bluuebunny/crossref_metadata_2025_split huggingface dataset:
DID THEOPHRASTUS HELP DELIVER ERESUS FROM TYRANTS?
Authors: Ebner-Landy Katie 
Published: July 2022

AbstractPlutarch's Moralia mentions that Theophrastus twice delivered his native city from tyrants (1097B, 1126F), a detail that has been difficult to make coherent with our existing understanding of Theophrastus’ life. Theophrastus seems to be in the wrong place at the wrong time for this to have been possible, or to have been too undemocratic and scholastic a philosopher to have wanted to participate in these struggles in the first place. By more closely examining the nature of Plutarch's comment and the evidence for Theophrastus’ political orientation and character, this article argues that there are, however, grounds on which to take Plutarch's report seriously. It presents a case for Theophrastus’ participation in two liberation struggles in 334 and 332, without complicating the trajectory of his accompanying Aristotle to both Macedonia and Athens during this period.
Movement pattern and population structure ofClibanarius antillensisStimpson, 1859 in south Brazil
Authors: da Silva Alexandre R. , dos Santos Renan A. P. , Gryszyszyn Luana Maria , Paluski Geovana Bastos , Gregati Rafael Augusto 
Published: July 2022

AbstractHermit crabs have soft abdomens and therefore must use empty gastropod shells as protection. Shell choices do not occur at random, and the animals often occupy shells with the best fit among the available ones. To live in intertidal and sublittoral zones, regions subjected to daily variations in abiotic factors, hermit crabs present a locomotory circadian rhythm.Clibanarius antillensishas been the object of several studies in Brazil's south-east, so this study was aimed at describing its population in the south of Brazil and its movement activity under laboratory conditions during night-time and daytime, while using two different shells. The animals were sampled from the Sepultura and Lagoinha beaches, in the state of Santa Catarina through free diving. Sex ratio was skewed for males, with ovigerous females present during the whole year but with a spring peak. Males were more abundant than females, ovigerous females and intersex individuals, being predominant in all size-classes analysed. The hermit crabs occupied mainly two gastropod shells:Cerithium atratumandAgathistoma viridulum, and ovigerous females used only the first.Clibanarius antillensisshowed nocturnal activity and the animals usingC. atratumshells were more active than those usingA. viridulum.Cerithium atratumshells are lighter and less bulky thanA. viridulum, implying that there might be a tradeoff in which the hermit crabs use lighter shells, that provide less protection in order to expend less energy and be more active.
Constraining Clouds and Convective Parameterizations in a Climate Model Using Paleoclimate Data
Authors: Ramos R. D. , LeGrande A. N. , Griffiths M. L. , Elsaesser G. S. , Litchmore D. T. , Tierney J. E. , Pausata F. S. R. , Nusbaumer J. 
Published: July 2022

AbstractCloud and convective parameterizations strongly influence uncertainties in equilibrium climate sensitivity. We provide a proof‐of‐concept study to constrain these parameterizations in a perturbed parameter ensemble of the atmosphere‐only version of the Goddard Institute for Space Studies Model E2.1 simulations by evaluating model biases in the present‐day runs using multiple satellite climatologies and by comparing simulated δ18O of precipitation (δ18Op), known to be sensitive to parameterization schemes, with a global database of speleothem δ18O records covering the Last Glacial Maximum (LGM), mid‐Holocene (MH) and pre‐industrial (PI) periods. Relative to modern interannual variability, paleoclimate simulations show greater sensitivity to parameter changes, allowing for an evaluation of model uncertainties over a broader range of climate forcing and the identification of parts of the world that are parameter sensitive. Certain simulations reproduced absolute δ18Op values across all time periods, along with LGM and MH δ18Op anomalies relative to the PI, better than the default parameterization. No single set of parameterizations worked well in all climate states, likely due to the non‐stationarity of cloud feedbacks under varying boundary conditions. Future work that involves varying multiple parameter sets simultaneously with coupled ocean feedbacks will likely provide improved constraints on cloud and convective parameterizations.
Attribution of Stratospheric and Tropospheric Ozone Changes Between 1850 and 2014 in CMIP6 Models
Authors: Zeng Guang , Morgenstern Olaf , Williams Jonny H. T. , O’Connor Fiona M. , Griffiths Paul T. , Keeble James , Deushi Makoto , Horowitz Larry W. , Naik Vaishali , Emmons Louisa K. , Abraham N. Luke , Archibald Alexander T. , Bauer Susanne E. , Hassler Birgit , Michou Martine , Mills Michael J. , Murray Lee T. , Oshima Naga , Sentman Lori T. , Tilmes Simone , Tsigaridis Kostas , Young Paul J. 
Published: July 2022

AbstractWe quantify the impacts of halogenated ozone‐depleting substances (ODSs), greenhouse gases (GHGs), and short‐lived ozone precursors on ozone changes between 1850 and 2014 using single‐forcing perturbation simulations from several Earth system models with interactive chemistry participating in the Coupled Model Intercomparison Project Aerosol and Chemistry Model Intercomparison Project. We present the responses of ozone to individual forcings and an attribution of changes in ozone columns and vertically resolved stratospheric and tropospheric ozone to these forcings. We find that whilst substantial ODS‐induced ozone loss dominates the stratospheric ozone changes since the 1970s, in agreement with previous studies, increases in tropospheric ozone due to increases in short‐lived ozone precursors and methane since the 1950s make increasingly important contributions to total column ozone (TCO) changes. Increases in methane also lead to substantial extra‐tropical stratospheric ozone increases. Impacts of nitrous oxide and carbon dioxide on stratospheric ozone are significant but their impacts on TCO are small overall due to several opposing factors and are also associated with large dynamical variability. The multi‐model mean (MMM) results show a clear change in the stratospheric ozone trends after 2000 due to now declining ODSs, but the trends are generally not significantly positive, except in the extra‐tropical upper stratosphere, due to relatively small changes in forcing over this period combined with large model uncertainty. Although the MMM ozone compares well with the observations, the inter‐model differences are large primarily due to the large differences in the models' representation of ODS‐induced ozone depletion.
Adverse childhood experiences, child poverty, and adiposity trajectories from childhood to adolescence: evidence from the Millennium Cohort Study
Authors: Deng Keyao , Lacey Rebecca E. 
Published: July 2022

Abstract
Objective
This study investigated associations between adverse childhood experiences (ACEs) in early childhood (at ages 9 months and 3 years) and adiposity trajectories of children/adolescents from age 5 to age 17, and the potential interaction between ACEs and poverty on adiposity trajectories.

Methods
Data from the UK Millennium Cohort Study was used. Eight commonly studied ACEs and poverty were measured when the child was aged 9 months and 3 years. ACEs were considered as a cumulative score and as individual experiences. Linear-mixed effect models were employed, modelling BMI and fat mass index (FMI) trajectories from age 5 to 17 (main outcome), adjusting for covariates and stratified by sex. Interactions with poverty were also tested. The sample sizes were 7282 and 6912 for BMI and FMI sample respectively.

Results
Cumulative ACE score was associated with steeper increase in BMI and FMI among boys with 3+ ACEs (BMI: β = 0.13, 95% CI: 0.02–0.24; FMI: β = 0.09, 95% CI: 0.01–0.19). For individual ACEs, parental depression was associated with steeper increase in BMI/FMI trajectories in both sexes (BMI: boys: β = 0.15, 95% CI: 0.07–0.23, girls: β = 0.13, 95% CI: 0.05–0.20; FMI: boys: β = 0.09, 95% CI: 0.03–0.15, girls: β = 0.09, 95% CI: 0.02–0.16). In addition, parental separation and physical punishment were associated with steeper increase in BMI/FMI trajectories among girls (BMI: parental separation: β = 0.25; 95% CI: 0.06–0.44, physical punishment: β = 0.14; 95% CI: 0.03–0.26; FMI: parental separation: β = 0.20; 95% CI: 0.03–0.37, physical punishment: β = 0.12; 95% CI: 0.02–0.22). No interaction effect had been found between ACEs and poverty on the adiposity trajectories.

Conclusions
A complex relationship between ACEs in early childhood and adiposity trajectories for children/adolescents was found, highlighting the different effects of specific ACEs and sex differences in the association.
Targeting the “hallmarks of aging” to slow aging and treat age-related disease: fact or fiction?
Authors: Keshavarz Maryam , Xie Kan , Schaaf Kristina , Bano Daniele , Ehninger Dan 
Published: July 2022

AbstractAging is a major risk factor for a number of chronic diseases, including neurodegenerative and cerebrovascular disorders. Aging processes have therefore been discussed as potential targets for the development of novel and broadly effective preventatives or therapeutics for age-related diseases, including those affecting the brain. Mechanisms thought to contribute to aging have been summarized under the term the “hallmarks of aging” and include a loss of proteostasis, mitochondrial dysfunction, altered nutrient sensing, telomere attrition, genomic instability, cellular senescence, stem cell exhaustion, epigenetic alterations and altered intercellular communication. We here examine key claims about the “hallmarks of aging”. Our analysis reveals important weaknesses that preclude strong and definitive conclusions concerning a possible role of these processes in shaping organismal aging rate. Significant ambiguity arises from the overreliance on lifespan as a proxy marker for aging, the use of models with unclear relevance for organismal aging, and the use of study designs that do not allow to properly estimate intervention effects on aging rate. We also discuss future research directions that should be taken to clarify if and to what extent putative aging regulators do in fact interact with aging. These include multidimensional analytical frameworks as well as designs that facilitate the proper assessment of intervention effects on aging rate.
N6-methyladenosine (m6A) methyltransferase METTL3 regulates sepsis-induced myocardial injury through IGF2BP1/HDAC4 dependent manner
Authors: Shen Hao , Xie Keliang , Li Miaomiao , Yang Qianyu , Wang Xiaoye 
Published: July 2022

AbstractRecent studies have identified that N6-methyladenosine (m6A) extensively participates in the myocardial injury pathophysiological process. However, the role of m6A on sepsis-induced myocardial injury is still unclear. Here, we investigated the functions and mechanism of m6A methyltransferase METTL3 for septic myocardial injury. Results illustrated that the m6A modification level and METTL3 up-regulated in the lipopolysaccharide (LPS)-induced cardiomyocytes (H9C2 cells). Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) revealed the m6A profile of the septic myocardial injury cellular model. Functionally, METTL3 knockdown repressed the inflammatory damage of cardiomyocytes induced by LPS. Mechanistically, we found that HDAC4 had remarkable m6A modification sites on its 3’-UTR genome, acting as the downstream target of METTL3. Besides, m6A reader IGF2BP1 recognized the m6A modification sites on HDAC4 mRNA and enhanced its RNA stability. In conclusion, the findings illustrated a role of METTL3/IGF2BP1/m6A/HDAC4 axis on sepsis-induced myocardial injury, which might provide novel therapeutic strategy for septic myocardial injury.
Efficient and interpretable graph network representation for angle-dependent properties applied to optical spectroscopy
Authors: Hsu Tim , Pham Tuan Anh , Keilbart Nathan , Weitzner Stephen , Chapman James , Xiao Penghao , Qiu S. Roger , Chen Xiao , Wood Brandon C. 
Published: July 2022

AbstractGraph neural networks are attractive for learning properties of atomic structures thanks to their intuitive graph encoding of atoms and bonds. However, conventional encoding does not include angular information, which is critical for describing atomic arrangements in disordered systems. In this work, we extend the recently proposed ALIGNN (Atomistic Line Graph Neural Network) encoding, which incorporates bond angles, to also include dihedral angles (ALIGNN-d). This simple extension leads to a memory-efficient graph representation that captures the complete geometry of atomic structures. ALIGNN-d is applied to predict the infrared optical response of dynamically disordered Cu(II) aqua complexes, leveraging the intrinsic interpretability to elucidate the relative contributions of individual structural components. Bond and dihedral angles are found to be critical contributors to the fine structure of the absorption response, with distortions that represent transitions between more common geometries exhibiting the strongest absorption intensity. Future directions for further development of ALIGNN-d are discussed.
Structure--property relationship and chemical durability of magnesium-containing borosilicate glasses with insight from topological constraints
Authors: Bisbrouck N. , Micoulaut M. , Delaye J. M. , Gin S. , Angeli F. 
Published: July 2022

AbstractThe initial dissolution rate of a series of multicomponent glasses is studied in order to discuss the influence of increasing magnesium content in the glass on this alteration regime and to highlight differences in behavior between calcium- and magnesium-bearing glasses. The application of MD-based topological constraint theory (TCT) is confronted to glass transition temperature (Tg) and initial dissolution rate (r0) on a glass series containing the main oxides of a French nuclear glass (AVM). In addition, a comparison between a reference magnesium-containing nuclear waste glass, AVMV4 and a proposed derived simplified composition N19M8 is performed regarding r0 values. Results indicate a similar behavior in this alteration regime for the two glasses, suggesting that this simple glass might be a good analogue to the complex one. Substituting calcium for magnesium decreases the initial dissolution rate by a factor two in the series, while an overall increase of magnesium leads to an increased dissolution rate. Analyses performed with TCT suggests that magnesium environment is better defined than calcium or sodium and may behave as an intermediate species. Finally, a correlation between the number of constraints per atom and Tg is established, while the model failed to link structural features to r0.
Validation and promise of a TCR mimic antibody for cancer immunotherapy of hepatocellular carcinoma
Authors: Liu Chang , Liu Hong , Dasgupta Moumita , Hellman Lance M. , Zhang Xiaogang , Qu Kai , Xue Hui , Wang Yun , Fan Fenling , Chang Qi , Yu Duo , Ge Linhu , Zhang Yu , Cui Ziyou , Zhang Pengbo , Heller Bradley , Zhang Hongbing , Shi Bingyin , Baker Brian M. , Liu Cheng 
Published: July 2022

AbstractMonoclonal antibodies are at the vanguard of the most promising cancer treatments. Whereas traditional therapeutic antibodies have been limited to extracellular antigens, T cell receptor mimic (TCRm) antibodies can target intracellular antigens presented by cell surface major histocompatibility complex (MHC) proteins. TCRm antibodies can therefore target a repertoire of otherwise undruggable cancer antigens. However, the consequences of off-target peptide/MHC recognition with engineered T cell therapies are severe, and thus there are significant safety concerns with TCRm antibodies. Here we explored the specificity and safety profile of a new TCRm-based T cell therapy for hepatocellular carcinoma (HCC), a solid tumor for which no effective treatment exists. We targeted an alpha-fetoprotein peptide presented by HLA-A*02 with a highly specific TCRm, which crystallographic structural analysis showed binds directly over the HLA protein and interfaces with the full length of the peptide. We fused the TCRm to the γ and δ subunits of a TCR, producing a signaling AbTCR construct. This was combined with an scFv/CD28 co-stimulatory molecule targeting glypican-3 for increased efficacy towards tumor cells. This AbTCR + co-stimulatory T cell therapy showed potent activity against AFP-positive cancer cell lines in vitro and an in an in vivo model and undetectable activity against AFP-negative cells. In an in-human safety assessment, no significant adverse events or cytokine release syndrome were observed and evidence of efficacy was seen. Remarkably, one patient with metastatic HCC achieved a complete remission after nine months and ultimately qualified for a liver transplant.
Ovicidal and repellent activities of several plant essential oils against Periplaneta americana L. and enhanced activities from their combined formulation
Authors: Soonwera Mayura , Moungthipmalai Tanapoom , Takawirapat Wacharaporn , Sittichok Sirawut 
Published: July 2022

AbstractNatural ovicidal and repellent agents against Periplaneta americana L. are urgently needed, and plant essential oils (EOs) can assume this role quite readily. In this study, ovicidal and repellent activities against Periplaneta americana of EOs from Cymbopogon citratus (Stapf.), Cinnamomum verum (J. Presl.), Eucalyptus globulus (Labill.), Illicium verum (Hook.f.), and Zanthoxylum limonella (Alston) in soybean oil and in ethyl alcohol were determined by topical and dual-choice assays, as well as 10% cypermethrin and a combined formulation of 5% C. verum EO + 5% I. verum EO. Cypermethrin at 10% provided the highest toxicity (100% inhibition rate) against the eggs, but only slightly higher than that (99.3%) provided by the combined EO formulation, while the highest repellent activity against the adults was provided by the combined formulation (89.5% repelled cockroaches at 48 h after treatment). In addition, all EO formulations in soybean oil provided higher ovicidal and repellent activities than those in ethyl alcohol. To conclude, the combined EO formulation in soybean oil can replace cypermethrin because their efficacy was nearly equivalent, but the combination should be much safer to use.
Swedish snuff (snus) dipping, cigarette smoking, and risk of peripheral artery disease: a prospective cohort study
Authors: Yuan Shuai , Titova Olga E. , Damrauer Scott M. , Åkesson Agneta , Larsson Susanna C. 
Published: July 2022

AbstractTobacco smoking is an important risk factor for peripheral artery disease (PAD), but it remains unknown whether smokeless tobacco, such as Swedish snuff (snus), is also associated with this disease. We used data from the Cohort of Swedish Men including 24,085 men. Individuals were grouped into never, past, and current snus dippers as well as never, past quitting ≥ 10 years, past, quitting < 10 years, and current smokers. Incident PAD cases were defined by linkage of the cohort with the Swedish National Patient Register. Cox proportional hazards regression was used to analyze the data. Over a mean follow-up period of 9.1 years (from July 1, 2009 to December 31, 2019), 655 incident PAD cases were ascertained. Cigarette smoking but not Swedish snus dipping was associated with an increased risk of PAD. Compared with never snus dippers, the hazard ratio of PAD was 0.95 (95% confidence interval [CI] 0.73–1.24) for past snus dippers and 0.88 (95% CI 0.66–1.17) for current snus dippers. Compared to never smokers, the hazard ratio of PAD was 1.38 (95% CI 1.14–1.68) for past smoker who stopped smoking for ≥ 10 years, 2.61 (95% CI 1.89–3.61) for past smoker who stopped smoking for < 10 years, and 4.01 (95% CI 3.17, 5.08) for current smoker. In conclusion, cigarette smoking but not Swedish snus dipping increases the risk of PAD.
Hybrid-control arm construction using historical trial data for an early-phase, randomized controlled trial in metastatic colorectal cancer
Authors: Li Chen , Ferro Ana , Mhatre Shivani K. , Lu Danny , Lawrance Marcus , Li Xiao , Li Shi , Allen Simon , Desai Jayesh , Fakih Marwan , Cecchini Michael , Pedersen Katrina S. , Kim Tae You , Reyes-Rivera Irmarie , Segal Neil H. , Lenain Christelle 
Published: July 2022

Abstract
Background
Treatment for metastatic colorectal cancer patients beyond the second line remains challenging, highlighting the need for early phase trials of combination therapies for patients who had disease progression during or following two prior lines of therapy. Leveraging hybrid control design in these trials may preserve the benefits of randomization while strengthening evidence by integrating historical trial data. Few examples have been established to assess the applicability of such design in supporting early phase metastatic colorectal cancer trials.

Methods
MORPHEUS-CRC is an umbrella, multicenter, open-label, phase Ib/II, randomized, controlled trial (NCT03555149), with active experimental arms ongoing. Patients enrolled were assigned to a control arm (regorafenib, 15 patients randomized and 13 analysed) or multiple experimental arms for immunotherapy-based treatment combinations. One experimental arm (atezolizumab + isatuximab, 15 patients randomized and analysed) was completed and included in the hybrid-control study, where the hybrid-control arm was constructed by integrating data from the IMblaze370 phase 3 trial (NCT02788279). To estimate treatment efficacy, Cox and logistic regression models were used in a frequentist framework with standardized mortality ratio weighting or in a Bayesian framework with commensurate priors. The primary endpoint is objective response rate, while disease control rate, progression-free survival, and overall survival were the outcomes assessed in the hybrid-control study.

Results
The experimental arm showed no efficacy signal, yet a well-tolerated safety profile in the MORPHEUS-CRC trial. Treatment effects estimated in hybrid control design were comparable to those in the MORPHEUS-CRC trial using either frequentist or Bayesian models.

Conclusions
Hybrid control provides comparable treatment-effect estimates with generally improved precision, and thus can be of value to inform early-phase clinical development in metastatic colorectal cancer.