bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of European badger setts by invasive raccoons and other mesocarnivores in western Poland
Authors: Ważna Agnieszka , Nowakowski Krzysztof , Kurek Przemysław , Ciepliński Mateusz , Cichocki Jan
Published: October 2024

We describe a cases of main setts of European badger Meles meles being used by non-native raccoons Procyon lotor and raccoon dogs Nyctereutes procyonoides and native red foxes Vulpes vulpes in western Poland. From April to June 2022 and from November 2022 to mid-April 2023, we monitored the main badger setts (27 in spring and 14 in winter) using camera traps. We recorded the presence of red foxes in 63.0%, raccoon dogs in 48.1% and raccoons in 22.2% of the setts. These species were more likely to occupy badger setts in winter. The raccoon is the second invasive species after the raccoon dog to use badger setts for shelter in Poland. In four setts, we observed that two native (badger and red fox) and two non-native (raccoon and raccoon dog) mesocarnivores cohabited the same sett.
Discrepancy between antibiotic pack sizes and guideline recommendations: a real-world analysis based on claims data
Authors: Stollberg Sabrina M. , Graber Sereina M. , Kronenberg Andreas , Senn Oliver , Neuner-Jehle Stefan , Pluess-Suard Catherine , Huber Carola A. , Plate Andreas
Published: October 2024

Purpose

Antibiotics are often only available in predefined pack sizes, which may not align with guideline recommendations. This can result in leftover pills, leading to inappropriate self-medication or waste disposal, which can both foster the development of antibiotic resistance. The magnitude of inappropriate pack sizes is largely unknown. The objective of this study was to evaluate the potential non-conformity of prescribed antibiotic pack sizes.

Methods

This retrospective observational study was based on claims data from a large Swiss health insurance company. The study analysed the prescriptions of eleven different antibiotic substances recommended for the five most common indications for antibiotics in Switzerland. All prescriptions for adult outpatients issued by general practitioners in 2022 were included and extrapolated to the entire Swiss population. Potential non-conformity was defined as a mismatch between the total dosage in a pack and the total dosage recommended.

Results

A total of n = 947,439 extrapolated prescriptions were analysed. In 10 of 23 of all analysed substance/indication combinations none of the prescribed packs aligned with the respective guideline recommendation. Considering pack sizes in which the total prescribed dosage of a substance did not correspond to any of the total dosages recommended in at least one of the guidelines, 31.6% of prescriptions were potentially non-conform and an estimated number of 2.7 million tablets were overprescribed.

Conclusions

We found a large discrepancy between prescribed pack sizes and guideline recommendations. Since inadequately prepacked antibiotics may lead to antibiotic resistance and unnecessary waste, efforts are needed to implement alternatives like exact pill dispensing.
Survey on current clinical practice in geriatric oncology: the individual experience in five European Cancer Centers
Authors: Javier-González M. , Boulahssass R. , Lago L. Dal , González-Senac N. M. , Nair S. , Vetter M.
Published: October 2024

Purpose

To gather information from clinicians on how geriatric oncology models of care have emerged in different European countries and describe current practice in this clinical area.

Methods

A semi-structured online interview was performed, exploring aspects related to implementation, perceived quality of care, and professional satisfaction.

Results

The centers participating in this interview showed significant differences in terms of resource allocation, team members, components of the comprehensive geriatric assessment (CGA), and CGA-driven interventions. High levels of professional satisfaction were expressed by all participants. This was deemed a consequence of a perception of increased quality in the provision of care and enhanced educational and academic opportunities.

Conclusion

Interdisciplinary models of care in geriatric oncology, regardless of implementation details, seem to provide grounds for increased professional satisfaction and perception of better provision of quality of care. These characteristics could support promoting and further developing similar collaborations on a wider scale.
Collaborative strategies for sustainable management of the Citarum Watershed in Indonesia: a Quintuple Helix approach
Authors: Abdillah Abdillah , Widianingsih Ida , Buchari Rd Ahmad , Nurasa Heru
Published: October 2024

The Citarum River revitalization program through the “Citarum Harum” program, focuses on integrated cooperation between multi-sector actors in managing the Citarum Watershed sustainably and improving the quality of life around the river. Such as ministries (central government) acting as policy and regulation providers and as the leading sector, local governments acting as program supervisors and monitors, academics/universities acting as knowledge creators and program management innovations, the private sector acting as important partners, communities acting as program supporters and participants, and the Indonesian National Army (Tentara National Indonesia, TNI) acting as initiators, law enforcers, and field supervisors. This article outlines some of the challenges faced by Citarum Watershed, as well as important findings regarding collaborative sustainable and resilient watershed management, particularly in the context of the Citarum River, Indonesia. In this commentary, we underscore the importance of collaborative efforts, effective policy frameworks, and adaptive management strategies in addressing the environmental challenges faced by the Citarum River, while highlighting the need for ongoing commitment from all stakeholders during program implementation and post-program. The implications of these findings suggest a holistic, inclusive, and adaptive approach to sustainable management of watersheds and the environment that can be applied to other regions facing similar challenges such as Pollution; Environmental Degradation; Critical Land and Sedimentation; Inadequate Infrastructure; Population Growth and Urbanization; Climate Change, Weak Law Enforcement, and Lack of Coordination Among Stakeholders.
Genetic variability and discriminatory power of RM Y-STRs in gilgit men: a population study
Authors: Ullah Muhammad Farhat , Khan Muhammad Ramzan , Khan Muhammad Ijaz , Rakhmatov Uchkun
Published: October 2024

Short Tandem Repeats (STRs) found on the Y chromosome have multiple applications, such as in forensic investigations, male identification for legal reasons, as well as population genetics. However, commercially accessible Y-STR tests are limited in their capability to distinguish closely linked male individuals in forensic genetics. Recent studies have revealed that Rapidly Mutating Y-STRs (RM Y-STRs) offer significantly greater haplotype diversity around the worldwide populations associated to conventional Y-STRs, though some RM Y-STR loci are not contained, current commercial kits. The objective of this research is to create a database of RM Y-STR haplotype frequencies for the Gilgit population in Pakistan and evaluate the effectiveness of these genetic markers in distinguishing individuals with genetic variations. The research involved examining several RM Y-STRs in 56 unrelated Gilgit men. The statistical analysis determined that the majority of the loci-maintained haplotype values, as specific varied in certain cases. The results presented that the RM Y-STRs were very effective in distinguishing genetic changes among the Gilgit population, through a GD value of 0 for DYD403S1 and GD values greater than 0.7 for all other loci, with maximum value of 0.9920 for the RM Y-STR DYS612.
Performance evaluation of fly ash–copper slag-based geopolymer bricks
Authors: Erunkulu Ibukunoluwa O. , Malumbela Goitseone , Oladijo Oluseyi P.
Published: October 2024

This study investigates the production and evaluation of geopolymer bricks made from a blend of fly ash, copper slag, soda ash activator, and sand as fillers. Locally abundant industrial and mining waste materials were selected as the primary components. The bricks were synthesized using two binders: 60% fly ash with 40% copper slag, or 70% fly ash with 30% copper slag. Both were milled with the activator at a 0.2 soda ash-to-precursor ratio. Fine sand was added to the mixes at 1:2 and 1:3 binders-to-sand ratios. The bricks’ physical, mechanical, and durability properties were examined through compressive strength, modulus of rupture, density, water absorption, drying shrinkage, and efflorescence test, and their performance was compared to established industry standards. The experimental findings indicate that bricks made with 60% fly ash, 40% copper slag, and a 1:2 binder-to-sand ratio exhibited optimal compressive strength (9.64 MPa) and water absorption (7.5%) at 28 days of curing age. Conversely, there was only a marginal increase of up to 4.7% in the strength of the formulation with 70% fly ash and 30% copper slag, attaining a compressive strength of 4.9 MPa between the curing ages. Furthermore, the results indicated a positive correlation between the density and compressive strength of the geopolymer bricks at similar curing ages. The bricks’ density showed minimal variation with curing age and the highest modulus of rupture value observed was 2.5 MPa. The optimal bricks also exhibited relatively low linear shrinkage, good resistance to efflorescence, and met the relevant industry standards.
A meta-analysis of the impact of water-solved pollutants on the protein content of Pistia stratiotes L.
Authors: Hernández-Hernández Eduardo , Cocoletzi-Vásquez Eliezer , Díaz-Martínez María Esther , Sánchez-Viveros Gabriela
Published: October 2024

Due to the high cost of conventional water cleaning procedures, an affordable alternative for developing countries is the use ofPistia stratiotesL. Although these plants adsorb toxic chemicals in their tissues, other studies report a high protein content in its biomass and propose to use it as a fodder or even for human consumption. Therefore, this study aimed to identify the impact of water-solved pollutants on the content of protein in the tissues ofP. stratiotesthrough a meta-analysis of currently available literature. Scientific reports, which included the biochemical analysis of the species when exposed to pollutants in the growing media were retrieved. The statistical analysis identified that chromium, wastewater sludge from a sugar factory, fluoride and linear alkyl benzene sulphonate reduce the content of protein. On the contrary, metals such as copper and zinc showed a slight tendency to promote the accumulation of protein in the biomass. Only the use of municipal wastewater sludge consistently promoted the increase of protein. Since most pollutants reduced the protein content and others also pose a bioaccumulation risk,P. stratiotesis not recommended to be considered as a fodder or to be included in human diet without previously ensuring its chemical innocuity.
Artificial Intelligence and Administrative Discretion: Exploring Adaptations and Boundaries
Authors: Covilla Juan Carlos
Published: October 2024

This paper explores the necessary adaptations to the theory of administrative discretion when using AI systems. Regulatory frameworks in the EU, US, and Spain do not prohibit the application of AI in discretionary decision-making. Particularly, AI systems can be used when discretionary power involves correlations. However, to meet Rule of Law conditions, it is essential to establish adaptations and boundaries in areas such as duty of care, reason-giving, and judicial review. These conditions should focus on the impact of decisions on the affected individuals.
Evolution of linear internal waves over large bottom topography in three-layer stratified fluids
Authors: Chai Jin , Wang Zhan
Published: October 2024

Evolutions of internal waves of different modes, particularly mode 1 and mode 2, passing over variable bathymetry are investigated based on a new numerical scheme. The problem is idealized as interfacial waves propagating on two interfaces of a three-layer density stratified fluid system with large-amplitude bottom topography. The Dirichlet-to-Neumann operators are introduced to reduce the spatial dimension by one and to adapt the three-layer system and significant topographic effects. However, for simplicity, nonlinear interactions between interfaces are neglected. Numerical techniques such as the Galerkin approximation, proven effective in previous works, are applied to save computational costs. Shoaling of linear waves on an uneven bottom is first studied to validate the proposed formulation and the corresponding numerical scheme. Then, for two-dimensional numerical experiments, mode transition phenomena excited by locally confined bottom obstacles and quickly varying topographies, including the Bragg resonance, mode-2 excitation, wave homogenization, etc., are investigated. In three-dimensional simulations, internal wave refraction by a Luneberg lens is considered, and good agreement is found in comparison with the ray theory. Finally, in the limiting case, when the top layer can be negligible (for example, a gas layer of extremely small density), the problem is reduced to a two-and-a-half-layer fluid system, where an interface and a surface are unknown free boundaries. In this situation, the surface signature of an internal wave is simulated and verified by introducing the realistic bathymetry of the Strait of Gibraltar and qualitatively compared with the satellite image.
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

The 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

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

Alzheimer’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

The 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

This 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

Boron 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

Variations 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

The 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

Newly 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

Motility 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

Selective 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

RNA 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

The 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

Achieving 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.
Interplay between metavalent bonds and dopant orbitals enables the design of SnTe thermoelectrics
Authors: Tang Guodong , Liu Yuqi , Yang Xiaoyu , Zhang Yongsheng , Nan Pengfei , Ying Pan , Gong Yaru , Zhang Xuemei , Ge Binghui , Lin Nan , Miao Xuefei , Song Kun , Schön Carl-Friedrich , Cagnoni Matteo , Kim Dasol , Yu Yuan , Wuttig Matthias
Published: October 2024

Engineering the electronic band structures upon doping is crucial to improve the thermoelectric performance of materials. Understanding how dopants influence the electronic states near the Fermi level is thus a prerequisite to precisely tune band structures. Here, we demonstrate that the Sn-s states in SnTe contribute to the density of states at the top of the valence band. This is a consequence of the half-filled p-p σ-bond (metavalent bonding) and its resulting symmetry of the orbital phases at the valence band maximum (L point of the Brillouin zone). This insight provides a recipe for identifying superior dopants. The overlap between the dopant s- and the Te p-state is maximized, if the spatial overlap of both orbitals is maximized and their energetic difference is minimized. This simple design rule has enabled us to screen out Al as a very efficient dopant to enhance the local density of states for SnTe. In conjunction with doping Sb to tune the carrier concentration and alloying with AgBiTe2 to promote band convergence, as well as introducing dislocations to impede phonon propagation, a record-high average ZT of 1.15 between 300 and 873 K and a large ZT of 0.36 at 300 K is achieved in Sn0.8Al0.08Sb0.15Te-4%AgBiTe2.
Coral photosymbiosis on Mid-Devonian reefs
Authors: Jung Jonathan , Zoppe Simon F. , Söte Till , Moretti Simone , Duprey Nicolas N. , Foreman Alan D. , Wald Tanja , Vonhof Hubert , Haug Gerald H. , Sigman Daniel M. , Mulch Andreas , Schindler Eberhard , Janussen Dorte , Martínez-García Alfredo
Published: October 2024

The ability of stony corals to thrive in the oligotrophic (low-nutrient, low-productivity) surface waters of the tropical ocean is commonly attributed to their symbiotic relationship with photosynthetic dinoflagellates1,2. The evolutionary history of this symbiosis might clarify its organismal and environmental roles3, but its prevalence through time, and across taxa, morphologies and oceanic settings, is currently unclear4–6. Here we report measurements of the nitrogen isotope (15N/14N) ratio of coral-bound organic matter (CB-δ15N) in samples from Mid-Devonian reefs (Givetian, around 385 million years ago), which represent a constraint on the evolution of coral photosymbiosis. Colonial tabulate and fasciculate (dendroid) rugose corals have low CB-δ15N values (2.51 ± 0.97‰) in comparison with co-occurring solitary and (pseudo)colonial (cerioid or phaceloid) rugose corals (5.52 ± 1.63‰). The average of the isotopic difference per deposit (3.01 ± 0.58‰) is statistically indistinguishable from that observed between modern symbiont-barren and symbiont-bearing corals (3.38 ± 1.05‰). On the basis of this evidence, we infer that Mid-Devonian tabulate and some fasciculate (dendroid) rugose corals hosted active photosymbionts, while solitary and some (pseudo)colonial (cerioid or phaceloid) rugose corals did not. The low CB-δ15N values of the Devonian tabulate and fasciculate rugose corals relative to the modern range suggest that Mid-Devonian reefs formed in biogeochemical regimes analogous to the modern oligotrophic subtropical gyres. Widespread oligotrophy during the Devonian may have promoted coral photosymbiosis, the occurrence of which may explain why Devonian reefs were the most productive reef ecosystems of the Phanerozoic.
Integrating observational and modelled data to advance the understanding of heat stress effects on pregnant subsistence farmers in the gambia
Authors: Bouverat Carole , Badjie Jainaba , Samateh Tida , Saidy Tida , Murray Kris A. , Prentice Andrew M. , Maxwell Neil , Haines Andy , Vicedo Cabrera Ana Maria , Bonell Ana
Published: October 2024

Studies on the effect of heat stress on pregnant women are scarce, particularly in highly vulnerable populations. To support the risk assessment of pregnant subsistence farmers in the West Kiang district, The Gambia we conducted a study on the pathophysiological effects of extreme heat stress and assessed the applicability of heat stress indices. From ERA5 climate reanalysis we added location-specific modelled solar radiation to datasets of a previous observational cohort study involving on-site measurements of 92 women working in the heat. Associations between physiological and environmental variables were assessed through Pearson correlation coefficient analysis, mixed effect linear models with random intercepts per participant and confirmatory composite analysis. We found Pearson correlations between r-values of 0 and 0.54, as well as independent effects of environmental variables on skin- and tympanic temperature, but not on heart rate, within a confidence interval of 98%. Pregnant women experienced stronger pathophysiological effects from heat stress in their third rather than in their second trimester. Environmental heat stress significantly altered maternal heat strain, particularly under humid conditions above a 50% relative humidity threshold, demonstrating interactive effects. Based on our results, we recommend including heat stress indices (e.g. UTCI or WBGT) in local heat-health warning systems.
Noise filter using a periodic system of dual Helmholtz resonators
Authors: El Malki Mohamed , Khettabi Ali , Sallah Mohammed , Zaky Zaky A.
Published: October 2024

This study investigates noise reduction using a periodic arrangement of dual Helmholtz resonators and explores the introduction of defects within this periodic structure. The transfer matrix method was employed to carry out theoretical research. The computations of the interface response function approach results are verified, and consistent outcomes are demonstrated. The simulation results highlight the distinctive dual resonance frequencies of dual Helmholtz resonators. By differentiating dual Helmholtz resonators from traditional Helmholtz resonators, prospective applications for low-frequency noise reduction are envisioned. In this contribution, introducing defects in the middle of perfect dual Helmholtz resonators adds more value to the acoustic filter. In particular, the first neck and cavity of the defective dual Helmholtz resonator. This study shows that introducing a 2D-defect into identical dual Helmholtz resonators can improve the transmission of defect modes by taking advantage of the advantageous interaction of the resonant modes. In such arrangements, the entire structure functioned as a potent selective filter.
Emotional contagion to vocal smile revealed by combined pupil reactivity and motor resonance
Authors: Merchie Annabelle , Ranty Zoé , Aguillon-Hernandez Nadia , Aucouturier Jean-Julien , Wardak Claire , Gomot Marie
Published: October 2024

The interplay between the different components of emotional contagion (i.e. emotional state and facial motor resonance), both during implicit and explicit appraisal of emotion, remains controversial. The aims of this study were (i) to distinguish between these components thanks to vocal smile processing and (ii) to assess how they reflect implicit processes and/or an explicit appraisal loop. Emotional contagion to subtle vocal emotions was studied in 25 adults through motor resonance and Autonomic Nervous System (ANS) reactivity. Facial expressions (fEMG: facial electromyography) and pupil dilation were assessed during the processing and judgement of artificially emotionally modified sentences. fEMG revealed that Zygomaticus major was reactive to the perceived valence of sounds, whereas the activity of Corrugator supercilii reflected explicit judgement. Timing analysis of pupil dilation provided further insight into both the emotional state and the implicit and explicit processing of vocal emotion, showing earlier activity for emotional stimuli than for neutral stimuli, followed by valence-dependent variations and a late judgement-dependent increase in pupil diameter. This innovative combination of different electrophysiological measures shed new light on the debate between central and peripherical views within the framework of emotional contagion.
Antibacterial activity of green synthesized copper oxide nanoparticles against multidrug-resistant bacteria
Authors: Khairy Toka , Amin Dina Hatem , Salama Hanaa Mohamed , Elkholy Iman Mohamed Amin , Elnakib Mostafa , Gebreel Hassan Mahmoud , Sayed Hayam Abd Elnabi
Published: October 2024

Using plant extracts in the green synthesis of nanoparticles has become an environmentally acceptable approach. In our study, copper oxide nanoparticles (CuO NPs) were synthesized using ethanolic extracts of Azadirachta indica and Simmondsia chinensis. CuO NP formation was confirmed by the change in color and by UV‒visible spectroscopy (CuO NPs peaked at a wavelength of 344 nm). TEM images confirmed the semispherical shape of the CuO NPs, with particle sizes ranging from 30.9 to 10.7 nm. The antibacterial activity of these NPs was evaluated by using the agar diffusion method against clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, Pseudomonas aeruginosa, Acinetobacter spp., Klebsiella pneumoniae, and Stenotrophomonas maltophilia. The minimum inhibitory concentration (MIC) of CuO NPs ranged from 62.5 to 125 µg/ml. In contrast, the antioxidant activity and antibiofilm activity of CuO NPs ranged from 31.1 to 92.2% at 125–500 µg/ml and 62.2–95%, respectively, at 125 –62.5 µg/ml. Our results confirmed that CuO NPs had IC50s of 383.41 ± 3.4 and 402.73 ± 1.86 at 250 µg/mL against the HBF4 cell line. Molecular docking studies with CuO NPs suggested that penicillin-binding protein 4 (PBP4) and beta-lactamase proteins (OXA-48) strongly bind to S. aureus and K. pneumoniae, respectively, with CuO NPs. Our study confirms the promising use of CuO NPs in treating pathogenic bacteria and that CuO NPs could be possible alternative antibiotics. This study supports the pharmaceutical and healthcare sectors in Egypt and worldwide.