bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differentiation of IL-26+ TH17 intermediates into IL-17A producers via epithelial crosstalk in psoriasis
Authors: Fries Anissa , Saidoune Fanny , Kuonen François , Dupanloup Isabelle , Fournier Nadine , Guerra de Souza Ana Cristina , Haniffa Muzlifah , Ma Feiyang , Gudjonsson Johann E. , Roesner Lennart , Li Yang , Werfel Thomas , Conrad Curdin , Gottardo Raphael , Modlin Robert L. , Di Domizio Jeremy , Gilliet Michel 
Published: June 2023

AbstractInterleukin (IL)-26 is a TH17 cytokine with known antimicrobial and pro-inflammatory functions. However, the precise role of IL-26 in the context of pathogenic TH17 responses is unknown. Here we identify a population of blood TH17 intermediates that produce high levels of IL-26 and differentiate into IL-17A-producing TH17 cells upon TGF-β1 exposure. By combining single cell RNA sequencing, TCR sequencing and spatial transcriptomics we show that this process occurs in psoriatic skin. In fact, IL-26+ TH17 intermediates infiltrating psoriatic skin induce TGF-β1 expression in basal keratinocytes and thereby promote their own differentiation into IL-17A-producing cells. Thus, our study identifies IL-26-producing cells as an early differentiation stage of TH17 cells that infiltrates psoriatic skin and controls its own maturation into IL17A-producing TH17 cells, via epithelial crosstalk involving paracrine production of TGF-β1.
Nuclear lamina strain states revealed by intermolecular force biosensor
Authors: Danielsson Brooke E. , George Abraham Bobin , Mäntylä Elina , Cabe Jolene I. , Mayer Carl R. , Rekonen Anna , Ek Frans , Conway Daniel E. , Ihalainen Teemu O. 
Published: June 2023

AbstractNuclear lamins have been considered an important structural element of the nucleus. The nuclear lamina is thought both to shield DNA from excessive mechanical forces and to transmit mechanical forces onto the DNA. However, to date there is not yet a technical approach to directly measure mechanical forces on nuclear lamins at the protein level. To overcome this limitation, we developed a nanobody-based intermolecular tension FRET biosensor capable of measuring the mechanical strain of lamin filaments. Using this sensor, we were able to show that the nuclear lamina is subjected to significant force. These forces are dependent on nuclear volume, actomyosin contractility, functional LINC complex, chromatin condensation state, cell cycle, and EMT. Interestingly, large forces were also present on nucleoplasmic lamins, indicating that these lamins may also have an important mechanical role in the nucleus. Overall, we demonstrate that the nanobody-based approach allows construction of biosensors for complex protein structures for mechanobiology studies.
Innovative design of minimal invasive biodegradable poly(glycerol-dodecanoate) nucleus pulposus scaffold with function regeneration
Authors: Wang Lizhen , Jin Kaixiang , Li Nan , Xu Peng , Yuan Hao , Ramaraju Harsha , Hollister Scott J. , Fan Yubo 
Published: June 2023

AbstractMinimally invasive biodegradable implants with regeneration have been a frontier trend in clinic. Degeneration of nucleus pulposus (NP) is irreversible in most of spine diseases, and traditional spinal fusion or discectomy usually injure adjacent segments. Here, an innovative minimally invasive biodegradable NP scaffold with function regeneration inspired by cucumber tendril is developed using shape memory polymer poly(glycerol-dodecanoate) (PGD), whose mechanical property is controlled to the similar with human NP by adjusting synthetic parameters. The chemokine stromal cell-derived factor-1α (SDF-1α) is immobilized to the scaffold recruiting autologous stem cells from peripheral tissue, which has better ability of maintaining disc height, recruiting autologous stem cells, and inducing regeneration of NP in vivo compared to PGD without chemokine group and hydrogel groups significantly. It provides an innovative way to design minimally invasive implants with biodegradation and functional recovery, especially for irreversible tissue injury, including NP, cartilage and so on.
Drug reinforcement impairs cognitive flexibility by inhibiting striatal cholinergic neurons
Authors: Gangal Himanshu , Xie Xueyi , Huang Zhenbo , Cheng Yifeng , Wang Xuehua , Lu Jiayi , Zhuang Xiaowen , Essoh Amanda , Huang Yufei , Chen Ruifeng , Smith Laura N. , Smith Rachel J. , Wang Jun 
Published: June 2023

AbstractAddictive substance use impairs cognitive flexibility, with unclear underlying mechanisms. The reinforcement of substance use is mediated by the striatal direct-pathway medium spiny neurons (dMSNs) that project to the substantia nigra pars reticulata (SNr). Cognitive flexibility is mediated by striatal cholinergic interneurons (CINs), which receive extensive striatal inhibition. Here, we hypothesized that increased dMSN activity induced by substance use inhibits CINs, reducing cognitive flexibility. We found that cocaine administration in rodents caused long-lasting potentiation of local inhibitory dMSN-to-CIN transmission and decreased CIN firing in the dorsomedial striatum (DMS), a brain region critical for cognitive flexibility. Moreover, chemogenetic and time-locked optogenetic inhibition of DMS CINs suppressed flexibility of goal-directed behavior in instrumental reversal learning tasks. Notably, rabies-mediated tracing and physiological studies showed that SNr-projecting dMSNs, which mediate reinforcement, sent axonal collaterals to inhibit DMS CINs, which mediate flexibility. Our findings demonstrate that the local inhibitory dMSN-to-CIN circuit mediates the reinforcement-induced deficits in cognitive flexibility.
Photoredox-catalyzed diastereoselective dearomative prenylation and reverse-prenylation of electron-deficient indole derivatives
Authors: Chang Xuexue , Zhang Fangqing , Zhu Shibo , Yang Zhuang , Feng Xiaoming , Liu Yangbin 
Published: June 2023

AbstractPrenylated and reverse-prenylated indolines are privileged scaffolds in numerous naturally occurring indole alkaloids with a broad spectrum of important biological properties. Development of straightforward and stereoselective methods to enable the synthesis of structurally diverse prenylated and reverse-prenylated indoline derivatives is highly desirable and challenging. In this context, the most direct approaches to achieve this goal generally rely on transition-metal-catalyzed dearomative allylic alkylation of electron-rich indoles. However, the electron-deficient indoles are much less explored, probably due to their diminished nucleophilicity. Herein, a photoredox-catalyzed tandem Giese radical addition/Ireland–Claisen rearrangement is disclosed. Diastereoselective dearomative prenylation and reverse-prenylation of electron-deficient indoles proceed smoothly under mild conditions. An array of tertiary α-silylamines as radical precursors is readily incorporated in 2,3-disubstituted indolines with high functional compatibility and excellent diastereoselectivity (>20:1 d.r.). The corresponding transformations of the secondary α-silylamines provide the biologically important lactam-fused indolines in one-pot synthesis. Subsequently, a plausible photoredox pathway is proposed based on control experiments. The preliminary bioactivity study reveals a potential anticancer property of these structurally appealing indolines.
Accelerating the prediction and discovery of peptide hydrogels with human-in-the-loop
Authors: Xu Tengyan , Wang Jiaqi , Zhao Shuang , Chen Dinghao , Zhang Hongyue , Fang Yu , Kong Nan , Zhou Ziao , Li Wenbin , Wang Huaimin 
Published: June 2023

AbstractThe amino acid sequences of peptides determine their self-assembling properties. Accurate prediction of peptidic hydrogel formation, however, remains a challenging task. This work describes an interactive approach involving the mutual information exchange between experiment and machine learning for robust prediction and design of (tetra)peptide hydrogels. We chemically synthesize more than 160 natural tetrapeptides and evaluate their hydrogel-forming ability, and then employ machine learning-experiment iterative loops to improve the accuracy of the gelation prediction. We construct a score function coupling the aggregation propensity, hydrophobicity, and gelation correctorCg, and generate an 8,000-sequence library, within which the success rate of predicting hydrogel formation reaches 87.1%. Notably, the de novo-designed peptide hydrogel selected from this work boosts the immune response of the receptor binding domain of SARS-CoV-2 in the mice model. Our approach taps into the potential of machine learning for predicting peptide hydrogelator and significantly expands the scope of natural peptide hydrogels.
Availability and use of Standards in vaccine development
Authors: Avumegah Michael Selorm , Mattiuzzo Giada , Särnefält Anna , Page Mark , Makar Karen , Lathey Janet , Kim June , Yimer Solomon Abebe , Craig Danielle , Knezevic Ivana , Bernasconi Valentina , Kristiansen Paul A. , Kromann Ingrid 
Published: June 2023

AbstractReference materials are critical in assay development for calibrating and assessing their suitability. The devasting nature of the COVID-19 pandemic and subsequent proliferation of vaccine platforms and technologies has meant that there is even a greater need for standards for immunoassay development, which are critical to assess and compare vaccines’ responses. Equally important are the standards needed to control the vaccine manufacturing processes. Standardized vaccine characterization assays throughout process development are essential for a successful Chemistry, Manufacturing and Controls (CMC) strategy. In this perspective paper, we advocate for reference material incorporation into assays and their calibration to International Standards from preclinical vaccine development through control testing and provide insight into why this is necessary. We also provide information on the availability of WHO international antibody standards for CEPI-priority pathogens.
A validated test has been developed for assessment of manual small incision cataract surgery skills using virtual reality simulation
Authors: Hutter Daniel E. , Wingsted Line , Cejvanovic Sanja , Jacobsen Mads Forslund , Ochoa Luis , González Daher Karla Pamela , la Cour Morten , Konge Lars , Thomsen Ann Sofia Skou 
Published: June 2023

AbstractThis study investigates the validity evidence of metrics used for the assessment of surgical skills for Manual Small Incision Cataract Surgery (MSICS) in a virtual reality simulator. MSICS surgery is a low-cost, low-technology cataract surgery technique, which is widely used in low- and middle-income countries. However, there is a lack of cataract surgeons globally, and efficient and evidence-based training of new surgeons is needed. In order to investigate the validity of simulator metrics, we included three groups of participants: (1) MSICS novices who were ophthalmologists with no cataract surgery experience, (2) MSICS novices who were experienced phacoemulsification cataract surgeons, but with no MSICS experience, and (3) experienced phacoemulsification and MSICS surgeons. The evaluation included 11 steps of the MSICS procedure, and all simulator metrics for those steps were reviewed. Of the 55 initial metrics, 30 showed high positive discriminative ability. A test passing score of 20 out of 30 was established, and one of 15 novices with no MSICS experience (mean score 15.5) and 7 out of 10 experienced MSICS surgeons (mean score 22.7) passed the test. We have developed and established validity evidence for a test for MSICS skills in a virtual reality simulator for future use in proficiency-based training and evidence-based testing of training interventions.
Generalized neural closure models with interpretability
Authors: Gupta Abhinav , Lermusiaux Pierre F. J. 
Published: June 2023

AbstractImproving the predictive capability and computational cost of dynamical models is often at the heart of augmenting computational physics with machine learning (ML). However, most learning results are limited in interpretability and generalization over different computational grid resolutions, initial and boundary conditions, domain geometries, and physical or problem-specific parameters. In the present study, we simultaneously address all these challenges by developing the novel and versatile methodology of unified neural partial delay differential equations. We augment existing/low-fidelity dynamical models directly in their partial differential equation (PDE) forms with both Markovian and non-Markovian neural network (NN) closure parameterizations. The melding of the existing models with NNs in the continuous spatiotemporal space followed by numerical discretization automatically allows for the desired generalizability. The Markovian term is designed to enable extraction of its analytical form and thus provides interpretability. The non-Markovian terms allow accounting for inherently missing time delays needed to represent the real world. Our flexible modeling framework provides full autonomy for the design of the unknown closure terms such as using any linear-, shallow-, or deep-NN architectures, selecting the span of the input function libraries, and using either or both Markovian and non-Markovian closure terms, all in accord with prior knowledge. We obtain adjoint PDEs in the continuous form, thus enabling direct implementation across differentiable and non-differentiable computational physics codes, different ML frameworks, and treatment of nonuniformly-spaced spatiotemporal training data. We demonstrate the new generalized neural closure models (gnCMs) framework using four sets of experiments based on advecting nonlinear waves, shocks, and ocean acidification models. Our learned gnCMs discover missing physics, find leading numerical error terms, discriminate among candidate functional forms in an interpretable fashion, achieve generalization, and compensate for the lack of complexity in simpler models. Finally, we analyze the computational advantages of our new framework.
The multi-mode acoustic gravitational wave experiment: MAGE
Authors: Campbell William M. , Goryachev Maxim , Tobar Michael E. 
Published: June 2023

AbstractThe Multi-mode Acoustic Gravitational wave Experiment (MAGE) is a high frequency gravitational wave detection experiment. In its first stage, the experiment features two near-identical quartz bulk acoustic wave resonators that act as strain antennas with spectral sensitivity as low as 6.6 × 10−21 [strain]/$$\sqrt{\text {Hz}}$$

Hz

in multiple narrow bands across MHz frequencies. MAGE is the successor to the initial path-finding experiments; GEN 1 and GEN 2. These precursor runs demonstrated the successful use of the technology, employing a single quartz gravitational wave detector that found significantly strong and rare transient features. As the next step to this initial experiment, MAGE will employ further systematic rejection strategies by adding an additional quartz detector such that localised strains incident on just a single detector can be identified. The primary goals of MAGE will be to target signatures arising from objects and/or particles beyond that of the standard model, as well as identifying the source of the rare events seen in the predecessor experiment. The experimental set-up, current status and future directions for MAGE are discussed. Calibration procedures of the detector and signal amplification chain are presented. The sensitivity of MAGE to gravitational waves is estimated from knowledge of the quartz resonators. Finally, MAGE is assembled and tested in order to determine the thermal state of its new components.
Effects of propolis-loaded nanoliposomes fortification in extender on buffalo semen cryopreservation
Authors: Abdelnour Sameh A. , Hassan Mahmoud A. E. , Shehabeldin Ahmed. M. , Omar Mohamed. E. A. , Khalil Wael A. , Aman Reham Mokhtar 
Published: June 2023

AbstractBuffalo sperm is sensitive to cryoinjuries, thus improving sperm cryoresistance is a critical approach for wide spreading the assisted reproductive technologies in buffalo. The intention of this work was to assess the effect of propolis-loaded in nanoliposomes (PRNL) supplementation of semen extender on semen quality, antioxidant status and some apoptotic genes of cryopreserved buffalo semen. PRNL were prepared using cholesterol (Chol) as well as soybean lecithin and their physicochemical properties were characterized. Egyptian buffalo bulls (4–6 years) were involved, and the semen samples were collected using the artificial vagina method. Buffalo semen was pooled (n = 25 ejaculates) and cryopreserved in tris extender containing PRNL at 0 (PRNL0), 2 (PRNL2), 4 (PRNL4) and 6 µg/mL (PRNL6), respectively. The PRNL had a size of 113.13 nm and a negative zeta potential (− 56.83 mV). Sperm progressive motility, viability, membrane integrity, abnormalities, chromatin damage, redox status, apoptosis status, and apoptotic genes were investigated after post-thawed buffalo semen. Using 2 or 4 µg/mL PRNL significantly increased sperm progressive motility, viability, and membrane integrity, while sperm abnormalities and the percentage of chromatin damages were the lowest in PRNL2 group. Moreover, the PRNL2 group exhibited the best results for all antioxidative activities (TAC, SOD, GPx and CAT) with significantly higher levels than the other groups (P < 0.05). The levels of ROS and MDA were significantly lower in the PRLN2 compared with other groups. The sperm caspase 3 enzyme activities showed the lowest values in PRNL2 groups followed by PRNL4 and PRNL6 groups with significant differences compared with the control. Adding 2 µg/mL PRNL to freezing media significantly reduced apoptotic genes such as Bax and Caspase 3 in sperm, while significantly increase in Bcl2 expression compared with the control (P < 0.001). The expression of Bcl2, Caspase 3 and Bax genes in sperm were not affected by the 6 µg/mL PRNL addition (P > 0.05). The electron micrography descriptions exemplified that the fortification of 2 or 4 µg/mL PRNL maintained the acrosomal and plasma membrane integrities as well as sustained the ultrastructure integrity of the cryopreserved buffalo spermatozoa when compared with control group, whereas the 6 µg/mL of PRNL demonstrated highest injury to the acrosome and plasma membranes. Results show supplementation of the buffalo freezing extender with 2 or 4 µg/mL of PRNL enhanced post-thawed sperm quality via boosting the antioxidant indices, diminishing the oxidative stress and apoptosis as well as maintained the ultrastructure integrity of frozen-thawed buffalo sperm.
Lipoxygenase inhibitory synthetic derivatives of methyl gallate regulate gene expressions of COX-2 and cytokines to reduce animal model arthritis
Authors: Sharanya C.S. , Abhithaj J. , Arun K.G. , Eeda Koti Reddy , Bhat Vignesh , Variyar E.J. , Sabu A. , Haridas M. 
Published: June 2023

AbstractMammalian lipoxygenases (LOXs) are involved in the biosynthesis of mediators of anaphylactic reactions and have been implicated in cell maturation, the pathogenesis of bronchial asthma, atherosclerosis, rheumatoid arthritis, cardiovascular diseases, Alzheimer’s disease and osteoporosis. Hence LOX inhibition in chronic conditions can lead to reducing the disease progression, which can be a good target for treating these diseases. The present study deals with designing methyl gallate derivatives and their anti-inflammatory effect by in silico, in vitro and in vivo methods. Designed derivatives were docked against LOX enzyme, and molecular dynamic simulations were carried out. Following the synthesis of derivatives, in vitro LOX inhibition assay, enzyme kinetics and fluorescence quenching studies were performed. One of the derivatives of methyl gallate (MGSD 1) was demonstrated as an anti-inflammatory agent for the treatment of rheumatoid arthritis in the animal model. Amelioration of Freund’s complete adjuvant (FCA)-induced arthritis by methyl gallate and its derivative with a concentration of 10–40 mg.kg−1 has been assessed in vivo in a 28-day-long study. TNF-α and COX-2 gene expression were also studied. Methyl gallate synthetic derivatives (MGSDs) inhibited LOX with an IC50 of 100 nM, 304 nM, and 226 nM for MGSD 1, MGSD 2, and MGSD 3, respectively. Fluorescence quenching methods also prove their binding characteristics, and 200 ns simulations studies showed that the RMSDs for the entire complex were less than 2.8 Å. The in vivo results showed that methyl gallate was required approximately five times diclofenac for the same level of effect, and the synthesised (MGSD 1) compound required only approximately 1/12 of diclofenac for the same level of effect in in-vivo studies. The preeminent expression of COX-2 and TNF-α genes was significantly decreased after the treatment of the methyl gallate derivative. Hence, the in vivo results showed that the referenced synthetic derivative might have more arthritis-reducing properties than the parent compound methyl gallate and is more potent than the standard drug diclofenac, with no apparent induced toxicity.
Spatio-temporal modelling of routine health facility data for malaria risk micro-stratification in mainland Tanzania
Authors: Thawer Sumaiyya G. , Golumbeanu Monica , Lazaro Samwel , Chacky Frank , Munisi Khalifa , Aaron Sijenunu , Molteni Fabrizio , Lengeler Christian , Pothin Emilie , Snow Robert W. , Alegana Victor A. 
Published: June 2023

AbstractAs malaria transmission declines, the need to monitor the heterogeneity of malaria risk at finer scales becomes critical to guide community-based targeted interventions. Although routine health facility (HF) data can provide epidemiological evidence at high spatial and temporal resolution, its incomplete nature of information can result in lower administrative units without empirical data. To overcome geographic sparsity of data and its representativeness, geo-spatial models can leverage routine information to predict risk in un-represented areas as well as estimate uncertainty of predictions. Here, a Bayesian spatio-temporal model was applied on malaria test positivity rate (TPR) data for the period 2017–2019 to predict risks at the ward level, the lowest decision-making unit in mainland Tanzania. To quantify the associated uncertainty, the probability of malaria TPR exceeding programmatic threshold was estimated. Results showed a marked spatial heterogeneity in malaria TPR across wards. 17.7 million people resided in areas where malaria TPR was high (≥ 30; 90% certainty) in the North-West and South-East parts of Tanzania. Approximately 11.7 million people lived in areas where malaria TPR was very low (< 5%; 90% certainty). HF data can be used to identify different epidemiological strata and guide malaria interventions at micro-planning units in Tanzania. These data, however, are imperfect in many settings in Africa and often require application of geo-spatial modelling techniques for estimation.