bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theory and rationale of interpretable all-in-one pattern discovery and disentanglement system
Authors: Wong Andrew K. C. , Zhou Pei-Yuan , Lee Annie E.-S. 
Published: May 2023

AbstractIn machine learning (ML), association patterns in the data, paths in decision trees, and weights between layers of the neural network are often entangled due to multiple underlying causes, thus masking the pattern-to-source relation, weakening prediction, and defying explanation. This paper presents a revolutionary ML paradigm: pattern discovery and disentanglement (PDD) that disentangles associations and provides an all-in-one knowledge system capable of (a) disentangling patterns to associate with distinct primary sources; (b) discovering rare/imbalanced groups, detecting anomalies and rectifying discrepancies to improve class association, pattern and entity clustering; and (c) organizing knowledge for statistically supported interpretability for causal exploration. Results from case studies have validated such capabilities. The explainable knowledge reveals pattern-source relations on entities, and underlying factors for causal inference, and clinical study and practice; thus, addressing the major concern of interpretability, trust, and reliability when applying ML to healthcare, which is a step towards closing the AI chasm.
Harnessing big data for health equity through a comprehensive public database and data collection framework
Authors: Sabet Cameron , Hammond Alessandro , Ravid Nim , Tong Michelle Sun , Stanford Fatima Cody 
Published: May 2023

AbstractThe United States Department of Health and Human Services (HHS) pledged $90 million to help reduce health disparities with data-driven solutions. The funds are being distributed to 1400 community health centers, serving over 30 million Americans. Given these developments, our piece examines the reasons behind the delayed adoption of big data for healthcare equity, recent efforts embracing big data tools, and methods to maximize potential without overburdening physicians. We additionally propose a public database for anonymized patient data, introducing diverse metrics and equitable data collection strategies, providing valuable insights for policymakers and health systems to better serve communities.
Repurposed inhibitor of bacterial dihydrodipicolinate reductase exhibits effective herbicidal activity
Authors: Mackie Emily R. R. , Barrow Andrew S. , Giel Marie-Claire , Hulett Mark D. , Gendall Anthony R. , Panjikar Santosh , Soares da Costa Tatiana P. 
Published: May 2023

AbstractHerbicide resistance represents one of the biggest threats to our natural environment and agricultural sector. Thus, new herbicides are urgently needed to tackle the rise in herbicide-resistant weeds. Here, we employed a novel strategy to repurpose a ‘failed’ antibiotic into a new and target-specific herbicidal compound. Specifically, we identified an inhibitor of bacterial dihydrodipicolinate reductase (DHDPR), an enzyme involved in lysine biosynthesis in plants and bacteria, that exhibited no antibacterial activity but severely attenuated germination of the plant Arabidopsis thaliana. We confirmed that the inhibitor targets plant DHDPR orthologues in vitro, and exhibits no toxic effects against human cell lines. A series of analogues were then synthesised with improved efficacy in germination assays and against soil-grown A. thaliana. We also showed that our lead compound is the first lysine biosynthesis inhibitor with activity against both monocotyledonous and dicotyledonous weed species, by demonstrating its effectiveness at reducing the germination and growth of Lolium rigidum (rigid ryegrass) and Raphanus raphanistrum (wild radish). These results provide proof-of-concept that DHDPR inhibition may represent a much-needed new herbicide mode of action. Furthermore, this study exemplifies the untapped potential of repurposing ‘failed’ antibiotic scaffolds to fast-track the development of herbicide candidates targeting the respective plant enzymes.
Improving the visibility of minorities through network growth interventions
Authors: Neuhäuser Leonie , Karimi Fariba , Bachmann Jan , Strohmaier Markus , Schaub Michael T. 
Published: May 2023

AbstractImproving the position of minority groups in networks through interventions is a challenge of high theoretical and societal importance. However, a systematic analysis of interventions that alter the network growth process is still missing. In this work, we propose a model to examine how network growth interventions impact the position of minority nodes in degree rankings over time. We distinguish between (i) group size interventions, such as introducing quotas; and (ii) behavioural interventions, such as varying how groups connect to each other. We find that even extreme quotas do not increase minority representation in rankings if the actors in the network do not adopt homophilic behaviour. Thus, interventions need to be coordinated in order to improve the visibility of minorities. In a real-world case study, we explore which interventions can reach gender parity in academia. Our work provides a theoretical and computational framework for investigating the effectiveness of interventions in growing networks.
Metabolic handoffs between multiple symbionts may benefit the deep-sea bathymodioline mussels
Authors: Zvi-Kedem Tal , Vintila Simina , Kleiner Manuel , Tchernov Dan , Rubin-Blum Maxim 
Published: May 2023

Abstract
Bathymodioline mussels rely on thiotrophic and/or methanotrophic chemosynthetic symbionts for nutrition, yet, secondary heterotrophic symbionts are often present and play an unknown role in the fitness of the organism. The bathymodioline Idas mussels that thrive in gas seeps and on sunken wood in the Mediterranean Sea and the Atlantic Ocean, host at least six symbiont lineages that often co-occur. These lineages include the primary symbionts chemosynthetic methane- and sulfur-oxidizing gammaproteobacteria, and the secondary symbionts, Methylophagaceae, Nitrincolaceae and Flavobacteriaceae, whose physiology and metabolism are obscure. Little is known about if and how these symbionts interact or exchange metabolites. Here we curated metagenome-assembled genomes of Idas modiolaeformis symbionts and used genome-centered metatranscriptomics and metaproteomics to assess key symbiont functions. The Methylophagaceae symbiont is a methylotrophic autotroph, as it encoded and expressed the ribulose monophosphate and Calvin-Benson-Bassham cycle enzymes, particularly RuBisCO. The Nitrincolaceae ASP10-02a symbiont likely fuels its metabolism with nitrogen-rich macromolecules and may provide the holobiont with vitamin B12. The Urechidicola (Flavobacteriaceae) symbionts likely degrade glycans and may remove NO. Our findings indicate that these flexible associations allow for expanding the range of substrates and environmental niches, via new metabolic functions and handoffs.
Capturing the domain crosstalk in full length LRRK2 and LRRK2RCKW
Authors: Störmer Eliza , Weng Jui-Hung , Wu Jian , Bertinetti Daniela , Kaila Sharma Pallavi , Ma Wen , Herberg Friedrich W. , Taylor Susan S. 
Published: May 2023

LRR-kinase 2 (LRRK2) is a multi-domain protein with three catalytically inert N-terminal domains (NtDs) and four C-terminal domains, including a kinase and a GTPase domain. LRRK2 mutations are linked to Parkinson's Disease (PD). Recent structures of LRRK2RCKW and a full-length inactive LRRK2 (fl-LRRK2INACT) monomer revealed that the kinase domain drives LRRK2 activation. The LRR domain and also an ordered LRR–COR linker, wrap around the C-lobe of the kinase domain and sterically block the substrate binding surface in fl-LRRK2INACT. Here, we focus on the crosstalk between domains. Our biochemical studies of GTPase and kinase activities of fl-LRRK2 and LRRK2RCKW reveal how mutations influence this crosstalk differently depending on the domain borders investigated. Furthermore, we demonstrate that removing the NtDs leads to altered intramolecular regulation. To further investigate the crosstalk, we used Hydrogen–Deuterium exchange Mass Spectrometry (HDX-MS) to characterize the conformation of LRRK2RCKW and Gaussian Accelerated Molecular Dynamics (GaMD) to create dynamic portraits of fl-LRRK2 and LRRK2RCKW. These models allowed us to investigate the dynamic changes in wild-type and mutant LRRK2s. Our data show that the α3ROC helix, the Switch II motif in the ROC domain, and the LRR–ROC linker play crucial roles in mediating local and global conformational changes. We demonstrate how these regions are affected by other domains in fl-LRRK2 and LRRK2RCKW and show how unleashing of the NtDs as well as PD mutations lead to changes in conformation and dynamics of the ROC and kinase domains which ultimately impact kinase and GTPase activities. These allosteric sites are potential therapeutic targets.
Optimal number and locations of automatic vehicle identification sensors considering link travel time estimation
Authors: Zhu Yiting , He Zhaocheng , Zhang Xinshao 
Published: May 2023

AbstractThe problem of optimally locating Automatic Vehicle Identification (AVI) sensors on a traffic network for travel time estimation has been a topic of growing interests in recent years. Even though great progresses have been made on AVI sensor deployment for path‐level travel time estimation, very few contributions exist in the literatures that address the AVI sensor deployment for link‐level travel time estimation on an urban network. In this paper, considering the link travel time estimation, two deployment sub‐problems are addressed: (1) where to deploy a certain number of AVI sensors? (2) What is a cost‐effective number of AVI sensors to deploy? To address the first problem, a potential game of sensors is developed to find their optimal locations which maximize the objective function that consists of estimation coverage and estimation accuracy. Then, based on the optimal locations, an incremental search method is proposed to find the optimal number of sensors considering the cost. The case in Shanghai shows the proposed game‐theoretic method is superior to other two heuristic algorithms. Moreover, compared to the real‐world sensor locations, the optimally redeployed locations improve both the estimation coverage and estimation accuracy. The case in Xuancheng City validates the proposed incremental search uses less computations to find an optimal number that close to the global optimal number solved from the brute‐force search.
A radar anti‐jamming strategy optimisation based on Stackelberg game
Authors: Feng Cheng , Fu Xiongjun , Dong Jian , Zhao Congxia , Chang Hao , Lang Ping , Pan Teng 
Published: May 2023

AbstractRadar is an important sensor in electromagnetic spectrum warfare. Its confrontation with naval vessels has become increasingly competitive in recent years. However, current radar anti‐jamming methods are limited to some extent in complex electromagnetic environments, which poses a severe challenge to radar's detection and anti‐jamming capabilities. To improve the anti‐jamming capacity of radar, the authors propose a Stackelberg game‐based optimisation method to enhance the decision‐making of anti‐jamming strategies. First, we analyse the radar's winning conditions by considering the temporal constraints of non‐real‐time radar recognition and preparation actions and construct the radar's actual utility matrix. Second, we construct a Stackelberg game‐based model under the condition of a certain recognition probability, and update the recognition probability and recognition interval during the game. Finally, we discuss the conditions under which the radar can obtain a positive benefit in the game and compare the benefit to the reinforcement learning optimisation method. The simulation experimental results show that the proposed strategy can significantly improve the radar's winning probability in the confrontation.
Manuelle Therapietechniken an der Wirbelsäule zur Stimulation des autonomen Nervensystems - ein Scoping Review
Authors: Rogan Slavko , Taeymans Jan , Berger Ina , Baur Heiner 
Published: May 2023

Zusammenfassung
Hintergrund Physikalische Maßnahmen oder manualtherapeutische Techniken (MTTe) wie Mobilisationen, Manipulationen oder Weichteiltechniken führen zu einer Verbesserung des Metabolismus oder einer Senkung hypertoner Muskulatur und werden auch zur Balanceregulierung bei zentralnervösen Veränderungen des autonomen Nervensystems (ANS) eingesetzt. Bisher fehlen empirische Erkenntnisse über Wirkungsmechanismen und Reizorte von MTTe auf das ANS. Das Ziel dieses vorliegenden Scoping Reviews war es, einen Überblick zu geben über den Erkenntnisstand der Anwendung von MTTe auf diverse Niveaus der Wirbelsäule auf das ANS.
Methode Als Grundlage für die Durchführung des Scoping Reviews dienten die Datenbanken CENTRAL, Osteopathic Research Web, PEDro und PubMed. Umfang und Inhalte der Literatur wurden dokumentiert. Die Ergebnisse der einbezogenen und herangezogenen Studien wurden in narrativer Weise zusammengefasst, wobei der Fokus auf den signifikantesten klinischen Aspekten lag.
Ergebnisse Manipulationen, Mobilisationen, myofasziale Techniken und zervikale Traktionen wurden als MTTe definiert. In 27 von 35 Studien wurden gesunde Probanden therapeutisch behandelt. Zehn Studien analysierten unmittelbare Effekte an Patienten, während 2 Studien als Longitudinalstudie bei Bluthochdruckpatienten konzipiert waren. In einem Zeitraum von 4–8 Wochen betrug die Interventionshäufigkeit wöchentlich zwischen einer und 3 MTTe-Einheiten.
Schlussfolgerung Die Studienergebnisse erweisen sich als heterogen. Aus diesem Grund lassen sich keine verbindlichen, eindeutigen und allgemeingültigen Aussagen ableiten, in welcher Form, Intensität sowie in welchem Umfang MTTe angewendet werden sollen, um gezielt positive Wirkungsmechanismen am ANS in Gang zu setzen. Für zukünftige Studien sind demzufolge Longitudinalstudien mit Follow-up empfehlenswert. Darüber hinaus sollten umfassende Effekte von MTTe bei Patientengruppen mit unterschiedlichen Ausprägungen untersucht werden.
A Nickel(II) Chloride and Tetrahydroxydiboron Cocatalyzed Facile Synthesis of Benzo[b]azepines with an Appended Fluorinated Side Chain
Authors: Zhao Wentao , Wang Guangwei , Lei Wenqing , Yang Yingfan , Guo Minjie 
Published: May 2023

AbstractA novel nickel-catalyzed chemoselective cascade reaction strategy towards the synthesis of benzo[b]azepines was developed. The method is characterized by simple and mild conditions, low cost, and a wide range of substrates. This method enabled the facile and efficient synthesis of a series of 2,3,4,5-tetrahydro-1H-benzo[b]azepine analogues with an appended fluorinated side chain.
The Association of Periconception Asthma Medication Discontinuation with Adverse Obstetric Outcomes
Authors: Rohn Matthew C. H. , Stevens Danielle R. , Grobman William A. , Kumar Rajesh , Chen Zhen , Deshane Jessy , Biggio Joseph R. , Subramaniam Akila , Grantz Katherine L. , Sherman Seth , Mendola Pauline 
Published: May 2023

Objective This study aimed to investigate asthma medication reduction in the periconceptional period as it relates to asthma status and adverse outcomes in pregnancy.
Study Design In a prospective cohort study, self-reported current and past asthma medications were collected and analyzes compared measures of asthma status in women who discontinued asthma medication in the 6 months prior to enrollment (“step-down”) versus those who did not (“no change”). Evaluation of asthma was done at three study visits (one per trimester) and by daily diaries, including measures of lung function (percent predicted forced expiratory volume in 1 and 6 s [%FEV1, %FEV6], peak expiratory flow [%PEF], forced vital capacity [%FVC], FEV1 to FVC ratio [FEV1/FVC]), lung inflammation (fractional exhaled nitric oxide [FeNO], ppb), rate of asthma symptoms (activity limitation, night symptoms, rescue inhaler use, wheeze, shortness of breath, cough, chest tightness, chest pain), and rate of asthma exacerbations. Adverse pregnancy outcomes were also evaluated. Adjusted regression analyses examined whether adverse outcomes differed by periconceptional asthma medication changes.
Results Of 279 participants included in analyses, 135 (48.4%) did not change asthma medication in the periconceptional period, whereas 144 (51.6%) reported a step down in medication. Those in the step-down group were more likely to have milder disease (88 [61.1%] in the step-down vs. 74 [54.8%] in the no change group), exhibited less activity limitation (rate ratio [RR]: 0.68, 95% confidence interval [CI]: 0.47–0.98), and experienced fewer asthma attacks (RR: 0.53, 95% CI: 0.34–0.84) during pregnancy. The step-down group had a nonsignificant increase in overall odds of experiencing an adverse pregnancy outcome (odds ratio: 1.62, 95% CI: 0.97–2.72).
Conclusion Over half of women with asthma reduce asthma medication in the periconceptional period. Although these women typically have milder disease, a step down in medication may be associated with an increased risk of adverse pregnancy outcomes.
Key Points
Chemoenzymatic Synthesis of arabino-Configured Bicyclic Nucleosides
Authors: Prasad Ashok K. , Singla Harbansh , Maity Jyotirmoy , Kumar Sandeep , Kavita Kavita , Chaudhary Riya 
Published: May 2023

AbstractA convergent route for the synthesis of a new class of bicyclic nucleosides has been developed. The synthetic route to the corresponding arabino-configured uracil and thymine bicyclic nucleosides proceeds in 24 and 27% overall yields, respectively, starting from 1,2,5,6-di-O-isopropylidene-α-d-glucofuranose. This synthetic protocol includes some crucial steps such as Vorbrüggen base coupling and chemo-enzymatic regioselective acetylation of the primary hydroxyl group by using Lipozyme® TL IM where it was found that Lipozyme® TL IM could be recovered and reused for selective acetylation without losing its selectivity.
Nickel-Catalyzed Asymmetric Arylation of H-Phosphinates
Authors: Zhang Qing , Cui Ran-Ran , Zhang Qing-Wei 
Published: May 2023

AbstractAn asymmetric arylation of H-phosphinates with aromatic iodo or bromo compounds, catalyzed by cheap and easily available nickel(II) salts, provides access to P-stereogenic phosphinates. This method features mild reaction conditions and a good functional-group compatibility that includes aniline and phenol derivatives.
Enhance high harmonic generation (HHG) efficiency via compact multi-plate continuum post-compression for time-resolved angle-resolved photoemission spectroscopy
Authors: Jia Hao-Hsiang , Yeh Tien-Tien , Cheng Cheng-Maw , Luo Chih-Wei , Chen Ming-Chang , Lin Ping-Hui 
Published: May 2023

Time-resolved angle-resolved photoemission spectroscopy (Tr-APRES) gives direct insight into electron dynamics by providing temporal-, energy-, and momentum-resolved information in one experiment. A major obstacle to using high harmonic generation (HHG) probe pulses for photoemission spectroscopy is the low conversion efficiency, that is, the low flux of probe photons. We use a Yb-KGW based duo-laser source with an oscillator to pump two separate amplifiers and generate two synchronized pulsed laser sources with average energies of 7.5 and 6 W. By using the multiplate continuum method and chirped mirrors, the resulting flux of HHG photons at 33–70 eV can be increased 50-fold (up to 1011 photons/s) by using post-compressed 30 fs pulses compared with the photon flux generated by the fundamental 190 fs pulses. Moreover, pulses from the 6 W amplifier are used to pump an optical parametric amplifier that can vary the wavelengths for photoexcitation. The system performance is demonstrated by applying Tr-ARPES to single-crystal graphite. The front tilt broadening is significantly suppressed by the off-plane mounted conical grating, leading to a 184 fs temporal resolution that is mainly limited by the pump pulse. The energy resolution is 176 meV.
Regenerative engineering of long bones using the small molecule forskolin
Authors: Awale Guleid M. , Barajaa Mohammed A. , Kan Ho-Man , Seyedsalehi Amir , Nam Ga Hie , Hosseini Fatemeh S. , Ude Chinedu C. , Schmidt Tannin A. , Lo Kevin W.-H. , Laurencin Cato T. 
Published: May 2023

Bone grafting procedures have become increasingly common in the United States, with approximately 500,000 cases occurring each year at a societal cost exceeding $2.4 billion. Recombinant human bone morphogenetic proteins (rhBMPs) are therapeutic agents that have been widely used by orthopedic surgeons to stimulate bone tissue formation alone and when paired with biomaterials. However, significant limitations such as immunogenicity, high production cost, and ectopic bone growth from these therapies remain. Therefore, efforts have been made to discover and repurpose osteoinductive small-molecule therapeutics to promote bone regeneration. Previously, we have demonstrated that a single-dose treatment with the small-molecule forskolin for just 24 h induces osteogenic differentiation of rabbit bone marrow–derived stem cells in vitro, while mitigating adverse side effects attributed with prolonged small-molecule treatment schemes. In this study, we engineered a composite fibrin–PLGA [poly(lactide-co-glycolide)]-sintered microsphere scaffold for the localized, short-term delivery of the osteoinductive small molecule, forskolin. In vitro characterization studies showed that forskolin released out of the fibrin gel within the first 24 h and retained its bioactivity toward osteogenic differentiation of bone marrow–derived stem cells. The forskolin-loaded fibrin–PLGA scaffold was also able to guide bone formation in a 3-mo rabbit radial critical-sized defect model comparable to recombinant human bone morphogenetic protein-2 (rhBMP-2) treatment, as demonstrated through histological and mechanical evaluation, with minimal systemic off-target side effects. Together, these results demonstrate the successful application of an innovative small-molecule treatment approach within long bone critical-sized defects.
ARL6IP1 mediates small-molecule-induced alleviation of Alzheimer pathology through FXR1-dependent BACE1 translation initiation
Authors: Zhou Gui-Feng , Tang Jing , Ma Yuan-Lin , Fu Xian , Liu Jun-Yan , Yang Ren-Zhi , Zhang Hong-Sheng , Cai Xiang-Hai , Wang Jing-Wen , Xie Xiao-Yong , Song Li , Luo Biao , Chen Jian , Chen Long , Deng Xiao-Juan , Chen Guo-Jun 
Published: May 2023

Exploring the potential lead compounds for Alzheimer’s disease (AD) remains one of the challenging tasks. Here, we report that the plant extract conophylline (CNP) impeded amyloidogenesis by preferentially inhibiting BACE1 translation via the 5′ untranslated region (5′UTR) and rescued cognitive decline in an animal model of APP/PS1 mice. ADP-ribosylation factor–like protein 6–interacting protein 1 (ARL6IP1) was then found to mediate the effect of CNP on BACE1 translation, amyloidogenesis, glial activation, and cognitive function. Through analysis of the 5′UTR-targetd RNA-binding proteins by RNA pulldown combined with LC-MS/MS, we found that FMR1 autosomal homolog 1 (FXR1) interacted with ARL6IP1 and mediated CNP-induced reduction of BACE1 by regulating the 5′UTR activity. Without altering the protein levels of ARL6IP1 and FXR1, CNP treatment promoted ARL6IP1 interaction with FXR1 and inhibited FXR1 binding to the 5′UTR both in vitro and in vivo. Collectively, CNP exhibited a therapeutic potential for AD via ARL6IP1. Through pharmacological manipulation, we uncovered a dynamic interaction between FXR1 and the 5′UTR in translational control of BACE1, adding to the understanding of the pathophysiology of AD.