4A1 is a mammalian olfactory receptor expressed in a subset of olfactory sensory neurons that mediates innate avoidance of predators
Authors: Jiang Hao-Ching , Park Sung Jin , Wang I-Hao , Bear Daniel M. , Nowlan Alexandra , Greer Paul L. 
Published: April 2024

AbstractThe mammalian olfactory system detects and discriminates between millions of odorants to elicit appropriate behavioral responses. While much has been learned about how olfactory sensory neurons detect odorants and signal their presence, how specific innate, unlearned behaviors are initiated in response to ethologically relevant odors remains poorly understood. Here, we show that the 4-transmembrane protein CD20, also known as MS4A1, is expressed in a previously uncharacterized subpopulation of olfactory sensory neurons in the main olfactory epithelium of the murine nasal cavity and functions as a mammalian olfactory receptor that recognizes compounds produced by mouse predators. While wildtype mice avoid these predator odorants, mice genetically deleted of CD20 do not appropriately respond. Together, this work reveals a CD20-mediated odor-sensing mechanism in the mammalian olfactory system that triggers innate behaviors critical for organismal survival.
Redefined ion association constants have consequences for calcium phosphate nucleation and biomineralization
Authors: McDonogh David P. , Gale Julian D. , Raiteri Paolo , Gebauer Denis 
Published: April 2024

AbstractCalcium orthophosphates (CaPs), as hydroxyapatite (HAP) in bones and teeth are the most important biomineral for humankind. While clusters in CaP nucleation have long been known, their speciation and mechanistic pathways to HAP remain debated. Evidently, mineral nucleation begins with two ions interacting in solution, fundamentally underlying solute clustering. Here, we explore CaP ion association using potentiometric methods and computer simulations. Our results agree with literature association constants for Ca2+ and H2PO4−, and Ca2+ and HPO42-, but not for Ca2+ and PO43− ions, which previously has been strongly overestimated by two orders of magnitude. Our data suggests that the discrepancy is due to a subtle, premature phase separation that can occur at low ion activity products, especially at higher pH. We provide an important revision of long used literature constants, where association of Ca2+ and PO43− actually becomes negligible below pH 9.0, in contrast to previous values. Instead, [CaHPO4]0 dominates the aqueous CaP speciation between pH ~6–10. Consequently, calcium hydrogen phosphate association is critical in cluster-based precipitation in the near-neutral pH regime, e.g., in biomineralization. The revised thermodynamics reveal significant and thus far unexplored multi-anion association in computer simulations, constituting a kinetic trap that further complicates aqueous calcium phosphate speciation.
Palladium-catalyzed asymmetric carbene coupling en route to inherently chiral heptagon-containing polyarenes
Authors: Zhang Huan , Lu Chuan-Jun , Cai Gao-Hui , Xi Long-Long , Feng Jia , Liu Ren-Rong 
Published: April 2024

AbstractDeveloping facile and direct synthesis routes for enantioselective construction of cyclic π-conjugated molecules is crucial. However, originate chirality from the distorted structure around heptagon-containing polyarenes is largely overlooked, the enantioselective construction of all-carbon heptagon-containing polyarenes remains a challenge. Herein, we present a highly enantioselective synthesis route for fabricating all carbon heptagon-containing polyarenes via palladium-catalyzed carbene-based cross–coupling of benzyl bromides and N-arylsulfonylhydrazones. A wide range of nonplanar, saddle-shaped tribenzocycloheptene derivatives are efficiently prepared in high yields with excellent enantioselectivities using this approach. In addition, stereochemical stability experiments show that these saddle-shaped tribenzocycloheptene derivatives have high inversion barriers.
Combined study of phase transitions in the P2-type NaXNi1/3Mn2/3O2 cathode material: experimental, ab-initio and multiphase-field results
Authors: Daubner Simon , Dillenz Manuel , Pfeiffer Lukas Fridolin , Gauckler Cornelius , Rosin Maxim , Burgard Nora , Martin Jan , Axmann Peter , Sotoudeh Mohsen , Groß Axel , Schneider Daniel , Nestler Britta 
Published: April 2024

AbstractThe research of new electrode materials such as sodium intercalation compounds is key to meet the challenges of future demands of sustainable energy storage. For these batteries, the intercalation behavior on the micro-scale is governed by a complex interplay of chemical, electrical and mechanical forces strongly influencing the overall cell performance. The multiphase-field method is a suitable tool to study these multi-physics and bridge the scale from ab-initio methods to the cell level. In this work, we follow a combined approach of experiments, density functional theory (DFT) calculations and multiphase-field simulations to predict thermodynamic and kinetic properties for the P2-type NaXNi1/3Mn2/3O2 sodium-ion cathode material. Experimentally, we obtain the thermodynamic potential and diffusion coefficients at various sodium contents using electrochemical techniques and discuss limitations of the experimentally applied methods. DFT is used to identify stable phases by calculating an energy hull curve. Then, the influence of long-range dispersion interactions and the exchange-correlation functional on the voltage curve is investigated by comparison with experimental results. Finally, multiphase-field simulations are performed based on inputs from experiments and DFT. The fitting of phase-specific chemical free energies from DFT calculations and experimental data is discussed. Our results highlight the thermodynamic consistency of all three approaches close to thermodynamic equilibrium. Furthermore, the phase-field method accurately describes the kinetics of the system including multiple phase transitions, by which we unravel the mechanism of the P2-O2 phase transition in a single crystal under the influence of intercalation reaction, bulk diffusion and elastic deformation. The model is able to predict the kinetic capacity loss depending on charging rate in agreement with C-rate experiments.
Genetic modifiers of rare variants in monogenic developmental disorder loci
Authors: Kingdom Rebecca , Beaumont Robin N. , Wood Andrew R. , Weedon Michael N. , Wright Caroline F. 
Published: April 2024

AbstractRare damaging variants in a large number of genes are known to cause monogenic developmental disorders (DDs) and have also been shown to cause milder subclinical phenotypes in population cohorts. Here, we show that carrying multiple (2−5) rare damaging variants across 599 dominant DD genes has an additive adverse effect on numerous cognitive and socioeconomic traits in UK Biobank, which can be partially counterbalanced by a higher educational attainment polygenic score (EA-PGS). Phenotypic deviators from expected EA-PGS could be partly explained by the enrichment or depletion of rare DD variants. Among carriers of rare DD variants, those with a DD-related clinical diagnosis had a substantially lower EA-PGS and more severe phenotype than those without a clinical diagnosis. Our results suggest that the overall burden of both rare and common variants can modify the expressivity of a phenotype, which may then influence whether an individual reaches the threshold for clinical disease.
RADReef: A global Holocene Reef Rate of Accretion Dataset
Authors: Hynes Michael G. , O’Dea Aaron , Webster Jody M. , Renema Willem 
Published: April 2024

AbstractReef cores are a powerful tool for investigating temporal changes in reef communities. Radiometric dating facilitates the determination of vertical accretion rates, which has allowed for examination of local-regional controlling factors, such as subsidence and sea level changes. Coral reefs must grow at sufficient rates to keep up with sea level rise, or risk ‘drowning.’ As sea level is expected to rise significantly in the next 100 years and beyond, it is important to understand whether reefs will be able to survive. Historical records of reef accretion rates extracted from cores provide valuable insights into extrinsic controlling factors of reef growth and are instrumental in helping predict if future reefs can accrete at rates needed to overcome predicted sea level changes. While extensive research exists at local and regional scales, limited attention has been given to identifying global patterns and drivers. To address this, we present “RADReef”: A global dataset of dated Holocene reef cores. RADReef serves as a foundation for further research on past, present and future reef accretion.