bluuebunny/crossref_metadata_2025 huggingface dataset:
Should Catholics Support Laws Prohibiting Abortion?
Authors: Ozar David
Published: April 2024

It has been a teaching of the Catholic Church for many centuries that the fact that an act is immoral is not itself a sufficient reason for acts of that kind to be punishable under the law. Therefore, before American Catholics or their bishops actively support laws making abortion illegal and punishable, they must carefully examine such laws to determine whether they are consistent with the common good and thus morally justifiable. This article first turns to the three conditions that Thomas Aquinas offers in the Treatise on Law (Summa Theologica, I-II, QQ. 90-105) that a law must fulfill in order for it to be consistent with the common good. Serious reasons are identified for doubting that laws prohibiting and punishing abortion can fulfill Aquinas’s three conditions. There are also serious reasons based on Catholic teaching, i.e., that we are always obliged to follow our conscience, for concluding that, contrary to the common good, many conscientious persons would be mistakenly punished by such laws. For these reasons, the article proposes that American Catholics and their bishops should reexamine their support for laws punishing abortion and should consider instead actively opposing such laws.
Cannabidiol modulates hippocampal genes involved in mitochondrial function, ribosome biogenesis, synapse organization, and chromatin modifications
Authors: Machado João P. D. , de Almeida Valéria , Zuardi Antonio W. , Hallak Jaime E. C. , Crippa José A. , Vieira André S.
Published: April 2024

Background:

Cannabidiol (CBD) is one of the main cannabinoids present in Cannabis sativa female flowers. Previous investigation has already provided insights into the CBD molecular mechanism; however, there is no transcriptome data for CBD effects on hippocampal subfields. Here, we investigate transcriptomic changes in dorsal and ventral CA1 of adult mice hippocampus after 100 mg/kg of CBD administration (i.p.) for one or seven consecutive days.

Methods:

C57BL/6JUnib mice were treated with either vehicle or CBD for 1 or 7 days. The collected brains were sectioned, and the hippocampal sub-regions were laser microdissected for RNA-Seq analysis.

Results:

The transcriptome analysis following 7 days of CBD administration indicates the differential expression of 1559 genes in dCA1 and 2924 genes in vCA1. Furthermore, GO/KEGG analysis identified 88 significantly enriched biological process and 26 significantly enriched pathways for dCBD7, whereas vCBD7 revealed 128 enriched BPs and 24 pathways.

Conclusion:

This dataset indicates a widespread decrease of electron transport chain and ribosome biogenesis transcripts in CA1, while chromatin modifications and synapse organization transcripts were increased following CBD administration for 7 days.
The unsettled effect of physical height on political preferences
Authors: Burden Barry C. , Herd Pamela , Moynihan Donald P.
Published: April 2024

We revisit Arunachalam and Watson's contention that a person's physical height may be used as instrument for income because it affects economic well-being solely by causing more conservative political preferences among people who are taller. To evaluate whether other early-life and genetic factors might serve as mechanisms connecting height and political preferences, we analyze a unique data source that includes political, economic, and demographic data on same-gender siblings. Models that include fixed effects for siblings provide a strong test of the Arunachalam and Watson thesis. We find that height is not a consistent predictor of political preferences once shared sibling characteristics are controlled in this way, raising doubt about whether height can in fact be used as an instrument for income.
Muddying the Waters: How Perceived Foreign Interference Affects Public Opinion on Protest Movements
Authors: CHOW WILFRED M. , LEVIN DOV H.
Published: April 2024

Does foreign interference help or harm protest movements? An extensive literature has debated this question but focuses on observational data, obscuring a crucial mechanism for protest success: its effect on public attitudes. We argue that public accusations of foreign meddling damage protest groups by reducing public support. In survey experiments conducted in the United States and Canada, we find that credible accusations of foreign interference erode support by discrediting protester groups among sympathizers and inflaming nationalist fears. Indeed, such accusations delegitimize protest movements even among those sympathetic to the cause. Conditional factors, such as the type of foreign assistance or the identity of the meddling state, have no impact. These findings reveal how referencing foreign backing is a potent discrediting tactic—it influences public opinion, a critical determinant for protest outcomes.
Pushforward of structure sheaf and virtual global generation
Authors: Biswas Indranil , Kumar Manish , Parameswaran A. J.
Published: April 2024

Let $f\,:\,X\,\longrightarrow \,Y$ be a generically smooth morphism between irreducible smooth projective curves over an algebraically closed field of arbitrary characteristic. We prove that the vector bundle $((f_*{\mathcal O}_X)/{\mathcal O}_Y)^*$ is virtually globally generated. Moreover, $((f_*{\mathcal O}_X)/{\mathcal O}_Y)^*$ is ample if and only if f is genuinely ramified.
Discounted cost exponential semi-Markov decision processes with unbounded transition rates: a service rate control problem with impatient customers
Authors: Çekyay Bora
Published: April 2024

We focus on exponential semi-Markov decision processes with unbounded transition rates. We first provide several sufficient conditions under which the value iteration procedure converges to the optimal value function and optimal deterministic stationary policies exist. These conditions are also valid for general semi-Markov decision processes possibly with accumulation points. Then, we apply our results to a service rate control problem with impatient customers. The resulting exponential semi-Markov decision process has unbounded transition rates, which makes the well-known uniformization technique inapplicable. We analyze the structure of the optimal policy and the monotonicity of the optimal value function by using the customization technique that was introduced by the author in prior work.
Exploration of COLREG-relevant parameters from historical AIS-data
Authors: Hagen Inger B. , Knutsen Karen S. , Johansen Tor Arne , Brekke Edmund
Published: April 2024

Reliable anti-collision control algorithms conforming with the rules regulating traffic at sea, the International Regulations for Preventing Collisions at Sea (COLREG), are essential for the deployment of autonomous vessels in waters shared with other ships. The development of such methods is an active field of research. However, little attention has been given to how these rules are interpreted by experienced mariners, and how such information can be parametrised for use in automatic control systems and autonomous ships. This paper presents a method for exploiting historical automatic identification system (AIS) data to characterise parameters indicating the prevalent practices at sea in encounters with high collision risk. The method has been tested on data gathered in areas off the Norwegian coast over several years. Statistics on relevant parameters from the resulting dataset and the relation between them is presented. The results indicate that the strongest influence on vessel behaviour is the type of situation, and the amount of land and grounding hazards in the vessel's proximity.
Equational theorem proving for clauses over strings
Authors: Kim Dohan
Published: April 2024

Although reasoning about equations over strings has been extensively studied for several decades, little research has been done for equational reasoning on general clauses over strings. This paper introduces a new superposition calculus with strings and present an equational theorem proving framework for clauses over strings. It provides a saturation procedure for clauses over strings and show that the proposed superposition calculus with contraction rules is refutationally complete. In particular, this paper presents a new decision procedure for solving word problems over strings and provides a new method of solving unification problems over strings w.r.t. a set of conditional equations R over strings if R can be finitely saturated under the proposed inference system with contraction rules.
A New Refinement of Mediterranean Tropical‐Like Cyclones Characteristics
Authors: Gutiérrez‐Fernández Jesús , Miglietta Mario Marcello , González‐Alemán Juan J. , Gaertner Miguel Angel
Published: April 2024

Several warm‐core cyclones in the Mediterranean, which were analyzed in the literature, are studied using ERA5 reanalysis, to identify the environment where they develop and distinguish tropical‐like cyclones from non‐tropical warm‐core cyclones. Initially, the cyclone phase space is analyzed to distinguish the cyclones that have a symmetrical deep warm core. Subsequently, the temporal evolution of several parameters is considered, including the distance between the area of maximum tangential wind speed and the cyclone center. Some differences are observed between the cyclones analyzed: one category of cyclones develops in areas of moderate‐low baroclinicity and intense convective processes, as occurs in tropical cyclones. Another group of cyclones develops in a strongly baroclinic environment with weak convective processes and intense vertical wind shear, as occurs in warm seclusions. Two cyclones, showing similarities with polar lows, are also identified.
On the Stability of Mantle‐Sensitive P‐Wave Interference During a Secondary Microseismic Event
Authors: Tomasetto L. , Boué P. , Stehly L. , Ardhuin F. , Nataf H.‐C.
Published: April 2024

Body wave extraction from oceanic secondary microseismic sources with seismic interferometry provides alternative information to better constrain the Earth's structure. However, sources' spatiotemporal variations raise concerns about travel time measurement robustness. Therefore, we study the cross‐correlations’ stability during a single oceanic event. This study focuses on 3 days of data and three seismic arrays' combinations between 8 and 11 December 2014 during storm Alexandra, a “weather bomb” event in southern Greenland. We use the WAVEWATCH III hindcast to model P‐wave noise sources and assess the impact of short‐term source variations on cross‐correlations. Model‐based cross‐correlations compared to data show coherent delays to reference 3D Earth models (∼0–3 s) confirming the robustness of the source model which could explain minor travel time variations (≤1 s).
Evaluating the Rheological Controls on Topography Development During Craton Stabilization: Objective Approaches to Comparing Geodynamic Models
Authors: Kublik Kristina , Currie Claire A. , Pearson D. Graham
Published: April 2024

Surface topography is an important yet largely neglected aspect of the early evolution of cratons. The lateral accretion of cratonic nuclei inevitably forms orogenic belts that subsequently provide a sediment source for large, resource‐rich intracratonic basins, but to date, geodynamic models have focused exclusively on lithospheric root processes. Here we use two‐dimensional thermal‐mechanical models to study the topography and lithospheric deformation during 50 Myr of compression of a cratonic nucleus, to simulate the lateral accretion phase of craton growth in the Neoarchean. Although the cratonic nucleus thickens slightly during the compression phase, most of the deformation occurs in the regions adjacent to the nucleus that have weaker lithosphere. Here, crustal thickness triples developing high topography in excess of 10 km without active erosion. Models with different initial rheological parameters will have different final topography and lithosphere geometry, but in general it is difficult to shorten and deform the depleted cratonic nucleus, unless there are significantly weak heterogeneities in the mantle lithosphere. We apply two quantitative analysis techniques to objectively evaluate a multitude of model outputs. Cross‐correlation clustering (CCC) measures the degree of similarity between topography profiles and categorizes models based on the general topographic character. Six different topography families are possible in the context of our models and crustal strength is the most important parameter affecting the shape. From principal component analysis (PCA) we identify four dominant lithosphere geometries. When used together, these two methods provide distinct yet complementary information about the surface and subsurface deformation features in our models.
Importance of Water‐Clay Interactions for Fault Slip in Clay‐Rich Rocks
Authors: Rast Markus , Madonna Claudio , Selvadurai Paul A. , Wenning Quinn C. , Ruh Jonas B.
Published: April 2024

Clay‐rich rocks are integral to subduction zone dynamics and of practical importance, for example, as barriers in nuclear waste and CO2 repositories. While the effects of swelling strain on the self‐sealing capabilities of these rocks are relatively well‐established, the implications of polar fluids interacting with charged clay particles on the frictional behavior, and the role of swelling stress in initiating slip in critically stressed faults, remain ambiguous. To address these uncertainties, we conducted triaxial friction experiments using saw‐cut samples, with the upper half composed of Opalinus claystone (OPA) and the lower half of Berea sandstone (BER). The frictional strength of the non‐wetted OPA‐BER interface was estimated based on experiments at confining pressures of 4–25 MPa and constant axial loading rate (0.1 mm/min). Fluid injection friction experiments were performed using decane (non‐polar fluid) or deionized water (polar fluid) at 10 and 25 MPa confining pressures and constant piston displacement control. Macroscopic mechanical data were complemented by distributed strain sensing on the sample surface. Compared to decane, the frictional strength of the OPA‐BER interface tended to decrease when injecting water, which is attributed to phyllosilicate lubrication and the transition of the OPA from a solid rock to an incohesive mud near the saw‐cut surface. When injecting water, slip was initiated during initial hydration of the OPA‐BER interface, although the apparent stress state was below the yield stress. To explain this behavior, we propose that the swelling stress is a crucial factor that should be integrated into the effective stress model.
Biogeochemical Properties and Transports in the North East Atlantic
Authors: Johnson Clare , Fraser Neil , Cunningham Stuart , Burmeister Kristin , Jones Sam , Drysdale Lewis , Abell Richard , Brown Peter , Dumont Estelle , Fox Alan , Holliday N. Penny , Inall Mark , Reed Sarah
Published: April 2024

The eastern subpolar North Atlantic is a source of nutrients to the Northwest European Shelf and Arctic; however, biogeochemical transports in this important region are unknown. We examine variability in nutrients and carbon at the eastern boundary of the subpolar North Atlantic between 2017 and 2020, and calculate their transport by a branch of the North Atlantic Current and the European Slope Current. By combining observations from moorings and ship‐based surveys, we derive novel biogeochemical property transports at high temporal resolution. Data from 63 m provide new evidence of a strong seasonal signal with silicate declining between April and May (−2.3 μmol kg−1) and a concurrent increase in pH (0.04) and oxygen saturation (3.5%). Additionally, pH and oxygen saturation show a secondary peak in October during the autumn bloom. Biogeochemical transports are northwards and highly variable with volume transport dominating the variability over a multi‐annual timescale. However, historical data suggests that nitrate and phosphate transports were 15% and 19% lower respectively in the late 2000s when the subpolar gyre circulation was weaker and lower nutrient source waters were dominant. These changes may have been amplified by concurrent reductions in volume transport. Changes in carbon and nutrient transports in the eastern subpolar North Atlantic may propagate downstream with potential effects on the Northwest European Shelf and Eurasian Arctic.
Enhancing Extreme Precipitation Predictions With Dynamical Downscaling: A Convection‐Permitting Modeling Study in Texas and Oklahoma
Authors: Chang Hsin‐I. , Chikamoto Yoshimitsu , Wang Simon S.‐Y. , Castro Christopher L. , LaPlante Matthew D. , Risanto C. Bayu , Huang Xingying , Bunn Patrick
Published: April 2024

Precipitation in the Southern Plains of the United States is relatively well depicted by the Community Earth System Model (CESM). However, despite its ability to capture seasonal mean precipitation anomalies, CESM consistently underestimates extreme pluvial and drought events, rendering it an insufficient tool for extending simulation lead times for exceptional events, such as the abnormally dry May 2011, which helped drive Texas into its worst period of drought in more than a century, and the abnormally wet May 2015, which led to widespread flooding in that state. Ensemble‐based regional climate experiments are completed for the two extreme years using Weather Research and Forecasting model (WRF) and downscaled from CESM. WRF simulations are at convection‐permitting grid resolution for improved physical representation of simulated precipitation over the Southern Great Plains. By integrating convection‐permitting models (CPMs) into each individual member of a CESM ocean data assimilation ensemble, this study demonstrates that high‐resolution dynamical downscaling can improve model skillfulness at capturing these two events and is thus a potentially useful tool for forecasting extremely high and extremely low precipitation events at subseasonal or even seasonal lead times.
Atmospheric Fronts Shaping the (Sub)Mesoscale SST‐Wind Coupling Over the Southern Ocean: Observational Case
Authors: Shao Mingming , Wu Lichuan
Published: April 2024

Surface wind divergence is largely modulated by the sea surface temperature (SST) gradient through vertical momentum mixing and pressure adjustment. Here, the two mechanisms affecting the coupling strength between SST gradient and surface wind divergence are examined during an atmospheric front passage in the Southern Ocean. This event is also recorded by an uncrewed surface vehicle (USV). The reanalysis product (ERA5) revealed that downward momentum mixing is the dominant mechanism on the daily time scale. The coupling strength during the day when the atmospheric front passed over declined by 75%, compared to the adjacent days. This implies that the atmospheric front can partially attenuate the SST gradient effect on the surface wind divergence. Furthermore, a decade‐long statistic also showed a decreasing trend of SST‐wind coupling when the atmospheric fronts occur more. Additionally, after removing the mesoscale weather variation, the USV observations showed a remarkable SST imprint on the atmospheric boundary layer in the oceanic submesoscale regime, which denotes the scale below the deformation radius (∼16 km). The submesoscale air‐sea interaction processes also displayed decreased air‐sea coupling strength during atmospheric front passage. This is possible as the vertical velocity induced by the atmospheric front can compensate for the daily averaged uprising vertical velocity due to surface wind convergence. This analysis indicates that the atmospheric front can diminish the coupling between the SST gradient and surface wind divergence, which contrasts the existing statistical results showing that atmospheric fronts tend to enhance such coupling.
Observing Gravity Waves Generated by Moving Sources With Ground‐Based Rayleigh Lidars
Authors: Binder Michael , Dörnbrack Andreas
Published: April 2024

Temperature measurements by zenith‐pointing ground‐based Rayleigh lidars are often used to detect middle atmospheric gravity waves. In time‐height diagrams of temperature perturbations, stationary mountain waves are identifiable by horizontal phase lines. Vertically tilted phase lines, on the other hand, indicate that the wave source or the propagation conditions are transient. Idealized numerical simulations illustrate that and how a wave source moving in the direction of the mean wind entails upward‐tilted phase lines. The inclination angle depends on the horizontal wavelength and the wave source’s propagation speed. On this basis, the goal is to identify and characterize non‐orographic gravity waves (NOGWs) from propagating sources, for example, upper‐level jet/front systems, in simulated lidar observations and actual Rayleigh lidar measurements. Compositions of selected atmospheric variables from a meteorological forecast or reanalysis are thoughtfully combined to associate NOGWs with processes in the troposphere and stratosphere. For a virtual observation over the Southern Ocean, upward‐tilted phase lines indeed dominate the time‐height diagram during the passage of an upper‐level trough. The example also emphasizes that temporal filtering of temperature measurements is appropriate for NOGWs, especially in the presence of a strong polar night jet that implies large vertical wavelengths. During two selected observational periods of the COmpact Rayleigh Autonomous Lidar (CORAL) in the lee of the southern Andes, upward‐tilted phase lines are mainly associated with mountain waves and transient background wind conditions. One nighttime measurement by CORAL coincides with the passage of an upper‐level trough, but large‐amplitude mountain waves superpose the small‐amplitude NOGWs in the middle atmosphere.
Contributions From Cloud Morphological Changes to the Interannual Shortwave Cloud Feedback Based on MODIS and ISCCP Satellite Observations
Authors: Tan Ivy , Zelinka Mark D. , Coopman Quentin , Kahn Brian H. , Oreopoulos Lazaros , Tselioudis George , McCoy Daniel T. , Li Ninghui
Published: April 2024

The surface temperature‐mediated change in cloud properties, referred to as the cloud feedback, continues to dominate the uncertainty in climate projections. A larger number of contemporary global climate models (GCMs) project a higher degree of warming than the previous generation of GCMs. This greater projected warming has been attributed to a less negative cloud feedback in the Southern Ocean. Here, we apply a novel “double decomposition method” that employs the “cloud radiative kernel” and “cloud regime” concepts, to two data sets of satellite observations to decompose the interannual cloud feedback into contributions arising from changes within and shifts between cloud morphologies. Our results show that contributions from the latter to the cloud feedback are large for certain regimes. We then focus on interpreting how both changes within and between cloud morphologies impact the shortwave cloud optical depth feedback over the Southern Ocean in light of additional observations. Results from the former cloud morphological changes reveal the importance of the wind response to warming increases low‐ and mid‐level cloud optical thickness in the same region. Results from the latter cloud morphological changes reveal that a general shift from thick storm‐track clouds to thinner oceanic low‐level clouds contributes to a positive feedback over the Southern Ocean that is offset by shifts from thinner broken clouds to thicker mid‐ and low‐level clouds. Our novel analysis can be applied to evaluate GCMs and potentially diagnose shortcomings pertaining to their physical parameterizations of particular cloud morphologies.
Atmospheric Tides in the Middle and Upper Atmosphere of Mars at Northern High Latitudes: A Comparison of MAVEN‐EUVM and MRO‐MCS Observations With Model Results
Authors: Kumar Aishwarya , England Scott L. , Liu Guiping , Thiemann Edward M. B.
Published: April 2024

Much of the variability in the Martian thermosphere can be attributed to vertically propagating atmospheric tides that are known to achieve significant amplitudes in this region. Concurrent observations from different altitudes have been used previously to discern the vertical propagation characteristics of tides but have primarily focused on low latitudes. The spectrum of tides and their vertical evolution are thereby less constrained at high latitudes. Few studies that have focused on high latitudes identified wavenumber‐3 structures which were interpreted to originate mainly from the non‐migrating tides SE1 and DE2. This paper presents the first analysis of MAVEN‐EUVM solar occultation observations to deduce atmospheric tides in the Martian thermosphere. These are compared to tides observed by MRO‐MCS in the middle atmosphere for six cases at high northern latitudes. To identify vertical propagation, wave signatures in the middle and upper atmosphere are compared and are found to be dominated by a mix of zonal wavenumbers‐2 and ‐3 in fixed local time. MCS observations show eastward propagating tides dominate, specifically highlighting SE1 near 76 km. Additionally, these observations indicate the presence of stationary planetary waves and terdiurnal tides. Mars Climate Database also indicates the presence of SE1, DE2, DE1, S0, TW1, and T0 tides. A change in the dominant wavenumber component with local time is seen, which is attributed to the presence of all three diurnal, semidiurnal and terdiurnal components at these latitudes. The significant decrease in the diurnal tide amplitude indicates the effect of zonal mean wind on vertical propagation.
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

Stable 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

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

Cancer, 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

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

Dysbiosis 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

Cisplatin (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

Stratospheric 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

Investigations 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

The 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

Calcium 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

Developing 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

The 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

Rare 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

Reef 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.