bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep state organisation of moderate to late preterm infants in the neonatal unit
Authors: Ryan Mary Anne J. , Mathieson Sean R. , Livingstone Vicki , O’Sullivan Marc Paul , Dempsey Eugene M. , Boylan Geraldine B. 
Published: December 2022

Abstract
Background
Sleep supports neurodevelopment and sleep architecture reflects brain maturation. This prospective observational study describes the nocturnal sleep architecture of healthy moderate to late preterm (MLP) infants in the neonatal unit at 36 weeks post menstrual age (PMA).

Methods
MLP infants, in the neonatal unit of a tertiary hospital in Ireland from 2017 to 2018, had overnight continuous electroencephalography (cEEG) with video for a minimum 12 h at 36 weeks PMA. The total sleep time (TST) including periods of active sleep (AS), quiet sleep (QS), indeterminate sleep (IS), wakefulness and feeding were identified, annotated and quantified.

Results
A total of 98 infants had cEEG with video monitoring suitable for analysis. The median (IQR) of TST in the 12 h period was 7.09 h (IQR 6.61–7.76 h), 4.58 h (3.69–5.09 h) in AS, 2.02 h (1.76–2.36 h) in QS and 0.65 h (0.48–0.89 h) in IS. The total duration of AS was significantly lower in infants born at lower GA (p = 0.007) whilst the duration of individual QS periods was significantly higher (p = 0.001).

Conclusion
Overnight cEEG with video at 36 weeks PMA showed that sleep state architecture is dependent on birth GA. Infants with a lower birth GA have less AS and more QS that may have implications for later neurodevelopment.

Impact

EEG provides objective information about the sleep organisation of the moderate to late preterm (MLP) infant.

Quantitative changes in sleep states occur with each week of advancing gestational age (GA).

Active sleep (AS) is the dominant sleep state that was significantly lower in infants born at lower GA.

MLP infants who were exclusively fed orally had a shorter total sleep time and less AS compared to infants who were fed via nasogastric tube.
Sex-specific roles of hippocampal microRNAs in stress vulnerability and resilience
Authors: Krispil-Alon Maayan , Jovasevic Vladimir , Radulovic Jelena , Richter-Levin Gal 
Published: December 2022

AbstractContrary to intuition, most individuals are resilient to psychological trauma and only a minority is vulnerable. Men and women are known to respond differently to trauma exposure, however, mechanisms underlying the relationship between sex differences and trauma resilience and vulnerability are not yet fully understood. Taking advantage of the Behavioral Profiling approach, which enables differentiating between ‘affected’ and ‘unaffected’ individuals, we examined sex-associated differences in stress exposure effects on hippocampal expression of selected stress-related GABA-A receptor targeting miRNAs. Levels of the miRNA-144 and miRNA-33 were measured in male and female affected (vulnerable, e.g., higher freezing time) and unaffected (resilient) rats. In male rats, increased levels of miRNA-144 and miRNA-33 were observed in the dorsal dentate gyrus (dDG) and ventral dentate gyrus (vDG) respectively, of stress-exposed but unaffected animals. In females, we observed an increased expression of miRNA-144 and miRNA-33 in the ventral cornu ammonis 1 (vCA1) of affected animals. Accordingly, we inhibited miRNAs expression selectively in hippocampal subregions using oligonucleotides containing locked nucleic acid bases, to examine the miRNAs’ causal contribution to either vulnerability or resilience to stress in each sex. Inhibition of miRNA-144 in dDG and miRNA-33 in vDG in males resulted in an increased prevalence of vulnerable animals, while inhibition of miRNA-144 and miRNA-33 in vCA1 in females increased the proportion of resilient animals. The current findings reveal a critical sex-associated difference in the role of miRNAs in stress vulnerability and resilience. This novel understanding of sex-associated epigenetic involvement in the mechanism of stress-related psychopathologies may help improve gender-specific diagnosis and effective treatment.
CaMKIV mediates spine growth deficiency of hippocampal neurons by regulation of EGR3/BDNF signal axis in congenital hypothyroidism
Authors: Wu Hui , Suo Guihai , Li Tianci , Zheng Yuqin , Li Haiying , Shen Feifei , Wang Yongjun , Ni Haidong , Wu Youjia 
Published: December 2022

AbstractCongenital hypothyroidism (CH) will cause cognitive impairment in the condition of delayed treatment. The hippocampus is one of the most affected tissues by CH, in which the functional structures of hippocampal neurons manifest deficiency due to aberrant expression of effector molecules. The Ca2+/Calmodulin-dependent protein kinase, CaMKIV, is downregulated in the hippocampal neurons, influencing the growth of dendritic spines in response to CH. However, the underlying mechanism is not fully elucidated. In the present study, the early growth response factor 3 (EGR3) was regulated by CaMKIV in the hippocampal neurons of CH rat pups, as was analyzed by transcriptome sequencing and in vitro cell experiments. EGR3 localized within hippocampal neurons in CA1, CA3, and dentate gyrus regions. Deficient EGR3 in the primary hippocampal neurons significantly reduced the density of dendritic spines by downregulating the expression of BDNF, and such effects could be rescued by supplementing recombinant BDNF protein. Taken together, CH mediates cognitive impairment of pups through the inactivation of CaMKIV in the hippocampal neurons, which decreases the expression of EGR3 and further reduces the production of BDNF, thereby impairing the growth of dendritic spines. Identifying CaMKIV/EGR3/BDNF pathway in the hippocampal neurons in the context of CH will benefit the drug development of intellectual disability caused by CH.
DAP5 enables main ORF translation on mRNAs with structured and uORF-containing 5′ leaders
Authors: Weber Ramona , Kleemann Leon , Hirschberg Insa , Chung Min-Yi , Valkov Eugene , Igreja Cátia 
Published: December 2022

AbstractHalf of mammalian transcripts contain short upstream open reading frames (uORFs) that potentially regulate translation of the downstream coding sequence (CDS). The molecular mechanisms governing these events remain poorly understood. Here, we find that the non-canonical initiation factor Death-associated protein 5 (DAP5 or eIF4G2) is required for translation initiation on select transcripts. Using ribosome profiling and luciferase-based reporters coupled with mutational analysis we show that DAP5-mediated translation occurs on messenger RNAs (mRNAs) with long, structure-prone 5′ leader sequences and persistent uORF translation. These mRNAs preferentially code for signalling factors such as kinases and phosphatases. We also report that cap/eIF4F- and eIF4A-dependent recruitment of DAP5 to the mRNA facilitates main CDS, but not uORF, translation suggesting a role for DAP5 in translation re-initiation. Our study reveals important mechanistic insights into how a non-canonical translation initiation factor involved in stem cell fate shapes the synthesis of specific signalling factors.
LY6D marks pre-existing resistant basosquamous tumor subpopulations
Authors: Haensel Daniel , Gaddam Sadhana , Li Nancy Y. , Gonzalez Fernanda , Patel Tiffany , Cloutier Jeffrey M. , Sarin Kavita Y. , Tang Jean Y. , Rieger Kerri E. , Aasi Sumaira Z. , Oro Anthony E. 
Published: December 2022

AbstractImproved response to canonical therapies requires a mechanistic understanding of dynamic tumor heterogeneity by identifying discrete cellular populations with enhanced cellular plasticity. We have previously demonstrated distinct resistance mechanisms in skin basal cell carcinomas, but a comprehensive understanding of the cellular states and markers associated with these populations remains poorly understood. Here we identify a pre-existing resistant cellular population in naive basal cell carcinoma tumors marked by the surface marker LY6D. LY6D+ tumor cells are spatially localized and possess basal cell carcinoma and squamous cell carcinoma-like features. Using computational tools, organoids, and spatial tools, we show that LY6D+ basosquamous cells represent a persister population lying on a central node along the skin lineage-associated spectrum of epithelial states with local environmental and applied therapies determining the kinetics of accumulation. Surprisingly, LY6D+ basosquamous populations exist in many epithelial tumors, such as pancreatic adenocarcinomas, which have poor outcomes. Overall, our results identify the resistant LY6D+ basosquamous population as an important clinical target and suggest strategies for future therapeutic approaches to target them.
Phonon behavior in a random solid solution: a lattice dynamics study on the high-entropy alloy FeCoCrMnNi
Authors: Turner Shelby R. , Pailhès Stéphane , Bourdarot Frédéric , Ollivier Jacques , Sidis Yvan , Castellan John-Paul , Zanotti Jean-Marc , Berrod Quentin , Porcher Florence , Bosak Alexei , Feuerbacher Michael , Schober Helmut , de Boissieu Marc , Giordano Valentina M. 
Published: December 2022

AbstractHigh-Entropy Alloys (HEAs) are a new family of crystalline random alloys with four or more elements in a simple unit cell, at the forefront of materials research for their exceptional mechanical properties. Their strong chemical disorder leads to mass and force-constant fluctuations which are expected to strongly reduce phonon lifetime, responsible for thermal transport, similarly to glasses. Still, the long range order would associate HEAs to crystals with a complex disordered unit cell. These two families of materials, however, exhibit very different phonon dynamics, still leading to similar thermal properties. The question arises on the positioning of HEAs in this context. Here we present an exhaustive experimental investigation of the lattice dynamics in a HEA, Fe20Co20Cr20Mn20Ni20, using inelastic neutron and X-ray scattering. We demonstrate that HEAs present unique phonon dynamics at the frontier between fully disordered and ordered materials, characterized by long-propagating acoustic phonons in the whole Brillouin zone.
GPR174 knockdown enhances blood flow recovery in hindlimb ischemia mice model by upregulating AREG expression
Authors: Liu Jin , Pan Lihong , Hong Wenxuan , Chen Siqin , Bai Peiyuan , Luo Wei , Sun Xiaolei , He Furong , Jia Xinlin , Cai Jialiang , Chen Yingjie , Hu Kai , Song Zhenju , Ge Junbo , Sun Aijun 
Published: December 2022

AbstractRegulatory T cells (Tregs) are critically involved in neovascularization, an important compensatory mechanism in peripheral artery disease. The contribution of G protein coupled receptor 174 (GPR174), which is a regulator of Treg function and development, in neovascularization remains elusive. Here, we show that genetic deletion of GPR174 in Tregs potentiated blood flow recovery in mice after hindlimb ischemia. GPR174 deficiency upregulates amphiregulin (AREG) expression in Tregs, thereby enhancing endothelial cell functions and reducing pro-inflammatory macrophage polarization and endothelial cell apoptosis. Mechanically, GPR174 regulates AREG expression by inhibiting the nuclear accumulation of early growth response protein 1 (EGR1) via Gαs/cAMP/PKA signal pathway activation. Collectively, these findings demonstrate that GPR174 negatively regulates angiogenesis and vascular remodeling in response to ischemic injury and that GPR174 may be a potential molecular target for therapeutic interventions of ischemic vascular diseases.
SESAME-catalyzed H3T11 phosphorylation inhibits Dot1-catalyzed H3K79me3 to regulate autophagy and telomere silencing
Authors: He Fei , Yu Qi , Wang Min , Wang Rongsha , Gong Xuanyunjing , Ge Feng , Yu Xilan , Li Shanshan 
Published: December 2022

AbstractThe glycolytic enzyme, pyruvate kinase Pyk1 maintains telomere heterochromatin by phosphorylating histone H3T11 (H3pT11), which promotes SIR (silent information regulator) complex binding at telomeres and prevents autophagy-mediated Sir2 degradation. However, the exact mechanism of action for H3pT11 is poorly understood. Here, we report that H3pT11 directly inhibits Dot1-catalyzed H3K79 tri-methylation (H3K79me3) and uncover how this histone crosstalk regulates autophagy and telomere silencing. Mechanistically, Pyk1-catalyzed H3pT11 directly reduces the binding of Dot1 to chromatin and inhibits Dot1-catalyzed H3K79me3, which leads to transcriptional repression of autophagy genes and reduced autophagy. Despite the antagonism between H3pT11 and H3K79me3, they work together to promote the binding of SIR complex at telomeres to maintain telomere silencing. Furthermore, we identify Reb1 as a telomere-associated factor that recruits Pyk1-containing SESAME (Serine-responsive SAM-containing Metabolic Enzyme) complex to telomere regions to phosphorylate H3T11 and prevent the invasion of H3K79me3 from euchromatin into heterochromatin to maintain telomere silencing. Together, these results uncover a histone crosstalk and provide insights into dynamic regulation of silent heterochromatin and autophagy in response to cell metabolism.
An embedded interfacial network stabilizes inorganic CsPbI3 perovskite thin films
Authors: Steele Julian A. , Braeckevelt Tom , Prakasam Vittal , Degutis Giedrius , Yuan Haifeng , Jin Handong , Solano Eduardo , Puech Pascal , Basak Shreya , Pintor-Monroy Maria Isabel , Van Gorp Hans , Fleury Guillaume , Yang Ruo Xi , Lin Zhenni , Huang Haowei , Debroye Elke , Chernyshov Dmitry , Chen Bin , Wei Mingyang , Hou Yi , Gehlhaar Robert , Genoe Jan , De Feyter Steven , Rogge Sven M. J. , Walsh Aron , Sargent Edward H. , Yang Peidong , Hofkens Johan , Van Speybroeck Veronique , Roeffaers Maarten B. J. 
Published: December 2022

AbstractThe black perovskite phase of CsPbI3 is promising for optoelectronic applications; however, it is unstable under ambient conditions, transforming within minutes into an optically inactive yellow phase, a fact that has so far prevented its widespread adoption. Here we use coarse photolithography to embed a PbI2-based interfacial microstructure into otherwise-unstable CsPbI3 perovskite thin films and devices. Films fitted with a tessellating microgrid are rendered resistant to moisture-triggered decay and exhibit enhanced long-term stability of the black phase (beyond 2.5 years in a dry environment), due to increasing the phase transition energy barrier and limiting the spread of potential yellow phase formation to structurally isolated domains of the grid. This stabilizing effect is readily achieved at the device level, where unencapsulated CsPbI3 perovskite photodetectors display ambient-stable operation. These findings provide insights into the nature of phase destabilization in emerging CsPbI3 perovskite devices and demonstrate an effective stabilization procedure which is entirely orthogonal to existing approaches.
Extracellular traps from activated vascular smooth muscle cells drive the progression of atherosclerosis
Authors: Zhai Ming , Gong Shiyu , Luan Peipei , Shi Yefei , Kou Wenxin , Zeng Yanxi , Shi Jiayun , Yu Guanye , Hou Jiayun , Yu Qing , Jian Weixia , Zhuang Jianhui , Feinberg Mark W. , Peng Wenhui 
Published: December 2022

AbstractExtracellular DNA traps (ETs) represent an immune response by which cells release essential materials like chromatin and granular proteins. Previous studies have demonstrated that the transdifferentiation of vascular smooth muscle cells (VSMCs) plays a crucial role in atherosclerosis. This study seeks to investigate the interaction between CD68+ VSMCs and the formation of ETs and highlight its function in atherosclerosis. Here we show that ETs are inhibited, and atherosclerotic plaque formation is alleviated in male Myh11CrePad4flox/flox mice undergoing an adeno-associated-virus-8 (AAV8) mediating overexpression of proprotein convertase subtilisin/kexin type 9 mutation (PCSK9) injection and being challenged with a high-fat diet. Obvious ETs generated from CD68+ VSMCs are inhibited by Cl-amidine and DNase I in vitro. By utilizing VSMCs-lineage tracing technology and single-cell RNA sequencing (scRNA-seq), we demonstrate that the ETs from CD68+ VSMCs influence the progress of atherosclerosis by regulating the direction of VSMCs’ transdifferentiation through STING-SOCS1 or TLR4 signaling pathway.
Validation and real-world clinical application of an artificial intelligence algorithm for breast cancer detection in biopsies
Authors: Sandbank Judith , Bataillon Guillaume , Nudelman Alona , Krasnitsky Ira , Mikulinsky Rachel , Bien Lilach , Thibault Lucie , Albrecht Shach Anat , Sebag Geraldine , Clark Douglas P. , Laifenfeld Daphna , Schnitt Stuart J. , Linhart Chaim , Vecsler Manuela , Vincent-Salomon Anne 
Published: December 2022

AbstractBreast cancer is the most common malignant disease worldwide, with over 2.26 million new cases in 2020. Its diagnosis is determined by a histological review of breast biopsy specimens, which can be labor-intensive, subjective, and error-prone. Artificial Intelligence (AI)—based tools can support cancer detection and classification in breast biopsies ensuring rapid, accurate, and objective diagnosis. We present here the development, external clinical validation, and deployment in routine use of an AI-based quality control solution for breast biopsy review. The underlying AI algorithm is trained to identify 51 different types of clinical and morphological features, and it achieves very high accuracy in a large, multi-site validation study. Specifically, the area under the receiver operating characteristic curves (AUC) for the detection of invasive carcinoma and of ductal carcinoma in situ (DCIS) are 0.99 (specificity and sensitivity of 93.57 and 95.51%, respectively) and 0.98 (specificity and sensitivity of 93.79 and 93.20% respectively), respectively. The AI algorithm differentiates well between subtypes of invasive and different grades of in situ carcinomas with an AUC of 0.97 for invasive ductal carcinoma (IDC) vs. invasive lobular carcinoma (ILC) and AUC of 0.92 for DCIS high grade vs. low grade/atypical ductal hyperplasia, respectively, as well as accurately identifies stromal tumor-infiltrating lymphocytes (TILs) with an AUC of 0.965. Deployment of this AI solution as a real-time quality control solution in clinical routine leads to the identification of cancers initially missed by the reviewing pathologist, demonstrating both clinical utility and accuracy in real-world clinical application.
Three-dimensional shape measurement for the steep surface using DMD camera
Authors: Zhao Shoubo , Yang Yuqiang 
Published: December 2022

AbstractThree-Dimensional shape measurement has been confronted with the ambiguity on the steep surface. To address the problem, compressed sensing theory is employed to reconstruct phase shifting images in DMD camera. Specially, every CCD pixel in the region of interest is aligned to N × N DMD mirrors to construct DMD camera. The one-dimensional measurement matrices are chosen to collect the measured values on CCD pixel according to the directional judgement of original gradient image. Due to the enhancement of the spatial sampling frequency and the noise robustness, the reconstructed sinusoidal stripe images are utilized to obtain the three-dimensional model of the steep surface accurately. We measure the planes with various slopes to discuss the measurement capability. The comparative experiments show that our proposed method can correct the deformed phase and repair the defect on the steep surface.
Particle exposure risk to a lavatory user after flushing a squat toilet
Authors: Zhang Tengfei , Yao Lifang , Gao Zilong , Wang Feng 
Published: December 2022

AbstractSquat toilets are widely used in developing countries due to local customs and low costs. The flushing of a squat toilet can entrain strong airflow and produce aerosols. This investigation constructed a lavatory mock-up with a squat toilet. The flushing-induced airflow was both visualized and quantitatively measured by particle image velocimetry. The maximum height of the impacted airflow was identified by an ultrasonic anemometer. For inference of the particle emission rate, the toilet bowl was covered by an enclosed box for particle concentration measurement. The risks from skin contact of the deposited particles on the flushing button and the door handle and the possible inhalation of the released aerosols were evaluated. The results revealed that flushing a squat toilet can drive toilet plume to rise up to 0.9 m above the toilet bowl. A single flushing process can produce 0.29 million particles with diameters greater than 0.3 μm, among which 90% of the particles are submicron-sized. The flushing may cause particles to deposit on the flushing button and lavatory door handle as well as inhalation exposure even remaining in the lavatory for half a minute after flushing, especially for those lavatory users whose respiratory zones are below 1.0 m.
The potential effect of BMSCs with miR‐27a in improving steroid-induced osteonecrosis of the femoral head
Authors: Cui Yong , Huang Tao , Zhang Zheng , Yang Zengqiang , Hao Feihu , Yuan Tianyi , Zhou Zhiheng 
Published: December 2022

AbstractSteroid induced osteonecrosis of the femoral head (ONFH) frequently leads to femoral head collapse and subsequent hip arthritis. This study aimed to investigate the potential therapeutic mechanism of miR‐27a on steroid-induced ONFH. Levels of IL-6, TNF-α, miR-27a, Runx2, PPAR-γ and ApoA5 were first examined in bone marrow tissues from steroid-induced ONFH and controls. Subsequently, we overexpressed or knocked down miR-27a in bone marrow mesenchymal stem cells (BMSCs) and detected cell proliferation, osteogenic differentiation, adipogenic differentiation. In addition, miR-27a mimics and BMSCs were injected into the established steroid-induced ONFH rats, and the osteoprotective effects of both were evaluated. Dual luciferase reporter was used to test the targeting effect of miR-27a-3p and PPARG. miR-27a and Runx2 were lowly expressed in steroid-induced ONFH, PPAR-γ and ApoA5 were highly expressed. Overexpression of miR-27a in BMSCs promoted cell proliferation and osteogenic differentiation, inhibited adipogenic differentiation. Furthermore, increasing miR-27a and BMSCs obviously reduced bone loss in steroid induced ONFH rats. The expressions of Runx2 in BMSCs and steroid-induced ONFH rats was significantly up‐regulated, while IL-6, TNF-α, PPAR-γ and ApoA5 were down‐regulated with miR-27a overexpression. Additionally, PPARG was the target of miR-27a-3p. The results of the present study reveal a role for miR-27a in promoting osteogenesis and may have a synergistic effect with BMSCs.
MDMX elevation by a novel Mdmx–p53 interaction inhibitor mitigates neuronal damage after ischemic stroke
Authors: Yan Haomin , Sasaki Tsutomu , Kanki Hideaki , Hirata Yoshiyuki , Nishiyama Kumiko , Hisada Sunao , Matsumura Shigenobu , Nagaoka Yasuo , Sumiyoshi Takaaki , Nagano Seiichi , Nakata Akiko , Yoshida Minoru , Uesato Shinichi , Mochizuki Hideki 
Published: December 2022

AbstractMdmx and Mdm2 are two major suppressor factors for the tumor suppressor gene p53. In central nervous system, Mdmx suppresses the transcriptional activity of p53 and enhances the binding of Mdm2 to p53 for degradation. But Mdmx dynamics in cerebral infarction remained obscure. Here we investigated the role of Mdmx under ischemic conditions and evaluated the effects of our developed small-molecule Protein–Protein Interaction (PPI) inhibitors, K-181, on Mdmx–p53 interactions in vivo and in vitro. We found ischemic stroke decreased Mdmx expression with increased phosphorylation of Mdmx Serine 367, while Mdmx overexpression by AAV-Mdmx showed a neuroprotective effect on neurons. The PPI inhibitor, K-181 attenuated the neurological deficits by increasing Mdmx expression in post-stroke mice brain. Additionally, K-181 selectively inhibited HDAC6 activity and enhanced tubulin acetylation. Our findings clarified the dynamics of Mdmx in cerebral ischemia and provide a clue for the future pharmaceutic development of ischemic stroke.