bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibiotic exposures and the development of pediatric autoimmune diseases: a register-based case–control study
Authors: Räisänen Laura K. , Kääriäinen Sohvi E. , Sund Reijo , Engberg Elina , Viljakainen Heli T. , Kolho Kaija-Leena 
Published: July 2022

Abstract
Background
Antibiotics have been associated with several individual autoimmune diseases (ADs). This study aims to discover whether pre-diagnostic antibiotics are associated with the onset of ADs in general.

Methods
From a cohort of 11,407 children, 242 developed ADs (type 1 diabetes, autoimmune thyroiditis, juvenile idiopathic arthritis (JIA), or inflammatory bowel diseases) by a median age of 16 years. Antibiotic purchases from birth until the date of diagnosis (or respective date in the matched controls n = 708) were traced from national registers.

Results
Total number of antibiotic purchases was not related to the onset of ADs when studied as a group. Of specific diagnoses, JIA was associated with the total number of antibiotics throughout the childhood and with broad-spectrum antibiotics before the age of 3 years. Intriguingly, recent and frequent antibiotic use (within 2 years before diagnosis and ≥3 purchases) was associated with the onset of ADs (OR 1.72, 95% CI 1.08–2.74). Regardless of frequent use in childhood (40% of all antibiotics), penicillin group antibiotics were not related to any ADs.

Conclusions
Use of antibiotics was relatively safe regarding the overall development of ADs. However, broad-spectrum antibiotics should be used considerately as they may associate with an increased likelihood of JIA.

Impact

Increasing numbers of antibiotic purchases before the age of 3 years or throughout childhood were not associated with the development of pediatric autoimmune diseases.

Broad-spectrum antibiotics were related to the development of autoimmune diseases, especially juvenile idiopathic arthritis in children, while penicillin group antibiotics were not.

The use of broad-spectrum antibiotics in children should be cautious as they may carry along a risk for autoimmune disease development.
N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells
Authors: Wang Rong , Wen Piaopiao , Yang Ganglong , Feng Yanyan , Mi Yuanyuan , Wang Xiaoying , Zhu Shenglong , Chen Yong Q. 
Published: July 2022

AbstractCastration-resistance of prostate cancer is one of the most challenging clinical problems. In the present study, we have performed proteomics and glycomics using LNCaP model. Growth differentiation factor-15 (GDF15) level is increased in androgen receptor (AR) inhibitor-resistant cells and the inhibitory effect of GDF15 on epithelial growth factor receptor (EGFR) pathway is relieved by GDF15 N70 glycosylation. Interference of GDF15 (siRNA or N70Q dominant negative) or EGFR pathway (inhibitor or siRNA for EGFR, SRC or ERK) decreases the resistant-cell survival in culture and tumor growth in mice. Our study reveals a novel regulatory mechanism of prostate cancer AR inhibitor resistance, raises the possibility of AR/SRC dual-targeting of castration-resistance of prostate cancer, and lays foundation for the future development of selective inhibitors of GDF15 glycosylation.
The mechanism of replication stalling and recovery within repetitive DNA
Authors: Casas-Delucchi Corella S. , Daza-Martin Manuel , Williams Sophie L. , Coster Gideon 
Published: July 2022

AbstractAccurate chromosomal DNA replication is essential to maintain genomic stability. Genetic evidence suggests that certain repetitive sequences impair replication, yet the underlying mechanism is poorly defined. Replication could be directly inhibited by the DNA template or indirectly, for example by DNA-bound proteins. Here, we reconstitute replication of mono-, di- and trinucleotide repeats in vitro using eukaryotic replisomes assembled from purified proteins. We find that structure-prone repeats are sufficient to impair replication. Whilst template unwinding is unaffected, leading strand synthesis is inhibited, leading to fork uncoupling. Synthesis through hairpin-forming repeats is rescued by replisome-intrinsic mechanisms, whereas synthesis of quadruplex-forming repeats requires an extrinsic accessory helicase. DNA-induced fork stalling is mechanistically similar to that induced by leading strand DNA lesions, highlighting structure-prone repeats as an important potential source of replication stress. Thus, we propose that our understanding of the cellular response to replication stress may also be applied to DNA-induced replication stalling.
Early Cambrian renewal of the geodynamo and the origin of inner core structure
Authors: Zhou Tinghong , Tarduno John A. , Nimmo Francis , Cottrell Rory D. , Bono Richard K. , Ibanez-Mejia Mauricio , Huang Wentao , Hamilton Matt , Kodama Kenneth , Smirnov Aleksey V. , Crummins Ben , Padgett Frank 
Published: July 2022

AbstractPaleomagnetism can elucidate the origin of inner core structure by establishing when crystallization started. The salient signal is an ultralow field strength, associated with waning thermal energy to power the geodynamo from core-mantle heat flux, followed by a sharp intensity increase as new thermal and compositional sources of buoyancy become available once inner core nucleation (ICN) commences. Ultralow fields have been reported from Ediacaran (~565 Ma) rocks, but the transition to stronger strengths has been unclear. Herein, we present single crystal paleointensity results from early Cambrian (~532 Ma) anorthosites of Oklahoma. These yield a time-averaged dipole moment 5 times greater than that of the Ediacaran Period. This rapid renewal of the field, together with data defining ultralow strengths, constrains ICN to ~550 Ma. Thermal modeling using this onset age suggests the inner core had grown to 50% of its current radius, where seismic anisotropy changes, by ~450 Ma. We propose the seismic anisotropy of the outermost inner core reflects development of a global spherical harmonic degree-2 deep mantle structure at this time that has persisted to the present day. The imprint of an older degree-1 pattern is preserved in the innermost inner core.
Stomatin modulates adipogenesis through the ERK pathway and regulates fatty acid uptake and lipid droplet growth
Authors: Wu Shao-Chin , Lo Yuan-Ming , Lee Jui-Hao , Chen Chin-Yau , Chen Tung-Wei , Liu Hong-Wen , Lian Wei-Nan , Hua Kate , Liao Chen-Chung , Lin Wei-Ju , Yang Chih-Yung , Tung Chien-Yi , Lin Chi-Hung 
Published: July 2022

AbstractRegulation of fatty acid uptake, lipid production and storage, and metabolism of lipid droplets (LDs), is closely related to lipid homeostasis, adipocyte hypertrophy and obesity. We report here that stomatin, a major constituent of lipid raft, participates in adipogenesis and adipocyte maturation by modulating related signaling pathways. In adipocyte-like cells, increased stomatin promotes LD growth or enlargements by facilitating LD-LD fusion. It also promotes fatty acid uptake from extracellular environment by recruiting effector molecules, such as FAT/CD36 translocase, to lipid rafts to promote internalization of fatty acids. Stomatin transgenic mice fed with high-fat diet exhibit obesity, insulin resistance and hepatic impairments; however, such phenotypes are not seen in transgenic animals fed with regular diet. Inhibitions of stomatin by gene knockdown or OB-1 inhibit adipogenic differentiation and LD growth through downregulation of PPARγ pathway. Effects of stomatin on PPARγ involves ERK signaling; however, an alternate pathway may also exist.
Reactivity-dependent profiling of RNA 5-methylcytidine dioxygenases
Authors: Arguello A. Emilia , Li Ang , Sun Xuemeng , Eggert Tanner W. , Mairhofer Elisabeth , Kleiner Ralph E. 
Published: July 2022

AbstractEpitranscriptomic RNA modifications can regulate fundamental biological processes, but we lack approaches to map modification sites and probe writer enzymes. Here we present a chemoproteomic strategy to characterize RNA 5-methylcytidine (m5C) dioxygenase enzymes in their native context based upon metabolic labeling and activity-based crosslinking with 5-ethynylcytidine (5-EC). We profile m5C dioxygenases in human cells including ALKBH1 and TET2 and show that ALKBH1 is the major hm5C- and f5C-forming enzyme in RNA. Further, we map ALKBH1 modification sites transcriptome-wide using 5-EC-iCLIP and ARP-based sequencing to identify ALKBH1-dependent m5C oxidation in a variety of tRNAs and mRNAs and analyze ALKBH1 substrate specificity in vitro. We also apply targeted pyridine borane-mediated sequencing to measure f5C sites on select tRNA. Finally, we show that f5C at the wobble position of tRNA-Leu-CAA plays a role in decoding Leu codons under stress. Our work provides powerful chemical approaches for studying RNA m5C dioxygenases and mapping oxidative m5C modifications and reveals the existence of novel epitranscriptomic pathways for regulating RNA function.
High-throughput fabrication of soft magneto-origami machines
Authors: Yi Shengzhu , Wang Liu , Chen Zhipeng , Wang Jian , Song Xingyi , Liu Pengfei , Zhang Yuanxi , Luo Qingqing , Peng Lelun , Wu Zhigang , Guo Chuan Fei , Jiang Lelun 
Published: July 2022

AbstractSoft magneto-active machines capable of magnetically controllable shape-morphing and locomotion have diverse promising applications such as untethered biomedical robots. However, existing soft magneto-active machines often have simple structures with limited functionalities and do not grant high-throughput production due to the convoluted fabrication technology. Here, we propose a facile fabrication strategy that transforms 2D magnetic sheets into 3D soft magneto-active machines with customized geometries by incorporating origami folding. Based on automated roll-to-roll processing, this approach allows for the high-throughput fabrication of soft magneto-origami machines with a variety of characteristics, including large-magnitude deploying, sequential folding into predesigned shapes, and multivariant actuation modes (e.g., contraction, bending, rotation, and rolling locomotion). We leverage these abilities to demonstrate a few potential applications: an electronic robot capable of on-demand deploying and wireless charging, a mechanical 8-3 encoder, a quadruped robot for cargo-release tasks, and a magneto-origami arts/craft. Our work contributes for the high-throughput fabrication of soft magneto-active machines with multi-functionalities.
An achromatic metafiber for focusing and imaging across the entire telecommunication range
Authors: Ren Haoran , Jang Jaehyuck , Li Chenhao , Aigner Andreas , Plidschun Malte , Kim Jisoo , Rho Junsuk , Schmidt Markus A. , Maier Stefan A. 
Published: July 2022

AbstractDispersion engineering is essential to the performance of most modern optical systems including fiber-optic devices. Even though the chromatic dispersion of a meter-scale single-mode fiber used for endoscopic applications is negligible, optical lenses located on the fiber end face for optical focusing and imaging suffer from strong chromatic aberration. Here we present the design and nanoprinting of a 3D achromatic diffractive metalens on the end face of a single-mode fiber, capable of performing achromatic and polarization-insensitive focusing across the entire near-infrared telecommunication wavelength band ranging from 1.25 to 1.65 µm. This represents the whole single-mode domain of commercially used fibers. The unlocked height degree of freedom in a 3D nanopillar meta-atom largely increases the upper bound of the time-bandwidth product of an achromatic metalens up to 21.34, leading to a wide group delay modulation range spanning from −8 to 14 fs. Furthermore, we demonstrate the use of our compact and flexible achromatic metafiber for fiber-optic confocal imaging, capable of creating in-focus sharp images under broadband light illumination. These results may unleash the full potential of fiber meta-optics for widespread applications including hyperspectral endoscopic imaging, femtosecond laser-assisted treatment, deep tissue imaging, wavelength-multiplexing fiber-optic communications, fiber sensing, and fiber lasers.
Palladium catalyzed radical relay for the oxidative cross-coupling of quinolines
Authors: Zhao Xiaorui , Zhu Xiaojuan , Wang Kang , Lv Junqian , Chen Shangjun , Yao Guohua , Lang Junyu , Lv Fei , Pu Yinghui , Yang Ruoou , Zhang Bingsen , Jiang Zheng , Wan Ying 
Published: July 2022

AbstractTraditional approaches for transition-metal catalyzed oxidative cross-coupling reactions rely on sp2-hybridized starting materials, such as aryl halides, and more specifically, homogeneous catalysts. We report a heterogeneous Pd-catalyzed radical relay method for the conversion of a heteroarene C(sp3)–H bond into ethers. Pd nanoparticles are supported on an ordered mesoporous composite which, when compared with microporous activated carbons, greatly increases the Pd d charge because of their strong interaction with N-doped anatase nanocrystals. Mechanistic studies provide evidence that electron-deficient Pd with Pd–O/N coordinations efficiently catalyzes the radical relay reaction to release diffusible methoxyl radicals, and highlight the difference between this surface reaction and C–H oxidation mediated by homogeneous catalysts that operate with cyclopalladated intermediates. The reactions proceed efficiently with a turn-over frequency of 84 h−1 and high selectivity toward ethers of >99%. Negligible Pd leaching and activity loss are observed after 7 catalytic runs.
Tibial sagittal and rotational alignment reduce patellofemoral stresses in posterior stabilized total knee arthroplasty
Authors: Mizu-uchi Hideki , Ma Yuan , Ishibashi Shojiro , Colwell Clifford W. , Nakashima Yasuharu , D’Lima Darryl D. 
Published: July 2022

AbstractPatellofemoral joint complications remain an important issue in total knee arthroplasty. We compared the patellofemoral contact status between cruciate-retaining and posterior-stabilized designs with varying degrees of tibial sagittal and rotational alignment using a computer simulation to ensure proper alignments in total knee arthroplasty. Knee kinematics, patellofemoral contact force and quadriceps force were computed using a musculoskeletal modeling program (LifeMOD/KneeSIM 2010; LifeModeler, Inc., San Clemente, California) during a weight-bearing deep knee bend. Two different posterior tibial slope (PTS)s (3° and 7°) and five different tibial tray rotational alignments (neutral, internal 5° and 10°, and external 5° and 10°) were simulated. Patellofemoral contact area and stresses were next computed using finite element analysis. The patellofemoral contact force for the posterior-stabilized design was substantially lower than the cruciate-retaining design after post-cam contact because of increasing femoral roll-back. Neutral rotational alignment of the tibial component resulted in smaller differences in patellofemoral contact stresses between cruciate-retaining and posterior-stabilized designs for PTSs of 3° or 7°. However, the patellar contact stresses in the cruciate-retaining design were greater than those in posterior-stabilized design at 120° of knee flexion with PTS of 3° combined with internal rotation of the tibial component. Our study provides biomechanical evidence implicating lower PTSs combined with internal malrotation of the tibial component and the resultant increase in patellofemoral stresses as a potential source of anterior knee pain in cruciate-retaining design.
Fluorescence and UV–visible reflectance in the fur of several Rodentia genera
Authors: Sobral Gisela , Souza-Gudinho Filipe 
Published: July 2022

AbstractMammals are generally brown in colour, but recent publications are showing that they may not be as uniform as once assumed. Monotremes, marsupials, and a handful of eutherians reflect various colours when lit with UV light, mostly purple. Because of these still scarce records, we aimed to explore UV reflectance among rodent genera, the most diverse mammalian group, and the group of eutherians with the most common records of biofluorescence. Here we report structures like nails and quills reflected green, but for most genera, it was faded. However, Hystrix, Erethizon, and Ctenomys showed intense and contrasting green glow, while Chaetomys presented a vivid orange anogenital. The main available explanation of fluorescence in mammals relies on porphyrin. This explanation applies to the cases like Chaetomys, where specimens showed anogenital orange biofluorescence, but does not apply to the green biofluorescence we observed. In our sample, because the structures that reflected green were all keratinized, we have reasons to believe that biofluorescence results from keratinization and is a structurally-based colouration. However, not all spines/quills equally biofluoresced, so we cannot rule out other explanations. Since Rodentia is the most common mammalian group with reports on biofluorescence, this trait likely serves various functions that match the species diversity of this group.
Serum RNA biomarkers for predicting survival in non-human primates following thoracic radiation
Authors: May Jared M. , Shankavaram Uma , Bylicky Michelle A. , Chopra Sunita , Scott Kevin , Martello Shannon , Thrall Karla , Axtelle Jim , Menon Naresh , Coleman C. Norman , Aryankalayil Molykutty J. 
Published: July 2022

AbstractIn a mass radiation exposure, the healthcare system may rely on differential expression of miRNA to determine exposure and effectively allocate resources. To this end, miRNome analysis was performed on non-human primate serum after whole thorax photon beam irradiation of 9.8 or 10.7 Gy with dose rate 600 cGy/min. Serum was collected up to 270 days after irradiation and sequenced to determine immediate and delayed effects on miRNA expression. Elastic net based GLM methods were used to develop models that predicted the dose vs. controls at 81% accuracy at Day 15. A three-group model at Day 9 achieved 71% accuracy in determining if an animal would die in less than 90 days, between 90 and 269 days, or survive the length of the study. At Day 21, we achieved 100% accuracy in determining whether an animal would later develop pleural effusion. These results demonstrate the potential ability of miRNAs to determine thorax partial-body irradiation dose and forecast survival or complications early following whole thorax irradiation in large animal models. Future experiments incorporating additional doses and independent animal cohorts are warranted to validate these results. Development of a serum miRNA assay will facilitate the administration of medical countermeasures to increase survival and limit normal tissue damage following a mass exposure.
Fecal amine metabolite analysis before onset of severe necrotizing enterocolitis in preterm infants: a prospective case–control study
Authors: Deianova N. , el Manouni el Hassani S. , Struijs E. A. , Jansen E. E. W. , Bakkali A. , van de Wiel M. A. , de Boode W. P. , Hulzebos C. V. , van Kaam A. H. , Kramer B. W. , d’Haens E. , Vijlbrief D. C. , van Weissenbruch M. M. , de Jonge W. J. , Benninga M. A. , Niemarkt H. J. , de Boer N. K. H. , de Meij T. G. J. 
Published: July 2022

AbstractInfants developing necrotizing enterocolitis (NEC) have a different metabolomic profile compared to controls. The potential of specific metabolomics, i.e. amino acids and amino alcohols (AAA), as early diagnostic biomarkers for NEC is largely unexplored. In this multicenter prospective case–control study, longitudinally collected fecal samples from preterm infants (born <30 weeks of gestation) from 1–3 days before diagnosis of severe NEC (Bell’s stage IIIA/IIIB), were analyzed by targeted high-performance liquid chromatography (HPLC). Control samples were collected from gestational and postnatal age-matched infants. Thirty-one NEC cases (15 NEC IIIA;16 NEC IIIB) with 1:1 matched controls were included. Preclinical samples of infants with NEC were characterized by five increased essential amino acids—isoleucine, leucine, methionine, phenylalanine and valine. Lysine and ethanolamine ratios were lower prior to NEC, compared to control samples. A multivariate model was rendered based on isoleucine, lysine, ethanolamine, tryptophan and ornithine, modestly discriminating cases from controls (AUC 0.67; p < 0.001). Targeted HPLC pointed to several specific AAA alterations in samples collected 1–3 days before NEC onset, compared to controls. Whether this reflects metabolic alterations and has a role in early biomarker development for NEC, has yet to be elucidated.
Comparing N-mixture models and GLMMs for relative abundance estimation in a citizen science dataset
Authors: Goldstein Benjamin R. , de Valpine Perry 
Published: July 2022

AbstractTo analyze species count data when detection is imperfect, ecologists need models to estimate relative abundance in the presence of unknown sources of heterogeneity. Two candidate models are generalized linear mixed models (GLMMs) and hierarchical N-mixture models. GLMMs are computationally robust but do not explicitly separate detection from abundance patterns. N-mixture models separately estimate detection and abundance via a latent state but are sensitive to violations in assumptions and subject to practical estimation issues. When one can assume that detection is not systematically confounded with ecological patterns of interest, these two models can be viewed as sharing a heuristic framework for relative abundance estimation. Model selection can then determine which predicts observed counts best, for example by AIC. We compared four N-mixture model variants and two GLMM variants for predicting bird counts in local subsets of a citizen science dataset, eBird, based on model selection and goodness-of-fit measures. We found that both GLMMs and N-mixture models—especially N-mixtures with beta-binomial detection submodels—were supported in a moderate number of datasets, suggesting that both tools are useful and that relative fit is context-dependent. We provide faster software implementations of N-mixture likelihood calculations and a reparameterization to interpret unstable estimates for N-mixture models.
Full etiologic spectrum of pediatric severe to profound hearing loss of consecutive 119 cases
Authors: Kim Young Seok , Kim Yoonjoong , Jeon Hyoung Won , Yi Nayoung , Lee Sang-Yeon , Kim Yehree , Han Jin Hee , Kim Min Young , Kim Bo Hye , Choi Hyeong Yun , Carandang Marge , Koo Ja-Won , Kim Bong Jik , Bae Yun Jung , Choi Byung Yoon 
Published: July 2022

AbstractDetermining the etiology of severe-to-profound sensorineural hearing loss (SP-SNHL) in pediatric subjects is particularly important in aiding the decision for auditory rehabilitation. We aimed to update the etiologic spectrum of pediatric SP-SNHL by combining internal auditory canal (IAC)-MRI with comprehensive and state-of-the-art genetic testings. From May 2013 to September 2020, 119 cochlear implantees under the age of 15 years with SP-SNHL were all prospectively recruited. They were subjected to genetic tests, including exome sequencing, and IAC-MRI for etiologic diagnosis. Strict interpretation of results were made based on ACMG/AMP guidelines and by an experienced neuroradiologist. The etiology was determined in of 65.5% (78/119) of our cohort. If only one of the two tests was done, the etiologic diagnostic rate would be reduced by at least 21.8%. Notably, cochlear nerve deficiency (n = 20) detected by IAC-MRI topped the etiology list of our cohort, followed by DFNB4 (n = 18), DFNB1 (n = 10), DFNB9 (n = 10) and periventricular leukomalacia associated with congenital CMV infection (n = 8). Simultaneous application of state-of-the-art genetic tests and IAC-MRI is essential for etiologic diagnosis, and if lesions of the auditory nerve or central nerve system are carefully examined on an MRI, we can identify the cause of deafness in more than 65% of pediatric SP-SNHL cases.