bluuebunny/crossref_metadata_2025 huggingface dataset:
The correlation between CpG methylation and gene expression is driven by sequence variants
Authors: Stefansson Olafur Andri , Sigurpalsdottir Brynja Dogg , Rognvaldsson Solvi , Halldorsson Gisli Hreinn , Juliusson Kristinn , Sveinbjornsson Gardar , Gunnarsson Bjarni , Beyter Doruk , Jonsson Hakon , Gudjonsson Sigurjon Axel , Olafsdottir Thorunn Asta , Saevarsdottir Saedis , Magnusson Magnus Karl , Lund Sigrun Helga , Tragante Vinicius , Oddsson Asmundur , Hardarson Marteinn Thor , Eggertsson Hannes Petur , Gudmundsson Reynir L. , Sverrisson Sverrir , Frigge Michael L. , Zink Florian , Holm Hilma , Stefansson Hreinn , Rafnar Thorunn , Jonsdottir Ingileif , Sulem Patrick , Helgason Agnar , Gudbjartsson Daniel F. , Halldorsson Bjarni V. , Thorsteinsdottir Unnur , Stefansson Kari
Published: July 2024

Gene promoter and enhancer sequences are bound by transcription factors and are depleted of methylated CpG sites (cytosines preceding guanines in DNA). The absence of methylated CpGs in these sequences typically correlates with increased gene expression, indicating a regulatory role for methylation. We used nanopore sequencing to determine haplotype-specific methylation rates of 15.3 million CpG units in 7,179 whole-blood genomes. We identified 189,178 methylation depleted sequences where three or more proximal CpGs were unmethylated on at least one haplotype. A total of 77,789 methylation depleted sequences (~41%) associated with 80,503 cis-acting sequence variants, which we termed allele-specific methylation quantitative trait loci (ASM-QTLs). RNA sequencing of 896 samples from the same blood draws used to perform nanopore sequencing showed that the ASM-QTL, that is, DNA sequence variability, drives most of the correlation found between gene expression and CpG methylation. ASM-QTLs were enriched 40.2-fold (95% confidence interval 32.2, 49.9) among sequence variants associating with hematological traits, demonstrating that ASM-QTLs are important functional units in the noncoding genome.
Cohesin prevents cross-domain gene coactivation
Authors: Dong Peng , Zhang Shu , Gandin Valentina , Xie Liangqi , Wang Lihua , Lemire Andrew L. , Li Wenhong , Otsuna Hideo , Kawase Takashi , Lander Arthur D. , Chang Howard Y. , Liu Zhe J.
Published: July 2024

The contrast between the disruption of genome topology after cohesin loss and the lack of downstream gene expression changes instigates intense debates regarding the structure–function relationship between genome and gene regulation. Here, by analyzing transcriptome and chromatin accessibility at the single-cell level, we discover that, instead of dictating population-wide gene expression levels, cohesin supplies a general function to neutralize stochastic coexpression tendencies of cis-linked genes in single cells. Notably, cohesin loss induces widespread gene coactivation and chromatin co-opening tens of million bases apart in cis. Spatial genome and protein imaging reveals that cohesin prevents gene co-bursting along the chromosome and blocks spatial mixing of transcriptional hubs. Single-molecule imaging shows that cohesin confines the exploration of diverse enhancer and core promoter binding transcriptional regulators. Together, these results support that cohesin arranges nuclear topology to control gene coexpression in single cells.
Seed germination, morphology and fruit phenology insight of Cylicomorpha solmsii (Urb.) Urb: a step towards sustainable restoration planning
Authors: Na-ah Raissa Fon , Ngwa Nadine Ndabeh , Tandzi Liliane Ngoune , Tchatchouang Eric Ngansop , Zerpa-Catanho Dessireé P. , Youmbi Emmanuel , Tonfack Libert Brice
Published: July 2024

Cylicomorpha solmsii (Urb.) Urb (Caricaceae) is a wild relative of domesticated Carica papaya native to the humid tropical forest of Cameroon. C. solmsii is becoming extinct due to rapid urbanization of its habitat. There is currently no restoration planning, no available data on seed germination, details on morphological description and fruit phenology. We investigated the effects of light and soil on seed germination, updated its morphological description and provided cues of its fruit phenology. In two series of experiments, a germination test was first conducted under light and dark conditions with three seed pre-treatments (scarification, drying and cold). Secondly, pre-treated seeds were sown in native soils of C. solmsii habitat collected at Eloumden I and II, two ex-situ and mixtures soil with sand. Qualitative and quantitative data were collected on different part of the plant and analyzed using R package version 4.3.2. Our findings showed that C. solmsii seeds can germinate only under light. The seeds manifested a physiological embryonic dormancy. The native soils showed the highest germination percentage and seedling establishment. The dioicy of C. solmsii was clearly described with incomplete staminate and pistillate unisexual flower whorls. C. solmsii was observed to produce fruits throughout the year at varying intensity. This information is a vital cue to species restoration and policy makers towards C. solmsii conservation.
Evolution of ion channels in cetaceans: a natural experiment in the tree of life
Authors: Uribe Cristóbal , Nery Mariana F. , Zavala Kattina , Mardones Gonzalo A. , Riadi Gonzalo , Opazo Juan C.
Published: July 2024

Cetaceans represent a natural experiment within the tree of life in which a lineage changed from terrestrial to aquatic habitats. This shift involved phenotypic modifications, representing an opportunity to explore the genetic bases of phenotypic diversity. Among the different molecular systems that maintain cellular homeostasis, ion channels are crucial for the proper physiological functioning of all living species. This study aims to explore the evolution of ion channels during the evolutionary history of cetaceans. To do so, we created a bioinformatic pipeline to annotate the repertoire of ion channels in the genome of the species included in our sampling. Our main results show that cetaceans have, on average, fewer protein-coding genes and a higher percentage of annotated ion channels than non-cetacean mammals. Signals of positive selection were detected in ion channels related to the heart, locomotion, visual and neurological phenotypes. Interestingly, we predict that the NaV1.5 ion channel of most toothed whales (odontocetes) is sensitive to tetrodotoxin, similar to NaV1.7, given the presence of tyrosine instead of cysteine, in a specific position of the ion channel. Finally, the gene turnover rate of the cetacean crown group is more than three times faster than that of non-cetacean mammals.
Modelling the implementation of narrow versus broader spectrum antibiotics in the empiric treatment of E. coli bacteraemia
Authors: Khurana Mark P. , Curran-Sebastian Jacob , Bhatt Samir , Knight Gwenan M.
Published: July 2024

The implementation of new antimicrobial resistance stewardship programs is crucial in optimizing antibiotic use. However, prescription choices can be difficult during empiric therapy; clinicians must balance the survival benefits of broader spectrum antibiotics with associated increases in resistance. The aim of this study was to evaluate the overall feasibility of switching to narrow spectrum antibiotics during the empiric treatment of E. coli bacteraemia by quantifying changes in resistance rates, antibiotic usage, and mortality using a deterministic state-transition model. Three unique model scenarios (A, B, and C), each representing a progressively broader spectrum empiric treatment regimen, were used to compare outcomes at 5 years. We show that the empiric use of the narrowest spectrum (first-line) antibiotics can lead to reductions in resistance to second-line antibiotics and the use of third-line antibiotics, but they also lead to increases in resistance to first-line therapy and higher mortality. Crucially, we find that shortening the duration of empiric and overall treatment, as well as reducing the baseline mortality rate, are important for increasing the feasibility of switching to narrow spectrum antibiotics in the empiric treatment of E. coli bacteraemia. We provide a flexible model design to investigate optimal treatment approaches for other bacterial infections.
Designing a productive, profitable integrated farming system model with low water footprints for small and marginal farmers of Telangana
Authors: Karthik Rayapati , Ramana M. Venkata , Kumari Ch. Pragathi , Prakash T. Ram , Goverdhan M. , Naik D. Saida , Chandra Mandapelli Sharath , Kumar M. Santhosh , Kumar Nallagatla Vinod , Raising L. Peace , Baral Kirttiranjan , Bhatt Rajan , Al-Ansari Nadhir , Elhindi Khalid M. , Mattar Mohamed A.
Published: July 2024

In the years 2021–2022 and 2022–2023, an experiment was carried out at the IFS Unit, College of Agriculture, PJTSAU, Rajendranagar in order to determine the best one-acre integrated farming system model for Telangana's small and marginal farmers. Seven farm models among which six models were developed by combining the various components i.e., cropping systems, fruit cropfodder crops and livestock components, in different proportions, and compared with rice-groundnut system which is a major farming approach in Telangana using randomized block design. The seven models were as follows: M1: Rice–Groundnut; M2: Rice–Groundnut, Pigeonpea + Sweetcorn (1:3)—Bajra, Bt cotton + Greengram (1:2)—Maize; M3: Rice–Groundnut, Pigeonpea + Sweetcorn (1:3)—Bajra, Pigeonpea + Maize (1:3)—Sunhemp; Napier grass, Sheep (5 + 1); M4: Rice–Groundnut, Pigeonpea + Sweetcorn (1:3)—Bajra, Bt cotton + Greengram (1:2)—Maize, Pigeonpea + Maize (1:3)—Sunhemp, Poultry unit; M5: Guava, Hedge Lucerne, Napier grass, Bt cotton + Greengram (1:2)—Maize, Sheep (5 + 1); M6: Guava, Bt cotton + Greengram (1:2)—Maize, Rice–Groundnut, Poultry; M7: Rice–Groundnut, Pigeonpea + Sweetcorn (1:3)—Bajra, Pigeonpea + Maize (1:3)—Sunhemp; Napier grass, Hedge lucerne, Poultry (100), Sheep (5 + 1). Based on a 2-year average, the Model M7 system produced 9980 Rice Grain Equivalent Yield(RGEY)kg of output per acre, with gross and net returns of ₹210,439 and ₹124,953 respectively, and recovered a B:C ratio of 2.46. It has recorded highest sustainable yield index (SYI) of 0.673 and value index of 0.772 with the lowest water footprint of 259.0 L/kg. This study reveals that adopting an integrated farming system is the optimal approach for effectively combining productive, financially rewarding, and diversified enterprises within a single acre of land.d. This system should be recommended for maximum benefits to smallto small and marginal farmers in Telangana's southern hills and plateau.
Detection of pharmacolipidodynamic effects following the intravenous and oral administration of gefitinib to C57Bl/6JRj mice by rapid UHPLC-MS analysis of plasma
Authors: Plumb Robert S. , Gethings Lee A. , Isaac Giorgis , Munjoma Nyasha C. , Wilson Ian D.
Published: July 2024

Omics-based biomarker technologies, including metabolic profiling (metabolomics/metabonomics) and lipidomics, are making a significant impact on disease understanding, drug development, and translational research. A wide range of patho-physiological processes involve lipids and monitoring changes in lipid abundance can give valuable insights into mechanisms of drug action, off target pharmacology and toxicity. Here we report changes, detected by untargeted LC–MS, in the plasma lipid profiles of male C57Bl/6JRj mice following the PO and IV administration of the epidermal growth factor receptor (EGFR) inhibitor gefitinib. Statistical analysis of the data obtained for both the IV and PO samples showed time-related changes in the amounts of lipids from several different classes. The largest effects were associated with a rapid onset of these changes following gefitinib administration followed by a gradual return by 24 h post dose to the type of lipid profile seen in predose samples. Investigation of the lipids responsible for the variance observed in the data showed that the PI, PC, LPC, PE and TG were subject to the largest disruption with both transient increases and decreases in relative amounts seen in response to administration of the drug. The pattern of the changes in the relative abundances of those lipids subject to variation appeared to be correlated to the pharmacokinetics of gefitinib (and its major metabolites). These observations support the concept of a distinct pharmacolipidodynamic relationship between drug exposure and plasma lipid abundance.
Adjusting microwave sensing frequency through aspect ratio variation and bending repetitions in Permalloy ellipses
Authors: Kim Nayeon , Seo Dongpyo , Kim ByungRo , Kim Youjung , Yoon Seungha , Kim Jin Hyeok
Published: July 2024

The Ferromagnetic Resonance (FMR) phenomenon, marked by the selective absorption of microwave radiation by magnetic materials in the presence of a magnetic field, plays a pivotal role in the development of radar absorbing materials, high speed magnetic storage, and magnetic sensors. This process is integral for technologies requiring precise control over microwave absorption frequencies. We explored how variations in resonance fields can be effectively modulated by adjusting both the shape and stress anisotropies of magnetic materials on a flexible substrate. Utilizing polyethylene-naphthalate (PEN) as the substrate and Permalloy (Ni79Fe21, noted for its positive magnetostriction coefficient) as the magnetic component, we demonstrated that modifications in the aspect ratio and bending repetitions can significantly alter the resonance field. The results, consistent with Kittel’s equation and the predictions of a uniaxial magnetic anisotropy model, underscore the potential for flexible substrates in enhancing the sensitivity and versatility of RF-based magnetic devices.
Microstructure and coupling mechanisms in MnBi–FeSiB nanocomposites obtained by spark plasma sintering
Authors: Alexandru-Dinu A. , Locovei C. , Bartha C. , Grigoroscuta M. A. , Burdusel M. , Kuncser A. , Palade P. , Schinteie G. , Iacob N. , Lu W. , Batalu D. , Badica P. , Kuncser V.
Published: July 2024

Fabrication and extensive characterization of hard-soft nanocomposites composed of hard magnetic low-temperature phase LTP-MnBi and amorphous Fe70Si10B20 soft magnetic phase for bulk magnets are reported. Samples with compositions Mn55Bi45 + x⋅(Fe70Si10B20) (x = 0, 3, 5, 10, 20 wt.%) were prepared by spark plasma sintering of powder mixtures. Characterization has been performed by X-ray diffraction, scanning and transmission electron microscopy, magnetometry and 57Fe Mӧssbauer spectroscopy. It was shown that samples contain crystallized and nanometric LTP-MnBi phases with various elemental compositions depending on the degree of Bi clustering. Complex correlations between starting compositions, processes during fabrication, and functional magnetic characteristics were observed. Unexpected special situations of the relation between microstructure and magnetic coupling mechanisms are discovered. Exchange spring effects of different strengths occur, being very sensitive to morpho-structural and compositional features, which in turn are controlled by processing conditions. An in-depth analysis of related microscopic characteristics is provided. Results of this work suggest that fabrication by powder metallurgy routes, such as spark plasma sintering of hard and soft magnetic powder mixtures, of MnBi-based composites with exchange spring phenomena have a high potential in designing and optimization of suitable materials with tunable magnetic properties towards rare-earth–free permanent magnet applications.
Development, modelling and optimization of process parameters on the tensile strength of aluminum, reinforced with pumice and carbonated coal hybrid composites for brake disc application
Authors: Ibrahim Tanimu Kogi , Yawas Danjuma Saleh , Thaddaeus Julius , Danasabe Bashar , Iliyasu Ibrahim , Adebisi Adetayo Abdulmumin , Ahmadu Talib Onimisi
Published: July 2024

This study focuses on optimizing double stir casting process parameters to enhance the tensile strength of hybrid composites comprising aluminum alloy, brown pumice, and coal ash, intended for brake disc applications. Analytical techniques including X-ray fluorescence, X-ray diffraction, thermogravimetric analysis, and scanning electron microscopy were employed to characterize the composite constituents. The Taguchi method was utilized for experimental design and optimization to determine the optimal weight compositions of brown pumice and coal ash, as well as stir casting parameters (stirrer speed, pouring temperature, and stirring duration). Regression analysis was employed to develop a predictive mathematical model for the tensile strength of the hybrid composites and to assess the significance of process parameters. The optimized composite achieved a predicted tensile strength of 186.81 MPa and an experimental strength of 190.67 MPa using 7.5 vol% brown pumice, 2.5 vol% coal ash, a pouring temperature of 700 °C, stirrer speed of 500 rpm, and stirring duration of 10 min. This represents a 52.23% improvement over the as-cast aluminum alloy’s tensile strength. Characterization results revealed that brown pumice and coal ash contain robust minerals (SiO2, Fe2O3, Al2O3) suitable for reinforcing metal matrices like aluminum, titanium, and magnesium. Thermogravimetric and differential thermal analyses demonstrated thermal stability up to 614.01 °C for the optimized composite, making it suitable for brake disc applications.
Immune cell population dynamics following neonatal BCG vaccination and aerosol BCG revaccination in rhesus macaques
Authors: Sibley Laura , Sarfas Charlotte , Morrison Alexandra L. , Williams Jessica , Gkolfinos Konstantinos , Mabbutt Adam , Eckworth William , Lawrence Steve , Dennis Mike , White Andrew , Sharpe Sally
Published: July 2024

The BCG vaccine is given to millions of children globally but efficacy wanes over time and differences in the immune systems between infants and adults can influence vaccine efficacy. To this end, 34 rhesus macaques were vaccinated with BCG within seven days of birth and blood samples were collected over 88 weeks for quantification of blood cell populations. Overall, the composition of cell populations did not change significantly between BCG vaccinated and unvaccinated groups, and that BCG vaccination did not perturb normal development. In comparison to adult macaques, higher numbers of CD4+ T-cells, Tregs and NK cells were measured in the infant age group, suggesting a potential bias towards immunosuppressive and innate immune populations. Antigen-specific IFNγ secreting cell frequencies in infant BCG vaccinated animals were detectable in peripheral blood samples for 36 weeks after vaccination but declined following this. To evaluate the long-term impact of infant BCG vaccination on subsequent revaccination with BCG, a pilot study of three adult macaques received an aerosol BCG revaccination approximately 3 years after their initial BCG vaccination as infants. This induced an increase in PPD-specific IFNγ secreting cells, and increased secretion of the cytokines IFNγ and IL-1β, following stimulation with other microorganisms, which are signals associated with trained innate immunity.
Predicting performance in attention by measuring key metabolites in the PCC with 7T MRS
Authors: Collée M. , Rajkumar R. , Farrher E. , Hagen J. , Ramkiran S. , Schnellbächer G. J. , Khudeish N. , Shah N. J. , Veselinović T. , Neuner I.
Published: July 2024

The posterior cingulate cortex (PCC) is a key hub of the default mode network and is known to play an important role in attention. Using ultra-high field 7 Tesla magnetic resonance spectroscopy (MRS) to quantify neurometabolite concentrations, this exploratory study investigated the effect of the concentrations of myo-inositol (Myo-Ins), glutamate (Glu), glutamine (Gln), aspartate or aspartic acid (Asp) and gamma-amino-butyric acid (GABA) in the PCC on attention in forty-six healthy participants. Each participant underwent an MRS scan and cognitive testing, consisting of a trail-making test (TMT A/B) and a test of attentional performance. After a multiple regression analysis and bootstrapping for correction, the findings show that Myo-Ins and Asp significantly influence (p < 0.05) attentional tasks. On one hand, Myo-Ins shows it can improve the completion times of both TMT A and TMT B. On the other hand, an increase in aspartate leads to more mistakes in Go/No-go tasks and shows a trend towards enhancing reaction time in Go/No-go tasks and stability of alertness without signal. No significant (p > 0.05) influence of Glu, Gln and GABA was observed.
Cytotoxicity and antibacterial susceptibility assessment of a newly developed pectin–chitosan polyelectrolyte composite for dental implants
Authors: Alsharbaty Mohammed Hussein M. , Naji Ghassan A. , Ghani Ban A. , Schagerl Michael , Khalil Maha A. , Ali Sameh S.
Published: July 2024

Biopolymers such as chitosan and pectin are currently attracting significant attention because of their unique properties, which are valuable in the food industry and pharmaceutical applications. These properties include non-toxicity, compatibility with biological systems, natural decomposition ability, and structural adaptability. The objective of this study was to assess the performance of two different ratios of pectin–chitosan polyelectrolyte composite (PCPC) after applying them as a coating to commercially pure titanium (CpTi) substrates using electrospraying. The PCPC was studied in ratios of 1:2 and 1:3, while the control group consisted of CpTi substrates without any coating. The pull-off adhesion strength, cytotoxicity, and antibacterial susceptibility tests were utilized to evaluate the PCPC coatings. In order to determine whether the composite coating was the result of physical blending or chemical bonding, the topographic surface parameters were studied using Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). PCPC (1:3) had the highest average cell viability of 93.42, 89.88, and 86.85% after 24, 48, and 72 h, respectively, as determined by the cytotoxicity assay, when compared to the other groups. According to the Kirby–Bauer disk diffusion method for testing antibacterial susceptibility, PCPC (1:3) showed the highest average diameter of the zone of inhibition, measuring 14.88, 14.43, and 11.03 mm after 24, 48, and 72 h of incubation, respectively. This difference was highly significant compared to Group 3 at all three time periods. PCPC (1:3) exhibited a significantly higher mean pull-off adhesion strength (521.6 psi) compared to PCPC (1:2), which revealed 419.5 psi. PCPC (1:3) coated substrates exhibited better surface roughness parameters compared to other groups based on the findings of the AFM. The FTIR measurement indicated that both PCPC groups exhibited a purely physical blending in the composite coating. Based on the extent of these successful in vitro experiments, PCPC (1:3) demonstrates its potential as an effective coating layer. Therefore, the findings of this study pave the way for using newly developed PCPC after electrospraying coating on CpTi for dental implants.
Tropical eastern Pacific cooling trend reinforced by human activity
Authors: Chung Eui-Seok , Kim Seong-Joong , Lee Sang-Ki , Ha Kyung-Ja , Yeh Sang-Wook , Kim Yong Sun , Jun Sang-Yoon , Kim Joo-Hong , Kim Dongmin
Published: July 2024

It remains unresolved whether the La Niña-like sea surface temperature (SST) trend pattern during the satellite era, featuring a distinct warming in the northwest/southwest Pacific but cooling in the tropical eastern Pacific, is driven by either external forcing or internal variability. Here, by conducting a comprehensive analysis of observations and a series of climate model simulations for the historical period, we show that a combination of internal variability and human activity may have shaped the observed La Niña-like SST trend pattern. As in observations, SSTs in each model ensemble member show a distinct multi-decadal swing between El Niño-like and La Niña-like trend patterns due to internal variability. The ensemble-mean trends for some models are, however, found to exhibit an enhanced zonal SST gradient along the equatorial Pacific over periods such as 1979–2010, suggesting a role of external forcing. In line with this hypothesis, single-forcing large ensemble model simulations show that human-induced stratospheric ozone depletion and/or aerosol changes have acted to enhance the zonal SST gradient via strengthening of Pacific trade winds, although the effect is model dependent. Our finding suggests that the La Niña-like SST trend is unlikely to persist under sustained global warming because both the ozone and aerosol impacts will eventually weaken.
The role of Arctic sea ice loss in the interdecadal trends of the East Asian summer monsoon in a warming climate
Authors: Zhang Xiaoqi , He Bian , Bao Qing , Liu Yimin , Wu Guoxiong , Duan Anmin , Hu Wenting , Sheng Chen , Rao Jian
Published: July 2024

The East Asian summer monsoon precipitation has exhibited a well-known “southern China flood and northern China drought” pattern in recent decades. The increase in aerosols and warming oceans are recognized as two important forcings that control of the precipitation trends over East Asian land. However, in this study, by using large ensemble simulations from the CMIP6 Polar Amplification Model Intercomparison Project (PAMIP), the influence of Arctic amplification, serving as the prominent feature of global warming, is very important in modulating the East Asian summer precipitation pattern, which is comparable to the influence of sea surface temperature (SST). Additionally, the observed “southern China flood and northern China drought” pattern only exists in July and August, whereas a triple pattern with the precipitation positive anomaly center over Middle China occurs in June. These patterns are closely connected with the regional differences in Arctic sea ice loss from June to July, affected through both the Rossby waves propagating in a weaker westerly jet and the decrease in the large-scale meridional thermal contrast in a warming climate.
Clinical phenotypes and short-term outcomes based on prehospital point-of-care testing and on-scene vital signs
Authors: López-Izquierdo Raúl , del Pozo Vegas Carlos , Sanz-García Ancor , Mayo Íscar Agustín , Castro Villamor Miguel A. , Silva Alvarado Eduardo , Gracia Villar Santos , Dzul López Luis Alonso , Aparicio Obregón Silvia , Calderon Iglesias Rubén , Soriano Joan B. , Martín-Rodríguez Francisco
Published: July 2024

Abstract

Emergency medical services (EMSs) face critical situations that require patient risk classification based on analytical and vital signs. We aimed to establish clustering-derived phenotypes based on prehospital analytical and vital signs that allow risk stratification. This was a prospective, multicenter, EMS-delivered, ambulance-based cohort study considering six advanced life support units, 38 basic life support units, and four tertiary hospitals in Spain. Adults with unselected acute diseases managed by the EMS and evacuated with discharge priority to emergency departments were considered between January 1, 2020, and June 30, 2023. Prehospital point-of-care testing and on-scene vital signs were used for the unsupervised machine learning method (clustering) to determine the phenotypes. Then phenotypes were compared with the primary outcome (cumulative mortality (all-cause) at 2, 7, and 30 days). A total of 7909 patients were included. The median (IQR) age was 64 (51–80) years, 41% were women, and 26% were living in rural areas. Three clusters were identified: alpha 16.2% (1281 patients), beta 28.8% (2279), and gamma 55% (4349). The mortality rates for alpha, beta and gamma at 2 days were 18.6%, 4.1%, and 0.8%, respectively; at 7 days, were 24.7%, 6.2%, and 1.7%; and at 30 days, were 33%, 10.2%, and 3.2%, respectively. Based on standard vital signs and blood test biomarkers in the prehospital scenario, three clusters were identified: alpha (high-risk), beta and gamma (medium- and low-risk, respectively). This permits the EMS system to quickly identify patients who are potentially compromised and to proactively implement the necessary interventions.
Diverting organic waste from landfills via insect biomanufacturing using engineered black soldier flies (Hermetia illucens)
Authors: Tepper Kate , Edwards Owain , Sunna Anwar , Paulsen Ian T. , Maselko Maciej
Published: July 2024

A major roadblock towards the realisation of a circular economy are the lack of high-value products that can be generated from waste. Black soldier flies (BSF; Hermetia illucens) are gaining traction for their ability to rapidly consume large quantities of organic wastes. However, these are primarily used to produce a small variety of products, such as animal feed ingredients and fertiliser. Using synthetic biology, BSF could be developed into a novel sustainable biomanufacturing platform to valorise a broader variety of organic waste feedstocks into enhanced animal feeds, a large variety of high-value biomolecules including industrial enzymes and lipids, and improved fertiliser.
Nuclear factor interleukin 3 and metabolic dysfunction-associated fatty liver disease development
Authors: Lin Yung-Ni , Hsu Jia-Rou , Wang Chih-Lin , Huang Yi-Chen , Wang Jzy-Yu , Wu Chun-Ying , Wu Li-Ling
Published: July 2024

This study investigates sex-specific effects in a gain-of-function model to evaluate Nfil3 function in relation to high-fat diet (HFD)-induced metabolic dysfunction-associated steatotic liver disease (MASLD) and gut microbiota (GM)-induced alterations in the bile acid (BA) profile. MASLD is induced in both wild type and Nfil3-deficient (NKO) C57BL/6 J mice through an HFD. The hepatic immune response is evaluated using flow cytometry, revealing that NKO mice exhibit lower body weight, serum triglyceride (TG) levels, tissue injury, inflammation, and fat accumulation. The Nfil3 deletion reduces macrophage counts in fibrotic liver tissues, decreases proinflammatory gene and protein expression, and diminishes gut barrier function. Alpha and beta diversity analysis reveal increased GM alpha diversity across different sexes. The Nfil3 gene deletion modifies the BA profile, suggesting that negative feedback through the Nfil3-FXR-FGF15 axis facilitates BA recycling from the liver via enterohepatic circulation. Therefore, inhibiting Nfil3 in the liver offers a viable treatment approach for MASLD.
Evolutionary paths toward multi-level convergence of lactic acid bacteria in fructose-rich environments
Authors: Konno Naoki , Maeno Shintaro , Tanizawa Yasuhiro , Arita Masanori , Endo Akihito , Iwasaki Wataru
Published: July 2024

Convergence provides clues to unveil the non-random nature of evolution. Intermediate paths toward convergence inform us of the stochasticity and the constraint of evolutionary processes. Although previous studies have suggested that substantial constraints exist in microevolutionary paths, it remains unclear whether macroevolutionary convergence follows stochastic or constrained paths. Here, we performed comparative genomics for hundreds of lactic acid bacteria (LAB) species, including clades showing a convergent gene repertoire and sharing fructose-rich habitats. By adopting phylogenetic comparative methods we showed that the genomic convergence of distinct fructophilic LAB (FLAB) lineages was caused by parallel losses of more than a hundred orthologs and the gene losses followed significantly similar orders. Our results further suggested that the loss of adhE, a key gene for phenotypic convergence to FLAB, follows a specific evolutionary path of domain architecture decay and amino acid substitutions in multiple LAB lineages sharing fructose-rich habitats. These findings unveiled the constrained evolutionary paths toward the convergence of free-living bacterial clades at the genomic and molecular levels.
Addressing the sustainable urbanism paradox: tipping points for the operational reconciliation of dense and green morphologies
Authors: Boutreux T. , Bourgeois M. , Bellec A. , Commeaux F. , Kaufmann B.
Published: July 2024

To improve biodiversity and human living conditions in the Anthropocene, urban forms must reconcile density with vegetation to meet the dual sustainability-liveability challenge. This paradox poses a dilemma for urban planners and is a critical research issue requiring comprehensive analyses. Multi-family residential housing holds the potential to achieve balanced density-greening, proximity ecosystem services and human-nature connectedness, but meeting such objectives relies on finding balanced morphologies and metrics at an operational scale. Analysing 11,593 plots in the Lyon metropolitan area (France) using a systemic approach, we identified critical tipping points in morphology and greening. Density explained only 6% of Plot Greening, while morphology and landscaping accounted for 94%. We identified an open-space ratio (unbuilt area/floor area) >0.3 as a morphological threshold to achieve sustainable green supply. Operational morphologies balancing density and greening were modelled and illustrated across building heights, providing guidelines for emerging regulatory tools in sustainable urban planning.
The distribution and drivers of tree cover in savannas and forests across India
Authors: Gopalakrishna Trisha , Rifai Sami W. , Ratnam Jayashree , Oliveras Menor Imma , Stevens Nicola , Malhi Yadvinder
Published: July 2024

The distribution of forest and savanna biomes and the role of resources (climate and soil) and disturbances (fire and herbivory) in determining tree-grass dynamics remains elusive and variable across geographies. This is especially problematic in Indian savannas which have been historically misclassified as degraded forests and are targeted for tree-planting. Here, we examine biome distribution and determinants through the lens of tree cover across India. Our analyses reveal four distinct zones of differing tree cover, with intermediate zones containing savanna vegetation. Rainfall seasonality determines maximum possible tree cover non-linearly. Once rainfall seasonality is factored out, soil sand fraction and topography partially explain residual variation of tree cover. High domestic livestock herbivory and other anthropogenic pressures reduce tree cover. Lastly, lack of detectable fires precludes robust conclusions about the relationship between fire and tree cover. By considering these environmental drivers in restoration planning, we can improve upon simplistic tree planting initiatives that may be detrimental to Indian savannas.
High-ambition climate action in all sectors can achieve a 65% greenhouse gas emissions reduction in the United States by 2035
Authors: Zhao Alicia , O’Keefe Kowan T. V. , Binsted Matthew , McJeon Haewon , Bryant Adriana , Squire Claire , Zhang Mengqi , Smith Steven J. , Cui Ryna , Ou Yang , Iyer Gokul , Kennedy Shannon , Hultman Nate
Published: July 2024

Under the next cycle of target setting under the Paris Agreement, countries will be updating and submitting new nationally determined contributions (NDCs) over the coming year. To this end, there is a growing need for the United States to assess potential pathways toward a new, maximally ambitious 2035 NDC. In this study, we use an integrated assessment model with state-level detail to model existing policies from both federal and non-federal actors, including the Inflation Reduction Act, Bipartisan Infrastructure Law, and key state policies, across all sectors and gases. Additionally, we develop a high-ambition scenario, which includes new and enhanced policies from these actors. We find that existing policies can reduce net greenhouse gas (GHG) emissions by 44% (with a range of 37% to 52%) by 2035, relative to 2005 levels. The high-ambition scenario can deliver net GHG reductions up to 65% (with a range of 59% to 71%) by 2035 under accelerated implementation of federal regulations and investments, as well as state policies such as renewable portfolio standards, EV sales targets, and zero-emission appliance standards. This level of reductions would provide a basis for continued progress toward the country’s 2050 net-zero emissions goal.
Holistic analysis of a gliding arc discharge using 3D tomography and single-shot fluorescence lifetime imaging
Authors: Nilsson Sebastian , Sanned David , Roth Adrian , Sun Jinguo , Berrocal Edouard , Richter Mattias , Ehn Andreas
Published: July 2024

Gliding arc plasmas, a versatile form of non-thermal plasma discharges, hold great promise for sustainable chemical conversion in electrified industrial applications. Their relatively high temperatures compared to other non-thermal plasmas, reactive species generation, and efficient energy transfer make them ideal for an energy-efficient society. However, plasma discharges are transient and complex 3D entities influenced by gas pressure, mixture, and power, posing challenges for in-situ measurements of chemical species and spatial dynamics. Here we demonstrate a combination of innovative approaches, providing a comprehensive view of discharges and their chemical surroundings by combining fluorescence lifetime imaging of hydroxyl (OH) radicals with optical emission 3D tomography. This reveals variations in OH radical distributions under different conditions and local variations in fluorescence quantum yield with high spatial resolution from a single laser shot. Our results and methodology offer a multidimensional platform for interdisciplinary research in plasma physics and chemistry.
Smartphone-based markers of social connectivity in schizophrenia and bipolar disorder
Authors: Valeri Linda , Cai Xiaoxuan , Rahimi Eichi Habiballah , Liebenthal Einat , Rauch Scott L. , Ongur Dost , Schutt Russell , Dixon Lisa , Onnela Jukka-Pekka , Baker Justin
Published: July 2024

Social isolation and social impairment are hallmarks of progression as well as predictors of relapse in psychiatric disorders. We conducted a pilot study to assess the feasibility of sensing the social activity phenotype and loneliness using active and passive markers collected using a smartphone application. The study included 9 schizophrenia and bipolar disorder patients followed in the Bipolar Longitudinal study for at least 1 month and for whom mobile communication data was collected using the Beiwe smartphone application. Subjects completed daily surveys on digital and in-person social activity, and feelings of being outgoing or lonely. We described the level and variability of social activity features. We employed k-means clustering to identify “important contacts”. Further, we investigated whether social network-derived features of mobile communication are independent predictors of weekly counts of outgoing calls and text, weekly average self-reported digital social activity, and loneliness using mixed effect models and clustering with dynamic time warping distance. Subjects were followed between 5 and 208 weeks (number of days of observation = 2538). The k-means cluster analysis approach identified the number of “important contacts” among close friends and family members as reported in clinical interviews. The cluster analysis and longitudinal regression analysis indicate that the number of individuals a person communicates with on their phone is an independent predictor of perceived loneliness, with stronger evidence when “important contacts” only are included. This study provides preliminary evidence that the number of “important contacts” a person communicates with on their phone is a promising marker to capture subjects’ engagement in mobile communication activity and perceived loneliness.
Rapid on-site amplification and visual detection of misfolded proteins via microfluidic quaking-induced conversion (Micro-QuIC)
Authors: Lee Dong Jun , Christenson Peter R. , Rowden Gage , Lindquist Nathan C. , Larsen Peter A. , Oh Sang-Hyun
Published: July 2024

Protein misfolding diseases, such as prion diseases, Alzheimer’s, and Parkinson’s, share a common molecular mechanism involving the misfolding and aggregation of specific proteins. There is an urgent need for point-of-care (POC) diagnostic technologies that can accurately detect these misfolded proteins, facilitating early diagnosis and intervention. Here, we introduce the microfluidic quaking-induced conversion (Micro-QuIC), a novel acoustofluidic platform for the rapid and sensitive detection of protein misfolding diseases. We demonstrate the utility of our technology using chronic wasting disease (CWD) as a model system, since samples from wild white-tailed deer are readily accessible, and CWD shares similarities with human protein misfolding diseases. Acoustofluidic mixing enables homogeneous mixing of reagents in a high-Reynolds-number regime, significantly accelerating the turnaround time for CWD diagnosis. Our Micro-QuIC assay amplifies prions significantly faster than the current gold standard, real-time quaking-induced conversion (RT-QuIC). Furthermore, we integrated Micro-QuIC with a gold nanoparticle-based, naked-eye detection method, which enables visual discrimination between CWD-positive and CWD-negative samples without the need for a bulky fluorescence detection module. This integration creates a rapid, POC testing platform capable of detecting misfolded proteins associated with a variety of protein misfolding diseases.
Surface functionalization of a chalcogenide IR photonic sensor by means of a polymer membrane for water pollution remediation
Authors: Vrážel Martin , Ismail Raïssa Kadar , Courson Rémi , Hammouti Abdelali , Bouška Marek , Larrodé Amélie , Baillieul Marion , Giraud William , Le Floch Stéphane , Bodiou Loïc , Charrier Joël , Boukerma Kada , Michel Karine , Němec Petr , Nazabal Virginie
Published: July 2024

Optimisation of the functionalisation of infrared chalcogenide sensors for accidental water pollution using a hydrophobic polymer.
Nanozymes in Alzheimer's disease diagnostics and therapy
Authors: Li Linquan , Zhang Wenyu , Cao Hengyi , Fang Leming , Wang Wenjing , Li Chengzhilin , He Qingbin , Jiao Jianwei , Zheng Runxiao
Published: July 2024

The principle and application of nanozymes in the early diagnosis and treatment of Alzheimer's disease.
Aggregation-induced emission micelle-based sensing array for discrimination of long-chain fatty acids
Authors: Yan Bingqian , Jia Yunxiu , Zhang Xin , Zhang Lijuan , Guan Weijiang , Lu Chao
Published: July 2024

A sensing array based on aggregation-induced emission (AIE) micelles was proposed for efficient discrimination of three typical long-chain fatty acids (lauric, palmitic, and stearic acids) and their mixtures.
Dilute but significant: low cation concentration affects field dependent properties of Eu2Ga11Sn35
Authors: Gunatilleke Wilarachchige D. C. B. , Nolas George S.
Published: July 2024

Temperature and magnetic field-dependent properties of the very low cation concentration clathrate-I Eu2.2Ga11Sn35 revealed a change in electronic structure with increasing field and the origin of magneto-suppressed thermal conductivity.
Modular access to diarylmethyl sulfonamides via visible light-promoted cross-coupling reactions
Authors: Mei Yu-Tong , Zhang Hui , Jiang Yu , Gu Yu-Jia , Deng Jiang-Lai , Yang Dan , Jing Lin-Hai , Shi Ming-Song
Published: July 2024

A novel and efficient method for the preparation of diarylmethyl sulfonamide derivatives has been achieved by visible-light-induced sulfamoylation of para-quinone methides with sulfamoyl chlorides under mild metal-free conditions.
A water-soluble mixed-valent {Mn11} cluster embedded heteropolyoxoniobate with magnetic properties
Authors: Wu Ping-Xin , Chen Chun-Xia , Sun Yan-Qiong , Zheng Shou-Tian
Published: July 2024

A rare all-inorganic high-nuclearity mixed-valent {Mn11} cluster embedded polyoxoniobate has been synthesized, which exhibits significant magnetic anisotropy and excellent water solubility and stability.
A non-enzymatic, isothermal amplification sensor for quantifying the relative abundance of Akkermansia muciniphila
Authors: Liu Bing , Shi Chen , Wang Fan , Xu Fangling , Chao Jie , Zhu Jiapeng , Yang Dongliang , Ouyang Xiangyuan
Published: July 2024

We have developed a non-enzymatic, isothermal amplification assay (NIA sensor) based on a catalytic hairpin assembly (CHA) reaction for quantifying the relative abundance of Akkermansia muciniphila.
Visible-light-induced redox-neutral difunctionalization of alkenes and alkynes
Authors: Mondal Susmita , Ghosh Sumit , Hajra Alakananda
Published: July 2024

This review provides a complete overview of various visible-light-induced redox-neutral difunctionalization methodologies with literature coverage up to May 2024.
Effect of cholesterol on nanoparticle translocation across a lipid bilayer
Authors: Tajima Masaya , Nakamura Hideya , Ohsaki Shuji , Watano Satoru
Published: July 2024

Nanoparticle translocation across a cholesterol-containing membrane induced by a unique domain at the contact interface.
Theoretical study of a new molecular ion species BeN+: molecular states and cross sections for electronic excitation and dissociation
Authors: Chakrabarti Kalyan , Neogi Poonam , Nandi Gargi
Published: July 2024

We present here a theoretical study of a new molecular ion species BeN+, which has not been reported before.
Examination of Nafion membrane performance with acid–base functionalized graphene oxide
Authors: Hu Yu , Zhu Yaochen , Lai Yuhua , Wang Shuai , Xu Yao
Published: July 2024

Functionalized graphene oxide (GO) as a good additive can improve the performance of a proton exchange membrane (PEM) via the introduction of various functional groups.
Two-dimensional phosphorus carbides (β-PC) as highly efficient metal-free electrocatalysts for lithium–sulfur batteries: a first-principles study
Authors: Wang Junru , Liu Zhichao , Zhao Yinchang , Dai Zhenhong , Hua Juan , Zhao Mingwen
Published: July 2024

Two-dimensional phosphorus carbides (β0-PC and β1-PC) as effective metal-free electrocatalysts in lithium–sulfur batteries.
Room temperature detection of the (H2)2 dimer
Authors: Fleurbaey H. , Kassi S. , Campargue A.
Published: July 2024

The absorption spectrum of the hydrogen dimer, (H2)2, is detected at room temperature while from its bond dissociation energy of only about 3 cm−1 (∼4.5 K), such a detection was unexpected.
Unveiling the electronic and magnetic landscape of 3d transition metal doped hydrogenated borophenes: a first-principles study
Authors: Poswal Paras , Shukla Neeraj
Published: July 2024

A controlled magnetic state in hydrogenated borophene by transition metal atom doping.
Unravelling the mechanism of apoptosis induced by copper(ii) complexes of NN2-pincer ligands in lung cancer cells
Authors: Das Athulya , Sankaralingam Muniyandi
Published: July 2024

Copper(ii) complexes of NN2-pincer type ligands are effective against lung cancer cells and their mechanism of action is found to be apoptosis induced by ROS.
Decrypting the hydrogen evolution in alkaline water with novel magnetoactive cobalt(ii) complex-driven cobalt oxide electrocatalysts
Authors: Saha Subhajit , Diyali Nilankar , Diyali Sangharaj , Panda Subhra Jyoti , Das Mainak , Acharya Sobhna , Mudi Prafullya Kumar , Singh Monika , Ray Partha Pratim , Purohit Chandra Shekhar , Biswas Bhaskar
Published: July 2024

This work emphasises the design and synthesis as well as the structural, electrical and magnetic characterisation of two cobalt(ii) complexes and their electrocatalytic fate towards sustainable hydrogen production in alkaline water.
Ni(ii) and Pd(ii) complexes of a new redox-active pentadentate azo-appended 2-aminophenol ligand: Pd(ii)-assisted intraligand cyclization forms a phenoxazinyl ring
Authors: Bhowmik Saumitra , Sengupta Arunava , Mukherjee Rabindranath
Published: July 2024

Molecular and electronic structures of square planar complexes (1, [NiII{(LISQ)˙2−}], St = 1/2; 2, [PdII{(LISQ)˙2−}], St = 1/2; ) 3, [NiII{(LIBQ)−}]+/ 1+, St = 0); 4, [PdII{(L*AP)˙2−}]/ 2+ (phenoxazinyl ring formation), St = 1/2) are reported.
Gastric stability of bare and chitosan-fabricated ferritin and its bio-mineral: implication for potential dietary iron supplements
Authors: Raut Rohit Kumar , Bhattacharyya Gargee , Behera Rabindra K.
Published: July 2024

Frog M ferritins retain their cage assembly and encapsulated iron mineral in simulated gastric fluid. Fabrication with chitosan further enhanced the cage stability and iron retention capability of ferritins.