bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current pain management practices for preterm infants with necrotizing enterocolitis: a European survey
Authors: ten Barge Judith A. , van den Bosch Gerbrich E. , Meesters Naomi J. , Allegaert Karel , Arribas Cristina , Cavallaro Giacomo , Garrido Felipe , Raffaeli Genny , Vermeulen Marijn J. , Simons Sinno H. P. ,   on behalf of the ESPR Special Interest Group for Neonatal Pain and the NEC Pain Study Group
Published: February 2023

Abstract
Background
Necrotizing enterocolitis (NEC) is a highly painful intestinal complication in preterm infants that requires adequate pain management to prevent short- and long-term effects of neonatal pain. There is a lack of international guidelines for pain management in NEC patients. Therefore, this study aims to describe current pain management for NEC patients in European neonatal intensive care units (NICUs).

Methods
An online survey was designed and conducted to assess current practices in pain management for NEC patients in European NICUs. The survey was distributed via neonatal societies, digital platforms, and professional contacts.

Results
Out of the 259 responding unique European NICUs from 36 countries, 61% had a standard protocol for analgesic therapy, 73% assessed pain during NEC, and 92% treated NEC patients with intravenous analgosedatives. There was strong heterogeneity in the used pain scales and initial analgesic therapy, which mainly included acetaminophen (70%), fentanyl (56%), and/or morphine (49%). A third of NICU representatives considered their pain assessment adequate, and half considered their analgesic therapy adequate for NEC patients.

Conclusions
Various pain scales and analgesics are used to treat NEC patients in European NICUs. Our results provide the first step towards an international guideline to improve pain management for NEC patients.

Impact

This study provides an overview of current pain management practices for infants with necrotizing enterocolitis (NEC) in European neonatal intensive care units.

Choice of pain assessment tools, analgosedatives, and dosages vary considerably among NICUs and countries.

A third of NICU representatives were satisfied with their current pain assessment practices and half of NICU representatives with their analgesic therapy practices in NEC patients in their NICU.

The results of this survey may provide a first step towards developing a European pain management consensus guideline for patients with NEC.
Single-cell RNA sequencing in orthopedic research
Authors: Wang Tao , Wang Ling , Zhang Liping , Long Yubin , Zhang Yingze , Hou Zhiyong 
Published: February 2023

AbstractAlthough previous RNA sequencing methods have been widely used in orthopedic research and have provided ideas for therapeutic strategies, the specific mechanisms of some orthopedic disorders, including osteoarthritis, lumbar disc herniation, rheumatoid arthritis, fractures, tendon injuries, spinal cord injury, heterotopic ossification, and osteosarcoma, require further elucidation. The emergence of the single-cell RNA sequencing (scRNA-seq) technique has introduced a new era of research on these topics, as this method provides information regarding cellular heterogeneity, new cell subtypes, functions of novel subclusters, potential molecular mechanisms, cell-fate transitions, and cell‒cell interactions that are involved in the development of orthopedic diseases. Here, we summarize the cell subpopulations, genes, and underlying mechanisms involved in the development of orthopedic diseases identified by scRNA-seq, improving our understanding of the pathology of these diseases and providing new insights into therapeutic approaches.
Minimally invasive selective caries removal: a clinical guide
Authors: Lim Zi En , Duncan Henry F. , Moorthy Advan , McReynolds David 
Published: February 2023

AbstractAn evolving understanding of the carious process, along with new research in adhesive restorative materials, has led to a more conservative, minimally invasive and biologically-based approach to managing dental carious lesions. The growing volume of literature has also demonstrated prognostic success in the selective caries excavation technique, subsequently preventing excessive tooth structure removal and injury to the dentine-pulp complex, which maintains pulp vitality and improves the long-term prognosis of the tooth. However, at present, there remains a limited volume of high-quality evidence to support selective caries removal, which subsequently could partly explain some resistance to its use in clinical practice. This clinical technique guide aims to demonstrate the management of carious lesions of moderate-to-deep depth in permanent teeth based on current minimally invasive dental literature.
Potential links between the microbiota and T cell immunity determine the tumor cell fate
Authors: Mohseni Amir Hossein , Taghinezhad-S Sedigheh , Casolaro Vincenzo , Lv Zhongwei , Li Dan 
Published: February 2023

AbstractThe central role of the microbiota as a pivotal factor regulating anti-tumor immune responses has recently been appreciated. Increasing evidence has put a spotlight on the connection of microbiota to T cells, by showing impaired effector and/or memory responses in germ-free (GF) mice or in the presence of dysbiotic communities, and association with tumor growth and overall survival (OS). These observations also have significant implications for anti-tumor therapy and vaccination, suggesting that the communication between T cells and the microbiota involves soluble mediators (microbiota-derived metabolites) that influence various functions of T cells. In addition, there is growing appreciation of the role of bacterial translocation into the peritumoral milieu from the intestinal tract, as well as of locally developed tumor microbial communities, spatially separated from the gut microbiota, in shaping the tumor microbiome. Collectively, these findings have added new support to the idea that tonic inputs mirroring the existence of tumor microbiome could regulate the function of tumor-infiltrating T cells and tissue-resident memory T (TRM) cells. In this review, we focus on recent advances and aspects of these active areas of investigation and provide a comprehensive overview of the unique mechanisms that play a pivotal role in the regulation of anti-tumor immunity by the microbiota, some of which could be of particular relevance for addressing problems caused by tumor heterogeneity. It is our hope that this review will provide a theoretical foundation for future investigations in this area.
MLKL signaling regulates macrophage polarization in acute pancreatitis through CXCL10
Authors: Peng Cheng , Tu Guangping , Wang Jiale , Wang Yilin , Wu Peng , Yu Li , Li Zhiqiang , Yu Xiao 
Published: February 2023

AbstractAcute pancreatitis (AP) is a disease characterized by local and systemic inflammation with an increasing incidence worldwide. Receptor-interacting serine/threonine protein kinase 3 (RIPK3), mixed-lineage kinase domain-like protein (MLKL), and innate immune cell macrophages have been reported to be involved in the pathogenesis of AP. However, the mechanisms by which RIPK3 and MLKL regulate pancreatic injury, as well as the interactions between injured pancreatic acinar cells and infiltrating macrophages in AP, remain poorly defined. In the present study, experimental pancreatitis was induced in C57BL/6J, Ripk3-/- and Mlkl-/- mice by cerulein plus lipopolysaccharide in vivo, and primary pancreatic acinar cells were also isolated to uncover cellular mechanisms during cerulein stimulation in vitro. The results showed that MLKL and its phosphorylated protein p-MLKL were upregulated in the pancreas of the mouse AP model and cerulein-treated pancreatic acinar cells, independent of its canonical upstream molecule Ripk3, and appeared to function in a cell death-independent manner. Knockout of Mlkl attenuated AP in mice by reducing the polarization of pancreatic macrophages toward the M1 phenotype, and this protective effect was partly achieved by reducing the secretion of CXCL10 from pancreatic acinar cells, whereas knockout of Ripk3 did not. In vitro neutralization of CXCL10 impaired the pro-M1 ability of the conditioned medium of cerulein-treated pancreatic acinar cells, whereas in vivo neutralization of CXCL10 reduced the polarization of pancreatic macrophages toward M1 and the severity of AP in mice. These findings suggested that targeting the MLKL-CXCL10-macrophage axis might be a promising strategy for the treatment of AP.
CD11c+ microglia promote white matter repair after ischemic stroke
Authors: Jia Junqiu , Zheng Lili , Ye Lei , Chen Jian , Shu Shu , Xu Siyi , Bao Xinyu , Xia Shengnan , Liu Renyuan , Xu Yun , Zhang Meijuan 
Published: February 2023

AbstractIschemic stroke leads to white matter damage and neurological deficits. However, the characteristics of white matter injury and repair after stroke are unclear. Additionally, the precise molecular communications between microglia and white matter repair during the stroke rehabilitation phase remain elusive. In this current study, MRI DTI scan and immunofluorescence staining were performed to trace white matter and microglia in the mouse transient middle cerebral artery occlusion (tMCAO) stroke model. We found that the most serious white matter damage was on Day 7 after the ischemic stroke, then it recovered gradually from Day 7 to Day 30. Parallel to white matter recovery, we observed that microglia centered around the damaged myelin sheath and swallowed myelin debris in the ischemic areas. Then, microglia of the ischemic hemisphere were sorted by flow cytometry for RNA sequencing and subpopulation analysis. We found that CD11c+ microglia increased from Day 7 to Day 30, demonstrating high phagocytotic capabilities, myelin-supportive genes, and lipid metabolism associated genes. CD11c+ microglia population was partly depleted by the stereotactic injecting of rAAV2/6M-taCasp3 (rAAV2/6M-CMV-DIO-taCasp3-TEVp) into CD11c-cre mice. Selective depletion of CD11c+ microglia disrupted white matter repair, oligodendrocyte maturation, and functional recovery after stroke by Rotarod test, Adhesive Removal test, and Morris Water Maze test. These findings suggest that spontaneous white matter repair occurs after ischemic stroke, while CD11c+ microglia play critical roles in this white matter restorative progress.
Impaired hepatic autophagy exacerbates hepatotoxin induced liver injury
Authors: Byrnes Katherine , Bailey Niani Tiaye , Baral Kamal , Mercer Arissa , Joshi Spandan , Wahby Nickol , Rorison Tyler , Liu Gang , Yin Xiao-Ming , Khambu Bilon 
Published: February 2023

AbstractHepatotoxins activate the hepatic survival pathway, but it is unclear whether impaired survival pathways contribute to liver injury caused by hepatotoxins. We investigated the role of hepatic autophagy, a cellular survival pathway, in cholestatic liver injury driven by a hepatotoxin. Here we demonstrate that hepatotoxin contained DDC diet impaired autophagic flux, resulting in the accumulation of p62-Ub-intrahyaline bodies (IHBs) but not the Mallory Denk-Bodies (MDBs). An impaired autophagic flux was associated with a deregulated hepatic protein-chaperonin system and significant decline in Rab family proteins. Additionally, p62-Ub-IHB accumulation activated the NRF2 pathway rather than the proteostasis-related ER stress signaling pathway and suppressed the FXR nuclear receptor. Moreover, we demonstrate that heterozygous deletion of Atg7, a key autophagy gene, aggravated the IHB accumulation and cholestatic liver injury. Conclusion: Impaired autophagy exacerbates hepatotoxin-induced cholestatic liver injury. The promotion of autophagy may represent a new therapeutic approach for hepatotoxin-induced liver damage.
Recent progress with one-dimensional metal halide perovskites: from rational synthesis to optoelectronic applications
Authors: Duan Dawei , Ge Chuangye , Rahaman Md Zahidur , Lin Chun-Ho , Shi Yumeng , Lin Haoran , Hu Hanlin , Wu Tom 
Published: February 2023

AbstractMetal halide perovskites can be readily synthesized, they exhibit tunable physical properties and excellent performance, and they are heavily studied optoelectronic materials. Compared to the typical three-dimensional perovskites, morphological-level one-dimensional (1D) nanostructures enable charge transport and photon propagation with low exciton binding energies and long charge-carrier diffusion lengths, while molecular-level 1D nanostructures exhibit good compositional and structural flexibilities, highly tunable bandgaps, strong quantum confinement effects, and excellent ambient stabilities. The 1D natures of these emerging halide perovskites enhance the performance of optoelectronic devices. Herein, we highlight recent progress realized in the syntheses and characterizations of both morphological- and molecular-level 1D halide perovskites with tunable structures, compositions, and properties, as well as their photovoltaic, light-emission, and photodetection applications. In addition, current challenges, future prospects, and promising research directions are discussed to provide guidance in advancing the field of 1D perovskites.
Up-to-fivefold reverberating waves through the Earth’s center and distinctly anisotropic innermost inner core
Authors: Phạm Thanh-Son , Tkalčić Hrvoje 
Published: February 2023

AbstractProbing the Earth’s center is critical for understanding planetary formation and evolution. However, geophysical inferences have been challenging due to the lack of seismological probes sensitive to the Earth’s center. Here, by stacking waveforms recorded by a growing number of global seismic stations, we observe up-to-fivefold reverberating waves from selected earthquakes along the Earth’s diameter. Differential travel times of these exotic arrival pairs, hitherto unreported in seismological literature, complement and improve currently available information. The inferred transversely isotropic inner-core model contains a ~650-km thick innermost ball with P-wave speeds ~4% slower at ~50° from the Earth’s rotation axis. In contrast, the inner core’s outer shell displays much weaker anisotropy with the slowest direction in the equatorial plane. Our findings strengthen the evidence for an anisotropically-distinctive innermost inner core and its transition to a weakly anisotropic outer shell, which could be a fossilized record of a significant global event from the past.
The usherin mutation c.2299delG leads to its mislocalization and disrupts interactions with whirlin and VLGR1
Authors: Tebbe Lars , Mwoyosvi Maggie L. , Crane Ryan , Makia Mustafa S. , Kakakhel Mashal , Cosgrove Dominic , Al-Ubaidi Muayyad R. , Naash Muna I. 
Published: February 2023

AbstractUsher syndrome (USH) is the leading cause of combined deafness-blindness with type 2 A (USH2A) being the most common form. Knockout models of USH proteins, like the Ush2a-/- model that develops a late-onset retinal phenotype, failed to mimic the retinal phenotype observed in patients. Since patient’s mutations result in the expression of a mutant protein and to determine the mechanism of USH2A, we generated and evaluated an usherin (USH2A) knock-in mouse expressing the common human disease-mutation, c.2299delG. This mouse exhibits retinal degeneration and expresses a truncated, glycosylated protein which is mislocalized to the photoreceptor inner segment. The degeneration is associated with a decline in retinal function, structural abnormalities in connecting cilium and outer segment and mislocaliztion of the usherin interactors very long G-protein receptor 1 and whirlin. The onset of symptoms is significantly earlier compared to Ush2a-/-, proving expression of mutated protein is required to recapitulate the patients’ retinal phenotype.
Complex-tensor theory of simple smectics
Authors: Paget Jack , Mazza Marco G. , Archer Andrew J. , Shendruk Tyler N. 
Published: February 2023

AbstractMatter self-assembling into layers generates unique properties, including structures of stacked surfaces, directed transport, and compact area maximization that can be highly functionalized in biology and technology. Smectics represent the paradigm of such lamellar materials — they are a state between fluids and solids, characterized by both orientational and partial positional ordering in one layering direction, making them notoriously difficult to model, particularly in confining geometries. We propose a complex tensor order parameter to describe the local degree of lamellar ordering, layer displacement and orientation of the layers for simple, lamellar smectics. The theory accounts for both dislocations and disclinations, by regularizing singularities within defect cores and so remaining continuous everywhere. The ability to describe disclinations and dislocation allows this theory to simulate arrested configurations and inclusion-induced local ordering. This tensorial theory for simple smectics considerably simplifies numerics, facilitating studies on the mesoscopic structure of topologically complex systems.
Spatially confined protein assembly in hierarchical mesoporous metal-organic framework
Authors: Wang Xiaoliang , He Lilin , Sumner Jacob , Qian Shuo , Zhang Qiu , O’Neill Hugh , Mao Yimin , Chen Chengxia , Al-Enizi Abdullah M. , Nafady Ayman , Ma Shengqian 
Published: February 2023

AbstractImmobilization of biomolecules into porous materials could lead to significantly enhanced performance in terms of stability towards harsh reaction conditions and easier separation for their reuse. Metal-Organic Frameworks (MOFs), offering unique structural features, have emerged as a promising platform for immobilizing large biomolecules. Although many indirect methods have been used to investigate the immobilized biomolecules for diverse applications, understanding their spatial arrangement in the pores of MOFs is still preliminary due to the difficulties in directly monitoring their conformations. To gain insights into the spatial arrangement of biomolecules within the nanopores. We used in situ small-angle neutron scattering (SANS) to probe deuterated green fluorescent protein (d-GFP) entrapped in a mesoporous MOF. Our work revealed that GFP molecules are spatially arranged in adjacent nanosized cavities of MOF-919 to form “assembly” through adsorbate-adsorbate interactions across pore apertures. Our findings, therefore, lay a crucial foundation for the identification of proteins structural basics under confinement environment of MOFs.
Citrullination modulates antigen processing and presentation by revealing cryptic epitopes in rheumatoid arthritis
Authors: Curran Ashley M. , Girgis Alexander A. , Jang Yura , Crawford Jonathan D. , Thomas Mekha A. , Kawalerski Ryan , Coller Jeff , Bingham Clifton O. , Na Chan Hyun , Darrah Erika 
Published: February 2023

AbstractCryptic peptides, hidden from the immune system under physiologic conditions, are revealed by changes to MHC class II processing and hypothesized to drive the loss of immune tolerance to self-antigens in autoimmunity. Rheumatoid arthritis (RA) is an autoimmune disease characterized by immune responses to citrullinated self-antigens, in which arginine residues are converted to citrullines. Here, we investigate the hypothesis that citrullination exposes cryptic peptides by modifying protein structure and proteolytic cleavage. We show that citrullination alters processing and presentation of autoantigens, resulting in the generation of a unique citrullination-dependent repertoire composed primarily of native sequences. This repertoire stimulates T cells from RA patients with anti-citrullinated protein antibodies more robustly than controls. The generation of this unique repertoire is achieved through altered protease cleavage and protein destabilization, rather than direct presentation of citrulline-containing epitopes, suggesting a novel paradigm for the role of protein citrullination in the breach of immune tolerance in RA.
Gasdermin-D activation promotes NLRP3 activation and host resistance to Leishmania infection
Authors: de Sá Keyla S. G. , Amaral Luana A. , Rodrigues Tamara S. , Ishimoto Adriene Y. , de Andrade Warrison A. C. , de Almeida Leticia , Freitas-Castro Felipe , Batah Sabrina S. , Oliveira Sergio C. , Pastorello Mônica T. , Fabro Alexandre T. , Zamboni Dario S. 
Published: February 2023

AbstractIntracellular parasites from the Leishmania genus cause Leishmaniasis, a disease affecting millions of people worldwide. NLRP3 inflammasome is key for disease outcome, but the molecular mechanisms upstream of the inflammasome activation are still unclear. Here, we demonstrate that despite the absence of pyroptosis, Gasdermin-D (GSDMD) is active at the early stages of Leishmania infection in macrophages, allowing transient cell permeabilization, potassium efflux, and NLRP3 inflammasome activation. Further, GSDMD is processed into a non-canonical 25 kDa fragment. Gsdmd–/– macrophages and mice exhibit less NLRP3 inflammasome activation and are highly susceptible to infection by several Leishmania species, confirming the role of GSDMD for inflammasome-mediated host resistance. Active NLRP3 inflammasome and GSDMD are present in skin biopsies of patients, demonstrating activation of this pathway in human leishmaniasis. Altogether, our findings reveal that Leishmania subverts the normal functions of GSDMD, an important molecule to promote inflammasome activation and immunity in Leishmaniasis.
Asymmetric activity of NetrinB controls laterality of the Drosophila brain
Authors: Lapraz F. , Boutres C. , Fixary-Schuster C. , De Queiroz B. R. , Plaçais P. Y. , Cerezo D. , Besse F. , Préat T. , Noselli S. 
Published: February 2023

AbstractLeft-Right (LR) asymmetry of the nervous system is widespread across animals and is thought to be important for cognition and behaviour. But in contrast to visceral organ asymmetry, the genetic basis and function of brain laterality remain only poorly characterized. In this study, we performed RNAi screening to identify genes controlling brain asymmetry in Drosophila. We found that the conserved NetrinB (NetB) pathway is required for a small group of bilateral neurons to project asymmetrically into a pair of neuropils (Asymmetrical Bodies, AB) in the central brain in both sexes. While neurons project unilaterally into the right AB in wild-type flies, netB mutants show a bilateral projection phenotype and hence lose asymmetry. Developmental time course analysis reveals an initially bilateral connectivity, eventually resolving into a right asymmetrical circuit during metamorphosis, with the NetB pathway being required just prior symmetry breaking. We show using unilateral clonal analysis that netB activity is required specifically on the right side for neurons to innervate the right AB. We finally show that loss of NetB pathway activity leads to specific alteration of long-term memory, providing a functional link between asymmetrical circuitry determined by NetB and animal cognitive functions.