bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ecocide, the Anthropocene, and the International Criminal Court
Authors: Branch Adam , Minkova Liana 
Published: April 2023

AbstractThe recent proposal by the Independent Expert Panel of the Stop Ecocide initiative to include the crime of ecocide in the International Criminal Court's Rome Statute has raised expectations for preventing and remedying severe environmental harm through international prosecution. As alluring as this image is, we argue that ecocide prosecutions may be the most difficult, perhaps even impossible, in precisely the cases that the ICC would need to be concerned with; namely, the gravest global incidents of environmental harm, including those associated with planetary climate change. We explore a series of questions about the panel's formulation of ecocide that resonate with longer debates around criminalizing environmental harm but take on new dimensions amid the Anthropocene and after twenty years of ICC trials. Ecocide must contend with the hard lessons learned concerning the ICC's limitations in realizing justice in a fraught international political context and also with fundamental challenges to knowledge and legitimacy arising from the uncertainty and dynamic socioenvironmental context of the Anthropocene. The proposed amendment, if adopted, risks ineffective prosecutions or even perverse outcomes for the environment itself. This risk, however, may characterize any effort to prosecute ecocide internationally in the Anthropocene unless the terms of international criminal law are fundamentally rethought.
Distributed Subweb Specifications for Traversing the Web
Authors: BOGAERTS BART , KETSMAN BAS , ZEBOUDJ YOUNES , AAMER HEBA , TAELMAN RUBEN , VERBORGH RUBEN 
Published: April 2023

AbstractLink traversal–based query processing (ltqp), in which a sparql query is evaluated over a web of documents rather than a single dataset, is often seen as a theoretically interesting yet impractical technique. However, in a time where the hypercentralization of data has increasingly come under scrutiny, a decentralized Web of Data with a simple document-based interface is appealing, as it enables data publishers to control their data and access rights. While (ltqp allows evaluating complex queries over such webs, it suffers from performance issues (due to the high number of documents containing data) as well as information quality concerns (due to the many sources providing such documents). In existing ltqp approaches, the burden of finding sources to query is entirely in the hands of the data consumer. In this paper, we argue that to solve these issues, data publishers should also be able to suggest sources of interest and guide the data consumer toward relevant and trustworthy data. We introduce a theoretical framework that enables such guided link traversal and study its properties. We illustrate with a theoretic example that this can improve query results and reduce the number of network requests. We evaluate our proposal experimentally on a virtual linked web with specifications and indeed observe that not just the data quality but also the efficiency of querying improves.
Comparing the Importance of Iodine and Isoprene on Tropospheric Photochemistry
Authors: Pound R. J. , Durcan D. P. , Evans M. J. , Carpenter L. J. 
Published: April 2023

AbstractIsoprene, arguably the most studied biogenically emitted gas, is thought to have a large impact on tropospheric composition. Other naturally emitted species have been considered to play a less important role. Here the GEOS‐Chem model is used to compare the impacts of isoprene and iodine emissions on present‐day tropospheric composition. Removing isoprene emissions leads to a 3.4% decrease in tropospheric O3 burden, a smaller absolute change than the 5.9% increase from removing iodine emissions. Iodine has a negligible impact on global mean OH concentrations and methane lifetime (+0.6% and +0.05%) whereas isoprene has a substantial impact on both (−4.3% and −4.2%). Isoprene emissions and chemistry are seen as essential for tropospheric chemistry models, but iodine is often not. We suggest that iodine should receive greater attention in model development and experimental research to allow improved predictions of past, present, and future tropospheric O3.
Climatology of Rossby Wave Breaking Over the Subtropical Indian Region
Authors: Thomas Biyo , Kunchala Ravi Kumar , Singh Bhupendra Bahadur , Kumar Kondapalli Niranjan 
Published: April 2023

AbstractThe weather of subtropical Indian region is frequently impacted by Rossby Wave Breaking (RWB) triggered dynamical changes in the atmosphere. However, studies are elusive on the comprehensive understanding of RWB events over the region. A Potential Vorticity (PV) contour searching algorithm based on existing literature, but implemented with more constraints appropriate for the Indian subcontinent, is used to detect the RWB events. We detect 513 RWB events during the analysis period (1979–2021) and utilize them to understand the RWB climatology and variability over the region. A significant increase in the frequency (about 20%) and intensity of RWB events noticed during the last two decades (1999–2018). The spatial distribution of RWB occurrences is prominent over the northwest parts of the Indian subcontinent during winter months. The most frequent breaking occurs in the wavenumbers ranging between 5 and 7, with stronger wave amplitudes and deeper tropospheric intrusions (∼650 hPa) during winter months that reach as low as 7.5°N in latitude. Further, our analysis shows that RWB promotes extreme rainfall by generating instability in the atmosphere allowing enhanced moisture influx over the region. It is also noted that interannual‐to‐decadal variations in the number of RWB events are linked to sea surface temperature conditions in the Pacific ocean. The findings of this study would contribute to an improved understanding of RWB and associated wave dynamics in triggering extreme weather and may find applications in climate studies on extremes in a warming climate.
Precipitation Bias Correction: A Novel Semi‐parametric Quantile Mapping Method
Authors: Rajulapati Chandra Rupa , Papalexiou Simon Michael 
Published: April 2023

AbstractBias correction methods are used to adjust simulations from global and regional climate models to use them in informed decision‐making. Here we introduce a semi‐parametric quantile mapping (SPQM) method to bias‐correct daily precipitation. This method uses a parametric probability distribution to describe observations and an empirical distribution for simulations. Bias‐correction techniques typically adjust the bias between observation and historical simulations to correct projections. The SPQM however corrects simulations based only on observations assuming the detrended simulations have the same distribution as the observations. Thus, the bias‐corrected simulations preserve the climate change signal, including changes in the magnitude and probability dry, and guarantee a smooth transition from observations to future simulations. The results are compared with popular quantile mapping techniques, that is, the quantile delta mapping (QDM) and the statistical transformation of the CDF using splines (SSPLINE). The SPQM performed well in reproducing the observed statistics, marginal distribution, and wet and dry spells. Comparatively, it performed at least equally well as the QDM and SSPLINE, specifically in reproducing observed wet spells and extreme quantiles. The method is further tested in a basin‐scale region. The spatial variability and statistics of the observed precipitation are reproduced well in the bias‐corrected simulations. Overall, the SPQM is easy to apply, yet robust in bias‐correcting daily precipitation simulations.
A Spectral Analysis of Near‐Surface Mean Wind Speed and Gusts Over the Iberian Peninsula
Authors: Utrabo‐Carazo Eduardo , Azorin‐Molina Cesar , Aguilar Enric , Brunet Manola 
Published: April 2023

AbstractThis study analyses for the first time observed surface mean wind speed (SWS) and gusts over the Iberian Peninsula (IP) in the frequency domain for 1961–2019, with the goal of exploring sources of predictability in the interannual and decadal scales. The main result is the high significant correlation between surface winds and the stratospheric polar vortex for periods close to 1 year with a time lag of about 2–3 months with respect to the antiphase, that is, a negative correlation in which the polar vortex modulates winds in the region. Furthermore, we found that the SWS and gusts are decoupled for periods between 9 and 11 years with a marked seasonal dependence in its intensity. Finally, we detected discrepancies between the spectra shown by surface winds from observations and ERA5‐Land reanalysis, suggesting that simulated data do not accurately reproduce the variability of surface wind speeds.
The effect of lysergic acid diethylamide (LSD) on whole-brain functional and effective connectivity
Authors: Bedford Peter , Hauke Daniel J. , Wang Zheng , Roth Volker , Nagy-Huber Monika , Holze Friederike , Ley Laura , Vizeli Patrick , Liechti Matthias E. , Borgwardt Stefan , Müller Felix , Diaconescu Andreea O. 
Published: April 2023

AbstractPsychedelics have emerged as promising candidate treatments for various psychiatric conditions, and given their clinical potential, there is a need to identify biomarkers that underlie their effects. Here, we investigate the neural mechanisms of lysergic acid diethylamide (LSD) using regression dynamic causal modelling (rDCM), a novel technique that assesses whole-brain effective connectivity (EC) during resting-state functional magnetic resonance imaging (fMRI). We modelled data from two randomised, placebo-controlled, double-blind, cross-over trials, in which 45 participants were administered 100 μg LSD and placebo in two resting-state fMRI sessions. We compared EC against whole-brain functional connectivity (FC) using classical statistics and machine learning methods. Multivariate analyses of EC parameters revealed predominantly stronger interregional connectivity and reduced self-inhibition under LSD compared to placebo, with the notable exception of weakened interregional connectivity and increased self-inhibition in occipital brain regions as well as subcortical regions. Together, these findings suggests that LSD perturbs the Excitation/Inhibition balance of the brain. Notably, whole-brain EC did not only provide additional mechanistic insight into the effects of LSD on the Excitation/Inhibition balance of the brain, but EC also correlated with global subjective effects of LSD and discriminated experimental conditions in a machine learning-based analysis with high accuracy (91.11%), highlighting the potential of using whole-brain EC to decode or predict subjective effects of LSD in the future.
Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies
Authors: Zhang Yinqiang , Li Chenggong , Du Mengyi , Jiang Huiwen , Luo Wenjing , Tang Lu , Kang Yun , Xu Jia , Wu Zhuolin , Wang Xindi , Huang Zhongpei , Zhang Yanlei , Wu Di , Chang Alex H. , Hu Yu , Mei Heng 
Published: April 2023

AbstractChimeric antigen receptor-T (CAR-T) therapy remains to be investigated in T-cell malignancies. CD7 is an ideal target for T-cell malignancies but is also expressed on normal T cells, which may cause CAR-T cell fratricide. Donor-derived anti-CD7 CAR-T cells using endoplasmic reticulum retention have shown efficacy in patients with T-cell acute lymphoblastic leukemia (ALL). Here we launched a phase I trial to explore differences between autologous and allogeneic anti-CD7 CAR-T therapies in T-cell ALL and lymphoma. Ten patients were treated and 5 received autologous CAR-T therapies. No dose-limiting toxicity or neurotoxicity was observed. Grade 1–2 cytokine release syndrome occurred in 7 patients, and grade 3 in 1 patient. Grade 1–2 graft-versus-host diseases were observed in 2 patients. Seven patients had bone marrow infiltration, and 100% of them achieved complete remission with negative minimal residual disease within one month. Two-fifths of patients achieved extramedullary or extranodular remission. The median follow-up was 6 (range, 2.7–14) months and bridging transplantation was not administrated. Patients treated with allogeneic CAR-T cells had higher remission rate, less recurrence and more durable CAR-T survival than those receiving autologous products. Allogeneic CAR-T cells appeared to be a better option for patients with T-cell malignancies.
Deciphering the involvement of the Hippo pathway co-regulators, YAP/TAZ in invadopodia formation and matrix degradation
Authors: Venghateri Jubina Balan , Dassa Bareket , Morgenstern David , Shreberk-Shaked Michal , Oren Moshe , Geiger Benjamin 
Published: April 2023

AbstractInvadopodia are adhesive, actin-rich protrusions formed by metastatic cancer cells that degrade the extracellular matrix and facilitate invasion. They support the metastatic cascade by a spatially and temporally coordinated process whereby invading cells bind to the matrix, degrade it by specific metalloproteinases, and mechanically penetrate diverse tissue barriers by forming actin-rich extensions. However, despite the apparent involvement of invadopodia in the metastatic process, the molecular mechanisms that regulate invadopodia formation and function are still largely unclear. In this study, we have explored the involvement of the key Hippo pathway co-regulators, namely YAP, and TAZ, in invadopodia formation and matrix degradation. Toward that goal, we tested the effect of depletion of YAP, TAZ, or both on invadopodia formation and activity in multiple human cancer cell lines. We report that the knockdown of YAP and TAZ or their inhibition by verteporfin induces a significant elevation in matrix degradation and invadopodia formation in several cancer cell lines. Conversely, overexpression of these proteins strongly suppresses invadopodia formation and matrix degradation. Proteomic and transcriptomic profiling of MDA-MB-231 cells, following co-knockdown of YAP and TAZ, revealed a significant change in the levels of key invadopodia-associated proteins, including the crucial proteins Tks5 and MT1-MMP (MMP14). Collectively, our findings show that YAP and TAZ act as negative regulators of invadopodia formation in diverse cancer lines, most likely by reducing the levels of essential invadopodia components. Dissecting the molecular mechanisms of invadopodia formation in cancer invasion may eventually reveal novel targets for therapeutic applications against invasive cancer.
Culture-expanded mesenchymal stromal cell therapy: does it work in knee osteoarthritis? A pathway to clinical success
Authors: Copp Griffin , Robb Kevin P. , Viswanathan Sowmya 
Published: April 2023

AbstractOsteoarthritis (OA) is a degenerative multifactorial disease with concomitant structural, inflammatory, and metabolic changes that fluctuate in a temporal and patient-specific manner. This complexity has contributed to refractory responses to various treatments. MSCs have shown promise as multimodal therapeutics in mitigating OA symptoms and disease progression. Here, we evaluated 15 randomized controlled clinical trials (RCTs) and 11 nonrandomized RCTs using culture-expanded MSCs in the treatment of knee OA, and we found net positive effects of MSCs on mitigating pain and symptoms (improving function in 12/15 RCTs relative to baseline and in 11/15 RCTs relative to control groups at study endpoints) and on cartilage protection and/or repair (18/21 clinical studies). We examined MSC dose, tissue of origin, and autologous vs. allogeneic origins as well as patient clinical phenotype, endotype, age, sex and level of OA severity as key parameters in parsing MSC clinical effectiveness. The relatively small sample size of 610 patients limited the drawing of definitive conclusions. Nonetheless, we noted trends toward moderate to higher doses of MSCs in select OA patient clinical phenotypes mitigating pain and leading to structural improvements or cartilage preservation. Evidence from preclinical studies is supportive of MSC anti-inflammatory and immunomodulatory effects, but additional investigations on immunomodulatory, chondroprotective and other clinical mechanisms of action are needed. We hypothesize that MSC basal immunomodulatory “fitness” correlates with OA treatment efficacy, but this hypothesis needs to be validated in future studies. We conclude with a roadmap articulating the need to match an OA patient subset defined by molecular endotype and clinical phenotype with basally immunomodulatory “fit” or engineered-to-be-fit-for-OA MSCs in well-designed, data-intensive clinical trials to advance the field.
Mitochondria and the eye—manifestations of mitochondrial diseases and their management
Authors: Chen Benson S. , Harvey Joshua P. , Gilhooley Michael J. , Jurkute Neringa , Yu-Wai-Man Patrick 
Published: April 2023

AbstractHistorically, distinct mitochondrial syndromes were recognised clinically by their ocular features. Due to their predilection for metabolically active tissue, mitochondrial diseases frequently involve the eye, resulting in a range of ophthalmic manifestations including progressive external ophthalmoplegia, retinopathy and optic neuropathy, as well as deficiencies of the retrochiasmal visual pathway. With the wider availability of genetic testing in clinical practice, it is now recognised that genotype-phenotype correlations in mitochondrial diseases can be imprecise: many classic syndromes can be associated with multiple genes and genetic variants, and the same genetic variant can have multiple clinical presentations, including subclinical ophthalmic manifestations in individuals who are otherwise asymptomatic. Previously considered rare diseases with no effective treatments, considerable progress has been made in our understanding of mitochondrial diseases with new therapies emerging, in particular, gene therapy for inherited optic neuropathies.
The most at-risk regions in the world for high-impact heatwaves
Authors: Thompson Vikki , Mitchell Dann , Hegerl Gabriele C. , Collins Matthew , Leach Nicholas J. , Slingo Julia M. 
Published: April 2023

AbstractHeatwaves are becoming more frequent under climate change and can lead to thousands of excess deaths. Adaptation to extreme weather events often occurs in response to an event, with communities learning fast following unexpectedly impactful events. Using extreme value statistics, here we show where regional temperature records are statistically likely to be exceeded, and therefore communities might be more at-risk. In 31% of regions examined, the observed daily maximum temperature record is exceptional. Climate models suggest that similar behaviour can occur in any region. In some regions, such as Afghanistan and parts of Central America, this is a particular problem - not only have they the potential for far more extreme heatwaves than experienced, but their population is growing and increasingly exposed because of limited healthcare and energy resources. We urge policy makers in vulnerable regions to consider if heat action plans are sufficient for what might come.
miR-483-5p offsets functional and behavioural effects of stress in male mice through synapse-targeted repression of Pgap2 in the basolateral amygdala
Authors: Mucha Mariusz , Skrzypiec Anna E. , Kolenchery Jaison B. , Brambilla Valentina , Patel Satyam , Labrador-Ramos Alberto , Kudla Lucja , Murrall Kathryn , Skene Nathan , Dymicka-Piekarska Violetta , Klejman Agata , Przewlocki Ryszard , Mosienko Valentina , Pawlak Robert 
Published: April 2023

AbstractSevere psychological trauma triggers genetic, biochemical and morphological changes in amygdala neurons, which underpin the development of stress-induced behavioural abnormalities, such as high levels of anxiety. miRNAs are small, non-coding RNA fragments that orchestrate complex neuronal responses by simultaneous transcriptional/translational repression of multiple target genes. Here we show that miR-483-5p in the amygdala of male mice counterbalances the structural, functional and behavioural consequences of stress to promote a reduction in anxiety-like behaviour. Upon stress, miR-483-5p is upregulated in the synaptic compartment of amygdala neurons and directly represses three stress-associated genes: Pgap2, Gpx3 and Macf1. Upregulation of miR-483-5p leads to selective contraction of distal parts of the dendritic arbour and conversion of immature filopodia into mature, mushroom-like dendritic spines. Consistent with its role in reducing the stress response, upregulation of miR-483-5p in the basolateral amygdala produces a reduction in anxiety-like behaviour. Stress-induced neuromorphological and behavioural effects of miR-483-5p can be recapitulated by shRNA mediated suppression of Pgap2 and prevented by simultaneous overexpression of miR-483-5p-resistant Pgap2. Our results demonstrate that miR-483-5p is sufficient to confer a reduction in anxiety-like behaviour and point to miR-483-5p-mediated repression of Pgap2 as a critical cellular event offsetting the functional and behavioural consequences of psychological stress.
Soluble pathogenic tau enters brain vascular endothelial cells and drives cellular senescence and brain microvascular dysfunction in a mouse model of tauopathy
Authors: Hussong Stacy A. , Banh Andy Q. , Van Skike Candice E. , Dorigatti Angela O. , Hernandez Stephen F. , Hart Matthew J. , Ferran Beatriz , Makhlouf Haneen , Gaczynska Maria , Osmulski Pawel A. , McAllen Salome A. , Dineley Kelly T. , Ungvari Zoltan , Perez Viviana I. , Kayed Rakez , Galvan Veronica 
Published: April 2023

AbstractVascular mechanisms of Alzheimer’s disease (AD) may constitute a therapeutically addressable biological pathway underlying dementia. We previously demonstrated that soluble pathogenic forms of tau (tau oligomers) accumulate in brain microvasculature of AD and other tauopathies, including prominently in microvascular endothelial cells. Here we show that soluble pathogenic tau accumulates in brain microvascular endothelial cells of P301S(PS19) mice modeling tauopathy and drives AD-like brain microvascular deficits. Microvascular impairments in P301S(PS19) mice were partially negated by selective removal of pathogenic soluble tau aggregates from brain. We found that similar to trans-neuronal transmission of pathogenic forms of tau, soluble tau aggregates are internalized by brain microvascular endothelial cells in a heparin-sensitive manner and induce microtubule destabilization, block endothelial nitric oxide synthase (eNOS) activation, and potently induce endothelial cell senescence that was recapitulated in vivo in microvasculature of P301S(PS19) mice. Our studies suggest that soluble pathogenic tau aggregates mediate AD-like brain microvascular deficits in a mouse model of tauopathy, which may arise from endothelial cell senescence and eNOS dysfunction triggered by internalization of soluble tau aggregates.
Insights into solvent and surface charge effects on Volmer step kinetics on Pt (111)
Authors: Wilson Jon C. , Caratzoulas Stavros , Vlachos Dionisios G. , Yan Yushan 
Published: April 2023

AbstractThe mechanism of pH-dependent hydrogen oxidation and evolution kinetics is still a matter of significant debate. To make progress, we study the Volmer step kinetics on platinum (111) using classical molecular dynamics simulations with an embedded Anderson-Newns Hamiltonian for the redox process and constant potential electrodes. We investigate how negative electrode electrostatic potential affects Volmer step kinetics. We find that the redox solvent reorganization energy is insensitive to changes in interfacial field strength. The negatively charged surface attracts adsorbed H as well as H+, increasing hydrogen binding energy, but also trapping H+in the double layer. While more negative electrostatic potential in the double layer accelerates the oxidation charge transfer, it becomes difficult for the proton to move to the bulk. Conversely, reduction becomes more difficult because the transition state occurs farther from equilibrium solvation polarization. Our results help to clarify how the charged surface plays a role in hydrogen electrocatalysis kinetics.