bluuebunny/crossref_metadata_2025 huggingface dataset:
Input data requirements for daylight simulations in urban densifications
Authors: Pantazatou Karolina , Kanters Jouri , Olsson Per-Ola , Nyborg Johannes Lande , Harrie Lars
Published: June 2023

One of the biggest challenges in urban densifications is securing adequate daylight access. This study examines the potential of using semantic 3D city models as input to daylight simulations. It is focusing on investigating input data requirements to these simulations from a geodata, 3D city model specification and measuring guideline perspective. To achieve this, geodata simulation input requirements for the most common daylight metrics are documented. Next, 3D city model data from two Swedish municipalities along with 3D data constructed by ourselves in CAD- and GIS-environments are utilized to explore the impact of using 3D city models of different levels of detail (LOD) and positional accuracy in daylight simulations linked to Swedish and European laws and recommendations. Similarly, the measuring guidelines and 3D city model specification requirements related to balconies and other façade accessories are also evaluated along with the utilization of façade reflectance properties and colour. It is found that LOD1 is sufficient for the obstruction angle metric for most roof types but for e.g., gabled roofs LOD2 should be used. A positional accuracy on a decimetre-level is accurate enough for the aforementioned metric. Daylight factor simulations require that balconies and façade accessories protruding more than a couple of decimetres must be represented in the 3D city model along with information on façade material and colour. The outcome of the study is expressed in the form of a list of recommendations for the creation of national profiles of 3D city models supporting daylight simulations.
Effect of Sivelestat in the Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis
Authors: Ding Qiongli , Wang Yi , Yang Chunbo , Tuerxun Dilireba , Yu Xiangyou
Published: June 2023

Background

The efficacy of neutrophil elastase inhibitor sivelestat in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remains controversial. A systematic review and meta-analysis were performed in accordance with the PRISMA guidelines assess the effect of sivelestat on ALI/ARDS patients, different studies were included.

Methods

Electronic databases, National Knowledge Infrastructure (CNKI), Wan fang data, VIP, PubMed, Embase, Springer, Ovid and the Cochrane Library were searched using the following key words: (“Sivelestat” OR “Elaspol”) AND (“ARDS” OR “adult respiratory distress syndrome” OR “acute lung injury”). All databases published from January 2000 to August 2022. The treatment group was treated with sivelestat and the control group was given normal saline. The outcome measurements include the mortality of 28–30 days, mechanical ventilation time, ventilation free days, intensive care unit (ICU) stays, oxygenation index (PaO2/FiO2) on day 3, the incidence of adverse events. The literature search was conducted independently by 2 researchers using standardized methods. We used the Cochrane risk-of-bias tool to assess the quality of the included studies. Mean difference (MD), Standardized mean difference (SMD) and relative risk (RR) were calculated using random effects model or fixed effects model. All statistical analyses were performed using RevMan software 5.4.

Results

A total of 2050 patients were enrolled in 15 studies, including 1069 patients in treatment group and 981 patients in the control group. The results of the meta-analysis showed that: compared with the control group, sivelestat can reduce the mortality of 28–30 days (RR = 0.81, 95% CI = 0.66–0.98, p = 0.03) and the incidence of adverse events (RR = 0.91, 95% CI = 0.85–0.98, p = 0.01), shortened mechanical ventilation time (SMD = − 0.32, 95% CI = − 0.60 to − 0.04, p = 0.02) and ICU stays (SMD = − 0.72, 95% CI = − 0.92 to − 0.52, p < 0.00001), increased the ventilation free days (MD = 3.57, 95% CI = 3.42–3.73, p < 0.00001) and improve oxygenation index (PaO2/FiO2) on day 3 (SMD = 0.88, 95% CI = 0.39–1.36, p = 0.0004).

Conclusions

Sivelestat can not only reduce the mortality of ALI/ARDS patients within 28–30 days and the incidence of adverse events, shorten the mechanical ventilation time and ICU stays, increase ventilation free days, but also improve the oxygenation index of patients on days 3, which has a good effect on the treatment of ALI/ARDS. These findings need to be verified in large-scale trials.
A serious video game—EmergenCSim™—for novice anesthesia trainees to learn how to perform general anesthesia for emergency cesarean delivery: a randomized controlled trial
Authors: Lee Allison J. , Goodman Stephanie , Corradini Beatriz , Cohn Sophie , Chatterji Madhabi , Landau Ruth
Published: June 2023

Purpose

We developed EmergenCSim™, a serious game (SG) with an embedded assessment, to teach and assess performing general anesthesia for cesarean delivery. We hypothesized that first-year anesthesiology trainees (CA-1) playing EmergenCSim™ would yield superior knowledge scores versus controls, and EmergenCSim™ and high-fidelity simulation (HFS) assessments would correlate.

Methods

This was a single-blinded, longitudinal randomized experiment. Following a lecture (week 3), trainees took a multiple-choice question (MCQ) test (week 4) and were randomized to play EmergenCSim™ (N = 26) or a non-content specific SG (N = 23). Participants repeated the MCQ test (week 8). Between month 3 and 12, all repeated the MCQ test, played EmergenCSim™ and participated in HFS of an identical scenario. HFS performance was rated using a behavior checklist.

Results

There was no significant change in mean MCQ scores over time between groups F (2, 94) = 0.870, p = 0.42, and no main effect on MCQ scores, F (1, 47) = 1.110, p = 0.20. There was significant three-way interaction between time, gender and group, F (2, 90) = 3.042, p = 0.053, and significant two-way interaction between gender and time on MCQ scores, F (2, 94) = 107.77, p = 0.036; outcomes improved over time among males. There was no group difference in HFS checklist and SG scores. Both instruments demonstrated good internal consistency reliability but non-significant score correlation.

Conclusions

Playing EmergenCSim™ once did not improve MCQ scores; nonetheless scores slightly improved among males over time, suggesting gender may impact learning outcomes with SGs.
White kidney bean extract as a nutraceutical: effects on gut microbiota, alpha-amylase inhibition, and user experiences
Authors: Houghton David , Shannon Oliver M. , Chater Peter I. , Wilcox Matthew D. , Pearson Jeffrey P. , Stanforth Kyle , Jordan Cara , Avery Leah , Blain Alasdair P. , Joel Abraham , Jeffers Ruth , Nolan Ruth , Nelson Andrew , Stewart Christopher J. , Malcomson Fiona C.
Published: June 2023

White kidney bean extract (WKBE) is a nutraceutical often advocated as an anti-obesity agent. The main proposed mechanism for these effects is alpha-amylase inhibition, thereby slowing carbohydrate digestion and absorption. Thus, it is possible that WKBE could impact the gut microbiota and modulate gut health. We investigated the effects of supplementing 20 healthy adults with WKBE for 1 week in a randomised, placebo-controlled crossover trial on the composition of the gut microbiota, gastrointestinal (GI) inflammation (faecal calprotectin), GI symptoms, and stool habits. We conducted in vitro experiments and used a gut model system to explore potential inhibition of alpha-amylase. We gained qualitative insight into participant experiences of using WKBE via focus groups. WKBE supplementation decreased the relative abundance of Bacteroidetes and increased that of Firmicutes, however, there were no significant differences in post-intervention gut microbiota measurements between the WKBE and control. There were no significant effects on GI inflammation or symptoms related to constipation, or stool consistency or frequency. Our in vitro and gut model system analyses showed no effects of WKBE on alpha-amylase activity. Our findings suggest that WKBE may modulate the gut microbiota in healthy adults, however, the underlying mechanism is unlikely due to active site inhibition of alpha-amylase.
Solenoidal force balances in numerical dynamos
Authors: Teed Robert J. , Dormy Emmanuel
Published: June 2023

Numerical simulations of the geodynamo (and other planetary dynamos) have made significant progress in recent years. As computing power has advanced, some new models claim to be ever more appropriate for understanding Earth's core dynamics. One measure of the success of such models is the ability to replicate the expected balance between forces operating within the core; Coriolis and Lorentz forces are predicted to be most important. The picture is complicated for an incompressible flow by the existence of the pressure gradient force which renders the gradient parts of all other forces dynamically unimportant. This can confuse the situation, especially when the scale dependence of forces is considered. In this work we investigate force balances through the alternative approach of eliminating gradient parts of each force to form ‘solenoidal force balances’. We perform a length-scale-dependent analysis for several spherical simulations and find that removal of gradient parts offers an alternative picture of the force balance compared with looking at traditional forces alone. Solenoidal force balances provide some agreement with the results of previous studies but also significant differences. They offer a cleaner overall picture of the dynamics and introduce differences at smaller scales. This has implications for geodynamo models purporting to have reached Earth-like regimes: in order to achieve a meaningful comparison of forces, only the solenoidal part of forces should be considered.
Strong impact of sub-shelf melt parameterisation on ice-sheet retreat in idealised and realistic Antarctic topography
Authors: Berends Constantijn J. , Stap Lennert B. , van de Wal Roderik S. W.
Published: June 2023

Future projections of sea-level rise under strong warming scenarios are dominated by mass loss in the marine-grounded sectors of West Antarctica, where thinning shelves as a result of warming oceans can lead to reduced buttressing. This consequently leads to accelerated flow from the upstream grounded ice. However, the relation between warming oceans and increased melt rates under the shelves is very uncertain, especially when interactions with the changing shelf geometry are considered. Here, we compare six widely used, highly parameterised formulations relating sub-shelf melt to thermal forcing. We implemented them in an ice-sheet model, and applied the resulting set-up to an idealised-geometry setting, as well as to the Antarctic ice sheet. In our simulations, the differences in modelled ice-sheet evolution resulting from the choice of parameterisation, as well as the choice of numerical scheme used to apply sub-shelf melt near the grounding line, generally are larger than differences from ice-dynamical processes such as basal sliding, as well as uncertainties from the forcing scenario of the model providing the ocean forcing. This holds for the idealised-geometry experiments as well as for the experiments using a realistic Antarctic topography.
Yield and water productivity of rice grown under different irrigation methods
Authors: Çebi U. , Özer S. , Öztürk O. , Aydın B. , Çakır R.
Published: June 2023

The aim of the study was to investigate the suitability of subsurface and surface drip irrigation methods in rice farming. The field studies were carried out in split plots in randomized blocks trial design, with three repetitions during 2019 and 2020 in Thrace Region/Türkiye. Irrigation methods, surface drip (DI), subsurface drip (SDI) and conventional flooding (CF) were the main treatments; however, water amounts (I1: Class A-pan evaporation rate × 1.00, I2: Class A-pan evaporation rate × 1.25, I3: Class A-pan evaporation rate × 1.50) were designed as sub-treatments of the study. The results of the statistical analyses indicated that, the rice grain yield was significantly (P < 0.01) affected by the amount of the irrigation water. According to the results; while two different drip irrigation methods did not make a difference to yield and yield components, the difference between drip irrigation and CF was significant (P < 0.01). While the grain yields reached 10.3 and 8.70 t/ha under conditions of CF control during 2019 and 2020, the highest yield values obtained from plots with drip irrigation system and the highest Class A-pan evaporation rate x pan coefficient of 1.50 were 8.10 and 6.90 t/ha during the same two study years, respectively. However, much more effective use of water was observed under conditions of drip system application providing approximately 60–70% water saving v. 20–25% yield loss. In addition, economic analysis results indicated a higher relative profit rate of 1.66 in the case of drip irrigation than 1.41 under CF application.
Interpolity Law and Jurisdictional Politics
Authors: Benton Lauren , Clulow Adam
Published: June 2023

Challenging the common assumption that legal misunderstanding was pervasive, this article analyzes jurisdictional politics as an element of “interpolity law”—a broad framework for legal interactions across polities and regions in the early modern world. It draws on recent research on jurisdictional politics to show how such an approach allows historians to avoid some of the familiar pitfalls associated with studies of legal pluralism. This approach provides clear methodological advantages over the study of global legal history as a function of multi-normativity. Political communities across the globe centered on internal and external conflicts on the nature and reach of legal authority. By focusing on jurisdiction as a touchstone of legal action and tracing how legal authority was produced through conflict, our approach treats legal pluralism as a valuable descriptive term rather than an analytical framework. The study of jurisdictional politics portrays state authority as potentially one among many forms of legal authority, and it brings into sharp focus continuities within and across pluri-political regions. By tracking broad institutional shifts that occurred when empires and states moved to assert power over multi-jurisdictional orders, the perspective informs new narratives about trajectories of regional and global legal order.
Concurrent Awareness Desire Satisfactionism
Authors: Forrester Paul
Published: May 2023

Desire satisfactionists are united by their belief that what makes someone well-off is the satisfaction of their desires. But this commitment obscures a number of underlying differences, since there are several theoretical choice points on the way to making this commitment precise. This article is about two of the most important choice points. The first concerns an epistemic requirement on well-being. Suppose that one's desire that P is satisfied. Must one also know (or believe, or justifiably believe) that one's desire that P is satisfied in order to benefit from P? If so, there is an epistemic requirement on well-being. The second concerns the time at which one benefits. Well-being is a temporal phenomenon: given that one benefits from the satisfaction of one's desire that P, when does one benefit? Perhaps one benefits at the times at which one desires P, or the times at which P obtains, or both. I defend a view I call “concurrent awareness desire satisfactionism”: one benefits only at times at which both one desires P and P obtains (concurrence) and one benefits only if one is aware that one's desire is satisfied (awareness). I motivate this view by showing how it gives us solutions to many of the canonical problems facing desire satisfactionism. Then I put the two parts of the view together and explore some of its further implications. Ultimately, I conclude that well-being is an organic unity composed of a desiderative component, an epistemic component, and a worldly component, none of which are valuable on their own, but which are valuable when they are related in the right way.
The endurance of the G77 in international relations: South–South ideology and voting at the United Nations 1970–2015
Authors: Lees Nicholas
Published: June 2023

The voting record of states of the global South at the United Nations General Assembly indicates they are dissatisfied with the US-led liberal international order. Against existing interpretations, this article challenges the notion that states belonging to the Group of 77 (G77) express discontent because they are illiberal and undemocratic. Instead, the article argues that the G77 is composed of a diverse group of states influenced by a common South–South ideology. This foreign policy ideology has a distinct intellectual history and conceptual morphology, grounded in common experience of colonial domination and international peripheralisation. These arguments are tested using a series of multiple regression models, controlling for illiberal characteristics of states and examining the reciprocal influence between G77 membership and voting stance at the United Nations. Disaggregation of General Assembly resolutions and analysis of the text of General Debate speeches corroborates the argument that a coherent set of shared ideas shape how global issues are conceptualised and framed by members of the G77. The results are consistent with the argument that states of the G77 have socialised one another into a shared South–South ideology and that domestic illiberalism is insufficient to explain why they express dissatisfaction with the US-led international order. Ideologies of foreign policy originating in the global South, therefore, should not be overlooked as an influence on world politics.
The paradox of global constitutionalism: Between sectoral integration and legitimacy
Authors: Çapar Gürkan
Published: June 2023

The liberal international legal order faces a legitimacy crisis today that becomes visible with the recent anti-internationalist turn, the rise of populism and the recent Russian invasion of Ukraine. Either its authority or legitimacy has been tested many times over the last three decades. The article argues that this anti-internationalist trend may be read as a reaction against the neoliberal form taken by international law, not least over the last three decades. In uncovering the intricacies of international law’s legitimacy crisis, the article uncovers the paradox of global constitutionalism: that its need to adopt a sectoral form of integration may cause a legitimacy gap/deficit because international authorities, resting their legitimacy primarily on instrumental grounds, may face problems in compensating for the legitimacy deficit caused by the erosion of domestic sovereignty and extending their legitimacy to non-instrumental grounds. This paradox has one necessary structural and two contingent content-related implications for domestic democracies: (1) it necessarily narrows down the regulatory space of nation-states; and this may in turn (2) impair democratic stability and solidarity, and (3) provide a fertile ground for populism. Drawing on Raz’s service conception, the article focuses on the interaction between international and domestic authorities and highlights the problematic aspects of the neoliberal constitutionalization of international law.
Lower Self‐Control Is Associated With More Standard, Reputation Management, and Maladaptive Facebook Use
Authors: Maranges Heather M. , Haddad Nour , Psihogios Sarah , Timbs Casey L. , Gobes Carina M. , Preston Thomas J.
Published: June 2023

Abstract: Social media can help fulfill the need for belonging. Past work suggests that frequent or extreme Facebook use can engender costs to the self and relationships, such that self-control may be associated with Facebook use. Indeed, trait self-control was negatively associated with standard, reputation management, and maladaptive Facebook use (Study 1, N = 309), above extraversion, self-esteem, and perceptions of own attractiveness (Study 2, N = 527). Further, trait self-control was negatively associated with actual reputation management behavior online: people with lower (vs. higher) self-control were more likely to post written or image content of themselves vs. a book in a Facebook group (Study 2). Together, results suggest that higher self-control is associated with less Facebook use across the spectrum – standard use (e.g., posting, commenting, changing pictures), reputation management use (i.e., use to manage others’ perceptions of oneself), and maladaptive use (i.e., feeling negative affect as a result of comparisons to others online or not receiving positive feedback to one’s use).
Two of a Kind or Distant Relatives?
Authors: Ruch Willibald , Vylobkova Valentina , Heintz Sonja
Published: June 2023

Abstract: Allport’s distinction of personality devaluated (personality) and personality evaluated (character) raised the question of whether the character is redundant with personality, which still remains open today. The present study hence compares the Five-Factor Model of personality and the VIA-classification (Values in Action) of character strengths across two methods (self- and peer-reports) and two levels of abstraction (domains/factors and scales/facets). A sample of 152 participants and 152 peer-raters completed the NEO-Personality Inventory-Revised and the VIA Inventory of Strengths (VIA-IS). Personality and character assessed with these inventories were found to strongly overlap, yet the different operationalizations were rarely redundant (except for three personality facets). Multitrait-multimethod analyses mostly supported the convergent and discriminant validity of personality and character. Interpersonal strengths (e.g., teamwork) and abstract character factors lacked discriminant validity to personality facets. The present investigation contributes to a better understanding of the interplay between personality and character and provides an impetus for future research on the “virtue gap” between devaluated and evaluated personality traits.
A Decision Support Framework for Pollution Source Detection via Coupled Forward‐Inverse Optimization and Multi‐Information Fusion
Authors: Zhu Zhe , Li Yu , Sun Yan , Liu Zhihong , Zhang Chi
Published: May 2023

Due to the uncertainty in sensor data, low model accuracy, and high parameter heterogeneity in water quality modeling, pollution source detection (PSD) typically results in a problem of multiple possible solutions, which is the so‐called non‐uniqueness effect. Identifying unique solution to PSD problems is fundamentally essential for water quality control in surface water and groundwater systems. This study proposes a decision support framework to reduce the impact of uncertainty and identify a unique solution using a consensus‐based multiple information fusion method. Multiple water quality information sources are fused in the framework via spatial clustering and temporal Bayesian updating. Considering the real‐world complexity, the recession‐curve displacement method is used to handle multi‐sources scenario to enhance the accuracy of the framework. Meanwhile, a coupled forward‐inverse model instead of random sampling is used to improve the solving efficiency of PSD. The framework is validated by a real water pollution event and a number of semi‐hypothetical case studies. The results show that the prediction accuracy of the single‐source and double‐source pollution problems are 88.40% and 82.69%, with an average relative error of 9.75% and 11.42%, respectively. In addition, the uncertainty contribution quantified by a variance decomposition approach suggests that the interaction between parameter and measurement uncertainties has the greatest impact on the PSD results. The results reveal the advantages of the proposed decision framework for government organizations and communities involved in water environment management.
Solar Geoengineering in the Polar Regions: A Review
Authors: Duffey Alistair , Irvine Peter , Tsamados Michel , Stroeve Julienne
Published: May 2023

Solar geoengineering refers to proposals, including stratospheric aerosol injection (SAI), to slow or reverse climate change by reflecting away incoming sunlight. The rapid changes ongoing in the Arctic and Antarctic, and the risk of exceeding tipping points in the cryosphere within decades, make limiting such changes a plausible objective of solar geoengineering. Here, we review the impacts of SAI on polar climate and cryosphere, including the dependence of these impacts on the latitude(s) of injection, and make recommendations for future research directions. SAI would cool the polar regions and reduce many changes in polar climate under future warming scenarios. Some under‐cooling of the polar regions relative to the global mean is expected under SAI without high latitude injection, due to latitudinal variation in insolation and CO2 forcing, the forcing dependence of the polar lapse rate feedback, and altered atmospheric dynamics. There are also potential limitations in the effectiveness of SAI to arrest changes in winter‐time polar climate and to prevent sea‐level rise from the Antarctic ice sheet. Finally, we also review the prospects for three other solar geoengineering proposals targeting the poles: marine cloud brightening, cirrus cloud thinning, and sea‐ice albedo modification. Sea‐ice albedo modification appears unlikely to be viable on pan‐Arctic or Antarctic scales. Whether marine cloud brightening or cirrus cloud thinning would be effective in the polar regions remains uncertain. Solar geoengineering is an increasingly prominent proposal and a robust understanding of its consequences in the polar regions is needed to inform climate policy in the coming decades.
Sediment Entrainment and Slump Blocks Limit Permafrost Riverbank Erosion
Authors: Douglas Madison M. , Dunne Kieran B. J. , Lamb Michael P.
Published: May 2023

Climatic warming and permafrost thaw are predicted to increase Arctic riverbank erosion, threatening communities and accelerating sediment, carbon and nutrient cycling between rivers and floodplains. Existing theory assumes that pore‐ice thaw sets riverbank erosion rates, but overpredicts observed erosion rates by orders of magnitude. Here, we developed a simple model that predicts more modest rates due to a sediment‐entrainment limitation and riverbank armoring by slump blocks. Results show that during times of thaw‐limited erosion, the river rapidly erodes permafrost and undercuts its banks, consistent with previous work. However, overhanging banks generate slump blocks that must thaw and erode by sediment entrainment. Sediment entrainment can limit bank and slump block erosion rates, producing seasonally averaged rates more consistent with observations. Importantly, entrainment‐limited riverbank erosion does not depend on water temperature, indicating that decadal erosion rates may be less sensitive to warming than predicted previously.
Strain and Stress Accumulation in Viscoelastic Splay Fault and Subducting Oceanic Crust
Authors: Muramoto Tomoya , Ito Yoshihiro , Miyakawa Ayumu , Furuichi Noriyuki
Published: May 2023

This study constructs a model to represent the strain–stress field surrounding a splay fault and demonstrates the accumulation processes of both strain and stress around the splay fault. We consider the case of multiple fault dislocations, construct the model as a function of the effective viscosity in the media, and investigate the influence of the effective viscosity on the strain and stress accumulation patterns. The results show that the strain and stress tend to accumulate in the splay fault and the subducting oceanic crust, and the rate of accumulation varies with the effective viscosity. The accumulation and relaxation of strain and stress are simultaneous, and the slower the effective viscosity, the slower the accumulation rate. We discuss the relationship between the splay faults, fluid, and intraslab earthquakes. Finally, the possibility that effective viscosity may contribute to the mode of occurrence of intraslab earthquakes at the Hikurangi subduction margin is discussed.
Warmth Favored Dust Activities on the Northeastern Qinghai‐Tibet Plateau
Authors: Feng Yuye , Long Hao , Yang Fei , Yang Fan , Cheng Hongyi , Zhang Ganlin
Published: May 2023

The limited availability of long‐term historical dust records has impeded comprehension of the mid‐latitude atmospheric circulation and underlying mechanisms of dust activities in arid Central Asia. We present a well‐dated 2,800‐year peat record from the northeastern Qinghai‐Tibet Plateau and identified the aeolian origin of archived particles by comparing grain‐size distribution and strontium isotope with those of modern dusts. We show that the reconstructed dust input was enhanced during warming periods, which also coincides with the variation of Westerlies, total solar irradiance, and North Atlantic Oscillation. We propose that warming climate may have contributed to a significant impact on the moisture balance and wind strength, and predict that this region may experience more frequent dust activity in the future. These findings contrast with meteorological observations of decreasing dust activities during the last 40 years despite a warming trend, suggesting different effects of natural processes versus anthropogenic impact on global warming.
Observations of the Roots of Plasma Bubbles: Are They Sometimes Foamy?
Authors: Bennett Charles L.
Published: May 2023

Dramatic irregularities in the plasma density of the ionosphere, first discovered by their effects on radio wave propagation in 1938, despite decades of investigation, still remain puzzling. Their deleterious effects on radio wave communication, satellite command and control, and GPS navigation strongly motivate better understanding of their nature. Many aspects of such irregularities are now understood, but the mechanism(s) of their formation and their detailed nature remain a topic of great interest. In this work, detailed time resolved measurements of lightning generated waves sometimes show dispersionless, strongly attenuated propagation with substantial propagation delays. These characteristics of the electromagnetic wave propagation in the hypothetical two‐phase bubble/non‐bubble lower ionosphere parallel the characteristics of acoustic wave propagation through two‐phase liquid/vapor foams. This motivates the suggestion that the bottomside layer of the ionosphere may sometimes be foamy.
Physiochemical Controls on the Horizontal Exchange of Blue Carbon Across the Salt Marsh‐Tidal Channel Interface
Authors: Fettrow Sean , Jeppi Virginia , Wozniak Andrew , Vargas Rodrigo , Michael Holly , Seyfferth Angelia L.
Published: May 2023

Tidal channels are biogeochemical hotspots that horizontally exchange carbon (C) with marsh platforms, but the physiochemical drivers controlling these dynamics are poorly understood. We hypothesized that C‐bearing iron (Fe) oxides precipitate and immobilize dissolved organic carbon (DOC) during ebb tide as the soils oxygenate, and dissolve into the porewater during flood tide, promoting transport to the channel. The hydraulic gradient physically controls how these solutes are horizontally exchanged across the marsh platform‐tidal channel interface; we hypothesized that this gradient alters the concentration and source of C being exchanged. We further hypothesized that trace soil gases (i.e., CO2, CH4, dimethyl sulfide) are pushed out of the channel bank as the groundwater rises. To test these hypotheses, we measured porewater, surface water, and soil trace gases over two 24‐hr monitoring campaigns (i.e., summer and spring) in a mesohaline tidal marsh. We found that Fe2+ and DOC were positively related during flood tide but not during ebb tide in spring when soils were more oxidized. This finding shows evidence for the formation and dissolution of C‐bearing Fe oxides across a tidal cycle. In addition, the tidal channel contained significantly (p < 0.05) more terrestrial‐like DOC when the hydraulic gradient was driving flow toward the channel. In comparison, the channel water was saltier and contained significantly (p < 0.05) more marine‐like DOC when the hydraulic gradient reversed direction. Trace gas fluxes increased with rising groundwater levels, particularly dimethyl sulfide. These findings suggest multiple physiochemical mechanisms controlling the horizontal exchange of C at the marsh platform‐tidal channel interface.
The tobacco-specific carcinogen NNK induces pulmonary tumorigenesis via nAChR/Src/STAT3-mediated activation of the renin-angiotensin system and IGF-1R signaling
Authors: Boo Hye-Jin , Min Hye-Young , Hwang Su Jung , Lee Hyo-Jong , Lee Jae-Won , Oh Sei-Ryang , Park Choon-Sik , Park Jong-Sook , Lee You Mie , Lee Ho-Young
Published: June 2023

The renin-angiotensin (RA) system has been implicated in lung tumorigenesis without detailed mechanistic elucidation. Here, we demonstrate that exposure to the representative tobacco-specific carcinogen nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) promotes lung tumorigenesis through deregulation of the pulmonary RA system. Mechanistically, NNK binding to the nicotinic acetylcholine receptor (nAChR) induces Src-mediated signal transducer and activator of transcription 3 (STAT3) activation, resulting in transcriptional upregulation of angiotensinogen (AGT) and subsequent induction of the angiotensin II (AngII) receptor type 1 (AGTR1) signaling pathway. In parallel, NNK concurrently increases insulin-like growth factor 2 (IGF2) production and activation of IGF-1R/insulin receptor (IR) signaling via a two-step pathway involving transcriptional upregulation of IGF2 through STAT3 activation and enhanced secretion from intracellular storage through AngII/AGTR1/PLC-intervened calcium release. NNK-mediated crosstalk between IGF-1R/IR and AGTR1 signaling promoted tumorigenic activity in lung epithelial and stromal cells. Lung tumorigenesis caused by NNK exposure or alveolar type 2 cell-specific Src activation was suppressed by heterozygous Agt knockout or clinically available inhibitors of the nAChR/Src or AngII/AGTR1 pathways. These results demonstrate that NNK-induced stimulation of the lung RA system leads to IGF2-mediated IGF-1R/IR signaling activation in lung epithelial and stromal cells, resulting in lung tumorigenesis in smokers.
The YTHDC1/GLUT3/RNF183 axis forms a positive feedback loop that modulates glucose metabolism and bladder cancer progression
Authors: Yan Bin , Li Xurui , Peng Mou , Zuo Yali , Wang Yinhuai , Liu Pian , Ren Weigang , Jin Xin
Published: June 2023

Aberrant glucose metabolism is a characteristic of bladder cancer. Hyperglycemia contributes to the development and progression of bladder cancer. However, the underlying mechanism by which hyperglycemia promotes the aggressiveness of cancers, especially bladder cancer, is still incompletely understood. N6-methyladenosine (m6A) modification is a kind of methylation modification occurring at the N6 position of adenosine that is important for the pathogenesis of urological tumors. Recently, it was found that the m6A reader YTHDC1 is regulated by high-glucose conditions. In our study, we revealed that YTHDC1 is not only regulated by high-glucose conditions but is also downregulated in bladder cancer tissue and associated with the prognosis of cancer. We also showed that YTHDC1 suppresses the malignant progression of and the glycolytic process in bladder cancer cells in an m6A-dependent manner and determined that this effect is partially mediated by GLUT3. Moreover, GLUT3 was found to destabilize YTHDC1 by upregulating RNF183 expression. In summary, we identified a novel YTHDC1/GLUT3/RNF183 feedback loop that regulates disease progression and glucose metabolism in bladder cancer. Collectively, this study provides new insight regarding the pathogenesis of bladder cancer under hyperglycemic conditions and might reveal ideal candidates for the development of drugs for bladder cancer.
Peptides as multifunctional players in cancer therapy
Authors: Vadevoo Sri Murugan Poongkavithai , Gurung Smriti , Lee Hyun-Su , Gunassekaran Gowri Rangaswamy , Lee Seok-Min , Yoon Jae-Won , Lee Yun-Ki , Lee Byungheon
Published: June 2023

Peptides exhibit lower affinity and a shorter half-life in the body than antibodies. Conversely, peptides demonstrate higher efficiency in tissue penetration and cell internalization than antibodies. Regardless of the pros and cons of peptides, they have been used as tumor-homing ligands for delivering carriers (such as nanoparticles, extracellular vesicles, and cells) and cargoes (such as cytotoxic peptides and radioisotopes) to tumors. Additionally, tumor-homing peptides have been conjugated with cargoes such as small-molecule or chemotherapeutic drugs via linkers to synthesize peptide–drug conjugates. In addition, peptides selectively bind to cell surface receptors and proteins, such as immune checkpoints, receptor kinases, and hormone receptors, subsequently blocking their biological activity or serving as hormone analogs. Furthermore, peptides internalized into cells bind to intracellular proteins and interfere with protein–protein interactions. Thus, peptides demonstrate great application potential as multifunctional players in cancer therapy.
Early life stress in male mice blunts responsiveness in a translationally-relevant reward task
Authors: Hisey Erin E. , Fritsch Emma L. , Newman Emily L. , Ressler Kerry J. , Kangas Brian D. , Carlezon William A.
Published: May 2023

Early-life stress (ELS) leaves signatures upon the brain that persist throughout the lifespan and increase the risk of psychiatric illnesses including mood and anxiety disorders. In humans, myriad forms of ELS—including childhood abuse, bullying, poverty, and trauma—are increasingly prevalent. Understanding the signs of ELS, including those associated with psychiatric illness, will enable improved treatment and prevention. Here, we developed a novel procedure to model human ELS in mice and identify translationally-relevant biomarkers of mood and anxiety disorders. We exposed male mice (C57BL/6 J) to an early-life (juvenile) chronic social defeat stress (jCSDS) and examined social interaction and responsivity to reward during adulthood. As expected, jCSDS-exposed mice showed a socially avoidant phenotype in open-field social interaction tests. However, sucrose preference tests failed to demonstrate ELS-induced reductions in choice for the sweetened solution, suggesting no effect on reward function. To explore whether other tasks might be more sensitive to changes in motivation, we tested the mice in the Probabilistic Reward Task (PRT), a procedure often used in humans to study reward learning deficits associated with depressive illness. In a touchscreen PRT variant that was reverse-translated to maximize alignment with the version used in human subjects, mice exposed to jCSDS displayed significant reductions in the tendency to develop response biases for the more richly-rewarded stimulus, a hallmark sign of anhedonia when observed in humans. Our findings suggest that translationally-relevant procedures that utilize the same endpoints across species may enable the development of improved model systems that more accurately predict outcomes in humans.
Higher immune-related gene expression in major depression is independent of CRP levels: results from the BIODEP study
Authors: Sforzini Luca , Cattaneo Annamaria , Ferrari Clarissa , Turner Lorinda , Mariani Nicole , Enache Daniela , Hastings Caitlin , Lombardo Giulia , Nettis Maria A. , Nikkheslat Naghmeh , Worrell Courtney , Zajkowska Zuzanna , Kose Melisa , Cattane Nadia , Lopizzo Nicola , Mazzelli Monica , Pointon Linda , Cowen Philip J. , Cavanagh Jonathan , Harrison Neil A. , Jones Declan , Drevets Wayne C. , Mondelli Valeria , Bullmore Edward T. ,   Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium, Mondelli Valeria , Pariante Carmine M. , Pariante Carmine M.
Published: June 2023

Compelling evidence demonstrates that some individuals suffering from major depressive disorder (MDD) exhibit increased levels of inflammation. Most studies focus on inflammation-related proteins, such as serum or plasma C-reactive protein (CRP). However, the immune-related modifications associated with MDD may be not entirely captured by CRP alone. Analysing mRNA gene expression levels, we aimed to identify broader molecular immune-related phenotypes of MDD. We examined 168 individuals from the non-interventional, case–control, BIODEP study, 128 with a diagnosis of MDD and 40 healthy controls. Individuals with MDD were further divided according to serum high-sensitivity (hs)CRP levels (n = 59 with CRP <1, n = 33 with CRP 1–3 and n = 36 with CRP >3 mg/L). We isolated RNA from whole blood and performed gene expression analyses using RT-qPCR. We measured the expression of 16 immune-related candidate genes: A2M, AQP4, CCL2, CXCL12, CRP, FKBP5, IL-1-beta, IL-6, ISG15, MIF, GR, P2RX7, SGK1, STAT1, TNF-alpha and USP18. Nine of the 16 candidate genes were differentially expressed in MDD cases vs. controls, with no differences between CRP-based groups. Only CRP mRNA was clearly associated with serum CRP. In contrast, plasma (proteins) IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-16, IL-17A, IFN-gamma and TNF-alpha, and neutrophils counts, were all differentially regulated between CRP-based groups (higher in CRP >3 vs. CRP <1 and/or controls), reflecting the gradient of CRP values. Secondary analyses on MDD individuals and controls with CRP values <1 mg/L (usually interpreted as 'no inflammation') confirmed MDD cases still had significantly different mRNA expression of immune-related genes compared with controls. These findings corroborate an immune-related molecular activation in MDD, which appears to be independent of serum CRP levels. Additional biological mechanisms may then be required to translate this mRNA signature into inflammation at protein and cellular levels. Understanding these mechanisms will help to uncover the true immune abnormalities in depression, opening new paths for diagnosis and treatment.
The blood proteome of imminent lung cancer diagnosis
Authors:   The Lung Cancer Cohort Consortium (LC3), Albanes Demetrius , Alcala Karine , Alcala Nicolas , Amos Christopher I. , Arslan Alan A. , Bassett Julie K. , Brennan Paul , Cai Qiuyin , Chen Chu , Feng Xiaoshuang , Freedman Neal D. , Guida Florence , Hung Rayjean J. , Hveem Kristian , Johansson Mikael , Johansson Mattias , Koh Woon-Puay , Langhammer Arnulf , Milne Roger L. , Muller David , Onwuka Justina , Sørgjerd Elin Pettersen , Robbins Hilary A. , Sesso Howard D. , Severi Gianluca , Shu Xiao-Ou , Sieri Sabina , Smith-Byrne Karl , Stevens Victoria , Tinker Lesley , Tjønneland Anne , Visvanathan Kala , Wang Ying , Wang Renwei , Weinstein Stephanie , Yuan Jian-Min , Zahed Hana , Zhang Xuehong , Zheng Wei
Published: June 2023

Identification of risk biomarkers may enhance early detection of smoking-related lung cancer. We measured between 392 and 1,162 proteins in blood samples drawn at most three years before diagnosis in 731 smoking-matched case-control sets nested within six prospective cohorts from the US, Europe, Singapore, and Australia. We identify 36 proteins with independently reproducible associations with risk of imminent lung cancer diagnosis (all p < 4 × 10−5). These include a few markers (e.g. CA-125/MUC-16 and CEACAM5/CEA) that have previously been reported in studies using pre-diagnostic blood samples for lung cancer. The 36 proteins include several growth factors (e.g. HGF, IGFBP-1, IGFP-2), tumor necrosis factor-receptors (e.g. TNFRSF6B, TNFRSF13B), and chemokines and cytokines (e.g. CXL17, GDF-15, SCF). The odds ratio per standard deviation range from 1.31 for IGFBP-1 (95% CI: 1.17–1.47) to 2.43 for CEACAM5 (95% CI: 2.04–2.89). We map the 36 proteins to the hallmarks of cancer and find that activation of invasion and metastasis, proliferative signaling, tumor-promoting inflammation, and angiogenesis are most frequently implicated.
Ecology of Endozoicomonadaceae in three coral genera across the Pacific Ocean
Authors: Hochart Corentin , Paoli Lucas , Ruscheweyh Hans-Joachim , Salazar Guillem , Boissin Emilie , Romac Sarah , Poulain Julie , Bourdin Guillaume , Iwankow Guillaume , Moulin Clémentine , Ziegler Maren , Porro Barbara , Armstrong Eric J. , Hume Benjamin C. C. , Aury Jean-Marc , Pogoreutz Claudia , Paz-García David A. , Nugues Maggy M. , Agostini Sylvain , Banaigs Bernard , Boss Emmanuel , Bowler Chris , de Vargas Colomban , Douville Eric , Flores Michel , Forcioli Didier , Furla Paola , Gilson Eric , Lombard Fabien , Pesant Stéphane , Reynaud Stéphanie , Thomas Olivier P. , Troublé Romain , Wincker Patrick , Zoccola Didier , Allemand Denis , Planes Serge , Thurber Rebecca Vega , Voolstra Christian R. , Sunagawa Shinichi , Galand Pierre E.
Published: June 2023

Health and resilience of the coral holobiont depend on diverse bacterial communities often dominated by key marine symbionts of theEndozoicomonadaceaefamily. The factors controlling their distribution and their functional diversity remain, however, poorly known. Here, we study the ecology ofEndozoicomonadaceaeat an ocean basin-scale by sampling specimens from three coral genera (Pocillopora,Porites,Millepora) on 99 reefs from 32 islands across the Pacific Ocean. The analysis of 2447 metabarcoding and 270 metagenomic samples reveals that each coral genus harbored a distinct new species ofEndozoicomonadaceae. These species are composed of nine lineages that have distinct biogeographic patterns. The most common one, found inPocillopora, appears to be a globally distributed symbiont with distinct metabolic capabilities, including the synthesis of amino acids and vitamins not produced by the host. The other lineages are structured partly by the host genetic lineage inPocilloporaand mainly by the geographic location inPorites.Milleporais more rarely associated toEndozoicomonadaceae. Our results show that different coral genera exhibit distinct strategies of host-Endozoicomonadaceaeassociations that are defined at the bacteria lineage level.
Vagus nerve stimulation primes platelets and reduces bleeding in hemophilia A male mice
Authors: Bravo-Iñiguez Carlos E. , Fritz Jason R. , Shukla Shilpa , Sarangi Susmita , Thompson Dane A. , Amin Seema G. , Tsaava Tea , Chaudhry Saher , Valentino Sara P. , Hoffman Hannah B. , Imossi Catherine W. , Addorisio Meghan E. , Valdes-Ferrer Sergio I. , Chavan Sangeeta S. , Blanc Lionel , Czura Christopher J. , Tracey Kevin J. , Huston Jared M.
Published: June 2023

Deficiency of coagulation factor VIII in hemophilia A disrupts clotting and prolongs bleeding. While the current mainstay of therapy is infusion of factor VIII concentrates, inhibitor antibodies often render these ineffective. Because preclinical evidence shows electrical vagus nerve stimulation accelerates clotting to reduce hemorrhage without precipitating systemic thrombosis, we reasoned it might reduce bleeding in hemophilia A. Using two different male murine hemorrhage and thrombosis models, we show vagus nerve stimulation bypasses the factor VIII deficiency of hemophilia A to decrease bleeding and accelerate clotting. Vagus nerve stimulation targets acetylcholine-producing T lymphocytes in spleen and α7 nicotinic acetylcholine receptors (α7nAChR) on platelets to increase calcium uptake and enhance alpha granule release. Splenectomy or genetic deletion of T cells or α7nAChR abolishes vagal control of platelet activation, thrombus formation, and bleeding in male mice. Vagus nerve stimulation warrants clinical study as a therapy for coagulation disorders and surgical or traumatic bleeding.