bluuebunny/crossref_metadata_2025 huggingface dataset:
AI-based histopathology image analysis reveals a distinct subset of endometrial cancers
Authors: Darbandsari Amirali , Farahani Hossein , Asadi Maryam , Wiens Matthew , Cochrane Dawn , Khajegili Mirabadi Ali , Jamieson Amy , Farnell David , Ahmadvand Pouya , Douglas Maxwell , Leung Samuel , Abolmaesumi Purang , Jones Steven J. M. , Talhouk Aline , Kommoss Stefan , Gilks C. Blake , Huntsman David G. , Singh Naveena , McAlpine Jessica N. , Bashashati Ali
Published: June 2024

Endometrial cancer (EC) has four molecular subtypes with strong prognostic value and therapeutic implications. The most common subtype (NSMP; No Specific Molecular Profile) is assigned after exclusion of the defining features of the other three molecular subtypes and includes patients with heterogeneous clinical outcomes. In this study, we employ artificial intelligence (AI)-powered histopathology image analysis to differentiate between p53abn and NSMP EC subtypes and consequently identify a sub-group of NSMP EC patients that has markedly inferior progression-free and disease-specific survival (termed ‘p53abn-like NSMP’), in a discovery cohort of 368 patients and two independent validation cohorts of 290 and 614 from other centers. Shallow whole genome sequencing reveals a higher burden of copy number abnormalities in the ‘p53abn-like NSMP’ group compared to NSMP, suggesting that this group is biologically distinct compared to other NSMP ECs. Our work demonstrates the power of AI to detect prognostically different and otherwise unrecognizable subsets of EC where conventional and standard molecular or pathologic criteria fall short, refining image-based tumor classification. This study’s findings are applicable exclusively to females.
Divergent landscapes of A-to-I editing in postmortem and living human brain
Authors: Rodriguez de los Santos Miguel , Kopell Brian H. , Buxbaum Grice Ariela , Ganesh Gauri , Yang Andy , Amini Pardis , Liharska Lora E. , Vornholt Eric , Fullard John F. , Dong Pengfei , Park Eric , Zipkowitz Sarah , Kaji Deepak A. , Thompson Ryan C. , Liu Donjing , Park You Jeong , Cheng Esther , Ziafat Kimia , Moya Emily , Fennessy Brian , Wilkins Lillian , Silk Hannah , Linares Lisa M. , Sullivan Brendan , Cohen Vanessa , Kota Prashant , Feng Claudia , Johnson Jessica S. , Rieder Marysia-Kolbe , Scarpa Joseph , Nadkarni Girish N. , Wang Minghui , Zhang Bin , Sklar Pamela , Beckmann Noam D. , Schadt Eric E. , Roussos Panos , Charney Alexander W. , Breen Michael S.
Published: June 2024

Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples, assuming it is an accurate representation of RNA biology in the living brain. We challenge this assumption by comparing A-to-I editing between postmortem and living prefrontal cortical tissues. Major differences were found, with over 70,000 A-to-I sites showing higher editing levels in postmortem tissues. Increased A-to-I editing in postmortem tissues is linked to higher ADAR and ADARB1 expression, is more pronounced in non-neuronal cells, and indicative of postmortem activation of inflammation and hypoxia. Higher A-to-I editing in living tissues marks sites that are evolutionarily preserved, synaptic, developmentally timed, and disrupted in neurological conditions. Common genetic variants were also found to differentially affect A-to-I editing levels in living versus postmortem tissues. Collectively, these discoveries offer more nuanced and accurate insights into the regulatory mechanisms of RNA editing in the human brain.
Achieving a solar-to-chemical efficiency of 3.6% in ambient conditions by inhibiting interlayer charges transport
Authors: Huang Yuyan , Shen Minhui , Yan Huijie , He Yingge , Xu Jianqiao , Zhu Fang , Yang Xin , Ye Yu-Xin , Ouyang Gangfeng
Published: June 2024

Efficiently converting solar energy into chemical energy remains a formidable challenge in artificial photosynthetic systems. To date, rarely has an artificial photosynthetic system operating in the open air surpassed the highest solar-to-biomass conversion efficiency (1%) observed in plants. In this study, we present a three-dimension polymeric photocatalyst achieving a solar-to-H2O2 conversion efficiency of 3.6% under ambient conditions, including real water, open air, and room temperature. The impressive performance is attributed to the efficient storage of electrons inside materials via expeditious intramolecular charge transfer, and the fast extraction of the stored electrons by O2 that can diffuse into the internal pores of the self-supporting three-dimensional material. This construction strategy suppresses the interlayer transfer of excitons, polarizers and carriers, effectively increases the utilization of internal excitons to 82%. This breakthrough provides a perspective to substantially enhance photocatalytic performance and bear substantial implications for sustainable energy generation and environmental remediation.
3D oxygen vacancy distribution and defect-property relations in an oxide heterostructure
Authors: Hunnestad Kasper A. , Das Hena , Hatzoglou Constantinos , Holtz Megan , Brooks Charles M. , van Helvoort Antonius T. J. , Muller David A. , Schlom Darrell G. , Mundy Julia A. , Meier Dennis
Published: June 2024

Oxide heterostructures exhibit a vast variety of unique physical properties. Examples are unconventional superconductivity in layered nickelates and topological polar order in (PbTiO3)n/(SrTiO3)n superlattices. Although it is clear that variations in oxygen content are crucial for the electronic correlation phenomena in oxides, it remains a major challenge to quantify their impact. Here, we measure the chemical composition in multiferroic (LuFeO3)9/(LuFe2O4)1 superlattices, mapping correlations between the distribution of oxygen vacancies and the electric and magnetic properties. Using atom probe tomography, we observe oxygen vacancies arranging in a layered three-dimensional structure with a local density on the order of 1014 cm−2, congruent with the formula-unit-thick ferrimagnetic LuFe2O4 layers. The vacancy order is promoted by the locally reduced formation energy and plays a key role in stabilizing the ferroelectric domains and ferrimagnetism in the LuFeO3 and LuFe2O4 layers, respectively. The results demonstrate pronounced interactions between oxygen vacancies and the multiferroic order in this system and establish an approach for quantifying the oxygen defects with atomic-scale precision in 3D, giving new opportunities for deterministic defect-enabled property control in oxide heterostructures.
Borg extrachromosomal elements of methane-oxidizing archaea have conserved and expressed genetic repertoires
Authors: Schoelmerich Marie C. , Ly Lynn , West-Roberts Jacob , Shi Ling-Dong , Shen Cong , Malvankar Nikhil S. , Taib Najwa , Gribaldo Simonetta , Woodcroft Ben J. , Schadt Christopher W. , Al-Shayeb Basem , Dai Xiaoguang , Mozsary Christopher , Hickey Scott , He Christine , Beaulaurier John , Juul Sissel , Sachdeva Rohan , Banfield Jillian F.
Published: June 2024

Borgs are huge extrachromosomal elements (ECE) of anaerobic methane-consuming “Candidatus Methanoperedens” archaea. Here, we used nanopore sequencing to validate published complete genomes curated from short reads and to reconstruct new genomes. 13 complete and four near-complete linear genomes share 40 genes that define a largely syntenous genome backbone. We use these conserved genes to identify new Borgs from peatland soil and to delineate Borg phylogeny, revealing two major clades. Remarkably, Borg genes encoding nanowire-like electron-transferring cytochromes and cell surface proteins are more highly expressed than those of host Methanoperedens, indicating that Borgs augment the Methanoperedens activity in situ. We reconstructed the first complete 4.00 Mbp genome for a Methanoperedens that is inferred to be a Borg host and predicted its methylation motifs, which differ from pervasive TC and CC methylation motifs of the Borgs. Thus, methylation may enable Methanoperedens to distinguish their genomes from those of Borgs. Very high Borg to Methanoperedens ratios and structural predictions suggest that Borgs may be capable of encapsulation. The findings clearly define Borgs as a distinct class of ECE with shared genomic signatures, establish their diversification from a common ancestor with genetic inheritance, and raise the possibility of periodic existence outside of host cells.
Deconstructing synthetic biology across scales: a conceptual approach for training synthetic biologists
Authors: Karim Ashty S. , Brown Dylan M. , Archuleta Chloé M. , Grannan Sharisse , Aristilde Ludmilla , Goyal Yogesh , Leonard Josh N. , Mangan Niall M. , Prindle Arthur , Rocklin Gabriel J. , Tyo Keith J. , Zoloth Laurie , Jewett Michael C. , Calkins Susanna , Kamat Neha P. , Tullman-Ercek Danielle , Lucks Julius B.
Published: June 2024

Synthetic biology allows us to reuse, repurpose, and reconfigure biological systems to address society’s most pressing challenges. Developing biotechnologies in this way requires integrating concepts across disciplines, posing challenges to educating students with diverse expertise. We created a framework for synthetic biology training that deconstructs biotechnologies across scales—molecular, circuit/network, cell/cell-free systems, biological communities, and societal—giving students a holistic toolkit to integrate cross-disciplinary concepts towards responsible innovation of successful biotechnologies. We present this framework, lessons learned, and inclusive teaching materials to allow its adaption to train the next generation of synthetic biologists.
An ultrawide-range photochromic molecular fluorescence emitter
Authors: Chen Xiao , Hou Xiao-Fang , Chen Xu-Man , Li Quan
Published: June 2024

Photocontrollable luminescent molecular switches capable of changing emitting color have been regarded as the ideal integration between intelligent and luminescent materials. A remaining challenge is to combine good luminescence properties with wide range of wavelength transformation, especially when confined in a single molecular system that forms well-defined nanostructures. Here, we report a π-expanded photochromic molecular photoswitch, which allows for the comprehensive achievements including wide emission wavelength variation (240 nm wide, 400–640 nm), high photoisomerization extent (95%), and pure emission color (<100 nm of full width at half maximum). We take the advantageous mechanism of modulating self-assembly and intramolecular charge transfer in the synthesis and construction, and further realize the full color emission by simple photocontrol. Based on this, both photoactivated anti-counterfeiting function and self-erasing photowriting films are achieved of fluorescence. This work will provide insight into the design of intelligent optical materials.
Uncovering 2-D toroidal representations in grid cell ensemble activity during 1-D behavior
Authors: Hermansen Erik , Klindt David A. , Dunn Benjamin A.
Published: June 2024

Minimal experiments, such as head-fixed wheel-running and sleep, offer experimental advantages but restrict the amount of observable behavior, making it difficult to classify functional cell types. Arguably, the grid cell, and its striking periodicity, would not have been discovered without the perspective provided by free behavior in an open environment. Here, we show that by shifting the focus from single neurons to populations, we change the minimal experimental complexity required. We identify grid cell modules and show that the activity covers a similar, stable toroidal state space during wheel running as in open field foraging. Trajectories on grid cell tori correspond to single trial runs in virtual reality and path integration in the dark, and the alignment of the representation rapidly shifts with changes in experimental conditions. Thus, we provide a methodology to discover and study complex internal representations in even the simplest of experiments.
Alkylamine-tethered molecules recruit FBXO22 for targeted protein degradation
Authors: Kagiou Chrysanthi , Cisneros Jose A. , Farnung Jakob , Liwocha Joanna , Offensperger Fabian , Dong Kevin , Yang Ka , Tin Gary , Horstmann Christina S. , Hinterndorfer Matthias , Paulo Joao A. , Scholes Natalie S. , Sanchez Avila Juan , Fellner Michaela , Andersch Florian , Hannich J. Thomas , Zuber Johannes , Kubicek Stefan , Gygi Steven P. , Schulman Brenda A. , Winter Georg E.
Published: June 2024

Targeted protein degradation (TPD) relies on small molecules to recruit proteins to E3 ligases to induce their ubiquitylation and degradation by the proteasome. Only a few of the approximately 600 human E3 ligases are currently amenable to this strategy. This limits the actionable target space and clinical opportunities and thus establishes the necessity to expand to additional ligases. Here we identify and characterize SP3N, a specific degrader of the prolyl isomerase FKBP12. SP3N features a minimal design, where a known FKBP12 ligand is appended with a flexible alkylamine tail that conveys degradation properties. We found that SP3N is a precursor and that the alkylamine is metabolized to an active aldehyde species that recruits the SCFFBXO22 ligase for FKBP12 degradation. Target engagement occurs via covalent adduction of Cys326 in the FBXO22 C-terminal domain, which is critical for ternary complex formation, ubiquitylation and degradation. This mechanism is conserved for two recently reported alkylamine-based degraders of NSD2 and XIAP, thus establishing alkylamine tethering and covalent hijacking of FBXO22 as a generalizable TPD strategy.
MRE11 and TREX1 control senescence by coordinating replication stress and interferon signaling
Authors: Técher Hervé , Gopaul Diyavarshini , Heuzé Jonathan , Bouzalmad Nail , Leray Baptiste , Vernet Audrey , Mettling Clément , Moreaux Jérôme , Pasero Philippe , Lin Yea-Lih
Published: June 2024

Oncogene-induced senescence (OIS) arrests cell proliferation in response to replication stress (RS) induced by oncogenes. OIS depends on the DNA damage response (DDR), but also on the cGAS-STING pathway, which detects cytosolic DNA and induces type I interferons (IFNs). Whether and how RS and IFN responses cooperate to promote OIS remains unknown. Here, we show that the induction of OIS by the H-RASV12 oncogene in immortalized human fibroblasts depends on the MRE11 nuclease. Indeed, treatment with the MRE11 inhibitor Mirin prevented RS, micronuclei formation and IFN response induced by RASV12. Overexpression of the cytosolic nuclease TREX1 also prevented OIS. Conversely, overexpression of a dominant negative mutant of TREX1 or treatment with IFN-β was sufficient to induce RS and DNA damage, independent of RASV12 induction. These data suggest that the IFN response acts as a positive feedback loop to amplify DDR in OIS through a process regulated by MRE11 and TREX1.
Selection and horizontal gene transfer underlie microdiversity-level heterogeneity in resistance gene fate during wastewater treatment
Authors: Brown Connor L. , Maile-Moskowitz Ayella , Lopatkin Allison J. , Xia Kang , Logan Latania K. , Davis Benjamin C. , Zhang Liqing , Vikesland Peter J. , Pruden Amy
Published: June 2024

Activated sludge is the centerpiece of biological wastewater treatment, as it facilitates removal of sewage-associated pollutants, fecal bacteria, and pathogens from wastewater through semi-controlled microbial ecology. It has been hypothesized that horizontal gene transfer facilitates the spread of antibiotic resistance genes within the wastewater treatment plant, in part because of the presence of residual antibiotics in sewage. However, there has been surprisingly little evidence to suggest that sewage-associated antibiotics select for resistance at wastewater treatment plants via horizontal gene transfer or otherwise. We addressed the role of sewage-associated antibiotics in promoting antibiotic resistance using lab-scale sequencing batch reactors fed field-collected wastewater, metagenomic sequencing, and our recently developed bioinformatic tool Kairos. Here, we found confirmatory evidence that fluctuating levels of antibiotics in sewage are associated with horizontal gene transfer of antibiotic resistance genes, microbial ecology, and microdiversity-level differences in resistance gene fate in activated sludge.
Tracking single hiPSC-derived cardiomyocyte contractile function using CONTRAX an efficient pipeline for traction force measurement
Authors: Pardon Gaspard , Vander Roest Alison S. , Chirikian Orlando , Birnbaum Foster , Lewis Henry , Castillo Erica A. , Wilson Robin , Denisin Aleksandra K. , Blair Cheavar A. , Holbrook Colin , Koleckar Kassie , Chang Alex C. Y. , Blau Helen M. , Pruitt Beth L.
Published: June 2024

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are powerful in vitro models to study the mechanisms underlying cardiomyopathies and cardiotoxicity. Quantification of the contractile function in single hiPSC-CMs at high-throughput and over time is essential to disentangle how cellular mechanisms affect heart function. Here, we present CONTRAX, an open-access, versatile, and streamlined pipeline for quantitative tracking of the contractile dynamics of single hiPSC-CMs over time. Three software modules enable: parameter-based identification of single hiPSC-CMs; automated video acquisition of >200 cells/hour; and contractility measurements via traction force microscopy. We analyze >4,500 hiPSC-CMs over time in the same cells under orthogonal conditions of culture media and substrate stiffnesses; +/− drug treatment; +/− cardiac mutations. Using undirected clustering, we reveal converging maturation patterns, quantifiable drug response to Mavacamten and significant deficiencies in hiPSC-CMs with disease mutations. CONTRAX empowers researchers with a potent quantitative approach to develop cardiac therapies.
Microglia contribute to neuronal synchrony despite endogenous ATP-related phenotypic transformation in acute mouse brain slices
Authors: Berki Péter , Cserép Csaba , Környei Zsuzsanna , Pósfai Balázs , Szabadits Eszter , Domonkos Andor , Kellermayer Anna , Nyerges Miklós , Wei Xiaofei , Mody Istvan , Kunihiko Araki , Beck Heinz , Kaikai He , Ya Wang , Lénárt Nikolett , Wu Zhaofa , Jing Miao , Li Yulong , Gulyás Attila I. , Dénes Ádám
Published: June 2024

Acute brain slices represent a workhorse model for studying the central nervous system (CNS) from nanoscale events to complex circuits. While slice preparation inherently involves tissue damage, it is unclear how microglia, the main immune cells and damage sensors of the CNS react to this injury and shape neuronal activity ex vivo. To this end, we investigated microglial phenotypes and contribution to network organization and functioning in acute brain slices. We reveal time-dependent microglial phenotype changes influenced by complex extracellular ATP dynamics through P2Y12R and CX3CR1 signalling, which is sustained for hours in ex vivo mouse brain slices. Downregulation of P2Y12R and changes of microglia-neuron interactions occur in line with alterations in the number of excitatory and inhibitory synapses over time. Importantly, functional microglia modulate synapse sprouting, while microglial dysfunction results in markedly impaired ripple activity both ex vivo and in vivo. Collectively, our data suggest that microglia are modulators of complex neuronal networks with important roles to maintain neuronal network integrity and activity. We suggest that slice preparation can be used to model time-dependent changes of microglia-neuron interactions to reveal how microglia shape neuronal circuits in physiological and pathological conditions.
Comparative optimization of polysaccharide-based nanoformulations for cardiac RNAi therapy
Authors: Gao Han , Li Sen , Lan Zhengyi , Pan Da , Naidu Gonna Somu , Peer Dan , Ye Chenyi , Chen Hangrong , Ma Ming , Liu Zehua , Santos Hélder A.
Published: June 2024

Ionotropic gelation is widely used to fabricate targeting nanoparticles (NPs) with polysaccharides, leveraging their recognition by specific lectins. Despite the fabrication scheme simply involves self-assembly of differently charged components in a straightforward manner, the identification of a potent combinatory formulation is usually limited by structural diversity in compound collections and trivial screen process, imposing crucial challenges for efficient formulation design and optimization. Herein, we report a diversity-oriented combinatory formulation screen scheme to identify potent gene delivery cargo in the context of precision cardiac therapy. Distinct categories of cationic compounds are tested to construct RNA delivery system with an ionic polysaccharide framework, utilizing a high-throughput microfluidics workstation coupled with streamlined NPs characterization system in an automatic, step-wise manner. Sequential computational aided interpretation provides insights in formulation optimization in a broader scenario, highlighting the usefulness of compound library diversity. As a result, the out-of-bag NPs, termed as GluCARDIA NPs, are utilized for loading therapeutic RNA to ameliorate cardiac reperfusion damages and promote the long-term prognosis. Overall, this work presents a generalizable formulation design strategy for polysaccharides, offering design principles for combinatory formulation screen and insights for efficient formulation identification and optimization.
Stabilizing atomic Ru species in conjugated sp2 carbon-linked covalent organic framework for acidic water oxidation
Authors: Jia Hongnan , Yao Na , Jin Yiming , Wu Liqing , Zhu Juan , Luo Wei
Published: June 2024

Suppressing the kinetically favorable lattice oxygen oxidation mechanism pathway and triggering the adsorbate evolution mechanism pathway at the expense of activity are the state-of-the-art strategies for Ru-based electrocatalysts toward acidic water oxidation. Herein, atomically dispersed Ru species are anchored into an acidic stable vinyl-linked 2D covalent organic framework with unique crossed π-conjugation, termed as COF-205-Ru. The crossed π-conjugated structure of COF-205-Ru not only suppresses the dissolution of Ru through strong Ru-N motifs, but also reduces the oxidation state of Ru by multiple π-conjugations, thereby activating the oxygen coordinated to Ru and stabilizing the oxygen vacancies during oxygen evolution process. Experimental results including X-ray absorption spectroscopy, in situ Raman spectroscopy, in situ powder X-ray diffraction patterns, and theoretical calculations unveil the activated oxygen with elevated energy level of O 2p band, decreased oxygen vacancy formation energy, promoted electrochemical stability, and significantly reduced energy barrier of potential determining step for acidic water oxidation. Consequently, the obtained COF-205-Ru displays a high mass activity with 2659.3 A g−1, which is 32-fold higher than the commercial RuO2, and retains long-term durability of over 280 h. This work provides a strategy to simultaneously promote the stability and activity of Ru-based catalysts for acidic water oxidation.
Phage predation accelerates the spread of plasmid-encoded antibiotic resistance
Authors: Ruan Chujin , Ramoneda Josep , Kan Anton , Rudge Timothy J. , Wang Gang , Johnson David R.
Published: June 2024

Phage predation is generally assumed to reduce microbial proliferation while not contributing to the spread of antibiotic resistance. However, this assumption does not consider the effect of phage predation on the spatial organization of different microbial populations. Here, we show that phage predation can increase the spread of plasmid-encoded antibiotic resistance during surface-associated microbial growth by reshaping spatial organization. Using two strains of the bacterium Escherichia coli, we demonstrate that phage predation slows the spatial segregation of the strains during growth. This increases the number of cell-cell contacts and the extent of conjugation-mediated plasmid transfer between them. The underlying mechanism is that phage predation shifts the location of fastest growth from the biomass periphery to the interior where cells are densely packed and aligned closer to parallel with each other. This creates straighter interfaces between the strains that are less likely to merge together during growth, consequently slowing the spatial segregation of the strains and enhancing plasmid transfer between them. Our results have implications for the design and application of phage therapy and reveal a mechanism for how microbial functions that are deleterious to human and environmental health can proliferate in the absence of positive selection.
Chameleon-inspired tunable multi-layered infrared-modulating system via stretchable liquid metal microdroplets in elastomer film
Authors: Zhang Yingyue , Zhu Hanrui , An Shun , Xing Wenkui , Fu Benwei , Tao Peng , Shang Wen , Wu Jianbo , Dickey Michael D. , Song Chengyi , Deng Tao
Published: June 2024

This report presents liquid metal-based infrared-modulating materials and systems with multiple modes to regulate the infrared reflection. Inspired by the brightness adjustment in chameleon skin, shape-morphing liquid metal droplets in silicone elastomer (Ecoflex) matrix are used to resemble the dispersed “melanophores”. In the system, Ecoflex acts as hormone to drive the deformation of liquid metal droplets. Both total and specular reflectance-based infrared camouflage are achieved. Typically, the total and specular reflectances show change of ~44.8% and 61.2%, respectively, which are among the highest values reported for infrared camouflage. Programmable infrared encoding/decoding is explored by adjusting the concentration of liquid metal and applying areal strains. By introducing alloys with different melting points, temperature-dependent infrared painting/writing can be achieved. Furthermore, the multi-layered structure of infrared-modulating system is designed, where the liquid metal-based infrared modulating materials are integrated with an evaporated metallic film for enhanced performance of such system.
Asthma and COPD management of patients with intellectual disabilities in general practice
Authors: Mastebroek Mathilde , Everlo Nadeem C. M. , Cuypers Maarten , Bischoff Erik W. M. A. , Schalk Bianca W. M.
Published: June 2024

People with intellectual disabilities experience overall poorer health and healthcare access than the general population. It is largely unknown how this applies to asthma and chronic obstructive pulmonary disease (COPD) management by general practitioners (GPs). In a 10-year retrospective matched cohort study, n = 34,429, we examined year prevalence of asthma and COPD in adult patients with and without intellectual disabilities and potential differences in the delivery of asthma and COPD disease management activities in Dutch general practices (2010–2019). We collected information on patient characteristics, comorbidity, consultation patterns, use and outcomes of asthma/COPD control questionnaires, spirometry measurement, pulmonology referrals, and prescribed medication. Asthma patients with intellectual disabilities suffered more frequently from obesity (53.2% vs. 39.5% without intellectual disabilities), and both asthma and COPD patients with intellectual disabilities were more frequently current smokers (45.2% vs. 22.1% without intellectual disabilities, and 76.6% vs. 51.4% without intellectual disabilities, respectively). Also, a statistically significant larger number of asthma patients with intellectual disabilities were prescribed antibiotics (69.9% vs. 54.5%). COPD patients with intellectual disabilities, compared with matched controls without intellectual disabilities, received significantly more often either no COPD-related practice consultation at all (respectively 20.8% vs. 8.5%, p = 0.004) or a large number of practice consultations (>31 consultations, respectively 16.7% vs. 5.3%, p = 0.004). For asthma, there was no statistical difference between patients with or without intellectual disabilities regarding the number and type of consultations. The asthma year point prevalence in patients with intellectual disabilities was, from 2014 onward, significantly higher, and in 2019 was 8.7% vs. 6.0% for people without intellectual disabilities. For COPD, it was comparable in both groups. Both asthma and COPD patients with intellectual disabilities appeared considerably younger in age than patients without intellectual disabilities. Our findings warrant further research into the causes of the differences found for asthma and COPD and whether they also infer differences in the quality or the effectiveness of GP disease management, especially for young adults with intellectual disabilities.
National-scale 10-m maps of cropland use intensity in China during 2018–2023
Authors: Qiu Bingwen , Liu Baoli , Tang Zhenghong , Dong Jinwei , Xu Weiming , Liang Juanzhu , Chen Nan , Chen Jiangping , Wang Laigang , Zhang Chengming , Li Zhengrong , Wu Fangzheng
Published: June 2024

The amount of actively cultivated land in China is increasingly threatened by rapid urbanization and rural population aging. Quantifying the extent and changes of active cropland and cropping intensity is crucial to global food security. However, national-scale datasets for smallholder agriculture are limited in spatiotemporal continuity, resolution, and precision. In this paper, we present updated annual Cropland Use Intensity maps in China (China-CUI10m) with descriptions of the extent of fallow/abandoned, actively cropped fields and cropping intensity at a 10-m resolution in recent six years (2018–2023). The dataset is produced by robust algorithms with no requirements for regional adjustments or intensive training samples, which take full advantage of the Sentinel-1 (S1) SAR and Sentinel-2 (S2) MSI time series. The China-CUI10m maps have achieved high accuracy when compared to ground truth data (Overall accuracy = 90.88%) and statistical data (R2 > 0.94). This paper provides the recent trends in cropland abandonment and agricultural intensification in China, which contributes to facilitating geographic-targeted cropland use control policies towards sustainable intensification of smallholder agricultural systems in developing countries.
An integrated remote sensing, petrology, and field geology analyses for Neoproterozoic basement rocks in some parts of the southern Egyptian-Nubian Shield
Authors: El-Desoky Hatem M. , Bachri Imane , El Mezayen Ahmed M. , Abdel-Rahman Ahmed M. , El-Awny Hamada , El-Gammal Arafa A. , Alshehri Fahad , Almadani Sattam
Published: June 2024

The main objective of this study was to use deep learning, and convolutional neural networks (CNN), integrated with field geology to identify distinct lithological units. The Samadia-Tunduba region of the South Eastern Desert of Egypt was mapped geologically for the first time thanks to the use of processed developed CNN algorithms using Landsat 9 OLI-2, which were further enhanced by geological fieldwork, spectral measurements of field samples, and petrographic examination. According to previously published papers, a significant difference was observed in the distribution of rocks and their boundaries, as well as the previously published geological maps that were not accurately compatible with the nature of the area. The many lithologic units in the region are refined using principal component analysis, color ratio composites, and false-color composites. These techniques demonstrated the ability to distinguish between various igneous and metamorphic rock types, especially metavolcanics, metasediments, granodiorite, and biotite monzogranite. The Key structural trends, lithological units, and wadis affecting the area under study are improved by the principal component analysis approach (PC 3, 2, 1), (PC 2, 3, 4), (PC 4, 3, 2), (PC 5, 4, 3), and (PC 6, 5, 4) in RGB, respectively. The best band ratios recorded in the area are recorded the good discrimination (6/5, 4/3, and 2/1), (4/2, 6/7, and 5/6), and (3/2, 5/6, and 4/6) for RGB. The classification map achieved an overall accuracy of 95.27%, and these results from Landsat-9 data were validated by field geology and petrographical studies. The results of this survey can make a significant difference to detailed geological studies. A detailed map of the new district has been prepared through a combination of deep learning and fieldwork.
Multiple talker processing in autistic adult listeners
Authors: Alispahic Samra , Pellicano Elizabeth , Cutler Anne , Antoniou Mark
Published: June 2024

Accommodating talker variability is a complex and multi-layered cognitive process. It involves shifting attention to the vocal characteristics of the talker as well as the linguistic content of their speech. Due to an interdependence between voice and phonological processing, multi-talker environments typically incur additional processing costs compared to single-talker environments. A failure or inability to efficiently distribute attention over multiple acoustic cues in the speech signal may have detrimental language learning consequences. Yet, no studies have examined effects of multi-talker processing in populations with atypical perceptual, social and language processing for communication, including autistic people. Employing a classic word-monitoring task, we investigated effects of talker variability in Australian English autistic (n = 24) and non-autistic (n = 28) adults. Listeners responded to target words (e.g., apple, duck, corn) in randomised sequences of words. Half of the sequences were spoken by a single talker and the other half by multiple talkers. Results revealed that autistic participants’ sensitivity scores to accurately-spotted target words did not differ to those of non-autistic participants, regardless of whether they were spoken by a single or multiple talkers. As expected, the non-autistic group showed the well-established processing cost associated with talker variability (e.g., slower response times). Remarkably, autistic listeners’ response times did not differ across single- or multi-talker conditions, indicating they did not show perceptual processing costs when accommodating talker variability. The present findings have implications for theories of autistic perception and speech and language processing.
Predictive modeling of pH on the transport of Co(II) Ions from aqueous solutions through supported ceramic polymer membrane
Authors: Kassem A. T. , Ali M. M. S. , Sami N. M.
Published: June 2024

Optimal pH is essential for efficient cobalt extraction from polymeric membrane systems, with D2EHPA used as an extractant for Co(II) at pH < 7, achieving 47% efficiency. The pH of piperazine as a stripping agent increases to a concentration of 0.48 M, and the extraction efficiency of Co(II) > 80%. Depending on the functional group of (C4H10N2), the optimal pH for separation was 9.8. The study revealed that pKa value was calculated to predict the ideal pH, and its value was 9.73, which is nearly to the pH, since the pH of the strip concentration and the properties of the membrane affect the extraction of cobalt at 30 °C. The partition ratio indicates the high distribution of the extract in supported ceramic polymer membrane (SCPM). The ceramic component provides mechanical strength and rigidity to the overall membrane structure, allowing it to withstand high pressures and temperatures during operation Study various factors such as the effect of pH on the ionization of the extract; effect of pH on band ionization; effect of pH on the temperature in the extract, effect of pH on the solute, effect of the band at different pH ranges and a comparison was made between the predictive model and experimental data that was proven through mathematical modeling using the MATLAB program.
KHSRP has oncogenic functions and regulates the expression and alternative splicing of DNA repair genes in breast cancer MDA-MB-231 cells
Authors: Paizula Xuelaiti , Wulaying Aliya , Chen Dong , Ou Jianghua
Published: June 2024

Breast cancer has become the most common type of cancers worldwide. Its high prevalence and malignant features are associated with various environmental factors and molecules. The KH-type splicing regulatory protein (KHSRP) participates in the development of breast cancer, while the underlying mechanisms are largely unknown. In this study, we silenced KHSRP expression in MDA-MB-231 cells by small interfering RNA (siKHSRP), and then assessed its effects on cellular features. Finally, we performed whole transcriptome sequencing (RNA-seq) experiments to explore the downstream targets of KHSRP, and validated their changed pattern using quantitative polymerase chain reaction. We found KHSRP showed higher expression level and was associated with worse prognosis in breast cancer patients. In siKHSRP samples, the proliferation, invasion, and migration abilities were significantly repressed compared with negative control (NC) samples, while the apoptosis level was increased. By investigating the RNA-seq data, we found KHSRP globally regulates the expression and alternative splicing profiles of MDA-MB-231 cells by identifying 1632 differentially expressed genes (DEGs) and 1630 HKSRP-regulated AS events (RASEs). Functional enriched analysis of DEGs demonstrated that cilium assembly and movement and extracellular matrix organization pathways were specifically enriched in up DEGs, consistent with the repressed migration and invasion abilities in siKHSRP cells. Interestingly, the cell cycle and DNA damage and repair associated pathways were enriched in both down DEGs and RASE genes, suggesting that KHSRP may modulate cell proliferation by regulating genes in these pathways. Finally, we validated the changed expression and AS patterns of genes in cell cycle and DNA damage/repair pathways. Expression levels of BIRC5, CCNA2, CDK1, FEN1, FOXM1, PTTG1, and UHRF1 were downregulated in siKHSRP samples. The AS patterns of PARK7, ERCC1, CENPX, and UBE2A were also dysregulated in siKHSRP samples and confirmed PCR experiments. In summary, our study comprehensively explored the downstream targets and their functions of KHSRP in breast cancer cells, highlighting the molecular mechanisms of KHSRP on the oncogenic features of breast cancer. The identified molecular targets could be served as potential therapeutic targets for breast cancer in future.
Associations of genetically predicted vitamin D status and deficiency with the risk of carotid artery plaque: a Mendelian randomization study
Authors: Meena Devendra , Dib Marie-Joe , Huang Jingxian , Smith Alexander , Huang Jian , Lota Amrit S. , Prasad Sanjay K. , Gill Dipender , Dehghan Abbas , Tzoulaki Ioanna
Published: June 2024

Low concentrations of circulating 25-hydroxy-vitamin D are observationally associated with an increased risk of subclinical atherosclerosis and cardiovascular disease. However, randomized controlled trials have not reported the beneficial effects of vitamin D supplementation on atherosclerotic cardiovascular disease (ASCVD) outcomes. Whether genetically predicted vitamin D status confers protection against the development of carotid artery plaque, a powerful predictor of subclinical atherosclerosis, remains unknown. We conducted a two-sample Mendelian randomization (MR) study to explore the association of genetically predicted vitamin D status and deficiency with the risk of developing carotid artery plaque. We leveraged three genome-wide association studies (GWAS) of vitamin D status and one GWAS of vitamin D deficiency. We used the inverse-variance weighted (IVW) approach as our main method, and MR-Egger, weighted-median, and radialMR as MR sensitivity analyses. We also conducted sensitivity analyses using biologically plausible genetic instruments located within genes encoding for vitamin D metabolism (GC, CYP2R1, DHCR7, CYP24A1). We did not find significant associations between genetically predicted vitamin D status (Odds ratio (OR) = 0.99, P = 0.91) and deficiency (OR = 1.00, P = 0.97) with the risk of carotid artery plaque. We additionally explored the potential causal effect of vitamin D status on coronary artery calcification (CAC) and carotid intima-media thickness (cIMT), two additional markers of subclinical atherosclerosis, and we did not find any significant association (βCAC = − 0.14, P = 0.23; βcIMT = 0.005, P = 0.19). These findings did not support the causal effects of vitamin D status and deficiency on the risk of developing subclinical atherosclerosis.
Functional analysis of two mutation sites in the OCA2 gene
Authors: Yuan XiaoHua , Dang Qun , Li Xue Lan
Published: June 2024

To analyse the genetic aetiology of a child with oculocutaneous albinism and to explore the effects of two mutation sites on the function of the OCA2 protein at the mRNA and protein levels via the use of recombinant carriers in vitro. Whole-exome sequencing (WES) and Sanger sequencing were used to analyse the pathogenic genes of the child and validate the mutations in the parents. pEGFP and phage vectors carrying wild-type and mutant OCA2 were constructed using the coding DNA sequence (CDS) of the whole gene-synthesized OCA2 as a template and transfected into HEK293T cells, after which expression analysis was performed. The child in this study was born with white skin, hair, eyelashes, and eyebrows and exhibited nystagmus. Genetic analysis indicated that the child carried two heterozygous mutations: c.1079C > T (p.Ser360Phe) of maternal origin and c.1095_1103delAGCACTGGC (p.Ala366_Ala368del) of paternal origin, conforming to an autosomal recessive inheritance pattern. In vitro analysis showed that the expression of the c.1079C > T (p.Ser360Phe) mutant did not significantly change at the mRNA level but did increase at the protein level, suggesting that the mutation may lead to enhanced protein stability, and the c.1095_1103delAGCACTGGC (p.Ala366_Ala368del) mutation resulted in the loss of three amino acids in exon 10, producing a truncated protein. In vitro expression analysis also revealed that the expression of the mutant gene was significantly downregulated at both the mRNA and protein levels, suggesting that the mutation can simultaneously produce truncated proteins and lead to protein degradation. This case study enriches the phenotypic spectrum of OCA2 gene disease. In vitro expression analysis confirmed that both mutations affect protein expression, providing a theoretical basis for analysing the pathogenicity of these two mutations.
Tailoring topology and bio-interactions of triazine frameworks
Authors: Bagheri Sara , Adeli Mohsen , Zabardasti Abedin , Beyranvand Siamak
Published: June 2024

The construction of covalent organic frameworks with special geometery and optical properties is of high interest, due to their unique physicochemical and biological properties. In this work, we report on a new method for the construction of triazine frameworks with defined topologies using coordination chemistry. Ball milling and wet chemical reactions between cyanuric chloride and melamine were directed in spatial arrangements and opposite optical activity. Cobalt was used as a directing agent to drive reactions into special morphologies, optical properties and biological activity. The enantiorecognition ability of triazine frameworks that was manifested in their activities against bacteria, demonstrated a new way for the construction of materials with specific interactions at biointerfaces.
Micro-CT-assisted identification of the optimal time-window for antifibrotic treatment in a bleomycin mouse model of long-lasting pulmonary fibrosis
Authors: Buccardi Martina , Grandi Andrea , Ferrini Erica , Buseghin Davide , Villetti Gino , Civelli Maurizio , Sverzellati Nicola , Aliverti Andrea , Pennati Francesca , Stellari Franco Fabio
Published: June 2024

Idiopathic Pulmonary Fibrosis (IPF) is a debilitating and fatal lung disease characterized by the excessive formation of scar tissue and decline of lung function. Despite extensive research, only two FDA-approved drugs exist for IPF, with limited efficacy and relevant side effects. Thus, there is an urgent need for new effective therapies, whose discovery strongly relies on IPF animal models. Despite some limitations, the Bleomycin (BLM)-induced lung fibrosis mouse model is widely used for antifibrotic drug discovery and for investigating disease pathogenesis. The initial acute inflammation triggered by BLM instillation and the spontaneous fibrosis resolution that occurs after 3 weeks are the major drawbacks of this system. In the present study, we applied micro-CT technology to a longer-lasting, triple BLM administration fibrosis mouse model to define the best time-window for Nintedanib (NINT) treatment. Two different treatment regimens were examined, with a daily NINT administration from day 7 to 28 (NINT 7–28), and from day 14 to 28 (NINT 14–28). For the first time, we automatically derived both morphological and functional readouts from longitudinal micro-CT. NINT 14–28 showed significant effects on morphological parameters after just 1 week of treatment, while no modulations of these biomarkers were observed during the preceding 7–14-days period, likely due to persistent inflammation. Micro-CT morphological data evaluated on day 28 were confirmed by lung histology and bronchoalveolar lavage fluid (BALF) cells; Once again, the NINT 7–21 regimen did not provide substantial benefits over the NINT 14–28. Interestingly, both NINT treatments failed to improve micro-CT-derived functional parameters. Altogether, our findings support the need for optimized protocols in preclinical studies to expedite the drug discovery process for antifibrotic agents. This study represents a significant advancement in pulmonary fibrosis animal modeling and antifibrotic treatment understanding, with the potential for improved translatability through the concurrent structural–functional analysis offered by longitudinal micro-CT.
PTPRS is a novel marker for early Tau pathology and synaptic integrity in Alzheimer’s disease
Authors: Poirier Alexandre , Picard Cynthia , Labonté Anne , Aubry Isabelle , Auld Daniel , Zetterberg Henrik , Blennow Kaj ,   the PREVENT-AD research group, Poirier Judes , Breitner John C. S. , Poirier Alexandre , Miron Justin , Picard Cynthia , Labonté Anne , Villeneuve Sylvia , Spreng R. Nathan , Rosa-Neto Pedro , Tremblay-Mercier Jennifer , Tremblay Michel L. , Poirier Judes
Published: June 2024

We examined the role of protein tyrosine phosphatase receptor sigma (PTPRS) in the context of Alzheimer’s disease and synaptic integrity. Publicly available datasets (BRAINEAC, ROSMAP, ADC1) and a cohort of asymptomatic but “at risk” individuals (PREVENT-AD) were used to explore the relationship between PTPRS and various Alzheimer’s disease biomarkers. We identified that PTPRS rs10415488 variant C shows features of neuroprotection against early Tau pathology and synaptic degeneration in Alzheimer’s disease. This single nucleotide polymorphism correlated with higher PTPRS transcript abundance and lower p(181)Tau and GAP-43 levels in the CSF. In the brain, PTPRS protein abundance was significantly correlated with the quantity of two markers of synaptic integrity: SNAP25 and SYT-1. We also found the presence of sexual dimorphism for PTPRS, with higher CSF concentrations in males than females. Male carriers for variant C were found to have a 10-month delay in the onset of AD. We thus conclude that PTPRS acts as a neuroprotective receptor in Alzheimer’s disease. Its protective effect is most important in males, in whom it postpones the age of onset of the disease.