bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infectious eye disease in the 21st century—an overview
Authors: Clare Gerry , Kempen John H. , Pavésio Carlos 
Published: February 2024

AbstractInfectious diseases affecting the eye often cause unilateral or asymmetric visual loss in children and people of working age. This group of conditions includes viral, bacterial, fungal and parasitic diseases, both common and rare presentations which, in aggregate, may account for a significant portion of the global visual burden. Diagnosis is frequently challenging even in specialist centres, and many disease presentations are highly regional. In an age of globalisation, an understanding of the various modes of transmission and the geographic distribution of infections can be instructive to clinicians. The impact of eye infections on global disability is currently not sufficiently captured in global prevalence studies on visual impairment and blindness, which focus on bilateral disease in the over-50s. Moreover, in many cases it is hard to differentiate between infectious and immune-mediated diseases. Since infectious eye diseases can be preventable and frequently affect younger people, we argue that in future prevalence studies they should be considered as a separate category, including estimates of disability-adjusted life years (DALY) as a measure of overall disease burden. Numbers of ocular infections are uniquely affected by outbreaks as well as endemic transmission, and their control frequently relies on collaborative partnerships that go well beyond the remit of ophthalmology, encompassing domains as various as vaccination, antibiotic development, individual healthcare, vector control, mass drug administration, food supplementation, environmental and food hygiene, epidemiological mapping, and many more. Moreover, the anticipated impacts of global warming, conflict, food poverty, urbanisation and environmental degradation are likely to magnify their importance. While remote telemedicine can be a useful aide in the diagnosis of these conditions in resource-poor areas, enhanced global reporting networks and artificial intelligence systems may ultimately be required for disease surveillance and monitoring.
Low on-treatment blood pressure and cardiovascular events in patients without elevated risk: a nationwide cohort study
Authors: Mori Yuichiro , Mizuno Atsushi , Fukuma Shingo 
Published: February 2024

AbstractsInsufficient blood pressure control among patients with hypertension without elevated risk is a global concern, suggesting the need for treatment optimization. However, the potential harm of excessive blood pressure lowering among these patients is understudied. This study addressed this evidence gap by using nationally representative public health insurer database covering 30 million working-age population. Patients who were continuously using antihypertensive drugs with 10-year cardiovascular risk <10% were identified. They were categorized by on-treatment systolic and diastolic blood pressures. The primary outcome was a composite of myocardial infarction, stroke, heart failure hospitalization, and peripheral artery disease. Of 920,533 participants (mean age, 57.3 years; female, 48.3%; mean follow-up, 2.75 years), the adjusted hazard ratios for systolic blood pressure of <110, 110–119, 120–129 (reference), 130–139, 140–149, 150–159, and ≥160 mmHg were 1.05 (95% confidence interval: 0.99–1.12), 0.97 (0.93–1.02), 1 (reference), 1.05 (1.01–1.09), 1.15 (1.11–1.20), 1.30 (1.23–1.37), and 1.76 (1.66–1.86), respectively; and for diastolic blood pressure of <60, 60–69, 70–79 (reference), 80–89, 90–99, and ≥100 mmHg were 1.25 (1.14–1.38), 0.99 (0.95–1.04), 1 (reference), 1.00 (0.96–1.03), 1.13 (1.09–1.18), and 1.66 (1.58–1.76), respectively. Among low-risk patients with hypertension, diastolic blood pressure <60 mmHg was associated with increased cardiovascular events, while systolic blood pressure <110 mmHg was not. Compared to previous investigations in high-risk patients, the potential harm of excessive blood pressure lowering was less pronounced in low-risk patients with hypertension.
The IL6/JAK/STAT3 signaling axis is a therapeutic vulnerability in SMARCB1-deficient bladder cancer
Authors: Amara Chandra Sekhar , Kami Reddy Karthik Reddy , Yuntao Yang , Chan Yuen San , Piyarathna Danthasinghe Waduge Badrajee , Dobrolecki Lacey Elizabeth , Shih David J. H. , Shi Zhongcheng , Xu Jun , Huang Shixia , Ellis Matthew J. , Apolo Andrea B. , Ballester Leomar Y. , Gao Jianjun , Hansel Donna E. , Lotan Yair , Hodges H. Courtney , Lerner Seth P. , Creighton Chad J. , Sreekumar Arun , Zheng W. Jim , Msaouel Pavlos , Kavuri Shyam M. , Putluri Nagireddy 
Published: February 2024

AbstractSMARCB1 loss has long been observed in many solid tumors. However, there is a need to elucidate targetable pathways driving growth and metastasis in SMARCB1-deficient tumors. Here, we demonstrate that SMARCB1 deficiency, defined as genomic SMARCB1 copy number loss associated with reduced mRNA, drives disease progression in patients with bladder cancer by engaging STAT3. SMARCB1 loss increases the chromatin accessibility of the STAT3 locus in vitro. Orthotopically implanted SMARCB1 knockout (KO) cell lines exhibit increased tumor growth and metastasis. SMARCB1-deficient tumors show an increased IL6/JAK/STAT3 signaling axis in in vivo models and patients. Furthermore, a pSTAT3 selective inhibitor, TTI-101, reduces tumor growth in SMARCB1 KO orthotopic cell line-derived xenografts and a SMARCB1-deficient patient derived xenograft model. We have identified a gene signature generated from SMARCB1 KO tumors that predicts SMARCB1 deficiency in patients. Overall, these findings support the clinical evaluation of STAT3 inhibitors for the treatment of SMARCB1-deficient bladder cancer.
Choreographing root architecture and rhizosphere interactions through synthetic biology
Authors: Ragland Carin J. , Shih Kevin Y. , Dinneny José R. 
Published: February 2024

AbstractClimate change is driving extreme changes to the environment, posing substantial threats to global food security and bioenergy. Given the direct role of plant roots in mediating plant-environment interactions, engineering the form and function of root systems and their associated microbiota may mitigate these effects. Synthetic genetic circuits have enabled sophisticated control of gene expression in microbial systems for years and a surge of advances has heralded the extension of this approach to multicellular plant species. Targeting these tools to affect root structure, exudation, and microbe activity on root surfaces provide multiple strategies for the advancement of climate-ready crops.
In vitro induction of patterned branchial arch-like aggregate from human pluripotent stem cells
Authors: Seto Yusuke , Ogihara Ryoma , Takizawa Kaori , Eiraku Mototsugu 
Published: February 2024

AbstractEarly patterning of neural crest cells (NCCs) in the craniofacial primordium is important for subsequent development of proper craniofacial structures. However, because of the complexity of the environment of developing tissues, surveying the early specification and patterning of NCCs is difficult. In this study, we develop a simplified in vitro 3D model using human pluripotent stem cells to analyze the early stages of facial development. In this model, cranial NCC-like cells spontaneously differentiate from neural plate border-like cells into maxillary arch-like mesenchyme after a long-term culture. Upon the addition of EDN1 and BMP4, these aggregates are converted into a mandibular arch-like state. Furthermore, temporary treatment with EDN1 and BMP4 induces the formation of spatially separated domains expressing mandibular and maxillary arch markers within a single aggregate. These results suggest that this in vitro model is useful for determining the mechanisms underlying cell fate specification and patterning during early facial development.
Navigating the 16-dimensional Hilbert space of a high-spin donor qudit with electric and magnetic fields
Authors: Fernández de Fuentes Irene , Botzem Tim , Johnson Mark A. I. , Vaartjes Arjen , Asaad Serwan , Mourik Vincent , Hudson Fay E. , Itoh Kohei M. , Johnson Brett C. , Jakob Alexander M. , McCallum Jeffrey C. , Jamieson David N. , Dzurak Andrew S. , Morello Andrea 
Published: February 2024

AbstractEfficient scaling and flexible control are key aspects of useful quantum computing hardware. Spins in semiconductors combine quantum information processing with electrons, holes or nuclei, control with electric or magnetic fields, and scalable coupling via exchange or dipole interaction. However, accessing large Hilbert space dimensions has remained challenging, due to the short-distance nature of the interactions. Here, we present an atom-based semiconductor platform where a 16-dimensional Hilbert space is built by the combined electron-nuclear states of a single antimony donor in silicon. We demonstrate the ability to navigate this large Hilbert space using both electric and magnetic fields, with gate fidelity exceeding 99.8% on the nuclear spin, and unveil fine details of the system Hamiltonian and its susceptibility to control and noise fields. These results establish high-spin donors as a rich platform for practical quantum information and to explore quantum foundations.
Modeling early pathophysiological phenotypes of diabetic retinopathy in a human inner blood-retinal barrier-on-a-chip
Authors: Maurissen Thomas L. , Spielmann Alena J. , Schellenberg Gabriella , Bickle Marc , Vieira Jose Ricardo , Lai Si Ying , Pavlou Georgios , Fauser Sascha , Westenskow Peter D. , Kamm Roger D. , Ragelle Héloïse 
Published: February 2024

AbstractDiabetic retinopathy (DR) is a microvascular disorder characterized by inner blood-retinal barrier (iBRB) breakdown and irreversible vision loss. While the symptoms of DR are known, disease mechanisms including basement membrane thickening, pericyte dropout and capillary damage remain poorly understood and interventions to repair diseased iBRB microvascular networks have not been developed. In addition, current approaches using animal models and in vitro systems lack translatability and predictivity to finding new target pathways. Here, we develop a diabetic iBRB-on-a-chip that produces pathophysiological phenotypes and disease pathways in vitro that are representative of clinical diagnoses. We show that diabetic stimulation of the iBRB-on-a-chip mirrors DR features, including pericyte loss, vascular regression, ghost vessels, and production of pro-inflammatory factors. We also report transcriptomic data from diabetic iBRB microvascular networks that may reveal drug targets, and examine pericyte-endothelial cell stabilizing strategies. In summary, our model recapitulates key features of disease, and may inform future therapies for DR.
Molecular basis of VEGFR1 autoinhibition at the plasma membrane
Authors: Chakraborty Manas Pratim , Das Diptatanu , Mondal Purav , Kaul Pragya , Bhattacharyya Soumi , Kumar Das Prosad , Das Rahul 
Published: February 2024

AbstractLigand-independent activation of VEGFRs is a hallmark of diabetes and several cancers. Like EGFR, VEGFR2 is activated spontaneously at high receptor concentrations. VEGFR1, on the other hand, remains constitutively inactive in the unligated state, making it an exception among VEGFRs. Ligand stimulation transiently phosphorylates VEGFR1 and induces weak kinase activation in endothelial cells. Recent studies, however, suggest that VEGFR1 signaling is indispensable in regulating various physiological or pathological events. The reason why VEGFR1 is regulated differently from other VEGFRs remains unknown. Here, we elucidate a mechanism of juxtamembrane inhibition that shifts the equilibrium of VEGFR1 towards the inactive state, rendering it an inefficient kinase. The juxtamembrane inhibition of VEGFR1 suppresses its basal phosphorylation even at high receptor concentrations and transiently stabilizes tyrosine phosphorylation after ligand stimulation. We conclude that a subtle imbalance in phosphatase activation or removing juxtamembrane inhibition is sufficient to induce ligand-independent activation of VEGFR1 and sustain tyrosine phosphorylation.
Resolving the topology of encircling multiple exceptional points
Authors: Guria Chitres , Zhong Qi , Ozdemir Sahin Kaya , Patil Yogesh S. S. , El-Ganainy Ramy , Harris Jack Gwynne Emmet 
Published: February 2024

AbstractNon-Hermiticity has emerged as a new paradigm for controlling coupled-mode systems in ways that cannot be achieved with conventional techniques. One aspect of this control that has received considerable attention recently is the encircling of exceptional points (EPs). To date, most work has focused on systems consisting of two modes that are tuned by two control parameters and have isolated EPs. While these systems exhibit exotic features related to EP encircling, it has been shown that richer behavior occurs in systems with more than two modes. Such systems can be tuned by more than two control parameters, and contain EPs that form a knot-like structure. Control loops that encircle this structure cause the system’s eigenvalues to trace out non-commutative braids. Here we consider a hybrid scenario: a three-mode system with just two control parameters. We describe the relationship between control loops and their topology in the full and two-dimensional parameter space. We demonstrate this relationship experimentally using a three-mode mechanical system in which the control parameters are provided by optomechanical interaction with a high-finesse optical cavity.
A deep-learning-based framework for identifying and localizing multiple abnormalities and assessing cardiomegaly in chest X-ray
Authors: Fan Weijie , Yang Yi , Qi Jing , Zhang Qichuan , Liao Cuiwei , Wen Li , Wang Shuang , Wang Guangxian , Xia Yu , Wu Qihua , Fan Xiaotao , Chen Xingcai , He Mi , Xiao JingJing , Yang Liu , Liu Yun , Chen Jia , Wang Bing , Zhang Lei , Yang Liuqing , Gan Hui , Zhang Shushu , Liu Guofang , Ge Xiaodong , Cai Yuanqing , Zhao Gang , Zhang Xi , Xie Mingxun , Xu Huilin , Zhang Yi , Chen Jiao , Li Jun , Han Shuang , Mu Ke , Xiao Shilin , Xiong Tingwei , Nian Yongjian , Zhang Dong 
Published: February 2024

AbstractAccurate identification and localization of multiple abnormalities are crucial steps in the interpretation of chest X-rays (CXRs); however, the lack of a large CXR dataset with bounding boxes severely constrains accurate localization research based on deep learning. We created a large CXR dataset named CXR-AL14, containing 165,988 CXRs and 253,844 bounding boxes. On the basis of this dataset, a deep-learning-based framework was developed to identify and localize 14 common abnormalities and calculate the cardiothoracic ratio (CTR) simultaneously. The mean average precision values obtained by the model for 14 abnormalities reached 0.572-0.631 with an intersection-over-union threshold of 0.5, and the intraclass correlation coefficient of the CTR algorithm exceeded 0.95 on the held-out, multicentre and prospective test datasets. This framework shows an excellent performance, good generalization ability and strong clinical applicability, which is superior to senior radiologists and suitable for routine clinical settings.
Genomic epidemiology reveals geographical clustering of multidrug-resistant Escherichia coli ST131 associated with bacteraemia in Wales
Authors: White Rhys T. , Bull Matthew J. , Barker Clare R. , Arnott Julie M. , Wootton Mandy , Jones Lim S. , Howe Robin A. , Morgan Mari , Ashcroft Melinda M. , Forde Brian M. , Connor Thomas R. , Beatson Scott A. 
Published: February 2024

AbstractAntibiotic resistance is a significant global public health concern. Uropathogenic Escherichia coli sequence type (ST)131, a widely prevalent multidrug-resistant clone, is frequently associated with bacteraemia. This study investigates third-generation cephalosporin resistance in bloodstream infections caused by E. coli ST131. From 2013-2014 blood culture surveillance in Wales, 142 E. coli ST131 genomes were studied alongside global data. All three major ST131 clades were represented across Wales, with clade C/H30 predominant (n = 102/142, 71.8%). Consistent with global findings, Welsh strains of clade C/H30 contain β-lactamase genes from the blaCTX-M-1 group (n = 65/102, 63.7%), which confer resistance to third-generation cephalosporins. Most Welsh clade C/H30 genomes belonged to sub-clade C2/H30Rx (58.3%). A Wales-specific sub-lineage, named GB-WLS.C2, diverged around 1996-2000. An introduction to North Wales around 2002 led to a localised cluster by 2009, depicting limited genomic diversity within North Wales. This investigation emphasises the value of genomic epidemiology, allowing the detection of genetically similar strains in local areas, enabling targeted and timely public health interventions.
Leukemic stem cells activate lineage inappropriate signalling pathways to promote their growth
Authors: Kellaway Sophie G. , Potluri Sandeep , Keane Peter , Blair Helen J. , Ames Luke , Worker Alice , Chin Paulynn S. , Ptasinska Anetta , Derevyanko Polina K. , Adamo Assunta , Coleman Daniel J. L. , Khan Naeem , Assi Salam A. , Krippner-Heidenreich Anja , Raghavan Manoj , Cockerill Peter N. , Heidenreich Olaf , Bonifer Constanze 
Published: February 2024

AbstractAcute Myeloid Leukemia (AML) is caused by multiple mutations which dysregulate growth and differentiation of myeloid cells. Cells adopt different gene regulatory networks specific to individual mutations, maintaining a rapidly proliferating blast cell population with fatal consequences for the patient if not treated. The most common treatment option is still chemotherapy which targets such cells. However, patients harbour a population of quiescent leukemic stem cells (LSCs) which can emerge from quiescence to trigger relapse after therapy. The processes that allow such cells to re-grow remain unknown. Here, we examine the well characterised t(8;21) AML sub-type as a model to address this question. Using four primary AML samples and a novel t(8;21) patient-derived xenograft model, we show that t(8;21) LSCs aberrantly activate the VEGF and IL-5 signalling pathways. Both pathways operate within a regulatory circuit consisting of the driver oncoprotein RUNX1::ETO and an AP-1/GATA2 axis allowing LSCs to re-enter the cell cycle while preserving self-renewal capacity.
Elastic porous microspheres/extracellular matrix hydrogel injectable composites releasing dual bio-factors enable tissue regeneration
Authors: Li Yi , Liu Siyang , Zhang Jingjing , Wang Yumeng , Lu Hongjiang , Zhang Yuexi , Song Guangzhou , Niu Fanhua , Shen Yufan , Midgley Adam C. , Li Wen , Kong Deling , Zhu Meifeng 
Published: February 2024

AbstractInjectable biomaterials have garnered increasing attention for their potential and beneficial applications in minimally invasive surgical procedures and tissue regeneration. Extracellular matrix (ECM) hydrogels and porous synthetic polymer microspheres can be prepared for injectable administration to achieve in situ tissue regeneration. However, the rapid degradation of ECM hydrogels and the poor injectability and biological inertness of most polymeric microspheres limit their pro-regenerative capabilities. Here, we develop a biomaterial system consisting of elastic porous poly(l-lactide-co-ε-caprolactone) (PLCL) microspheres mixed with ECM hydrogels as injectable composites with interleukin-4 (IL-4) and insulin-like growth factor-1 (IGF-1) dual-release functionality. The developed multifunctional composites have favorable injectability and biocompatibility, and regulate the behavior of macrophages and myogenic cells following injection into muscle tissue. The elicited promotive effects on tissue regeneration are evidenced by enhanced neomusle formation, vascularization, and neuralization at 2-months post-implantation in a male rat model of volumetric muscle loss. Our developed system provides a promising strategy for engineering bioactive injectable composites that demonstrates desirable properties for clinical use and holds translational potential for application as a minimally invasive and pro-regenerative implant material in multiple types of surgical procedures.
Epiallelic variation of non-coding RNA genes and their phenotypic consequences
Authors: Liu Jie , Zhong Xuehua 
Published: February 2024

AbstractEpigenetic variations contribute greatly to the phenotypic plasticity and diversity. Current functional studies on epialleles have predominantly focused on protein-coding genes, leaving the epialleles of non-coding RNA (ncRNA) genes largely understudied. Here, we uncover abundant DNA methylation variations of ncRNA genes and their significant correlations with plant adaptation among 1001 natural Arabidopsis accessions. Through genome-wide association study (GWAS), we identify large numbers of methylation QTL (methylQTL) that are independent of known DNA methyltransferases and enriched in specific chromatin states. Proximal methylQTL closely located to ncRNA genes have a larger effect on DNA methylation than distal methylQTL. We ectopically tether a DNA methyltransferase MQ1v to miR157a by CRISPR-dCas9 and show de novo establishment of DNA methylation accompanied with decreased miR157a abundance and early flowering. These findings provide important insights into the genetic basis of epigenetic variations and highlight the contribution of epigenetic variations of ncRNA genes to plant phenotypes and diversity.
Observation of Josephson harmonics in tunnel junctions
Authors: Willsch Dennis , Rieger Dennis , Winkel Patrick , Willsch Madita , Dickel Christian , Krause Jonas , Ando Yoichi , Lescanne Raphaël , Leghtas Zaki , Bronn Nicholas T. , Deb Pratiti , Lanes Olivia , Minev Zlatko K. , Dennig Benedikt , Geisert Simon , Günzler Simon , Ihssen Sören , Paluch Patrick , Reisinger Thomas , Hanna Roudy , Bae Jin Hee , Schüffelgen Peter , Grützmacher Detlev , Buimaga-Iarinca Luiza , Morari Cristian , Wernsdorfer Wolfgang , DiVincenzo David P. , Michielsen Kristel , Catelani Gianluigi , Pop Ioan M. 
Published: February 2024

AbstractApproaches to developing large-scale superconducting quantum processors must cope with the numerous microscopic degrees of freedom that are ubiquitous in solid-state devices. State-of-the-art superconducting qubits employ aluminium oxide (AlOx) tunnel Josephson junctions as the sources of nonlinearity necessary to perform quantum operations. Analyses of these junctions typically assume an idealized, purely sinusoidal current–phase relation. However, this relation is expected to hold only in the limit of vanishingly low-transparency channels in the AlOx barrier. Here we show that the standard current–phase relation fails to accurately describe the energy spectra of transmon artificial atoms across various samples and laboratories. Instead, a mesoscopic model of tunnelling through an inhomogeneous AlOx barrier predicts percent-level contributions from higher Josephson harmonics. By including these in the transmon Hamiltonian, we obtain orders of magnitude better agreement between the computed and measured energy spectra. The presence and impact of Josephson harmonics has important implications for developing AlOx-based quantum technologies including quantum computers and parametric amplifiers. As an example, we show that engineered Josephson harmonics can reduce the charge dispersion and associated errors in transmon qubits by an order of magnitude while preserving their anharmonicity.