bluuebunny/crossref_metadata_2025_split huggingface dataset:
Yeast β-glucan supplementation lowers insulin resistance without altering microbiota composition compared with placebo in subjects with type II diabetes: a phase I exploratory study
Authors: Cronin Peter , Hurley Cian , Ryan Andrew , Zamora-Úbeda María , Govindan Ashokkumar , Stanton Catherine , Lane Ger P. , Joyce Susan A. , O’Toole Paul W. , O’Connor Eibhlís M. 
Published: October 2024

AbstractThe increased global prevalence of type II diabetes mellitus (T2DM) is associated with consumption of low fibre ‘Western diets’. Characteristic metabolic parameters of these individuals include insulin resistance, high fasting and postprandial glucose, as well as low-grade systemic inflammation. Gut microbiota composition is altered significantly in these cohorts suggesting a causative link between diet, microbiota and disease. Dietary fibre consumption has been shown to alleviate these changes and improve glucose parameters in individuals with metabolic disease. We previously reported that yeast β-glucan (yeast beta-1,3/1,6-D-glucan; Wellmune) supplementation ameliorated hyperinsulinaemia and insulin resistance in a murine model. Here, we conducted a randomised, placebo-controlled, two-armed dietary fibre phase I exploratory intervention study in patients with T2DM. The primary outcome measure was alteration to microbiota composition, while the secondary outcome measures included markers of glycaemic control, inflammation as well as metabolomics. Patients were supplemented with 2·5g/day of maltodextrin (placebo) or yeast β-1,3/1,6-D-glucan (treatment). Yeast β-glucan (Wellmune) lowered insulin resistance compared with the placebo maltodextrin after 8 weeks of consumption. TNFα was significantly lower after 4 weeks of β-glucan supplementation. Significantly higher fecal concentrations of several bile acids were detected in the treatment group when compared with the placebo after 8 weeks. These included tauroursodeoxycholic acid, which was previously shown to improve glucose control and lower insulin resistance. Interestingly, the hypoglycaemic and anti-inflammatory effect of yeast β-glucan was independent of any changes in fecal microbiota composition or short-chain fatty acid levels. Our findings highlight the potential of yeast β-glucan to lower insulin resistance in patients with T2DM.
Risk factors associated with antibiotic prescriptions for cases of enteric pathogens in Canada, 2015–2019
Authors: Dougherty Brendan , Finley Rita , Dumoulin Danielle , Weese J. Scott , Harper Sherilee , Parmley E. Jane , Papadopoulos Andrew 
Published: October 2024

Abstract
Inappropriate antibiotic use is a key driver of antibiotic resistance and one that can be mitigated through stewardship. A better understanding of current prescribing practices is needed to develop successful stewardship efforts. This study aims to identify factors that are associated with human cases of enteric illness receiving an antibiotic prescription. Cases of laboratory-confirmed enteric illness reported to the FoodNet Canada surveillance system between 2015 and 2019 were the subjects of this study. Laboratory data were combined with self-reported data collected from an enhanced case questionnaire that included demographic data, illness duration and symptoms, and antibiotic prescribing. The data were used to build univariable logistic regression models and a multivariable logistic regression model to explore what factors were associated with a case receiving an antibiotic prescription. The final multivariable model identified several factors as being significantly associated with cases being prescribed an antibiotic. Some of the identified associations indicate that current antibiotic prescribing practices include a substantial level of inappropriate use. This study provides evidence that antibiotic stewardship initiatives targeting infectious diarrhoea are needed to optimize antibiotic use and combat the rise of antibiotic resistance.
An overview of the pathophysiology of agitation in Alzheimer’s dementia with a focus on neurotransmitters and circuits
Authors: Cummings Jeffrey L. , Brubaker Malaak , Selzler Katherine J. , Gonzalez Sarah T. , Patel Mehul , Stahl Stephen M. 
Published: October 2024

AbstractAlzheimer’s dementia (AD) is a progressive, neurodegenerative disease often accompanied by neuropsychiatric symptoms that profoundly impact both patients and caregivers. Agitation is among the most prevalent and distressing of these symptoms and often requires treatment. Appropriate therapeutic interventions depend on understanding the biological basis of agitation and how it may be affected by treatment. This narrative review discusses a proposed pathophysiology of agitation in Alzheimer’s dementia based on convergent evidence across research approaches. Available data indicate that agitation in Alzheimer’s dementia is associated with an imbalance of activity between key prefrontal and subcortical brain regions. The monoamine neurotransmitter systems serve as key modulators of activity within these brain regions and circuits and are rendered abnormal in AD. Patients with AD who exhibited agitation symptoms during life have alterations in neurotransmitter nuclei and related systems when the brain is examined at autopsy. The authors present a model of agitation in Alzheimer’s dementia in which noradrenergic hyperactivity along with serotonergic deficits and dysregulated striatal dopamine release contribute to agitated and aggressive behaviors.
Sharing economy: tensions in renting others’ possessions
Authors: Guyader Hugo 
Published: October 2024

AbstractThe sharing economy is anchored to two opposite logics: sharing and market exchange. This results in tensions between a pro-social orientation and communal norms on the one hand (i.e. solidarity, mutuality, generalized reciprocity and communal belonging) and a for-profit orientation and market norms on the other hand (i.e. profit maximization, self-interest and utilitarian motives). This article aims to distinguish among the different practices and phenomena related to the sharing economy, focusing on the tensions emanating from renting private possessions through collaborative consumption platforms.
Joint multitemporal SAR and optical mapping of urban changes
Authors: Marzi David , Munoz Rios Erith , Sorriso Antonietta , Dell’Acqua Fabio , Gamba Paolo 
Published: October 2024

AbstractThis paper presents a methodology designed to leverage multitemporal sequences of synthetic aperture radar (SAR) and multispectral data and automatically extract urban changes. The approach compares results using different radar and optical sensors, describing the advantages and drawbacks of using SAR data from the COnstellation of small Satellites for the Mediterranean basin Observation (COSMO)/SkyMed, SAtélite Argentino de Observación COn Microondas (SAOCOM), and Sentinel-1 constellations, as well as nighttime light data or Sentinel-2 images. Multiple indexes obtained from multispectral data are compared, too, and results obtained by an unsupervised clustering procedure are analyzed. The results show that using different datasets it is possible to obtain consistent results about different types of changes in urban areas (e.g., demolition, development, and densification) with different levels of spatial details.
A Sequential Leaching Protocol for δ11B and Trace Element Analyses of Multi‐Phase Carbonate Rocks
Authors: Hong Wei‐Li , Lepland Aivo , Crémière Antoine , Kirsimäe Kalle , Stüeken Eva E. , Dumont Matthew , Block Heidi E. , Rae James W. B. 
Published: October 2024

AbstractBoron geochemistry from biogenic carbonates offer valuable information about ocean pH and CO2 chemistry. However, application to geological carbonate deposits suffers from analytical difficulties in obtaining geochemical signals exclusively from the carbonate phase. Sequential leaching with reagents and acids has the potential to overcome such an issue. There is, however, little systematic investigation about the efficiency of sequential leaching in isolating carbonate‐associated boron from siliciclastic matrix. Here, we developed a sequential leaching protocol and applied it to methane‐derived‐authigenic‐carbonate samples. Using the leachate δ11B signatures, elemental composition, and mineral composition of residues, we show that the sequential leaching is able to improve the separation of boron from different phases. Buffered hydrogen peroxide removes organic matter and also some silicate phases resulting low δ11B values. Leaching with NH4Ac removes adsorbed boron though may also partially leach some carbonate phases. The first few leaching steps with diluted acetic acid dissolve carbonate phases. Depending on the sample type, these may also capture some remaining adsorbed boron from the preceding NH4Ac leaching. Once the adsorbed boron is completely removed, as indicated by the progressively higher δ11B values during the following acid leaching steps, representative carbonate composition can be derived. The accuracy of this protocol is demonstrated with leaching experiments using artificial deep sea coral carbonate and clay mixtures that give the representative carbonate‐associated δ11B within error of the pure coral value. Our results provide insights into characteristic signatures derived from silicates and organic matter that need to be considered in boron isotope analyses of impure marine carbonates.
A Comparative Study of Cave System Calcium Isotope Ratios: Implications for Quantitative Reconstruction of Paleorainfall From Speleothems
Authors: de Wet Cameron B. , Griffith Elizabeth M. , Erhardt Andrea M. , Oster Jessica L. 
Published: October 2024

AbstractVariations in speleothem calcium isotope ratios (δ44Ca) are thought to be uniquely controlled by prior carbonate precipitation (PCP) above a drip site and, when calibrated with modern data, show promise as a semi‐quantitative proxy for paleorainfall. However, few monitoring studies have focused on δ44Ca in modern cave systems. We present a multi‐year comparative study of δ44Ca, carbon isotopes (δ13C), and trace elemental ratios from cave drip waters, modern calcite, and host rocks from two cave systems in California—White Moon Cave (WMC) and Lake Shasta Caverns (LSC). Drip water and calcite δ44Ca from both caves indicate PCP‐driven enrichment, and we used a simple Rayleigh fractionation model to quantify PCP variability over the monitoring period. Modern calcite trace element and δ44Ca data positively correlate at WMC, but not at LSC, indicating a shared PCP control on these proxies at WMC but not at LSC. At both WMC and LSC, we observe an inverse relationship between PCP and rainfall amounts, though this relationship is variable across individual drip sites. Our modeled data suggest that WMC experiences ∼20% more PCP than LSC, consistent with the fact that WMC receives less annual rainfall. This work supports speleothem δ44Ca as an independent constraint on PCP that can aid in the interpretation of other hydrologically sensitive proxies and provide quantitative estimates of paleorainfall. Additional, long‐term monitoring studies from a variety of climate settings will be key for understanding δ44Ca variability in cave systems more fully and better constraining the relationship between PCP and rainfall.
Investigating the Last Millennium Coulomb Stress Transfer in the Central Apennine Fault System (CAFS)
Authors: Valentini G. , Volatili T. , Galli P. , Tondi E. 
Published: October 2024

AbstractThe Central Apennine Fault System (CAFS) characterizes an active tectonic region of significant importance, witnessing numerous destructive seismic events over the last millennia. Although numerous studies have underscored the role of Coulomb stress transfer (CST) in initiating some of the most catastrophic earthquakes, investigations focusing on its specific influence within the CAFS are limited. This research delves into a thorough examination of the effects of CST on both historical and instrumental seismic events of significant magnitude associated with the CAFS. We selected nine seismic events for the CST investigation, dating from 1279 CE to present. Beyond analyzing the static stress transfer for each individual seismic event, the cumulative CST of recent instrumental earthquakes was also examined to provide a comprehensive overview of the current stress scenario. Leveraging an innovative approach, faults were modeled adopting a variable strike three‐dimensional elliptical shape, ensuring enhanced calculation accuracy. Significant findings emerge from the analysis: CST has played a pivotal role in either activating or inhibiting the faults of the CAFS over the centuries. Several examined instances showcase fault reactivation following increased transferred stress within relatively short time frames, while others highlight the inhibitory effect of stress shadows. Examining the differences in seismic moment release across three seismicity windows (the first one between 1300 and 1400, the second around 1700, and the last one from 1979 to 2016) reveals distinct periods of higher seismicity in the past millennium. The latter shows the lowest cumulative seismic moment, suggesting a potential seismic gap equivalent to a Mw 6.67 earthquake. Deepening our understanding of CST illuminates the role of fault interactions in past earthquake occurrences, offering valuable insights into forecasting potential future seismic sequences. This awareness is vital in crafting targeted seismic risk mitigation strategies, thereby safeguarding local communities from the profound consequences of earthquakes.
Ruxolitinib plus steroids for acute graft versus host disease: a multicenter, randomized, phase 3 trial
Authors: Dou Liping , Zhao Yanli , Yang Jingjing , Deng Lei , Wang Nan , Zhang Xiawei , Liu Qingyang , Yang Yan , Wei Zhijie , Wang Fuxu , Jiao Yifan , Li Fei , Luan Songhua , Hu Liangding , Gao Sujun , Liu Chuanfang , Liu Xiangjun , Yan Jinsong , Zhang Xuejun , Zhou Fang , Lu Peihua , Liu Daihong 
Published: October 2024

AbstractNewly diagnosed patients with high-risk acute graft-versus-host disease (aGVHD) often experience poor clinical outcomes and low complete remission rates. Ruxolitinib with corticosteroids showed promising efficacy in improving response and failure free survival in our phase I study. This study (ClinicalTrials.gov: NCT04061876) sought to evaluate the safety and effectiveness of combining ruxolitinib (RUX, 5 mg/day) with corticosteroids (1 mg/kg/day methylprednisolone, RUX/steroids combined group) versus using methylprednisolone alone (2 mg/kg/day, steroids-only group). Newly diagnosed patients with intermediate- or high-risk aGVHD were included, with risk levels classified by either the Minnesota aGVHD Risk Score or biomarker assessment. Patients were randomized in a ratio of 1:1 into 2 groups: 99 patients received RUX combined with methylprednisolone, while the other 99 received methylprednisolone alone as the initial treatment. The RUX/steroids group showed a significantly higher overall response rate (ORR) on day 28 (92.9%) compared to the steroids-only group (70.7%, Odds Ratio [OR] = 5.8; 95% Confidence Interval [CI], 2.4–14.0; P < 0.001). Similarly, the ORR on day 56 was higher in the RUX/steroids group (85.9% vs. 46.5%; OR = 7.07; 95% CI, 3.36–15.75; P < 0.001). Additionally, the 18-month failure-free survival was significantly better in the RUX/steroids group (57.2%) compared to the steroids-only group (33.3%; Hazard Ratio = 0.46; 95% CI, 0.31–0.68; P < 0.001). Adverse events (AEs) frequencies were comparable between both groups, with the exception of fewer grade 4 AEs in the RUX/steroids group (26.3% vs. 50.5% P = 0.005). To our knowledge, this study is the first prospective, randomized controlled trial to demonstrate that adding ruxolitinib to the standard methylprednisolone regimen provides an effective and safe first-line treatment for newly diagnosed high-risk acute GVHD.
Collective self-caging of active filaments in virtual confinement
Authors: Kurjahn Maximilian , Abbaspour Leila , Papenfuß Franziska , Bittihn Philip , Golestanian Ramin , Mahault Benoît , Karpitschka Stefan 
Published: October 2024

AbstractMotility coupled to responsive behavior is essential for many microorganisms to seek and establish appropriate habitats. One of the simplest possible responses, reversing the direction of motion, is believed to enable filamentous cyanobacteria to form stable aggregates or accumulate in suitable light conditions. Here, we demonstrate that filamentous morphology in combination with responding to light gradients by reversals has consequences far beyond simple accumulation: Entangled aggregates form at the boundaries of illuminated regions, harnessing the boundary to establish local order. We explore how the light pattern, in particular its boundary curvature, impacts aggregation. A minimal mechanistic model of active flexible filaments resembles the experimental findings, thereby revealing the emergent and generic character of these structures. This phenomenon may enable elongated microorganisms to generate adaptive colony architectures in limited habitats or guide the assembly of biomimetic fibrous materials.
Chemical inhibition of stomatal differentiation by perturbation of the master-regulatory bHLH heterodimer via an ACT-Like domain
Authors: Nakagawa Ayami , Sepuru Krishna Mohan , Yip Shu Jan , Seo Hyemin , Coffin Calvin M. , Hashimoto Kota , Li Zixuan , Segawa Yasutomo , Iwasaki Rie , Kato Hiroe , Kurihara Daisuke , Aihara Yusuke , Kim Stephanie , Kinoshita Toshinori , Itami Kenichiro , Han Soon-Ki , Murakami Kei , Torii Keiko U. 
Published: October 2024

AbstractSelective perturbation of protein interactions with chemical compounds enables dissection and control of developmental processes. Differentiation of stomata, cellular valves vital for plant growth and survival, is specified by the basic-helix-loop-helix (bHLH) heterodimers. Harnessing a new amination reaction, we here report a synthesis, derivatization, target identification, and mode of action of an atypical doubly-sulfonylated imidazolone, Stomidazolone, which triggers stomatal stem cell arrest. Our forward chemical genetics followed by biophysical analyses elucidates that Stomidazolone directly binds to the C-terminal ACT-Like (ACTL) domain of MUTE, a master regulator of stomatal differentiation, and perturbs its heterodimerization with a partner bHLH, SCREAM in vitro and in plant cells. On the other hand, Stomidazolone analogs that are biologically inactive do not bind to MUTE or disrupt the SCREAM-MUTE heterodimers. Guided by structural docking modeling, we rationally design MUTE with reduced Stomidazolone binding. These engineered MUTE proteins are fully functional and confer Stomidazolone resistance in vivo. Our study identifies doubly-sulfonylated imidazolone as a direct inhibitor of the stomatal master regulator, further expanding the chemical space for perturbing bHLH-ACTL proteins to manipulate plant development.
LoDEI: a robust and sensitive tool to detect transcriptome-wide differential A-to-I editing in RNA-seq data
Authors: Torkler Phillipp , Sauer Marina , Schwartz Uwe , Corbacioglu Selim , Sommer Gunhild , Heise Tilman 
Published: October 2024

AbstractRNA editing is a highly conserved process. Adenosine deaminase acting on RNA (ADAR) mediated deamination of adenosine (A-to-I editing) is associated with human disease and immune checkpoint control. Functional implications of A-to-I editing are currently of broad interest to academic and industrial research as underscored by the fast-growing number of clinical studies applying base editors as therapeutic tools. Analyzing the dynamics of A-to-I editing, in a biological or therapeutic context, requires the sensitive detection of differential A-to-I editing, a currently unmet need. We introduce thelocaldifferentialeditingindex (LoDEI) to detect differential A-to-I editing in RNA-seq datasets using a sliding-window approach coupled with an empirical q value calculation that detects more A-to-I editing sites at the same false-discovery rate compared to existing methods. LoDEI is validated on known and novel datasets revealing that the oncogene MYCN increases and that a specific small non-coding RNA reduces A-to-I editing.
Isotopic evidence of acetate turnover in Precambrian continental fracture fluids
Authors: Mueller Elliott P. , Panehal Juliann , Meshoulam Alexander , Song Min , Hansen Christian T. , Warr Oliver , Boettger Jason , Heuer Verena B. , Bach Wolfgang , Hinrichs Kai-Uwe , Eiler John M. , Orphan Victoria , Lollar Barbara Sherwood , Sessions Alex L. 
Published: October 2024

AbstractThe deep continental crust represents a vast potential habitat for microbial life where its activity remains poorly constrained. Organic acids like acetate are common in these ecosystems, but their role in the subsurface carbon cycle - including the mechanism and rate of their turnover - is still unclear. Here, we develop an isotope-exchange ‘clock’ based on the abiotic equilibration of H-isotopes between acetate and water, which can be used to define the maximum in situ acetate residence time. We apply this technique to the fracture fluids in Birchtree and Kidd Creek mines within the Canadian Precambrian crust. At both sites, we find that acetate residence times are <1 million years and calculated a rate of turnover that could theoretically support microbial life. However, radiolytic water-rock reactions could also contribute to acetate production and degradation, a process that would have global relevance for the deep biosphere. More broadly, our study demonstrates the utility of isotope-exchange clocks in determining residence times of biomolecules with possible applications to other environments.
Over-reliance on land for carbon dioxide removal in net-zero climate pledges
Authors: Dooley Kate , Christiansen Kirstine Lund , Lund Jens Friis , Carton Wim , Self Alister 
Published: October 2024

AbstractAchieving net-zero climate targets requires some level of carbon dioxide removal. Current assessments focus on tonnes of CO2 removed, without specifying what form these removals will take. Here, we show that countries’ climate pledges require approximately 1 (0.9–1.1) billion ha of land for removals. For over 40% of this area, the pledges envisage the conversion of existing land uses to forests, while the remaining area restores existing ecosystems and land uses. We analyse how this demand for land is distributed geographically and over time. The results are concerning, both in terms of the aggregate area of land, but also the rate and extent of land use change. Our findings demonstrate a gap between governments’ expected reliance on land and the role that land can realistically play in climate mitigation. This adds another layer to the observed shortcomings of national climate pledges and indicates a need for more transparency around the role of land in national climate mitigation plans.