bluuebunny/crossref_metadata_2025_split huggingface dataset:
A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosis
Authors: Li Yong , Cai Zhengwen , Ma Wenjuan , Bai Long , Luo En , Lin Yunfeng 
Published: February 2024

AbstractDiabetic osteoporosis (DOP) is a significant complication that poses continuous threat to the bone health of patients with diabetes; however, currently, there are no effective treatment strategies. In patients with diabetes, the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells (BMSCs), leading to significant skeletal changes. To address this issue, we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP. We synthesized ferroptosis-suppressing nanoparticles, which could deliver curcumin, a natural compound, to the bone marrow using tetrahedral framework nucleic acid (tFNA). This delivery system demonstrated excellent curcumin bioavailability and stability, as well as synergistic properties with tFNA. Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) pathway, inhibiting ferroptosis, promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment, reducing trabecular loss, and increasing bone formation. These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosis-suppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.
Redefining cancer research for therapeutic breakthroughs
Authors: Yuzhalin Arseniy E. 
Published: February 2024

AbstractCancer research has played a pivotal role in improving patient outcomes. However, despite the significant investment in fundamental cancer research over the past few decades, the translation of funding into substantial advancements in cancer treatment has been limited. This perspective article employs a detailed analysis to outline strategies for promoting innovation and facilitating discoveries within the field of cancer research.
Global conservation status of the jawed vertebrate Tree of Life
Authors: Gumbs Rikki , Scott Oenone , Bates Ryan , Böhm Monika , Forest Félix , Gray Claudia L. , Hoffmann Michael , Kane Daniel , Low Christopher , Pearse William D. , Pipins Sebastian , Tapley Benjamin , Turvey Samuel T. , Jetz Walter , Owen Nisha R. , Rosindell James 
Published: February 2024

AbstractHuman-driven extinction threatens entire lineages across the Tree of Life. Here we assess the conservation status of jawed vertebrate evolutionary history, using three policy-relevant approaches. First, we calculate an index of threat to overall evolutionary history, showing that we expect to lose 86–150 billion years (11–19%) of jawed vertebrate evolutionary history over the next 50–500 years. Second, we rank jawed vertebrate species by their EDGE scores to identify the highest priorities for species-focused conservation of evolutionary history, finding that chondrichthyans, ray-finned fish and testudines rank highest of all jawed vertebrates. Third, we assess the conservation status of jawed vertebrate families. We found that species within monotypic families are more likely to be threatened and more likely to be in decline than other species. We provide a baseline for the status of families at risk of extinction to catalyse conservation action. This work continues a trend of highlighting neglected groups—such as testudines, crocodylians, amphibians and chondrichthyans—as conservation priorities from a phylogenetic perspective.
General alkyl fluoride functionalization via short-lived carbocation-organozincate ion pairs
Authors: Lucas Kane D. , Figula Bryan C. , Balaraman Kaluvu , Bertke Jeffery A. , Wolf Christian 
Published: February 2024

AbstractFluorinated organic compounds are frequently used across the chemical and life sciences. Although a large, structurally diverse pool of alkyl fluorides is nowadays available, synthetic applications trail behind the widely accepted utility of other halides. We envisioned that C(sp2)-C(sp3) cross-coupling reactions of alkyl fluorides with fluorophilic organozinc compounds should be possible through a heterolytic mechanism that involves short-lived ion pairs and uses the stability of the Zn-F bond as the thermodynamic driving force. This would be mechanistically different from previously reported radical reactions and overcome long-standing limitations of organometallic cross-coupling methodology, including competing β-hydride elimination, homodimerization and hydrodefluorination. Here, we show a practical Csp3-F bond functionalization method that expands the currently restricted synthetic space of unactivated primary, secondary and tertiary C(sp3)-F bonds but also uses benzylic, propargylic and acyl fluorides. Many functional groups and sterically demanding substrates are tolerated, which allows practical carbon-carbon bond formation and late-stage functionalization.
MYC induces CDK4/6 inhibitors resistance by promoting pRB1 degradation
Authors: Ma Jian , Li Lei , Ma Bohan , Liu Tianjie , Wang Zixi , Ye Qi , Peng Yunhua , Wang Bin , Chen Yule , Xu Shan , Wang Ke , Dang Fabin , Wang Xinyang , Zeng Zixuan , Jian Yanlin , Ren Zhihua , Fan Yizeng , Li Xudong , Liu Jing , Gao Yang , Wei Wenyi , Li Lei 
Published: February 2024

AbstractCDK4/6 inhibitors (CDK4/6i) show anticancer activity in certain human malignancies, such as breast cancer. However, their application to other tumor types and intrinsic resistance mechanisms are still unclear. Here, we demonstrate that MYC amplification confers resistance to CDK4/6i in bladder, prostate and breast cancer cells. Mechanistically, MYC binds to the promoter of the E3 ubiquitin ligase KLHL42 and enhances its transcription, leading to RB1 deficiency by inducing both phosphorylated and total pRB1 ubiquitination and degradation. We identify a compound that degrades MYC, A80.2HCl, which induces MYC degradation at nanomolar concentrations, restores pRB1 protein levels and re-establish sensitivity of MYC high-expressing cancer cells to CDK4/6i. The combination of CDK4/6i and A80.2HCl result in marked regression in tumor growth in vivo. Altogether, these results reveal the molecular mechanisms underlying MYC-induced resistance to CDK4/6i and suggest the utilization of the MYC degrading molecule A80.2HCl to potentiate the therapeutic efficacy of CDK4/6i.
Diagnosis and management of subarachnoid haemorrhage
Authors: Thilak Suneesh , Brown Poppy , Whitehouse Tony , Gautam Nandan , Lawrence Errin , Ahmed Zubair , Veenith Tonny 
Published: February 2024

AbstractAneurysmal subarachnoid haemorrhage (aSAH) presents a challenge to clinicians because of its multisystem effects. Advancements in computed tomography (CT), endovascular treatments, and neurocritical care have contributed to declining mortality rates. The critical care of aSAH prioritises cerebral perfusion, early aneurysm securement, and the prevention of secondary brain injury and systemic complications. Early interventions to mitigate cardiopulmonary complications, dyselectrolytemia and treatment of culprit aneurysm require a multidisciplinary approach. Standardised neurological assessments, transcranial doppler (TCD), and advanced imaging, along with hypertensive and invasive therapies, are vital in reducing delayed cerebral ischemia and poor outcomes. Health care disparities, particularly in the resource allocation for SAH treatment, affect outcomes significantly, with telemedicine and novel technologies proposed to address this health inequalities. This article underscores the necessity for comprehensive multidisciplinary care and the urgent need for large-scale studies to validate standardised treatment protocols for improved SAH outcomes.
OrthoID: profiling dynamic proteomes through time and space using mutually orthogonal chemical tools
Authors: Lee Ara , Sung Gihyun , Shin Sanghee , Lee Song-Yi , Sim Jaehwan , Nhung Truong Thi My , Nghi Tran Diem , Park Sang Ki , Sathieshkumar Ponnusamy Pon , Kang Imkyeung , Mun Ji Young , Kim Jong-Seo , Rhee Hyun-Woo , Park Kyeng Min , Kim Kimoon 
Published: February 2024

AbstractIdentifying proteins at organelle contact sites, such as mitochondria-associated endoplasmic reticulum membranes (MAM), is essential for understanding vital cellular processes, yet challenging due to their dynamic nature. Here we report “OrthoID”, a proteomic method utilizing engineered enzymes, TurboID and APEX2, for the biotinylation (Bt) and adamantylation (Ad) of proteins close to the mitochondria and endoplasmic reticulum (ER), respectively, in conjunction with high-affinity binding pairs, streptavidin-biotin (SA-Bt) and cucurbit[7]uril-adamantane (CB[7]-Ad), for selective orthogonal enrichment of Bt- and Ad-labeled proteins. This approach effectively identifies protein candidates associated with the ER-mitochondria contact, including LRC59, whose roles at the contact site were—to the best of our knowledge—previously unknown, and tracks multiple protein sets undergoing structural and locational changes at MAM during mitophagy. These findings demonstrate that OrthoID could be a powerful proteomics tool for the identification and analysis of spatiotemporal proteins at organelle contact sites and revealing their dynamic behaviors in vital cellular processes.
Altered receptor binding, antibody evasion and retention of T cell recognition by the SARS-CoV-2 XBB.1.5 spike protein
Authors: Mannar Dhiraj , Saville James W. , Poloni Chad , Zhu Xing , Bezeruk Alison , Tidey Keith , Ahmed Sana , Tuttle Katharine S. , Vahdatihassani Faezeh , Cholak Spencer , Cook Laura , Steiner Theodore S. , Subramaniam Sriram 
Published: February 2024

AbstractThe XBB.1.5 variant of SARS-CoV-2 has rapidly achieved global dominance and exhibits a high growth advantage over previous variants. Preliminary reports suggest that the success of XBB.1.5 stems from mutations within its spike glycoprotein, causing immune evasion and enhanced receptor binding. We present receptor binding studies that demonstrate retention of binding contacts with the human ACE2 receptor and a striking decrease in binding to mouse ACE2 due to the revertant R493Q mutation. Despite extensive evasion of antibody binding, we highlight a region on the XBB.1.5 spike protein receptor binding domain (RBD) that is recognized by serum antibodies from a donor with hybrid immunity, collected prior to the emergence of the XBB.1.5 variant. T cell assays reveal high frequencies of XBB.1.5 spike-specific CD4+ and CD8+ T cells amongst donors with hybrid immunity, with the CD4+ T cells skewed towards a Th1 cell phenotype and having attenuated effector cytokine secretion as compared to ancestral spike protein-specific cells. Thus, while the XBB.1.5 variant has retained efficient human receptor binding and gained antigenic alterations, it remains susceptible to recognition by T cells induced via vaccination and previous infection.
Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial
Authors: Ni Lochlainn Mary , Bowyer Ruth C. E. , Moll Janne Marie , García María Paz , Wadge Samuel , Baleanu Andrei-Florin , Nessa Ayrun , Sheedy Alyce , Akdag Gulsah , Hart Deborah , Raffaele Giulia , Seed Paul T. , Murphy Caroline , Harridge Stephen D. R. , Welch Ailsa A. , Greig Carolyn , Whelan Kevin , Steves Claire J. 
Published: February 2024

AbstractStudies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI −1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = −0.482; 95% CI,−0.813, −0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.
Electrofreezing of liquid water at ambient conditions
Authors: Cassone Giuseppe , Martelli Fausto 
Published: February 2024

AbstractWater is routinely exposed to external electric fields. Whether, for example, at physiological conditions, in contact with biological systems, or at the interface of polar surfaces in countless technological settings, water responds to fields on the order of a few V Å−1 in a manner that is under intense investigation. Dating back to the 19th century, the possibility of solidifying water upon applying electric fields – a process known as electrofreezing – is an alluring promise that has canalized major efforts since, with uncertain outcomes. Here, we perform long (up to 500 ps per field strength) ab initio molecular dynamics simulations of water at ambient conditions under external electric fields. We show that fields of 0.10 − 0.15 V Å−1 induce electrofreezing to a ferroelectric amorphous phase which we term f-GW (ferroelectric glassy water). The transition occurs after ~ 150 ps for a field of 0.15 V Å−1 and after ~ 200 ps for a field of 0.10 V Å−1 and is signaled by a structural and dynamic arrest and the suppression of the fluctuations of the hydrogen bond network. Our work reports evidence of electrofreezing of bulk liquid water at ambient conditions and therefore impacts several fields, from fundamental chemical physics to biology and catalysis.
Emergent constraints on carbon budgets as a function of global warming
Authors: Cox Peter M. , Williamson Mark S. , Friedlingstein Pierre , Jones Chris D. , Raoult Nina , Rogelj Joeri , Varney Rebecca M. 
Published: February 2024

AbstractEarth System Models (ESMs) continue to diagnose a wide range of carbon budgets for each level of global warming. Here, we present emergent constraints on the carbon budget as a function of global warming, which combine the available ESM historical simulations and future projections for a range of scenarios, with observational estimates of global warming and anthropogenic CO2 emissions to the present day. We estimate mean and likely ranges for cumulative carbon budgets for the Paris targets of 1.5 °C and 2 °C of global warming of 812 [691, 933] PgC and 1048 [881, 1216] PgC, which are more than 10% larger than the ensemble mean values from the CMIP6 models. The linearity between cumulative emissions and global warming is found to be maintained at least until 4 °C, and is consistent with an effective Transient Climate Response to Emissions (eTCRE) of 2.1 [1.8, 2.6] °C/1000PgC, from a global warming of 1.2 °C onwards.
Scalable production of structurally colored composite films by shearing supramolecular composites of polymers and colloids
Authors: Li Miaomiao , Peng Bolun , Lyu Quanqian , Chen Xiaodong , Hu Zhen , Zhang Xiujuan , Xiong Bijin , Zhang Lianbin , Zhu Jintao 
Published: February 2024

AbstractStructurally colored composite films, composed of orderly arranged colloids in polymeric matrix, are emerging flexible optical materials, but their production is bottlenecked by time-consuming procedures and limited material choices. Here, we present a mild approach to producing large-scale structurally colored composite films by shearing supramolecular composites composed of polymers and colloids with supramolecular interactions. Leveraging dynamic connection and dissociation of supramolecular interactions, shearing force stretches the polymer chains and drags colloids to migrate directionally within the polymeric matrix with reduced viscous resistance. We show that meter-scale structurally colored composite films with iridescence color can be produced within several minutes at room temperature. Significantly, the tunability and diversity of supramolecular interactions allow this shearing approach extendable to various commonly-used polymers. This study overcomes the traditional material limitations of manufacturing structurally colored composite films by shearing method and opens an avenue for mildly producing ordered composites with commonly-available materials via supramolecular strategies.
Sleep disorders in Parkinson’s disease, an early and multiple problem
Authors: Dodet Pauline , Houot Marion , Leu-Semenescu Smaranda , Corvol Jean-Christophe , Lehéricy Stéphane , Mangone Graziella , Vidailhet Marie , Roze Emmanuel , Arnulf Isabelle 
Published: February 2024

AbstractIn Parkinson’s disease (PD), it remains unclear whether sleep disorders including insomnia, REM sleep behavior disorder (RBD), excessive daytime sleepiness (EDS), restless legs syndrome (RLS) and sleep-disordered breathing (SDB), are isolated or combined, interact with each other and are associated with clinical factors. We sought to determine the prevalence and combinations of the main sleep disorders, and their clinical and polysomnographic associations in early stage PD. Sleep disorders were systematically diagnosed after medical interview and video-polysomnography in 162 participants with early stage PD and 58 healthy controls from the baseline of the longitudinal ICEBERG cohort. Demographic, clinical (motor, cognitive, autonomic, psychological and sensory tests), therapeutic and polysomnographic associations of sleep disorders were investigated. Sleep disorders were frequent (71%) and combined in half of the patients. The number of sleep disorders increased with disease duration and dysautonomia. Insomnia was the most common (41%), followed by definite RBD (25%), EDS (25%), and RLS (16%). These disorders were more frequent than in controls whereas SDB was rare, moderate and similar in both groups. In patients, insomnia (mainly difficulties maintaining sleep) was associated with female gender, shorter sleep time and RLS, but not with motor or psychological symptoms. RBD was associated with dysautonomia and advanced age, but not with motor and cognitive measures. EDS was associated with psychiatric and motor symptoms as well as the sedative effects of dopamine agonists but not with other sleep disturbances. Sleep disturbances are frequent and combined in early patients with PD. Their determinants and markers are more organic than psychological.
Analyzing variational quantum landscapes with information content
Authors: Pérez-Salinas Adrián , Wang Hao , Bonet-Monroig Xavier 
Published: February 2024

AbstractThe parameters of the quantum circuit in a variational quantum algorithm induce a landscape that contains the relevant information regarding its optimization hardness. In this work, we investigate such landscapes through the lens of information content, a measure of the variability between points in parameter space. Our major contribution connects the information content to the average norm of the gradient, for which we provide robust analytical bounds on its estimators. This result holds for any (classical or quantum) variational landscape. We validate the analytical understating by numerically studying the scaling of the gradient in an instance of the barren plateau problem. In such instance, we are able to estimate the scaling pre-factors in the gradient. Our work provides a way to analyze variational quantum algorithms in a data-driven fashion well-suited for near-term quantum computers.
Immune persistence after different polio sequential immunization schedules in Chinese infants
Authors: Zhao Ting , Li Jing , Huang Teng , Ying Zhi-Fang , Che Yan-Chun , Zhao Zhi-Mei , Fu Yu-Ting , Tao Jun-Hui , Yang Qing-Hai , Wei Ding-Kai , Li Guo-Liang , Yi Li , Zhao Yu-Ping , Chen Hong-Bo , Wang Jian-Feng , Jiang Rui-Ju , Yu Lei , Cai Wei , Yang Wei , Xie Ming-Xue , Yin Qiong-Zhou , Pu Jing , Shi Li , Hong Chao , Deng Yan , Cai Lu-Kui , Zhou Jian , Wen Yu , Li Hong-Sen , Huang Wei , Mo Zhao-Jun , Li Chang-Gui , Li Qi-Han , Yang Jing-Si 
Published: February 2024

AbstractTrivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.
Leuven-Haifa High-Resolution Fundus Image Dataset for Retinal Blood Vessel Segmentation and Glaucoma Diagnosis
Authors: Van Eijgen Jan , Fhima Jonathan , Billen Moulin-Romsée Marie-Isaline , Behar Joachim A. , Christinaki Eirini , Stalmans Ingeborg 
Published: February 2024

AbstractThe Leuven-Haifa dataset contains 240 disc-centered fundus images of 224 unique patients (75 patients with normal tension glaucoma, 63 patients with high tension glaucoma, 30 patients with other eye diseases and 56 healthy controls) from the University Hospitals of Leuven. The arterioles and venules of these images were both annotated by master students in medicine and corrected by a senior annotator. All senior segmentation corrections are provided as well as the junior segmentations of the test set. An open-source toolbox for the parametrization of segmentations was developed. Diagnosis, age, sex, vascular parameters as well as a quality score are provided as metadata. Potential reuse is envisioned as the development or external validation of blood vessels segmentation algorithms or study of the vasculature in glaucoma and the development of glaucoma diagnosis algorithms. The dataset is available on theKU Leuven Research Data Repository(RDR).