bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineering programmable material-to-cell pathways via synthetic notch receptors to spatially control differentiation in multicellular constructs
Authors: Garibyan Mher , Hoffman Tyler , Makaske Thijs , Do Stephanie K. , Wu Yifan , Williams Brian A. , March Alexander R. , Cho Nathan , Pedroncelli Nicolas , Lima Ricardo Espinosa , Soto Jennifer , Jackson Brooke , Santoso Jeffrey W. , Khademhosseini Ali , Thomson Matt , Li Song , McCain Megan L. , Morsut Leonardo
Published: July 2024

Synthetic Notch (synNotch) receptors are genetically encoded, modular synthetic receptors that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Although some materials have been modified to present synNotch ligands with coarse spatial control, applications in tissue engineering generally require extracellular matrix (ECM)-derived scaffolds and/or finer spatial positioning of multiple ligands. Thus, we develop here a suite of materials that activate synNotch receptors for generalizable engineering of material-to-cell signaling. We genetically and chemically fuse functional synNotch ligands to ECM proteins and ECM-derived materials. We also generate tissues with microscale precision over four distinct reporter phenotypes by culturing cells with two orthogonal synNotch programs on surfaces microcontact-printed with two synNotch ligands. Finally, we showcase applications in tissue engineering by co-transdifferentiating fibroblasts into skeletal muscle or endothelial cell precursors in user-defined micropatterns. These technologies provide avenues for spatially controlling cellular phenotypes in mammalian tissues.
Tradeoff between speed and robustness in primordium initiation mediated by auxin-CUC1 interaction
Authors: Kong Shuyao , Zhu Mingyuan , Pan David , Lane Brendan , Smith Richard S. , Roeder Adrienne H. K.
Published: July 2024

Robustness is the reproducible development of a phenotype despite stochastic noise. It often involves tradeoffs with other performance metrics, but the mechanisms underlying such tradeoffs were largely unknown. An Arabidopsis flower robustly develops four sepals from four precisely positioned auxin maxima. The development related myb-like 1 (drmy1) mutant generates noise in auxin signaling that disrupts robustness in sepal initiation. Here, we find that increased expression of CUP-SHAPED COTYLEDON1 (CUC1), a boundary specification transcription factor, in drmy1 underlies this loss of robustness. CUC1 surrounds and amplifies stochastic auxin noise in drmy1 to form variably positioned auxin maxima and sepal primordia. Removing CUC1 from drmy1 provides time for noisy auxin signaling to resolve into four precisely positioned auxin maxima, restoring robust sepal initiation. However, removing CUC1 decreases the intensity of auxin maxima and slows down sepal initiation. Thus, CUC1 increases morphogenesis speed but impairs robustness against auxin noise. Further, using a computational model, we find that the observed phenotype can be explained by the effect of CUC1 in repolarizing PIN FORMED1 (PIN1), a polar auxin transporter. Lastly, our model predicts that reducing global growth rate improves developmental robustness, which we validate experimentally. Thus, our study illustrates a tradeoff between speed and robustness during development.
GLP-1 receptor agonists’ impact on cardio-renal outcomes and mortality in T2D with acute kidney disease
Authors: Pan Heng-Chih , Chen Jui-Yi , Chen Hsing-Yu , Yeh Fang-Yu , Sun Chiao-Yin , Huang Thomas Tao-Min , Wu Vin-Cent
Published: July 2024

Previous studies have explored the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in reducing cardiovascular events in type 2 diabetes. Here we show that GLP-1 RAs are associated with lower risks of mortality, major cardiovascular events (MACEs), and major adverse kidney events (MAKEs) in type 2 diabetes patients with acute kidney disease (AKD). Utilizing global data from the TriNetX database (2002/09/01-2022/12/01) and propensity score matching, we compare 7511 GLP-1 RAs users to non-users among 165,860 AKD patients. The most common causes of AKI are sepsis (55.2%) and cardiorenal syndrome (34.2%). After a median follow-up of 2.3 years, GLP-1 RAs users exhibit reduced risks of mortality (adjusted hazard ratio [aHR]: 0.57), MACEs (aHR: 0.88), and MAKEs (aHR: 0.73). External validation in a multicenter dataset of 1245 type 2 diabetes patients with AKD supports the favorable outcomes. These results emphasize the potential of GLP-1 RAs in individualized treatment for this population.
Ising meson spectroscopy on a noisy digital quantum simulator
Authors: Lamb Christopher , Tang Yicheng , Davis Robert , Roy Ananda
Published: July 2024

Quantum simulation has the potential to be an indispensable technique for the investigation of non-perturbative phenomena in strongly-interacting quantum field theories (QFTs). In the modern quantum era, with Noisy Intermediate Scale Quantum (NISQ) simulators widely available and larger-scale quantum machines on the horizon, it is natural to ask: what non-perturbative QFT problems can be solved with the existing quantum hardware? We show that existing noisy quantum machines can be used to analyze the energy spectrum of several strongly-interacting 1+1D QFTs, which exhibit non-perturbative effects like ‘quark confinement’ and ‘false vacuum decay’. We perform quench experiments on IBM’s quantum simulators to compute the energy spectrum of 1+1D quantum Ising model with a longitudinal field. Our results demonstrate that digital quantum simulation in the NISQ era has the potential to be a viable alternative to numerical techniques such as density matrix renormalization group or the truncated conformal space methods for analyzing QFTs.
TracrRNA reprogramming enables direct PAM-independent detection of RNA with diverse DNA-targeting Cas12 nucleases
Authors: Jiao Chunlei , Peeck Natalia L. , Yu Jiaqi , Ghaem Maghami Mohammad , Kono Sarah , Collias Daphne , Martinez Diaz Sandra L. , Larose Rachael , Beisel Chase L.
Published: July 2024

Many CRISPR-Cas immune systems generate guide (g)RNAs using trans-activating CRISPR RNAs (tracrRNAs). Recent work revealed that Cas9 tracrRNAs could be reprogrammed to convert any RNA-of-interest into a gRNA, linking the RNA’s presence to Cas9-mediated cleavage of double-stranded (ds)DNA. Here, we reprogram tracrRNAs from diverse Cas12 nucleases, linking the presence of an RNA-of-interest to dsDNA cleavage and subsequent collateral single-stranded DNA cleavage—all without the RNA necessarily encoding a protospacer-adjacent motif (PAM). After elucidating nuclease-specific design rules, we demonstrate PAM-independent RNA detection with Cas12b, Cas12e, and Cas12f nucleases. Furthermore, rationally truncating the dsDNA target boosts collateral cleavage activity, while the absence of a gRNA reduces background collateral activity and enhances sensitivity. Finally, we apply this platform to detect 16 S rRNA sequences from five different bacterial pathogens using a universal reprogrammed tracrRNA. These findings extend tracrRNA reprogramming to diverse dsDNA-targeting Cas12 nucleases, expanding the flexibility and versatility of CRISPR-based RNA detection.
Silicon photocathode functionalized with osmium complex catalyst for selective catalytic conversion of CO2 to methane
Authors: Li Xing-Yi , Zhu Ze-Lin , Dagnaw Fentahun Wondu , Yu Jie-Rong , Wu Zhi-Xing , Chen Yi-Jing , Zhou Mu-Han , Wang Tieyu , Tong Qing-Xiao , Jian Jing-Xin
Published: July 2024

Solar-driven CO2 reduction to yield high-value chemicals presents an appealing avenue for combating climate change, yet achieving selective production of specific products remains a significant challenge. We showcase two osmium complexes, przpOs, and trzpOs, as CO2 reduction catalysts for selective CO2-to-methane conversion. Kinetically, the przpOs and trzpOs exhibit high CO2 reduction catalytic rate constants of 0.544 and 6.41 s−1, respectively. Under AM1.5 G irradiation, the optimal Si/TiO2/trzpOs have CH4 as the main product and >90% Faradaic efficiency, reaching −14.11 mA cm−2 photocurrent density at 0.0 VRHE. Density functional theory calculations reveal that the N atoms on the bipyrazole and triazole ligands effectively stabilize the CO2-adduct intermediates, which tend to be further hydrogenated to produce CH4, leading to their ultrahigh CO2-to-CH4 selectivity. These results are comparable to cutting-edge Si-based photocathodes for CO2 reduction, revealing a vast research potential in employing molecular catalysts for the photoelectrochemical conversion of CO2 to methane.
Effects of diets on risks of cancer and the mediating role of metabolites
Authors: Fan Yi , Hu Chanchan , Xie Xiaoxu , Weng Yanfeng , Chen Chen , Wang Zhaokun , He Xueqiong , Jiang Dongxia , Huang Shaodan , Hu Zhijian , Liu Fengqiong
Published: July 2024

Research on the association between dietary adherence and cancer risk is limited, particularly concerning overall cancer risk and its underlying mechanisms. Using the UK Biobank data, we prospectively investigate the associations between adherence to a Mediterranean diet (MedDiet) or a Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurodegenerative Delay diet (MINDDiet) and the risk of overall and 22 specific cancers, as well as the mediating effects of metabolites. Here we show significant negative associations of MedDiet and MINDDiet adherence with overall cancer risk. These associations remain robust across 14 and 13 specific cancers, respectively. Then, a sequential analysis, incorporating Cox regression, elastic net and gradient boost models, identify 10 metabolites associated with overall cancer risk. Mediation results indicate that these metabolites play a crucial role in the association between adherence to a MedDiet or a MINDDiet and cancer risk, independently and cumulatively. These findings deepen our understanding of the intricate connections between diet, metabolites, and cancer development.
Overhauser enhanced liquid state nuclear magnetic resonance spectroscopy in one and two dimensions
Authors: Levien Marcel , Yang Luming , van der Ham Alex , Reinhard Maik , John Michael , Purea Armin , Ganz Jürgen , Marquardsen Thorsten , Tkach Igor , Orlando Tomas , Bennati Marina
Published: July 2024

Nuclear magnetic resonance (NMR) is fundamental in the natural sciences, from chemical analysis and structural biology, to medicine and physics. Despite its enormous achievements, one of its most severe limitations is the low sensitivity, which arises from the small population difference of nuclear spin states. Methods such as dissolution dynamic nuclear polarization and parahydrogen induced hyperpolarization can enhance the NMR signal by several orders of magnitude, however, their intrinsic limitations render multidimensional hyperpolarized liquid-state NMR a challenge. Here, we report an instrumental design for 9.4 Tesla liquid-state dynamic nuclear polarization that enabled enhanced high-resolution NMR spectra in one and two-dimensions for small molecules, including drugs and metabolites. Achieved enhancements of up to two orders of magnitude translate to signal acquisition gains up to a factor of 10,000. We show that hyperpolarization can be transferred between nuclei, allowing DNP-enhanced two-dimensional 13C–13C correlation experiments at 13C natural abundance. The enhanced sensitivity opens up perspectives for structural determination of natural products or characterization of drugs, available in small quantities. The results provide a starting point for a broader implementation of DNP in liquid-state NMR.
Selective and stable CO2 electroreduction at high rates via control of local H2O/CO2 ratio
Authors: Chen Junmei , Qiu Haoran , Zhao Yilin , Yang Haozhou , Fan Lei , Liu Zhihe , Xi ShiBo , Zheng Guangtai , Chen Jiayi , Chen Lei , Liu Ya , Guo Liejin , Wang Lei
Published: July 2024

Controlling the concentrations of H2O and CO2 at the reaction interface is crucial for achieving efficient electrochemical CO2 reduction. However, precise control of these variables during catalysis remains challenging, and the underlying mechanisms are not fully understood. Herein, guided by a multi-physics model, we demonstrate that tuning the local H2O/CO2 concentrations is achievable by thin polymer coatings on the catalyst surface. Beyond the often-explored hydrophobicity, polymer properties of gas permeability and water-uptake ability are even more critical for this purpose. With these insights, we achieve CO2 reduction on copper with Faradaic efficiency exceeding 87% towards multi-carbon products at a high current density of −2 A cm−2. Encouraging cathodic energy efficiency (>50%) is also observed at this high current density due to the substantially reduced cathodic potential. Additionally, we demonstrate stable CO2 reduction for over 150 h at practically relevant current densities owning to the robust reaction interface. Moreover, this strategy has been extended to membrane electrode assemblies and other catalysts for CO2 reduction. Our findings underscore the significance of fine-tuning the local H2O/CO2 balance for future CO2 reduction applications.
Self-supervised learning for characterising histomorphological diversity and spatial RNA expression prediction across 23 human tissue types
Authors: Cisternino Francesco , Ometto Sara , Chatterjee Soumick , Giacopuzzi Edoardo , Levine Adam P. , Glastonbury Craig A.
Published: July 2024

As vast histological archives are digitised, there is a pressing need to be able to associate specific tissue substructures and incident pathology to disease outcomes without arduous annotation. Here, we learn self-supervised representations using a Vision Transformer, trained on 1.7 M histology images across 23 healthy tissues in 838 donors from the Genotype Tissue Expression consortium (GTEx). Using these representations, we can automatically segment tissues into their constituent tissue substructures and pathology proportions across thousands of whole slide images, outperforming other self-supervised methods (43% increase in silhouette score). Additionally, we can detect and quantify histological pathologies present, such as arterial calcification (AUROC = 0.93) and identify missing calcification diagnoses. Finally, to link gene expression to tissue morphology, we introduce RNAPath, a set of models trained on 23 tissue types that can predict and spatially localise individual RNA expression levels directly from H&E histology (mean genes significantly regressed = 5156, FDR 1%). We validate RNAPath spatial predictions with matched ground truth immunohistochemistry for several well characterised control genes, recapitulating their known spatial specificity. Together, these results demonstrate how self-supervised machine learning when applied to vast histological archives allows researchers to answer questions about tissue pathology, its spatial organisation and the interplay between morphological tissue variability and gene expression.
Diameter-dependent phase selectivity in 1D-confined tungsten phosphides
Authors: Jin Gangtae , Multunas Christian D. , Hart James L. , Kiani Mehrdad T. , Duong Nghiep Khoan , Sam Quynh P. , Wang Han , Cheon Yeryun , Hynek David J. , Han Hyeuk Jin , Sundararaman Ravishankar , Cha Judy J.
Published: July 2024

Topological materials confined in 1D can transform computing technologies, such as 1D topological semimetals for nanoscale interconnects and 1D topological superconductors for fault-tolerant quantum computing. As such, understanding crystallization of 1D-confined topological materials is critical. Here, we demonstrate 1D template-assisted nanowire synthesis where we observe diameter-dependent phase selectivity for tungsten phosphides. A phase bifurcation occurs to produce tungsten monophosphide and tungsten diphosphide at the cross-over nanowire diameter regime of 35–70 nm. Four-dimensional scanning transmission electron microscopy is used to identify the two phases and to map crystallographic orientations of grains at a few nm resolution. The 1D-confined phase selectivity is attributed to the minimization of the total surface energy, which depends on the nanowire diameter and chemical potentials of precursors. Theoretical calculations are carried out to construct the diameter-dependent phase diagram, which agrees with experimental observations. Our findings suggest a crystallization route to stabilize topological materials confined in 1D.
Enhanced electrocatalytic biomass oxidation at low voltage by Ni2+-O-Pd interfaces
Authors: Pei An , Wang Peng , Zhang Shiyi , Zhang Qinghua , Jiang Xiaoyi , Chen Zhaoxi , Zhou Weiwei , Qin Qizhen , Liu Renfeng , Du Ruian , Li Zhengjian , Qiu Yongcai , Yan Keyou , Gu Lin , Ye Jinyu , Waterhouse Geoffrey I. N. , Huang Wei-Hsiang , Chen Chi-Liang , Zhao Yun , Chen Guangxu
Published: July 2024

Challenges in direct catalytic oxidation of biomass-derived aldehyde and alcohol into acid with high activity and selectivity hinder the widespread biomass application. Herein, we demonstrate that a Pd/Ni(OH)2 catalyst with abundant Ni2+-O-Pd interfaces allows electrooxidation of 5-hydroxymethylfurfural to 2, 5-furandicarboxylic acid with a selectivity near 100 % and 2, 5-furandicarboxylic acid yield of 97.3% at 0.6 volts (versus a reversible hydrogen electrode) in 1 M KOH electrolyte under ambient conditions. The rate-determining step of the intermediate oxidation of 5-hydroxymethyl-2-furancarboxylic acid is promoted by the increased OH species and low C–H activation energy barrier at Ni2+-O-Pd interfaces. Further, the Ni2+-O-Pd interfaces prevent the agglomeration of Pd nanoparticles during the reaction, greatly improving the stability of the catalyst. In this work, Pd/Ni(OH)2 catalyst can achieve 100% 5-hydroxymethylfurfural conversion and >90% 2, 5-furandicarboxylic acid selectivity in a flow-cell and work stably over 200 h under a fixed cell voltage of 0.85 V.
Elucidating the catalytic mechanism of Prussian blue nanozymes with self-increasing catalytic activity
Authors: Feng Kaizheng , Wang Zhenzhen , Wang Shi , Wang Guancheng , Dong Haijiao , He Hongliang , Wu Haoan , Ma Ming , Gao Xingfa , Zhang Yu
Published: July 2024

Although Prussian blue nanozymes (PBNZ) are widely applied in various fields, their catalytic mechanisms remain elusive. Here, we investigate the long-term catalytic performance of PBNZ as peroxidase (POD) and catalase (CAT) mimetics to elucidate their lifespan and underlying mechanisms. Unlike our previously reported Fe3O4 nanozymes, which exhibit depletable POD-like activity, the POD and CAT-like activities of PBNZ not only persist but slightly enhance over prolonged catalysis. We demonstrate that the irreversible oxidation of PBNZ significantly promotes catalysis, leading to self-increasing catalytic activities. The catalytic process of the pre-oxidized PBNZ can be initiated through either the conduction band pathway or the valence band pathway. In summary, we reveal that PBNZ follows a dual-path electron transfer mechanism during the POD and CAT-like catalysis, offering the advantage of a long service life.
A strategy for tough and fatigue-resistant hydrogels via loose cross-linking and dense dehydration-induced entanglements
Authors: Zhong Danming , Wang Zhicheng , Xu Junwei , Liu Junjie , Xiao Rui , Qu Shaoxing , Yang Wei
Published: July 2024

Outstanding overall mechanical properties are essential for the successful utilization of hydrogels in advanced applications such as human-machine interfaces and soft robotics. However, conventional hydrogels suffer from fracture toughness-stiffness conflict and fatigue threshold-stiffness conflict, limiting their applicability. Simultaneously enhancing the fracture toughness, fatigue threshold, and stiffness of hydrogels, especially within a homogeneous single network structure, has proven to be a formidable challenge. In this work, we overcome this challenge through the design of a loosely cross-linked hydrogel with slight dehydration. Experimental results reveal that the slightly-dehydrated, loosely cross-linked polyacrylamide hydrogel, with an original/current water content of 87%/70%, exhibits improved mechanical properties, which is primarily attributed to the synergy between the long-chain structure and the dense dehydration-induced entanglements. Importantly, the creation of these microstructures does not require intricate design or processing. This simple approach holds significant potential for hydrogel applications where excellent anti-fracture and fatigue-resistant properties are necessary.
Recent advances in the pathogenesis and prevention strategies of dental calculus
Authors: Wei Yu , Dang Gao-peng , Ren Zhao-yang , Wan Mei-chen , Wang Chen-yu , Li Hong-bo , Zhang Tong , Tay Franklin R. , Niu Li-na
Published: July 2024

Dental calculus severely affects the oral health of humans and animal pets. Calculus deposition affects the gingival appearance and causes inflammation. Failure to remove dental calculus from the dentition results in oral diseases such as periodontitis. Apart from adversely affecting oral health, some systemic diseases are closely related to dental calculus deposition. Hence, identifying the mechanisms of dental calculus formation helps protect oral and systemic health. A plethora of biological and physicochemical factors contribute to the physiological equilibrium in the oral cavity. Bacteria are an important part of the equation. Calculus formation commences when the bacterial equilibrium is broken. Bacteria accumulate locally and form biofilms on the tooth surface. The bacteria promote increases in local calcium and phosphorus concentrations, which triggers biomineralization and the development of dental calculus. Current treatments only help to relieve the symptoms caused by calculus deposition. These symptoms are prone to relapse if calculus removal is not under control. There is a need for a treatment regime that combines short-term and long-term goals in addressing calculus formation. The present review introduces the mechanisms of dental calculus formation, influencing factors, and the relationship between dental calculus and several systemic diseases. This is followed by the presentation of a conceptual solution for improving existing treatment strategies and minimizing recurrence.
Susceptibility gene mutations in germline and tumors of patients with HER2-negative advanced breast cancer
Authors: Fasching Peter A. , Hu Chunling , Hart Steven N. , Ruebner Matthias , Polley Eric C. , Gnanaolivu Rohan D. , Hartkopf Andreas D. , Huebner Hanna , Janni Wolfgang , Hadji Peyman , Tesch Hans , Uhrig Sabrina , Ettl Johannes , Lux Michael P. , Lüftner Diana , Wallwiener Markus , Wurmthaler Lena A. , Goossens Chloë , Müller Volkmar , Beckmann Matthias W. , Hein Alexander , Anetsberger Daniel , Belleville Erik , Wimberger Pauline , Untch Michael , Ekici Arif B. , Kolberg Hans-Christian , Hartmann Arndt , Taran Florin-Andrei , Fehm Tanja N. , Wallwiener Diethelm , Brucker Sara Y. , Schneeweiss Andreas , Häberle Lothar , Couch Fergus J.
Published: July 2024

Germline mutations in BRCA1 and BRCA2 (gBRCA1/2) are required for a PARP inhibitor therapy in patients with HER2-negative (HER2−) advanced breast cancer (aBC). However, little is known about the prognostic impact of gBRCA1/2 mutations in aBC patients treated with chemotherapy. This study aimed to investigate the frequencies and prognosis of germline and somatic BRCA1/2 mutations in HER2- aBC patients receiving the first chemotherapy in the advanced setting. Patients receiving their first chemotherapy for HER2- aBC were retrospectively selected from the prospective PRAEGNANT registry (NCT02338167). Genotyping of 26 cancer predisposition genes was performed with germline DNA of 471 patients and somatic tumor DNA of 94 patients. Mutation frequencies, progression-free and overall survival (PFS, OS) according to germline mutation status were assessed. gBRCA1/2 mutations were present in 23 patients (4.9%), and 33 patients (7.0%) had mutations in other cancer risk genes. Patients with a gBRCA1/2 mutation had a better OS compared to non-mutation carriers (HR: 0.38; 95%CI: 0.17–0.86). PFS comparison was not statistically significant. Mutations in other risk genes did not affect prognosis. Two somatic BRCA2 mutations were found in 94 patients without gBRCA1/2 mutations. Most frequently somatic mutated genes were TP53 (44.7%), CDH1 (10.6%) and PTEN (6.4%). In conclusion, aBC patients with gBRCA1/2 mutations had a more favorable prognosis under chemotherapy compared to non-mutation carriers. The mutation frequency of ~5% with gBRCA1/2 mutations together with improved outcome indicates that germline genotyping of all metastatic patients for whom a PARP inhibitor therapy is indicated should be considered.
High pressure suppression of plasticity due to an overabundance of shear embryo formation
Authors: Hamilton Brenden W. , Germann Timothy C.
Published: July 2024

High pressure shear band formation is a critical phenomenon in energetic materials due to its influence on both mechanical strength and mechanochemical activation. While shear banding is known to occur in a variety of these materials, the governing dynamics of the mechanisms are not well defined for molecular crystals. We conduct molecular dynamics simulations of shock wave induced shear band formation in the energetic material 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) to assess shear band nucleation processes. We find, that at high pressures, the initial formation sites for shear bands, “embryos”, form in excess and rapidly lower deviatoric stresses prior to shear band formation and growth. This results in the suppression of plastic deformation. A local cluster analysis is used to quantify and contrast this mechanism with a more typical shear banding seen at lower pressures. These results demonstrate a mechanism that is reversible in nature and that supersedes shear band formation at increased pressures. We anticipate that these results will have a broad impact on the modeling and development of high-strain rate application materials such as those for high explosives and hypersonic systems.
Cancer mutationscape: revealing the link between modular restructuring and intervention efficacy among mutations
Authors: Plaugher Daniel , Murrugarra David
Published: July 2024

There is increasing evidence that biological systems are modular in both structure and function. Complex biological signaling networks such as gene regulatory networks (GRNs) are proving to be composed of subcategories that are interconnected and hierarchically ranked. These networks contain highly dynamic processes that ultimately dictate cellular function over time, as well as influence phenotypic fate transitions. In this work, we use a stochastic multicellular signaling network of pancreatic cancer (PC) to show that the variance in topological rankings of the most phenotypically influential modules implies a strong relationship between structure and function. We further show that induction of mutations alters the modular structure, which analogously influences the aggression and controllability of the disease in silico. We finally present evidence that the impact and location of mutations with respect to PC modular structure directly corresponds to the efficacy of single agent treatments in silico, because topologically deep mutations require deep targets for control.
Internal pipe corrosion assessment method in water distribution system using ultrasound and convolutional neural networks
Authors: Sung Yeongho , Jeon Hyeon-Ju , Kim Daehun , Kim Min-Seo , Choi Jaeyeop , Jo Hwan Ryul , Oh Junghwan , Lee O-Joun , Lim Hae Gyun
Published: July 2024

Internal pipe corrosion within water distribution systems leads to iron oxide deposits on pipe walls, potentially contaminating the water supply. Consuming iron oxide-contaminated water can cause significant health issues such as gastrointestinal infections, dermatological problems, and lymph node complications. Therefore, non-destructive and continuous monitoring of pipe corrosion is imperative for water sustainability initiatives. This study introduces a dual-mode methodology utilizing advanced ultrasound technology and convolutional neural networks (CNN) to quantify pipe corrosion. Scanning acoustic microscopy (SAM) employs high-frequency ultrasound to generate high-resolution images of pipe thickness, indicating iron oxide accumulation. SAM also captures internal pipe data to measure iron oxide concentration in the water. This data, analyzed by CNN, achieves an impressive 95% accuracy. This dual-mode system effectively assesses both the extent of pipe corrosion and water contamination, exemplifying the successful integration of SAM and CNN for precise and reliable monitoring.
Effect of different MoS2 morphologies on the formation and performance of adsorptive-catalytic nanocomposite membranes
Authors: Al Momani Delal E. , Arshad Fathima , Taha Inas , Anjum Dalaver H. , Zou Linda
Published: July 2024

This study synthesized three MoS₂ morphologies—nanospheres, nanoplatelets, and nanosheets—under varied conditions and incorporated them into chitosan membranes. TEM confirmed unique morphologies and crystallinity. Clean water flux showed that the nanoplatelet (P-CM) membrane had the highest flux due to higher porosity. The P-CM membrane excelled in removing Mn²⁺ and Zn²⁺ ions, achieving 93.0 ± 0.5% and 90.4 ± 1.5% removal, outperforming membranes with nanospheres (S-CM) and nanosheets (T-CM). Its superior performance is attributed to thicker nanoplatelets forming more water channels. The MoS₂‘s tri-layered structure generated reactive oxygen species (ROS) via H₂O₂ catalysis, contributing to enhanced heavy metal removal. These adsorptive-catalytic membranes combine adsorption with catalytic decomposition of heavy metals, highlighting the work’s novelty and superior performance. The membranes demonstrated excellent flux recovery and reusability (96.0 ± 0.5% for P-CM) after chemical cleaning. The findings emphasize the impact of nanomaterial morphologies on membrane performance in water treatment and environmental remediation.
Tracing Opioids Across the US: A High-Resolution Pharmaceutical Distribution Dataset
Authors: Amico Ambra , Verginer Luca , Schweitzer Frank
Published: July 2024

In the field of pharmaceutical supply chains, there is a lack of comprehensive historical data, representing a significant barrier to advancing research. To address this gap, we introduce a high-resolution dataset comprising drug packages distributed to approximately 300,000 pharmacies, hospitals, and practitioners across the US. We reconstruct 375 million distribution paths from ARCOS, a DEA-maintained database comprising half a billion shipping records between 2006 and 2014. While ARCOS tracks dyadic shipments, it does not provide information on the complete journey of single packages from manufacturers to final destinations. Our algorithm is able to reconstruct complete distribution paths from these dyadic records. The reconstructed dataset, with its high temporal and spatial resolution, offers an unprecedented view of US pharmaceutical distribution and is a valuable resource for investigating supply and distribution networks.
Chromosome-level genome assembly of Hippophae rhamnoides variety
Authors: Yang Xingyu , Luo Shujie , Yang Shihai , Duoji Ciren , Wang Qianwen , Chen Zhiyu , Yang Danni , Yang Tianyu , Wan Xi , Yang Yunqiang , Liu Tianmeng , Yang Yongping
Published: July 2024

Fructus hippophae (Hippophae rhamnoides spp. mongolica×Hippophae rhamnoides sinensis), a hybrid variety of sea buckthorn that Hippophae rhamnoides spp. mongolica serves as the female parent and Hippophae rhamnoidessinensis serves as the male parent, is a traditional plant with great potentials of economic and medical values. Herein, we gained a chromosome-level genome of Fructus hippophae about 918.59 Mb, with the scaffolds N50 reaching 83.65 Mb. Then, we anchored 440 contigs with 97.17% of the total genome sequences onto 12 pseudochromosomes. Next, de-novo, homology and transcriptome assembly strategies were adopted for gene structure prediction. This predicted 36475 protein-coding genes, of which 36226 genes could be functionally annotated. Simultaneously, various strategies were used for quality assessment, both the complete BUSCO value (98.80%) and the mapping rate indicated the high assembly quality. Repetitive elements, which occupied 63.68% of the genome, and 1483600 bp of non-coding RNA were annotated. Here, we provide genomic information on female plants of a popular variety, which can provide data for pan-genomic construction of sea buckthorn and for the resolution of the mechanism of sex differentiation.
Transcriptomic and metabolomic data of goat ovarian and uterine tissues during sexual maturation
Authors: Wang Yanyan , Wang Jianmin , Li Qing , Xuan Rong , Guo Yanfei , He Peipei , Duan Qingling , Du Shanfeng , Chao Tianle
Published: July 2024

The ovaries and uterus are crucial reproductive organs in mammals, and their coordinated development ensures the normal development of sexual maturity and reproductive capacity. This study aimed to comprehensively capture the different physiological stages of the goat’s sexual maturation by selecting four specific time points. We collected samples of ovarian and uterine tissues from five female Jining Gray goats at each time point: after birth (D1), 2-month-old (M2), 4-month-old (M4), and 6-month-old (M6). By combining transcriptomic sequencing of 40 samples (including rRNA-depleted RNA-seq libraries with 3607.8 million reads and miRNA-seq libraries with 444.0 million reads) and metabolomics analysis, we investigated the transcriptomic mechanisms involved in reproductive regulation in the ovary and uterus during sexual maturation, as well as the changes in metabolites and their functional potential. Additionally, we analyzed blood hormone indices and uterine tissue sections to examine temporal changes. These datasets will provide a valuable reference for the reproductive regulation of the ovary and uterus, as well as the regulation of metabolites during sexual maturation in goats.
Tibetan Plateau Runoff and Evapotranspiration Dataset by an observation-constrained cryosphere-hydrology model
Authors: Fan Xinfeng , Wang Lei , Liu Hu , Chen Deliang , Song Lei , Wang Yuanwei , Qi Jia , Chai Chenhao , Liu Ruishun , Li Xiuping , Zhou Jing , Guo Xiaoyu , Long Junshui
Published: July 2024

Runoff and evapotranspiration (ET) are pivotal constituents of the water, energy, and carbon cycles. This research presents a 5-km monthly gridded runoff and ET dataset for 1998–2017, encompassing seven headwaters of Tibetan Plateau rivers (Yellow, Yangtze, Mekong, Salween, Brahmaputra, Ganges, and Indus) (hereinafter TPRED). The dataset was generated using the advanced cryosphere-hydrology model WEB-DHM, yielding a Nash coefficient ranging from 0.77 to 0.93 when compared to the observed discharges. The findings indicate that TPRED’s monthly runoff notably outperforms existing datasets in capturing hydrological patterns, as evidenced by robust metrics such as the correlation coefficient (CC) (0.944–0.995), Bias (−0.68-0.53), and Root Mean Square Error (5.50–15.59 mm). Additionally, TPRED’s monthly ET estimates closely align with expected seasonal fluctuations, as reflected by a CC ranging from 0.94 to 0.98 when contrasted with alternative ET products. Furthermore, TPRED’s annual values exhibit commendable concordance with operational products across multiple dimensions. Ultimately, the TPRED will have great application on hydrometeorology, carbon transport, water management, hydrological modeling, and sustainable development of water resources.
Sustainable green synthesis and characterization of nanocomposites for synergistic photocatalytic degradation of Reactive Orange 16 in textile wastewater using CuO@A-TiO2/Ro-TiO2
Authors: Nassar Amal A. , Elfiky Aya Abd El Aziz , El-Sawaf Ayman K. , Mubarak Mahmoud F.
Published: July 2024

This paper explores the photocatalytic degradation of Reactive Orange 16 (RO16) dye in textile wastewater employing a novel CuO@A-TiO2/Ro-TiO2 nanocomposite. The nanocomposite was synthesized via a hydrothermal technique, resulting in a monoclinic phase of leaf-shaped CuO loaded on a hexagonal wurtzite structure of rod-shaped ZnO, as confirmed by FE-SEM and XRD analyses. Optical experiments revealed band gap energies of 1.99 eV for CuO, 2.19 eV for ZnO, and 3.34 eV for the CuO@A-TiO2/Ro-TiO2 nanocomposite. Photocatalytic degradation experiments showcased complete elimination of a 100 mg/L RO16 solution (150 mL) after 120 min of UV light illumination and 100 min of sunlight illumination, emphasizing the nanocomposite's efficiency under both light sources. The study further delves into the application of the CuO@A-TiO2/Ro-TiO2 nanocomposite for the degradation of actual textile wastewater samples under sunlight irradiation. The results underscore the nanocomposite's remarkable efficacy in treating RO16 in textile wastewater, positioning it as a promising candidate for sustainable and efficient wastewater treatment applications. This research contributes valuable insights into the development of advanced photocatalytic materials for textile dye degradation in wastewater treatment.
Computational screening combined with well-tempered metadynamics simulations identifies potential TMPRSS2 inhibitors
Authors: Sharanya C. S. , Wilbee D. Sasikala , Sathi Shijulal Nelson , Natarajan Kathiresan
Published: July 2024

Type-II transmembrane serine proteases are effective pharmacological targets for host defence against viral entry and in certain cancer cell progressions. These serine proteases cleave viral spike proteins to expose the fusion peptide for cell entry, which is essential to the life cycle of the virus. TMPRSS2 inhibitors can also fight against respiratory viruses that employ them for cell entry. Our study combining virtual screening, all-atom molecular dynamics, and well-tempered metadynamics simulation identifies vicenin-2, neohesperidin, naringin, and rhoifolin as promising TMPRSS2 antagonists. The binding energies obtained are − 16.3, − 15.4, − 13.6, and − 13.8 kcal/mol for vicenin-2, neohesperidin, naringin, and rhoifolin respectively. The RMSD, RMSF, PCA, DCCM, and binding free energy profiles also correlate with the stable binding of these ligands at the active site of TMPRSS2. The study reveals that these molecules could be promising lead molecules for combating future outbreaks of coronavirus and other respiratory viruses.
Identifying symptom etiologies using syntactic patterns and large language models
Authors: Taub-Tabib Hillel , Shamay Yosi , Shlain Micah , Pinhasov Menny , Polak Mark , Tiktinsky Aryeh , Rahamimov Sigal , Bareket Dan , Eyal Ben , Kassis Moriya , Goldberg Yoav , Kaminski Rosenberg Tal , Vulfsons Simon , Ben Sasson Maayan
Published: July 2024

Differential diagnosis is a crucial aspect of medical practice, as it guides clinicians to accurate diagnoses and effective treatment plans. Traditional resources, such as medical books and services like UpToDate, are constrained by manual curation, potentially missing out on novel or less common findings. This paper introduces and analyzes two novel methods to mine etiologies from scientific literature. The first method employs a traditional Natural Language Processing (NLP) approach based on syntactic patterns. By using a novel application of human-guided pattern bootstrapping patterns are derived quickly, and symptom etiologies are extracted with significant coverage. The second method utilizes generative models, specifically GPT-4, coupled with a fact verification pipeline, marking a pioneering application of generative techniques in etiology extraction. Analyzing this second method shows that while it is highly precise, it offers lesser coverage compared to the syntactic approach. Importantly, combining both methodologies yields synergistic outcomes, enhancing the depth and reliability of etiology mining.
Automatic 3D reconstruction of vertebrae from orthogonal bi-planar radiographs
Authors: Chen Yuepeng , Gao Yue , Fu Xiangling , Chen Yingyin , Wu Ji , Guo Chenyi , Li Xiaodong
Published: July 2024

When conducting spine-related diagnosis and surgery, the three-dimensional (3D) upright posture of the spine under natural weight bearing is of significant clinical value for physicians to analyze the force on the spine. However, existing medical imaging technologies cannot meet current requirements of medical service. On the one hand, the mainstream 3D volumetric imaging modalities (e.g. CT and MRI) require patients to lie down during the imaging process. On the other hand, the imaging modalities conducted in an upright posture (e.g. radiograph) can only realize 2D projections, which lose the valid information of spinal anatomy and curvature. Developments of deep learning-based 3D reconstruction methods bring potential to overcome the limitations of the existing medical imaging technologies. To deal with the limitations of current medical imaging technologies as is described above, in this paper, we propose a novel deep learning framework, ReVerteR, which can realize automatic 3D Reconstruction of Vertebrae from orthogonal bi-planar Radiographs. With the utilization of self-attention mechanism and specially designed loss function combining Dice, Hausdorff, Focal, and MSE, ReVerteR can alleviate the sample-imbalance problem during the reconstruction process and realize the fusion of the centroid annotation and the focused vertebra. Furthermore, aiming at automatic and customized 3D spinal reconstruction in real-world scenarios, we extend ReVerteR to a clinical deployment-oriented framework, and develop an interactive interface with all functions in the framework integrated so as to enhance human–computer interaction during clinical decision-making. Extensive experiments and visualization conducted on our constructed datasets based on two benchmark datasets of spinal CT, VerSe 2019 and VerSe 2020, demonstrate the effectiveness of our proposed ReVerteR. In this paper, we propose an automatic 3D reconstruction method of vertebrae based on orthogonal bi-planar radiographs. With the 3D upright posture of the spine under natural weight bearing effectively constructed, our proposed method is expected to better support doctors make clinical decision during spine-related diagnosis and surgery.
Design and stability analysis of a new six-floater oscillating water column-based floating offshore wind turbine platform
Authors: Cayuela-Padilla Salvador , M’zoughi Fares , Garrido Izaskun , Garrido Aitor J.
Published: July 2024

The operational efficiency and lifespan of Floating Offshore Wind Turbines (FOWTs) are adversely impacted by the inherent platform motions and undesired vibrations induced by wind and wave loads. To effectively address these effects, the control of specific structural motions is of utmost importance, with platform pitch and yaw identified as the primary Degrees Of Freedom (DOF) that require attention. This study proposes a novel utilization of Oscillating Water Columns (OWCs) as a reliable and viable solution to mitigate platform pitch and yaw motions, thereby significantly enhancing the efficiency and reducing fatigue in wind turbines. This article aims to evaluate the impact resulting from integrating OWCs within each discrete floater of a Six-Floater platform. By considering different combinations of OWCs, a comprehensive analysis of the Response Amplitude Operators (RAOs) associated with pitch and yaw motions is presented. The primary objective is to identify the most efficient arrangements of OWCs and determine suitable combinations that effectively stabilize platform pitch and yaw motions. The empirical results substantiate that specific OWC configurations exhibit notable dampening effects on both pitch and yaw motions, particularly within specific wave frequency intervals. Consequently, it can be inferred that the integration and adequate operation of OWCs facilitate a substantial improvement in the stabilization of multi-floater platforms.
High-intensity interval training improves bone remodeling, lipid profile, and physical function in multiple sclerosis patients
Authors: Amato Alessandra , Proia Patrizia , Alioto Anna , Rossi Carlo , Pagliaro Andrea , Ragonese Paolo , Schirò Giuseppe , Salemi Giuseppe , Caldarella Rosalia , Vasto Sonya , Nowak Robert , Kostrzewa-Nowak Dorota , Musumeci Giuseppe , Baldassano Sara
Published: July 2024

Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease due to an autoimmune chronic inflammatory response, yet the etiology is currently not completely understood. It is already known that physical activity plays an essential role in improving quality of life, especially in neuropathological conditions. The study was aimed to investigate the possible benefits of high-intensity interval training (HIIT) in bone and lipid metabolism markers, and neuromotor abilities in MS patients. 130 participants were recruited; 16 subjects with MS met the inclusion criteria and were included in the data analysis. The patients were randomly assigned to two groups: a Control group (CG) (34.88 ± 4.45 yrs) that didn’t perform any physical activity and the Exercise group (EG) (36.20 ± 7.80 yrs) that performed HIIT protocol. The training program was conducted remotely by a kinesiologist. It was performed three times a week for 8 weeks. At the beginning (T0) and the end of the study (T1) physical function tests, bone remodelling markers, and lipid markers analyses were performed. After 8 weeks of training the wall squat (s) (T0 = 27.18  ±  4.21; T1 = 41.68 ± 5.38, p ≤ 0.01) and Time Up and Go test (s) (T0 = 7.65 ± 0.43; T1 = 6.34 ± 0.38 p ≤ 0.01) performances improved; lipid markers analysis showed a decrease in Total (mg/dl) (T0 = 187.22 ± 15.73; T1 = 173.44 ± 13.03, p ≤ 0.05) and LDL (mg/dl) (T0 = 108 ± 21.08; T1 = 95.02 ± 17.99, p < 0.05) cholesterol levels. Additionally, the levels of osteocalcin (µg/L), a marker of bone formation increased (T0 = 20.88 ± 4.22; T1 = 23.66 ± 6.24, p < 0.05), 25-OH Vitamin D (µg/L) improved after 8 weeks (T0 = 21.11 ± 7.11; T1 = 27.66 ± 7.59, p < 0.05). HIIT had an effect on lower limb strength and gait control, improved bone formation, and lipid management, in MS patients.
The contribution of community-based conservation models to conserving large herbivore populations
Authors: Kiffner Christian , Foley Charles A. H. , Lee Derek E. , Bond Monica L. , Kioko John , Kissui Bernard M. , Lobora Alex L. , Foley Lara S. , Nelson Fred
Published: July 2024

In East Africa, community-based conservation models (CBCMs) have been established to support the conservation of wildlife in fragmented landscapes like the Tarangire Ecosystem, Tanzania. To assess how different management approaches maintained large herbivore populations, we conducted line distance surveys and estimated seasonal densities of elephant, giraffe, zebra, and wildebeest in six management units, including three CBCMs, two national parks (positive controls), and one area with little conservation interventions (negative control). Using a Monte-Carlo approach to propagate uncertainties from the density estimates and trend analysis, we analyzed the resulting time series (2011–2019). Densities of the target species were consistently low in the site with little conservation interventions. In contrast, densities of zebra and wildebeest in CBCMs were similar to national parks, providing evidence that CBCMs contributed to the stabilization of these migratory populations in the central part of the ecosystem. CBCMs also supported giraffe and elephant densities similar to those found in national parks. In contrast, the functional connectivity of Lake Manyara National Park has not been augmented by CBCMs. Our analysis suggests that CBCMs can effectively conserve large herbivores, and that maintaining connectivity through CBCMs should be prioritized.