bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intratumoral Delivery of Chlorine Dioxide Exploits its ROS-like Properties: A Novel Paradigm for Effective Cancer Therapy
Authors: Liu Xuewu , Liu Zhaoyang , Liu Xueyan , Liu Shuangning , Zhang Jiao 
Published: November 2023

AbstractOur study underscores the potential of chlorine dioxide, resembling reactive oxygen species, in promoting tissue regeneration and executing similar functions. Direct intratumoral administration of chlorine dioxide conveniently and sustainably kills cancer cells, without the risk of developing drug resistance. Given that tumors are viewed as non-healing wounds, the regenerative capabilities of chlorine dioxide offer an innovative method to expedite wound healing and enhance patient outcomes in cancer treatment. Compared to traditional methods, chlorine dioxide treatment reduces complications and risks, presenting a safer alternative. Notably, higher concentrations of chlorine dioxide in promoting tumor ablation can particularly demonstrate the potential to disrupt tumor vasculature. We advocate for the intratumoral injection of chlorine dioxide to achieve direct tumor ablation and boost antitumor immunity while minimizing harm to healthy tissues. Although initial findings indicate that chlorine dioxide stimulates an antitumor immune response, further investigation is essential. As oncology advances with the use of immune checkpoint inhibitors, intratumoral chlorine dioxide administration emerges as a promising strategy, potentially extending survival and alleviating treatment burdens. Future research should focus on refining chlorine dioxide protocols, exploring synergistic therapies, and understanding its systemic immune effects, thereby establishing chlorine dioxide’s role in cancer therapy.HighlightsChlorine dioxide demonstrates potent ROS-like capabilities for both cancer elimination and tissue regeneration, offering a and effective treatment approach.Direct intratumoral administration of chlorine dioxide conveniently and sustainably kills cancer cells, without the risk of developing drug resistance.Chlorine dioxide can enhance tumor ablation potential by disrupting tumor vasculature, contributing to its overall effectiveness.Chlorine dioxide promotes an immune response against cancer, significantly enhancing its therapeutic effectiveness.Intratumoral injections of chlorine dioxide represent an innovative and promising strategy for efficacious cancer therapy.
Neural crest mural cells of forebrain meninges harbor innate immune functions during early brain development and exhibit different responses to septic and toxic insults
Authors: Amarante-Silva Diego , Bruet Emmanuel , Gars Rémy , Piechon Margaux , Gorojankina Tatiana , Bignon Jérôme , Creuzet Sophie E. 
Published: November 2023

AbstractIn vertebrates, the cephalic neural crest (CNC), an embryonic multipotent cell population, gives rise to meningeal derivatives, covering and protecting the developing forebrain. In postnatal life, the meninges exert a prime role in developing and maintaining the central nervous system’s homeostasis and help modulate the immune capacities of resident cells and the blood-brain barrier. However, their role in the embryo remains elusive before the formation of brain barriers. Here, we explore whether meningeal CNC-mural cells participate in immunosurveillance during the early stages of embryogenesis. Using primary cultures of E8 chicken forebrain meningeal mural cells, immuno-phenotyping, and flow cytometry analyses, we demonstrated the expression of specific receptors, including TLRs and MHC class II molecules typically expressed in myeloid cells. Our experiments showed that when challenged by bacterial particles, CNC mural cells also have phagocytic capacities. Transcriptomic analysis revealed activation of inflammatory pathways leading to increased expression of myeloid surface markers and the production of cytokines and interleukins in the presence of bacterial particles. Our in vitro assays also show the capacities of mural cells to present and transfer antigen particles and recruit cooperant cells, both locally and at a distance. Moreover, we revealed that pericytes could deploy DNA traps like neutrophils to stop pathogens. We show that mural cells use extracellular DNA shedding against pathogenic conditions and communicate with each other to mobilize cell cooperation. Transcriptomic analyses revealed that exposure to bacterial particles leads to severe impairment of morphogenetic and neuro-developmental pathways and shed light on the possible detrimental effect of bacterial infection on brain development and maturation of cognitive functions. To reinforce the possible link between neurodevelopmental defects and immune activation, we challenged the immune capacities of CNC pericytes after exposure to toxic medication. We used Valproate (VPA), an antiepileptic drug associated with developmental disorders in newborns when administered during pregnancy. We show that VPA injection into chicken embryos triggered exacerbated myeloid traits and DNA trap releases in CNC pericytes. Our studies show that CNC mural cells are professional innate immune cells capable of pathogen recognition and antigen presentation. This notion breaks the prevailing concept that only mesodermal lineage can participate in the innate immune defense. It opens new avenues for elaborating brain-specific immunity before birth, which may have important biomedical implications for neurodevelopmental disorders.
Wearable Disposable Electrotherapy
Authors: FallahRad Mohamad , Chaudhry Zeeshan , Belali Koochesfahani Mojtaba , Bhuiyan Rayyan , Zaman Mahdi , Liu Tiffany , Saha Kisholoy , Diaz Uraga Miguel R , Velarde Osvaldo , Donnery Kyle , Babaev Benjamin , Saw Matthew , Rddad Ayman , Thahsin Myesha , Couzis Alexander , Bikson Marom 
Published: November 2023

AbstractWe design and validate a novel electrotherapy platform without electronic components, using printed abundant, environmentally benign materials. Whereas existing electrotherapy devices use an independent power source and electronics to generate and control stimulation currents, our design eliminates the need for these components. Device production relies only on scalable additive manufacturing and common materials, minimizing cost and environmental impact. The disposable single-use platform (as discreet as adhesive bandages) is activated simply by placement on the body. A prescribed electrotherapy discharge is regulated by a flexible 3D electrochemical architecture tailored to each application by a novel operational theory. The single-dose usability of this platform is a categorical shift from existing approaches with durable equipment that require programming and assembly to disposable electrodes for each use. Our Wearable Disposable Electrotherapy technology can be distributed like pharmacotherapy, with indications spanning neuromodulation of brain disorders, wound healing, transcutaneous drug delivery, bioelectronic medicine, and aesthetics.
Probabilistic ecological risk assessment for deep-sea mining: a Bayesian Network for Chatham Rise, SW Pacific Ocean
Authors: Kaikkonen Laura , Clark Malcolm R. , Leduc Daniel , Nodder Scott D. , Rowden Ashley A. , Bowden David A. , Beaumont Jennifer , Cummings Vonda 
Published: November 2023

AbstractIncreasing interest in seabed resource use in the ocean is introducing new pressures on deep-sea environments, the ecological impacts of which need to be evaluated carefully. The complexity of these ecosystems and the dearth of comprehensive data pose significant challenges to predicting potential impacts. In this study, we demonstrate the use of Bayesian Networks (BNs) as a modelling framework to address these challenges and enhance the development of robust quantitative predictions concerning the effects of human activities on deep-seafloor ecosystems. The approach consists of iterative model building with experts, and quantitative probability estimates of the relative decrease in abundance of different functional groups of benthos following seabed mining. The model is then used to evaluate two alternative seabed mining scenarios to identify the major sources of uncertainty associated with the mining impacts. By establishing causal connections between the pressures associated with potential mining activities and various components of the benthic ecosystem, our model offers an improved comprehension of potential impacts on the seafloor environment. We illustrate this approach using the example of potential phosphorite nodule mining on the Chatham Rise, offshore Aotearoa/New Zealand, SW Pacific Ocean, and examine ways to incorporate knowledge from both empirical data and expert assessments into quantitative risk assessments. We further discuss how ecological risk assessments can be constructed to better inform decision-making, using metrics relevant to both ecology and policy. The findings from this study highlight the valuable insights that BNs can provide in evaluating the potential impacts of human activities. However, continued research and data collection are crucial for refining and ground truthing these models and improving our understanding of the long-term consequences of deep-sea mining and other anthropogenic activities on marine ecosystems. By leveraging such tools, policymakers, researchers, and stakeholders can work together towards human activities in the deep sea that minimise ecological harm and ensure the conservation of these environments.
Cellular Lipids Regulate the Conformational Ensembles of the Disordered Intracellular Loop 3 in β2 Adrenergic Receptor
Authors: Mukhaleva Elizaveta , Yang Tianyi , Sadler Fredrik , Sivaramakrishnan Sivaraj , Ma Ning , Vaidehi Nagarajan 
Published: November 2023

AbstractThe structurally disordered intracellular loops (ICLs) of G protein-coupled receptors (GPCRs) play a critical role in G protein coupling. In our previous work, we used a combination of FRET-based and computational methodologies to show that the third intracellular loop (ICL3) modulates the activity and G protein coupling selectivity in GPCRs. In the current study, we have uncovered the role of several lipid components in modulating the conformational ensemble of ICL3 of the β2-adrenergic receptor (β2AR). Our findings indicate that phosphatidylinositol 4,5-bisphosphate (PIP2) in the inner leaflet of the membrane bilayer acts as a stabilizing anchor for ICL3, opening the intracellular cavity to facilitate G protein coupling. This interaction between PIP2 and ICL3 causes tilting of β2AR within the cellular membrane. Notably, this tilting of the receptor is supported by ganglioside GM3 stabilizing the extracellular loops on the outer leaflet of the bilayer, thereby exerting an allosteric effect on the orthosteric ligand binding pocket. Our results underscore the significance of lipids in modulating GPCR activity, proposing an allosteric mechanism that occurs through the receptor’s orientation within the membrane.
An Efficient Parallel Sketch-based Algorithmic Workflow for Mapping Long Reads
Authors: Rahman Tazin , Bhowmik Oieswarya , Kalyanaraman Ananth 
Published: November 2023

1AbstractLong read technologies are continuing to evolve at a rapid pace, with the latest of the high fidelity technologies delivering reads over 10Kbp with high accuracy (99.9%). Classical long read assemblers produce assemblies directly from long reads. Hybrid assembly workflows provide a way to combine partially constructed assemblies (or contigs) with newly sequenced long reads in order to generate improved and near-complete genomic scaffolds. Under either setting, the main computational bottleneck is the step of mapping the long reads—against other long reads or pre-constructed contigs. While many tools implement the mapping step through alignments and overlap computations, alignment-free approaches have the benefit of scaling in performance. Designing a scalable alignment-free mapping tool while maintaining the accuracy of mapping (precision and recall) is a significant challenge. In this paper, we visit the generic problem of mapping long reads to a database of subject sequences, in a fast and accurate manner. More specifically, we present an efficient parallel algorithmic workflow, calledJEM-mapper, that uses a new minimizer-based Jaccard estimator (or JEM) sketch to perform alignment-free mapping of long reads. For implementation and evaluation, we consider two application settings: (i) the hybrid scaffolding setting, where the goal is to map a large collection of long reads to a large collection of partially constructed assemblies or contigs; and (ii) the classical long read assembly setting, where the goal is to map long reads to one another to identify overlapping long reads. Our algorithms and implementations are designed for execution on distributed memory parallel machines. Experimental evaluation shows that our parallel algorithm is highly effective in producing high-quality mapping while significantly improving the time to solution compared to state-of-the-art mapping tools. For instance, in the hybrid setting for a large genomeBetta splendens(≈350Mbpgenome) with 429KHiFi long reads and 98Kcontigs,JEM-mapperproduces a mapping with 99.41% precision and 97.91% recall, while yielding 6.9×speedup over a state-of-the-art mapper.
Human Heart Failure Alters Mitochondria and Fiber 3D Structure Triggering Metabolic Shifts
Authors: Vue Zer , Ajayi Peter T. , Neikirk Kit , Murphy Alexandria C. , Prasad Praveena , Jenkins Brenita C. , Vang Larry , Garza-Lopez Edgar , Mungai Margaret , Marshall Andrea G. , Beasley Heather K. , Killion Mason , Parker Remi , Anukodem Josephs , Lavine Kory , Ajijola Olujimi , Mobley Bret C. , Dai Dao-Fu , Exil Vernat , Kirabo Annet , Ru Su Yan , Tomasek Kelsey , Zhang Xiuqi , Wanjalla Celestine , Hubert David L. , Phillips Mark A. , Shao Jian-qiang , McReynolds Melanie R. , Glancy Brian , Hinton Antentor 
Published: November 2023

AbstractThis study, utilizing SBF-SEM, reveals structural alterations in mitochondria and myofibrils in human heart failure (HF). Mitochondria in HF show changes in structure, while myofibrils exhibit increased cross-sectional area and branching. Metabolomic and lipidomic analyses indicate concomitant dysregulation in key pathways. The findings underscore the need for personalized treatments considering individualized structural changes in HF.
Benchmarking AlphaSC: A Leap in Single-Cell Data Processing
Authors: Vuong Hy , Luu Tam , Nguyen Nhat , Tra Nghia , Nguyen Ha , Nguyen Huy , Truong Thao , Pham Son 
Published: November 2023

AbstractWe benchmarked AlphaSC, BioTuring’s GPU-accelerated single-cell analytics package, against other popular tools including Scanpy, Seurat, and RAPIDS. The results demonstrate that AlphaSC operates thousands of times faster than Seurat and Scanpy. Additionally, it surpasses RAPIDS, another GPU-accelerated package from NVIDIA, by an order of magnitude in terms of speed while also consuming considerably less RAM and GPU memory. Importantly, this significant increase in AlphaSC’s performance does not compromise its quality.1
Streamlining remote nanopore data access withslow5curl
Authors: Wong Bonson , Ferguson James M. , Gamaarachchi Hasindu , Deveson Ira W. 
Published: November 2023

ABSTRACTAs adoption of nanopore sequencing technology continues to advance, the need to maintain large volumes of raw current signal data for reanalysis with updated algorithms is a growing challenge. Here we introduceslow5curl, a software package designed to streamline nanopore data sharing, accessibility and reanalysis.Slow5curlallows a user to fetch a specified read or group of reads from a raw nanopore dataset stored on a remote server, such as a public data repository, without downloading the entire file.Slow5curluses an index to quickly fetch specific reads from a large dataset in SLOW5/BLOW5 format and highly parallelised data access requests to maximise download speeds. Using all public nanopore data from the Human Pangenome Reference Consortium (>22 TB), we demonstrate howslow5curlcan be used to quickly fetch and reanalyse signal reads corresponding to a set of target genes from each individual in large cohort dataset (n= 91), minimising the time, egress costs, and local storage requirements for their reanalysis. We provideslow5curlas a free, open-source package that will reduce frictions in data sharing for the nanopore community:https://github.com/BonsonW/slow5curl
Apgr5suppressor screen uncovers a distinct mechanism safeguarding the cytochromeb6fcomplex from damage through PGR5
Authors: Penzler Jan-Ferdinand , Naranjo Belen , Walz Sabrina , Marino Giada , Kleine Tatjana , Leister Dario 
Published: November 2023

ABSTRACTPROTON GRADIENT REGULATION5 (PGR5) is thought to promote cyclic electron flow (CEF) and its deficiency causes increased photosensitivity of photosystem I (PSI), leading to lethality under fluctuating light (FL). By screening for suppressor mutations that rescue FL lethality ofpgr5plants, we identified a portfolio of mutations affecting 12 photosynthesis-related proteins. Six are required for proper PSII function, one (CcdA) promotes cytochrome (cyt)b6fassembly, and another (PAA1) provides plastocyanin with its copper cofactor. Two other mutations are associated with the chloroplast FBPase cFBP1. This, together with targeted knockout of other genes in thepgr5background, suggests three pathways to restore FL viability: (i) reduced electron flow to PSI due to defects in PSII, cytb6for plastocyanin but not PSI, (ii) increased electron flow from PSI due to inactivation of ACHT2, a regulator of cFBP1 activity, and (iii) hyperactivity of the NDH-dependent CEF due to inactivation of cFBP1. The remaining two suppressor mutations affected the cytb6fcomplex. PFSC1 controls cytb6faccumulation at early developmental stages. DEIP1/NTA1, previously suggested to be essential for cytb6fassembly, appears to protect cytb6ffrom deleterious effects of PGR5, since plants lacking both DEIP1/NTA1 and PGR5 are viable and accumulate cytb6f.
Multitrait engineering of Hassawi red rice for sustainable cultivation
Authors: Sedeek Khalid , Mohammed Nahed , Zhou Yong , Zuccolo Andrea , Sanikommu Krishnaveni , Kantharajappa Sunitha , Al-Bader Noor , Tashkandi Manal , Wing Rod A. , Mahfouz Magdy M. 
Published: November 2023

AbstractSustainable agriculture requires locally adapted varieties that produce nutritious food with limited agricultural inputs. Genome engineering represents a viable approach to develop cultivars that fulfill these criteria. For example, the red Hassawi rice, a native landrace of Saudi Arabia, tolerates local drought and high-salinity conditions and produces grain with diverse health-promoting phytochemicals. However, Hassawi has a long growth cycle, high cultivation costs, low productivity, and susceptibility to lodging. Here, to improve these undesirable traits via genome editing, we established efficient regeneration and Agrobacterium-mediated transformation protocols for Hassawi. In addition, we generated the first high-quality reference genome and targeted the key flowering repressor gene,Hd4, thus shortening the plant’s lifecycle and height. Using CRISPR/Cas9 multiplexing, we simultaneously disrupted negative regulators of flowering time (Hd2, Hd4, andHd5), grain size (GS3), grain number (GN1a), and plant height (Sd1). The resulting homozygous mutant lines flowered extremely early (∼56 days) and had shorter stems (approximately 107 cm), longer grains (by 5.1%), and more grains per plant (by 50.2%), thereby enhancing overall productivity. Furthermore, the awns of grains were 86.4% shorter compared to unedited plants. Moreover, the modified rice grain displayed improved nutritional attributes. As a result, the modified Hassawi rice combines several desirable traits that can incentivize large-scale cultivation and reduce malnutrition.
Prognostic significance of AI-identified markers for isoniazid resistance in Mycobacterium tuberculosis
Authors: Valafar Siavash , Valafar Aram 
Published: November 2023

AbstractAntibiotic resistance in tuberculosis (TB), a disease that kills 1.5 million people annually, is a great concern. The emergence of drug resistance inM. tuberculosis, the obligate pathogen of TB seems to follow an order. In most cases resistance to isoniazid (INH) emerges first, followed by rifampicin, then either pyrazinamide or ethambutol, and finally followed by resistance to second-line drugs. Prevention of emergence of INH resistance can go a long way to prevent the emergence of resistance to other drugs. In this manuscript we present the prognostic value of specific mutations in the hope that resistance can be e predicted and hence avoided. Here we present evidence that resistance to INH follows a stepwise evolutionary trajectory in most cases. This information can therefore be used to predict and avoid INH resistance. In our approach, we used genomic and phenotypic data from over 16,000 samples collected by two large databases, the TB Portals and the CRyPTIC consortium. We used a deep learning neural network model to identify promising mutations using the TB Portal data. We then tested the prognostic value of the identified mutations using the CRyPTIC consortium data. In this manuscript, we estimate a prognostic accuracy of 73% for correctly predicting the emergence of three canonical INH resistance mutations (katG315, inhA-15, and inhA-8) by using two prognostic markers. Additional time course samples and analysis will undoubtedly uncover prognostic markers for other evolutionary trajectories that lead to resistance.
Smartphone keyboard dynamics predict affect in suicidal ideation
Authors: Knol Loran , Nagpal Anisha , Leaning Imogen E. , Idda Elena , Hussain Faraz , Ning Emma , Eisenlohr-Moul Tory A. , Beckmann Christian F. , Marquand Andre F. , Leow Alex 
Published: November 2023

AbstractWhile digital phenotyping provides opportunities for unobtrusive, real-time mental health assessments, the integration of its modalities is not trivial due to high dimensionalities and discrepancies in sampling frequencies. We provide an integrated pipeline that solves these issues by transforming all modalities to the same time unit, applying temporal independent component analysis (ICA) to high-dimensional modalities, and fusing the modalities with linear mixed-effects models. We applied our approach to integrate high-quality, daily self-report data with BiAffect keyboard dynamics derived from a clinical suicidality sample of mental health outpatients. Applying the ICA to the self-report data (104 participants, 5712 days of data) revealed components related to well-being, anhedonia, and irritability and social dysfunction. Mixed-effects models (55 participants, 1794 days) showed that less phone movement while typing was associated with more anhedonia (β = -0.12, p = 0.00030). We consider this method to be widely applicable to dense, longitudinal digital phenotyping data.