bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving bowel preparation for colonoscopy with a smartphone application driven by artificial intelligence
Authors: Zhu Yan , Zhang Dan-Feng , Wu Hui-Li , Fu Pei-Yao , Feng Li , Zhuang Kun , Geng Zi-Han , Li Kun-Kun , Zhang Xiao-Hong , Zhu Bo-Qun , Qin Wen-Zheng , Lin Sheng-Li , Zhang Zhen , Chen Tian-Yin , Huang Yuan , Xu Xiao-Yue , Liu Jing-Zheng , Wang Shuo , Zhang Wei , Li Quan-Lin , Zhou Ping-Hong 
Published: March 2023

AbstractOptimal bowel preparation is a prerequisite for a successful colonoscopy; however, the rate of inadequate bowel preparation remains relatively high. In this study, we establish a smartphone app that assesses patient bowel preparation using an artificial intelligence (AI)-based prediction system trained on labeled photographs of feces in the toilet and evaluate its impact on bowel preparation quality in colonoscopy outpatients. We conduct a prospective, single-masked, multicenter randomized clinical trial, enrolling outpatients who own a smartphone and are scheduled for a colonoscopy. We screen 578 eligible patients and randomize 524 in a 1:1 ratio to the control or AI-driven app group for bowel preparation. The study endpoints are the percentage of patients with adequate bowel preparation and the total BBPS score, compliance with dietary restrictions and purgative instructions, polyp detection rate, and adenoma detection rate (secondary). The prediction system has an accuracy of 95.15%, a specificity of 97.25%, and an area under the curve of 0.98 in the test dataset. In the full analysis set (n = 500), adequate preparation is significantly higher in the AI-driven app group (88.54 vs. 65.59%; P < 0.001). The mean BBPS score is 6.74 ± 1.25 in the AI-driven app group and 5.97 ± 1.81 in the control group (P < 0.001). The rates of compliance with dietary restrictions (93.68 vs. 83.81%, P = 0.001) and purgative instructions (96.05 vs. 84.62%, P < 0.001) are significantly higher in the AI-driven app group, as is the rate of additional purgative intake (26.88 vs. 17.41%, P = 0.011). Thus, our AI-driven smartphone app significantly improves the quality of bowel preparation and patient compliance.
SARAspeech—Feasibility of automated assessment of ataxic speech disturbance
Authors: Grobe-Einsler M. , Faber J. , Taheri A. , Kybelka J. , Raue J. , Volkening J. , Helmhold F. , Synofzik M. , Klockgether T. 
Published: March 2023

AbstractAtaxias are a group of movement disorders that are characterized by progressive loss of balance, impaired coordination and speech disturbance, which together lead to markedly reduced quality of life. Speech disturbance is clinically diagnosed, but methods for objective assessment of severity are lacking. Using 71 sets of speech recordings from ataxia patients, we developed an automated classification system. With a tolerance of ±1 point, this classification system correctly predicted experts’ ratings of speech disturbance according to item 4 of the Scale for Assessment and rating of ataxia (SARA) in 80% of cases. We thereby demonstrate feasibility of computer-assisted voice analysis for automated assessment of severity of speech disturbance.
Generalizable and robust deep learning algorithm for atrial fibrillation diagnosis across geography, ages and sexes
Authors: Biton Shany , Aldhafeeri Mohsin , Marcusohn Erez , Tsutsui Kenta , Szwagier Tom , Elias Adi , Oster Julien , Sellal Jean Marc , Suleiman Mahmoud , Behar Joachim A. 
Published: March 2023

AbstractTo drive health innovation that meets the needs of all and democratize healthcare, there is a need to assess the generalization performance of deep learning (DL) algorithms across various distribution shifts to ensure that these algorithms are robust. This retrospective study is, to the best of our knowledge, an original attempt to develop and assess the generalization performance of a DL model for AF events detection from long term beat-to-beat intervals across geography, ages and sexes. The new recurrent DL model, denoted ArNet2, is developed on a large retrospective dataset of 2,147 patients totaling 51,386 h obtained from continuous electrocardiogram (ECG). The model’s generalization is evaluated on manually annotated test sets from four centers (USA, Israel, Japan and China) totaling 402 patients. The model is further validated on a retrospective dataset of 1,825 consecutives Holter recordings from Israel. The model outperforms benchmark state-of-the-art models and generalized well across geography, ages and sexes. For the task of event detection ArNet2 performance was higher for female than male, higher for young adults (less than 61 years old) than other age groups and across geography. Finally, ArNet2 shows better performance for the test sets from the USA and China. The main finding explaining these variations is an impairment in performance in groups with a higher prevalence of atrial flutter (AFL). Our findings on the relative performance of ArNet2 across groups may have clinical implications on the choice of the preferred AF examination method to use relative to the group of interest.
Sustained overexpression of spliced X-box-binding protein-1 in neurons leads to spontaneous seizures and sudden death in mice
Authors: Wang Zhuoran , Li Qiang , Kolls Brad J. , Mace Brian , Yu Shu , Li Xuan , Liu Wei , Chaparro Eduardo , Shen Yuntian , Dang Lihong , del Águila Ángela , Bernstock Joshua D. , Johnson Kory R. , Yao Junjie , Wetsel William C. , Moore Scott D. , Turner Dennis A. , Yang Wei 
Published: March 2023

AbstractThe underlying etiologies of seizures are highly heterogeneous and remain incompletely understood. While studying the unfolded protein response (UPR) pathways in the brain, we unexpectedly discovered that transgenic mice (XBP1s-TG) expressing spliced X-box–binding protein-1 (Xbp1s), a key effector of UPR signaling, in forebrain excitatory neurons, rapidly develop neurologic deficits, most notably recurrent spontaneous seizures. This seizure phenotype begins around 8 days after Xbp1s transgene expression is induced in XBP1s-TG mice, and by approximately 14 days post induction, the seizures evolve into status epilepticus with nearly continuous seizure activity followed by sudden death. Animal death is likely due to severe seizures because the anticonvulsant valproic acid could significantly prolong the lives of XBP1s-TG mice. Mechanistically, our gene profiling analysis indicates that compared to control mice, XBP1s-TG mice exhibit 591 differentially regulated genes (mostly upregulated) in the brain, including several GABAA receptor genes that are notably downregulated. Finally, whole-cell patch clamp analysis reveals a significant reduction in both spontaneous and tonic GABAergic inhibitory responses in Xbp1s-expressing neurons. Taken together, our findings unravel a link between XBP1s signaling and seizure occurrence.
Protein fibril length in cerebrospinal fluid is increased in Alzheimer’s disease
Authors: Nirmalraj Peter Niraj , Schneider Thomas , Lüder Lars , Felbecker Ansgar 
Published: March 2023

AbstractAlzheimer’s disease (AD) associated proteins exist in cerebrospinal fluid (CSF). This paper evidences that protein aggregate morphology distinctly differs in CSF of patients with AD dementia (ADD), mild cognitive impairment due to AD (MCI AD), with subjective cognitive decline without amyloid pathology (SCD) and with non-AD MCI using liquid-based atomic force microscopy (AFM). Spherical-shaped particles and nodular-shaped protofibrils were present in the CSF of SCD patients, whereas CSF of ADD patients abundantly contained elongated mature fibrils. Quantitative analysis of AFM topographs confirms fibril length is higher in CSF of ADD than in MCI AD and lowest in SCD and non-AD dementia patients. CSF fibril length is inversely correlated with CSF amyloid beta (Aβ) 42/40 ratio and CSF p-tau protein levels (obtained from biochemical assays) to predict amyloid and tau pathology with an accuracy of 94% and 82%, respectively, thus identifying ultralong protein fibrils in CSF as a possible signature of AD pathology.
Antimicrobial protein REG3A regulates glucose homeostasis and insulin resistance in obese diabetic mice
Authors: Gonzalez Patrick , Dos Santos Alexandre , Darnaud Marion , Moniaux Nicolas , Rapoud Delphine , Lacoste Claire , Nguyen Tung-Son , Moullé Valentine S. , Deshayes Alice , Amouyal Gilles , Amouyal Paul , Bréchot Christian , Cruciani-Guglielmacci Céline , Andréelli Fabrizio , Magnan Christophe , Faivre Jamila 
Published: March 2023

AbstractInnate immune mediators of pathogen clearance, including the secreted C-type lectins REG3 of the antimicrobial peptide (AMP) family, are known to be involved in the regulation of tissue repair and homeostasis. Their role in metabolic homeostasis remains unknown. Here we show that an increase in human REG3A improves glucose and lipid homeostasis in nutritional and genetic mouse models of obesity and type 2 diabetes. Mice overexpressing REG3A in the liver show improved glucose homeostasis, which is reflected in better insulin sensitivity in normal weight and obese states. Delivery of recombinant REG3A protein to leptin-deficient ob/ob mice or wild-type mice on a high-fat diet also improves glucose homeostasis. This is accompanied by reduced oxidative protein damage, increased AMPK phosphorylation and insulin-stimulated glucose uptake in skeletal muscle tissue. Oxidative damage in differentiated C2C12 myotubes is greatly attenuated by REG3A, as is the increase in gp130-mediated AMPK activation. In contrast, Akt-mediated insulin action, which is impaired by oxidative stress, is not restored by REG3A. These data highlight the importance of REG3A in controlling oxidative protein damage involved in energy and metabolic pathways during obesity and diabetes, and provide additional insight into the dual function of host-immune defense and metabolic regulation for AMP.
Chronological age-related metabolome responses in the dinoflagellate Karenia mikimotoi, can predict future bloom demise
Authors: Hano Takeshi , Tomaru Yuji 
Published: March 2023

AbstractKarenia mikimotoi is a common harmful algal bloom (HAB)-forming dinoflagellate and has caused severe financial loss in aquaculture. There are limited metabolomic studies on dinoflagellate biology. Here, we examined alterations in metabolic profiles over the growth curve of K. mikimotoi under nitrogen or phosphorus deficiency and further explored a key criterion for the diagnosis of late stationary phase to identify when the dinoflagellate cells will enter bloom demise. The results demonstrate the differential expression of metabolites for coping with chronological aging or nutrient deprivation. Furthermore, an increase in the glucose to glycine ratio in the late stationary phase was indicative of dinoflagellate cells entering bloom demise; this was also detected in the cultured diatom, Chaetoceros tenuissimus, indicating that this may be the general criterion for phytoplankton species. Our findings provide insights regarding chronological aging and the criterion for the prediction of phytoplankton bloom demise.
Dissociation between phase and power correlation networks in the human brain is driven by co-occurrent bursts
Authors: Hindriks Rikkert , Tewarie Prejaas K. B. 
Published: March 2023

AbstractWell-known haemodynamic resting-state networks are better mirrored in power correlation networks than phase coupling networks in electrophysiological data. However, what do these power correlation networks reflect? We address this long-outstanding question in neuroscience using rigorous mathematical analysis, biophysical simulations with ground truth and application of these mathematical concepts to empirical magnetoencephalography (MEG) data. Our mathematical derivations show that for two non-Gaussian electrophysiological signals, their power correlation depends on their coherence, cokurtosis and conjugate-coherence. Only coherence and cokurtosis contribute to power correlation networks in MEG data, but cokurtosis is less affected by artefactual signal leakage and better mirrors haemodynamic resting-state networks. Simulations and MEG data show that cokurtosis may reflect co-occurrent bursting events. Our findings shed light on the origin of the complementary nature of power correlation networks to phase coupling networks and suggests that the origin of resting-state networks is partly reflected in co-occurent bursts in neuronal activity.
CD115− monocytic myeloid-derived suppressor cells are precursors of OLFM4high polymorphonuclear myeloid-derived suppressor cells
Authors: Zou Yunyun , Kamada Nobuhiko , Seong Seung-Yong , Seo Sang-Uk 
Published: March 2023

AbstractMyeloid-derived suppressor cells (MDSCs) consist of monocytic (M-) MDSCs and polymorphonuclear (PMN-) MDSCs that contribute to an immunosuppressive environment in tumor-bearing hosts. However, research on the phenotypic and functional heterogeneity of MDSCs in tumor-bearing hosts and across different disease stage is limited. Here we subdivide M-MDSCs based on CD115 expression and report that CD115− M-MDSCs are functionally distinct from CD115+ M-MDSCs. CD115− M-MDSCs increased in bone marrow and blood as tumors progressed. Transcriptome analysis revealed that CD115− M-MDSCs expressed higher levels of neutrophil-related genes. Moreover, isolated CD115− M-MDSCs had higher potential to be differentiated into PMN-MDSCs compared with CD115+ M-MDSCs. Of note, CD115− M-MDSCs were able to differentiate into both olfactomedin 4 (OLFM4)hi and OLFM4lo PMN-MDSCs, whereas CD115+ M-MDSCs differentiated into a smaller proportion of OLFM4lo PMN-MDSCs. In vivo, M-MDSC to PMN-MDSC differentiation occurred most frequently in bone marrow while M-MDSCs preferentially differentiated into tumor-associated macrophages in the tumor mass. Our study reveals the presence of previously unrecognized subtypes of CD115− M-MDSCs in tumor-bearing hosts and demonstrates their cellular plasticity during tumorigenesis.
In vivo characterization of the bacterial intramembrane-cleaving protease RseP using the heme binding tag-based assay iCliPSpy
Authors: Kupke Thomas , Götz Rabea M. , Richter Florian M. , Beck Rainer , Lolicato Fabio , Nickel Walter , Hopf Carsten , Brügger Britta 
Published: March 2023

AbstractRegulated intramembrane proteolysis (RIP) describes the protease-dependent cleavage of transmembrane proteins within the hydrophobic core of cellular membranes. Intramembrane-cleaving proteases (I-CliPs) that catalyze these reactions are found in all kingdoms of life and are involved in a wide range of cellular processes, including signaling and protein homeostasis. I-CLiPs are multispanning membrane proteins and represent challenging targets in structural and enzyme biology. Here we introduce iCLiPSpy, a simple assay to study I-CLiPs in vivo. To allow easy detection of enzyme activity, we developed a heme-binding reporter based on TNFα that changes color after I-CLiP-mediated proteolysis. Co-expression of the protease and reporter in Escherichia coli (E. coli) results in white or green colonies, depending on the activity of the protease. As a proof of concept, we use this assay to study the bacterial intramembrane-cleaving zinc metalloprotease RseP in vivo. iCLiPSpy expands the methodological repertoire for identifying residues important for substrate binding or activity of I-CLiPs and can in principle be adapted to a screening assay for the identification of inhibitors or activators of I-CLiPs, which is of great interest for proteases being explored as biomedical targets.
ClpC2 protects mycobacteria against a natural antibiotic targeting ClpC1-dependent protein degradation
Authors: Taylor Gabrielle , Cui Hengjun , Leodolter Julia , Giese Christoph , Weber-Ban Eilika 
Published: March 2023

AbstractMycobacterium tuberculosis Clp proteases are targeted by several antitubercular compounds, including cyclomarin A (CymA). CymA exerts its toxicity by binding to AAA + chaperone ClpC1. Here, we show that CymA can also bind a partial homologue of ClpC1, known as ClpC2, and we reveal the molecular basis of these interactions by determining the structure of the M. tuberculosis ClpC2:CymA complex. Furthermore, we show deletion of clpC2 in Mycobacterium smegmatis increases sensitivity to CymA. We find CymA exposure leads to a considerable upregulation of ClpC2 via a mechanism in which binding of CymA to ClpC2 prevents binding of ClpC2 to its own promoter, resulting in upregulation of its own transcription in response to CymA. Our study reveals that ClpC2 not only senses CymA, but that through this interaction it can act as a molecular sponge to counteract the toxic effects of CymA and possibly other toxins targeting essential protease component ClpC1 in mycobacteria.
The SGLT2 inhibitor empagliflozin improves cardiac energy status via mitochondrial ATP production in diabetic mice
Authors: Choi Jungmi , Matoba Naoki , Setoyama Daiki , Watanabe Daiki , Ohnishi Yuichiro , Yasui Ryuto , Kitai Yuichirou , Oomachi Aki , Kotobuki Yutaro , Nishiya Yoichi , Pieper Michael Paul , Imamura Hiromi , Yanagita Motoko , Yamamoto Masamichi 
Published: March 2023

AbstractEmpagliflozin, a sodium-glucose co-transporter 2 inhibitor developed, has been shown to reduce cardiovascular events in patients with type 2 diabetes and established cardiovascular disease. Several studies have suggested that empagliflozin improves the cardiac energy state which is a partial cause of its potency. However, the detailed mechanism remains unclear. To address this issue, we used a mouse model that enabled direct measurement of cytosolic and mitochondrial ATP levels. Empagliflozin treatment significantly increased cytosolic and mitochondrial ATP levels in the hearts of db/db mice. Empagliflozin also enhanced cardiac robustness by maintaining intracellular ATP levels and the recovery capacity in the infarcted area during ischemic-reperfusion. Our findings suggest that empagliflozin enters cardiac mitochondria and directly causes these effects by increasing mitochondrial ATP via inhibition of NHE1 and Nav1.5 or their common downstream sites. These cardioprotective effects may be involved in the beneficial effects on heart failure seen in clinical trials.
Domain adaptation for supervised integration of scRNA-seq data
Authors: Sun Yutong , Qiu Peng 
Published: March 2023

AbstractLarge-scale scRNA-seq studies typically generate data in batches, which often induce nontrivial batch effects that need to be corrected. Given the global efforts for building cell atlases and the increasing number of annotated scRNA-seq datasets accumulated, we propose a supervised strategy for scRNA-seq data integration called SIDA (SupervisedIntegration usingDomainAdaptation), which uses the cell type annotations to guide the integration of diverse batches. The supervised strategy is based on domain adaptation that was initially proposed in the computer vision field. We demonstrate that SIDA is able to generate comprehensive reference datasets that lead to improved accuracy in automated cell type mapping analyses.
The microbiome of the marine flatworm Macrostomum lignano provides fitness advantages and exhibits circadian rhythmicity
Authors: Ma Yuanyuan , He Jinru , Sieber Michael , von Frieling Jakob , Bruchhaus Iris , Baines John F. , Bickmeyer Ulf , Roeder Thomas 
Published: March 2023

AbstractThe close association between animals and their associated microbiota is usually beneficial for both partners. Here, we used a simple marine model invertebrate, the flatworm Macrostomum lignano, to characterize the host-microbiota interaction in detail. This analysis revealed that the different developmental stages each harbor a specific microbiota. Studies with gnotobiotic animals clarified the physiological significance of the microbiota. While no fitness benefits were mediated by the microbiota when food was freely available, animals with microbiota showed significantly increased fitness with a reduced food supply. The microbiota of M. lignano shows circadian rhythmicity, affecting both the total bacterial load and the behavior of specific taxa. Moreover, the presence of the worm influences the composition of the bacterial consortia in the environment. In summary, the Macrostomum-microbiota system described here can serve as a general model for host-microbe interactions in marine invertebrates.
Correlation-temperature phase diagram of prototypical infinite layer rare earth nickelates
Authors: Pascut Gheorghe Lucian , Cosovanu Lucian , Haule Kristjan , Quader Khandker F. 
Published: March 2023

AbstractThe discovery of superconductivity in hole-doped infinite layer nickelates, RNiO2 (R = Nd, Pr, La) has resulted in sustained interest in the field. A definitive picture of low-energy many-body states has not yet emerged. Here we provide insights into the low-energy physics, based on our embedded dynamical mean-field theory calculations, and propose a correlation (U)-temperature (T) phase diagram. The key features are a low-T Fermi liquid (FL) phase, a high-T Curie-Weiss regime, and an antiferromagnetic phase in a narrow U-T region. We associate the onset of the FL phase with partial screening of Ni-d moments; however, full screening occurs at lower temperatures. This may be related to insufficiency of conduction electrons to effectively screen the Ni-d moments, suggestive of Nozieres Exhaustion Principle. Our results suggest that RNiO2 are in the paramagnetic state, close to an antiferromagnetic dome, making magnetic fluctuations feasible. This may be consequential for superconductivity.
Observation of terahertz-induced dynamical spin canting in orthoferrite magnon by magnetorefractive probing
Authors: Kurihara Takayuki , Bamba Motoaki , Watanabe Hiroshi , Nakajima Makoto , Suemoto Tohru 
Published: March 2023

AbstractIntense terahertz pulses offer unique pathway to resonantly drive the correlated spin systems up to the nonlinear regime. However, detection of such nonlinear spin dynamics often suffers from the small signal amplitude that can be easily hindered by the linear background components. In order to efficiently extract the nonlinear signals, here we demonstrate that magnetooptical effect can be utilized. We excite spin precession in orthoferrite YFeO3 by the magnetic field of intense terahertz pulse and probe its dynamics by transient transmissivity change in the near infrared. The observed waveforms contain quasi-ferromagnetic-mode magnon oscillation and its second harmonics with a comparably strong amplitude. The result can be explained by dielectric function derived from magnetorefractive Hamiltonian. We reveal that the strong second harmonic signal microscopically originates from the dynamics of the quasi-ferromagnetic mode magnon at nonlinear regime, wherein spin canting angle periodically oscillates.
The transformative potential of a Global Urban Agenda and its lessons in a time of crisis
Authors: Espey Jessica , Parnell Susan , Revi Aromar 
Published: March 2023

Abstract2015 was a seismic moment for urban stakeholders around the world. A coalition of policymakers, academics and practitioners came together to successfully advocate for an urban goal to be included in the UN Sustainable Development Goal framework. Although the value of a place-based approach to development has been demonstrated by a number of cities and countries worldwide, it was 2020–2022 (three years of cataclysmic global events) that highlighted the necessity for a universal place-based approach to planning in order to foster resilience and sustainability. In this article, three academic-practitioners reflect upon the transformative potential of the 2015–16 urban agendas.