bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Large Simulation Set of Geomagnetic Storms—Can Simulations Predict Ground Magnetometer Station Observations of Magnetic Field Perturbations?
Authors: Al Shidi Q. , Pulkkinen T. , Toth G. , Brenner A. , Zou S. , Gjerloev J. 
Published: October 2022

AbstractWe use the Space Weather Modeling Framework Geospace configuration to simulate a total of 122 storms from the period 2010–2019. With the focus on the storm main phase, each storm period was run for 54 hr starting from 6 hr prior to the start of the Dst depression. The simulation output of ground magnetic variations, ΔBH in particular, were compared with ground magnetometer station data provided by SuperMAG to statistically assess the Geospace model regional magnetic perturbation prediction performance. Our results show that the regional predictions at mid‐latitudes are quite accurate, but the high‐latitude regional disturbances are still difficult to predict.
Two kinds of transcription factors mediate chronic morphine-induced decrease in miR-105 in medial prefrontal cortex of rats
Authors: Zhang Junfang , Guo Xinli , Cai Zhangyin , Pan Yan , Yang Hao , Fu Yali , Cao Zixuan , Wen Yaxian , Lei Chao , Chu Chenshan , Yuan Yu , Cui Dongyang , Gao Pengyu , Lai Bin , Zheng Ping 
Published: October 2022

AbstractChronic morphine administration alters gene expression in different brain regions, an effect which may contribute to plastic changes associated with addictive behavior. This change in gene expression is most possibly mediated by addictive drug-induced epigenetic remodeling of gene expression programs. Our previous studies showed that chronic morphine-induced decrease of miR-105 in the medial prefrontal cortex (mPFC) contributed to context-induced retrieval of morphine withdrawal memory. However, how chronic morphine treatment decreases miR-105 in the mPFC still remains unknown. The present study shows that chronic morphine induces addiction-related change in miR-105 in the mPFC via two kinds of transcription factors: the first transcription factor is CREB activated by mu receptors-ERK-p90RSK signaling pathway and the second transcription factor is glucocorticoid receptor (GR), which as a negative transcription factor, mediates chronic morphine-induced decrease in miR-105 in the mPFC of rats.
Nrf2 regulates the arginase 1+ microglia phenotype through the initiation of TREM2 transcription, ameliorating depression-like behavior in mice
Authors: He Lujuan , Zheng Yi , Huang Lixuan , Ye Jingyi , Ye Yinyi , Luo Hanyue , Chen Xi , Yao Wei , Chen Jiaxu , Zhang Ji-chun 
Published: October 2022

AbstractThe expression of the triggering receptor on myeloid cell-2 (TREM2) knockdown in microglia from the lateral habenula (LHb) reportedly induces depression-like behaviors in mice. However, the key molecular mechanism that mediates major depressive disorder (MDD) pathogenesis remains elusive. We herein show that Nrf2 regulates TREM2 transcription and effects TREM2 mRNA and protein expression. The activation of Nrf2 by sulforaphane (Nrf2 activator) increases the microglial arginase 1+ phenotype by initiating TREM2 transcription in the medial prefrontal cortex (mPFC) and ameliorates depression-like behavior in CSDS mice. The knockout of Nrf2 decreases TREM2 and the microglial arginase 1+ phenotype in the mPFC of Nrf2 KO mice with depression-like behavior. Downregulating TREM2 expression decreases the microglial arginase 1+ phenotype in the mPFC, resulting in depression-like behavior in SFN-treated CSDS mice. Finally, the knockout of Nrf2 and downregulation of TREM2 expression decreases the microglial arginase 1+ phenotype in the mPFC of Nrf2 KO mice and SFN-treated CSDS mice were associated with the brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling pathway. These data indicate that alterations in the interaction between Nrf2 and TREM2 may play a role in the pathophysiology of depression-like behavior in mice.
Impact of the COVID-19 pandemic on the research activities of UK ophthalmologists
Authors: Hogg H. D. J. , Low L. , Self J. E. ,   Royal College of Ophthalmologists’ Academic and Research Subcommittee, Allen Louise , Atan Denize , Bourne Rupert R. A. , Dick Andrew D. , Foster Paul J. , Gale Richard P. , Hammond Christopher J. , Megaw Roly , Moosajee Mariya , Sivaprasad Sobha , Rahi J. S. 
Published: October 2022

Abstract
Background
The COVID-19 pandemic has impacted negatively on many areas of biomedical research and there is concern that academic recovery will take several years. This survey aimed to define the impact of the COVID-19 pandemic on UK ophthalmologists’ research activities and understand the implications for recovery.

Methods
An online survey comprising multiple choice and free-text questions was designed, piloted and then distributed to Royal College of Ophthalmologists (RCOphth) members in January 2021. Respondent characteristics, research expectations and experiences through the pandemic were captured. Descriptive and comparative statistics were applied to quantitative data alongside content analysis of qualitative data.

Results
In total, 148 respondents (3.7% of RCOphth membership) comprised 46 trainees (31.1%), 97 consultants (65.5%) and 5 SAS doctors (3.4%); 54 had clinical-academic roles (36.5%) and 65/94 (69.1%) ophthalmologists with fully clinical posts identified as research-active. Of 114 research-active respondents, 104 (91.2%) reported an impact on their research from COVID-19; negative impacts included loss of research time (n = 69), research delays (n = 96) and funding shortfalls (n = 63). Content analysis identified five common themes; type of research activity, clinical demands, institutional challenges, COVID-19 alignment and work-life balance.

Conclusions
UK ophthalmology research has been adversely impacted by the pandemic. A substantial proportion of UK ophthalmologists are research active, but 20.4% of those surveyed felt that the pandemic had made research less attractive. Strategic steps must be taken to nurture UK ophthalmologists’ engagement with research, especially for those who currently do no research, if the profession is to align itself with the Government vision of ‘Research for All’.
Prolonged in situ self-healing in structural composites via thermo-reversible entanglement
Authors: Snyder Alexander D. , Phillips Zachary J. , Turicek Jack S. , Diesendruck Charles E. , Nakshatrala Kalyana B. , Patrick Jason F. 
Published: October 2022

AbstractNatural processes continuously degrade a material’s performance throughout its life cycle. An emerging class of synthetic self-healing polymers and composites possess property-retaining functions with the promise of longer lifetimes. But sustained in-service repair of structural fiber-reinforced composites remains unfulfilled due to material heterogeneity and thermodynamic barriers in commonly cross-linked polymer-matrix constituents. Overcoming these inherent challenges for mechanical self-recovery is vital to extend in-service operation and attain widespread adoption of such bioinspired structural materials. Here we transcend existing obstacles and report a fiber-composite capable of minute-scale and prolonged in situ healing — 100 cycles: an order of magnitude higher than prior studies. By 3D printing a mendable thermoplastic onto woven glass/carbon fiber reinforcement and co-laminating with electrically resistive heater interlayers, we achieve in situ thermal remending of internal delamination via dynamic bond re-association. Full fracture recovery occurs below the glass-transition temperature of the thermoset epoxy-matrix composite, thus preserving stiffness during and after repair. A discovery of chemically driven improvement in thermal remending of glass- over carbon-fiber composites is also revealed. The marked lifetime extension offered by this self-healing strategy mitigates costly maintenance, facilitates repair of difficult-to-access structures (e.g., wind-turbine blades), and reduces part replacement, thereby benefiting economy and environment.
Formation of supramolecular channels by reversible unwinding-rewinding of bis(indole) double helix via ion coordination
Authors: Mondal Debashis , Ahmad Manzoor , Dey Bijoy , Mondal Abhishek , Talukdar Pinaki 
Published: October 2022

AbstractStimulus-responsive reversible transformation between two structural conformers is an essential process in many biological systems. An example of such a process is the conversion of amyloid-β peptide into β-sheet-rich oligomers, which leads to the accumulation of insoluble amyloid in the brain, in Alzheimer’s disease. To reverse this unique structural shift and prevent amyloid accumulation, β-sheet breakers are used. Herein, we report a series of bis(indole)-based biofunctional molecules, which form a stable double helix structure in the solid and solution state. In presence of chloride anion, the double helical structure unwinds to form an anion-coordinated supramolecular polymeric channel, which in turn rewinds upon the addition of Ag+ salts. Moreover, the formation of the anion-induced supramolecular ion channel results in efficient ion transport across lipid bilayer membranes with excellent chloride selectivity. This work demonstrates anion-cation-assisted stimulus-responsive unwinding and rewinding of artificial double-helix systems, paving way for smart materials with better biomedical applications.
B cells oppose Mycoplasma pneumoniae vaccine enhanced disease and limit bacterial colonization of the lungs
Authors: Gavitt Tyler D. , Mara Arlind B. , Goodridge Meagan L. , Ozyck Rosemary Grace , Reinhardt Emily , Miller Jeremy M. , Hunte Morgan , Tulman Edan R. , Frasca Jr Salvatore , Silbart Lawrence K. , Geary Steven J. , Szczepanek Steven M. 
Published: October 2022

AbstractDevelopment of an effective vaccine for Mycoplasma pneumoniae has been hindered by reports of Vaccine Enhanced Disease (VED) in test subjects vaccinated and challenged in studies conducted in the 1960s. The exact mechanism of disease exacerbation has yet to be fully described, but host immune responses to Lipid-Associated Membrane Proteins (LAMPs) lipoprotein lipid moieties have been implicated. LAMPs-induced exacerbation appears to involve helper T cell recall responses, due in part to their influence on neutrophil recruitment and subsequent inflammatory responses in the lung. Herein, we characterized the functions of host B cell responses to M. pneumoniae LAMPs and delipidated-LAMPs (dLAMPs) by conducting passive transfer and B cell depletion studies to assess their contribution to disease exacerbation or protection using a BALB/c mouse model. We found that antibody responses to M. pneumoniae LAMPs and dLAMPs differ in magnitude, but not in isotype or subclass. Passive transfer, dLAMP denaturation, and monoclonal antibody studies indicate that antibodies do not cause VED, but do appear to contribute to control of bacterial loads in the lungs. Depletion of B cells prior to LAMPs-vaccination results in significantly enhanced pathology in comparison to B cell competent controls, suggesting a possible regulatory role of B cells distinct from antibody secretion. Taken together, our findings suggest that B cell antibody responses to M. pneumoniae contribute to, but are insufficient for protection against challenge on their own, and that other functional properties of B cells are necessary to limit exacerbation of disease in LAMPs-vaccinated mice after infection.
Characterization of an Escherichia coli-derived triple-type chimeric vaccine against human papillomavirus types 39, 68 and 70
Authors: Qian Ciying , Yang Yurou , Xu Qin , Wang Zhiping , Chen Jie , Chi Xin , Yu Miao , Gao Fei , Xu Yujie , Lu Yihan , Sun Hui , Shen Jingjia , Wang Daning , Zhou Lizhi , Li Tingting , Wang Yingbin , Zheng Qingbing , Yu Hai , Zhang Jun , Gu Ying , Xia Ningshao , Li Shaowei 
Published: October 2022

AbstractIn vaccinology, a potent immunogen has two prerequisite attributes—antigenicity and immunogenicity. We have rational designed a triple-type HPV vaccine against HPV58, −33 and −52 covered in Gardasil 9 based on the sequence homology and similar surface loop structure of L1 protein, which is related to cross-type antigenicity. Here, we design another triple-type vaccine against non-vaccine types HPV39, −68 and −70 by immunogenicity optimization considering type specific immunodominant epitopes located in separate region for different types. First, we optimized the expression of wild-type HPV39, −68 and −70 L1-only virus-like particles (VLPs) in E. coli through N-terminal truncation of HPV L1 proteins and non-fusion soluble expression. Second, based on genetic relationships and an L1 homologous loop-swapping rationale, we constructed several triple-type chimeric VLPs for HPV39, −68 and −70, and obtained the lead candidate named H39–68FG-70DE by the immunogenicity optimization using reactivity profile of a panel type-specific monoclonal antibodies. Through comprehensive characterization using various biochemical, VLP-based analyses and immune assays, we show that H39–68FG-70DE assumes similar particulate properties as that of its parental VLPs, along with comparable neutralization immunogenicity for all three HPV types. Overall, this study shows the promise and translatability of an HPV39/68/70 triple-type vaccine, and the possibility of expanding the type-coverage of current HPV vaccines. Our study further expanded the essential criteria on the rational design of a cross-type vaccine, i.e. separate sites with inter-type similar sequence and structure as well as type-specific immunodominant epitope to be clustered together.
Toxoplasmosis vaccines: what we have and where to go?
Authors: Zhang Yizhuo , Li Dan , Lu Shaohong , Zheng Bin 
Published: October 2022

AbstractDespite recent major advances in developing effective vaccines against toxoplasmosis, finding new protective vaccination strategies remains a challenging and elusive goal as it is critical to prevent the disease. Over the past few years, various experimental approaches have shown that developing an effective vaccine against T. gondii is achievable. However, more remains unknown due to its complicated life cycle, difficulties in clinical translation, and lack of a standardized platform. This minireview summarizes the recent advances in the development of T. gondii vaccines and the main obstacles to developing a safe, effective and durable T. gondii vaccine. The successes and failures in developing and testing vaccine candidates for the T. gondii vaccine are also discussed, which may facilitate the future development of T. gondii vaccines.
A split, conditionally active mimetic of IL-2 reduces the toxicity of systemic cytokine therapy
Authors: Quijano-Rubio Alfredo , Bhuiyan Aladdin M. , Yang Huilin , Leung Isabel , Bello Elisa , Ali Lestat R. , Zhangxu Kevin , Perkins Jilliane , Chun Jung-Ho , Wang Wentao , Lajoie Marc J. , Ravichandran Rashmi , Kuo Yun-Huai , Dougan Stephanie K. , Riddell Stanley R. , Spangler Jamie B. , Dougan Michael , Silva Daniel-Adriano , Baker David 
Published: October 2022

AbstractThe therapeutic potential of recombinant cytokines has been limited by the severe side effects of systemic administration. We describe a strategy to reduce the dose-limiting toxicities of monomeric cytokines by designing two components that require colocalization for activity and that can be independently targeted to restrict activity to cells expressing two surface markers. We demonstrate the approach with a previously designed mimetic of cytokines interleukin-2 and interleukin-15—Neoleukin-2/15 (Neo-2/15)—both for trans-activating immune cells surrounding targeted tumor cells and for cis-activating directly targeted immune cells. In trans-activation mode, tumor antigen targeting of the two components enhanced antitumor activity and attenuated toxicity compared with systemic treatment in syngeneic mouse melanoma models. In cis-activation mode, immune cell targeting of the two components selectively expanded CD8+ T cells in a syngeneic mouse melanoma model and promoted chimeric antigen receptor T cell activation in a lymphoma xenograft model, enhancing antitumor efficacy in both cases.
Multifactorial profiling of epigenetic landscapes at single-cell resolution using MulTI-Tag
Authors: Meers Michael P. , Llagas Geneva , Janssens Derek H. , Codomo Christine A. , Henikoff Steven 
Published: October 2022

AbstractChromatin profiling at locus resolution uncovers gene regulatory features that define cell types and developmental trajectories, but it remains challenging to map and compare different chromatin-associated proteins in the same sample. Here we describe Multiple Target Identification by Tagmentation (MulTI-Tag), an antibody barcoding approach for profiling multiple chromatin features simultaneously in single cells. We optimized MulTI-Tag to retain high sensitivity and specificity, and we demonstrate detection of up to three histone modifications in the same cell: H3K27me3, H3K4me1/2 and H3K36me3. We apply MulTI-Tag to resolve distinct cell types and developmental trajectories; to distinguish unique, coordinated patterns of active and repressive element regulatory usage associated with differentiation outcomes; and to uncover associations between histone marks. Multifactorial epigenetic profiling holds promise for comprehensively characterizing cell-specific gene regulatory landscapes in development and disease.
Incorporating the image formation process into deep learning improves network performance
Authors: Li Yue , Su Yijun , Guo Min , Han Xiaofei , Liu Jiamin , Vishwasrao Harshad D. , Li Xuesong , Christensen Ryan , Sengupta Titas , Moyle Mark W. , Rey-Suarez Ivan , Chen Jiji , Upadhyaya Arpita , Usdin Ted B. , Colón-Ramos Daniel Alfonso , Liu Huafeng , Wu Yicong , Shroff Hari 
Published: October 2022

AbstractWe present Richardson–Lucy network (RLN), a fast and lightweight deep learning method for three-dimensional fluorescence microscopy deconvolution. RLN combines the traditional Richardson–Lucy iteration with a fully convolutional network structure, establishing a connection to the image formation process and thereby improving network performance. Containing only roughly 16,000 parameters, RLN enables four- to 50-fold faster processing than purely data-driven networks with many more parameters. By visual and quantitative analysis, we show that RLN provides better deconvolution, better generalizability and fewer artifacts than other networks, especially along the axial dimension. RLN outperforms classic Richardson–Lucy deconvolution on volumes contaminated with severe out of focus fluorescence or noise and provides four- to sixfold faster reconstructions of large, cleared-tissue datasets than classic multi-view pipelines. We demonstrate RLN’s performance on cells, tissues and embryos imaged with widefield-, light-sheet-, confocal- and super-resolution microscopy.
Amino acids for the prevention of mortality and morbidity in preterm infants: a systematic review and network meta-analysis
Authors: Wang Xiaoqin , Sadeghirad Behnam , Morgan Rebecca L. , Zeratkaar Dena , Chang Yaping , Crandon Holly N. , Couban Rachel , Foroutan Farid , Florez Ivan D. 
Published: October 2022

AbstractTo determine the effectiveness and safety of amino acids in preventing the mortality and morbidity among preterm infants. We conducted a systematic review and network meta-analysis. We searched MEDLINE, EMBASE, Web of Science, CINAHL, Scopus, Cochrane, and Google Scholar, and grey literature, from databases inception to January 2021. We included randomized trials that evaluated any amino acids on preterm or low-birth weight infants. We performed frequentist pairwise and network meta-analyses and used the GRADE methodology to assess the certainty of the evidence and provide a summary of the results.We included 18 trials (3702 infants). Low certainty evidence showed that there seems to be no benefit for arginine, glutamine, or N-acetylcysteine in reducing all-cause mortality. Oral arginine likely results in reduction of necrotizin enterocolitis (NEC) stage ≥ II (OR 0.48; 95% CI 0.26–0.90; moderate certainty). Oral glutamine may reduce the likelihood of developing late-onset sepsis (LOS) compared to placebo (OR 0.62; 95% CI 0.47–0.82; low certainty); and likely reduces time to reach full enteral feeding (MD = − 2.63 days; 95% CI − 4.99 to − 0.27; moderate certainty). Amino acids may have no effect on mortality. Oral arginine may reduce severe NEC, and oral glutamine may reduce LOS and the time to reach full feeding.Systematic review registration: PROSPERO registration number: CRD4201603873.
Increased retinal drusen in IgA glomerulonephritis are further evidence for complement activation in disease pathogenesis
Authors: Harraka P. , Wightman Tony , Akom Sarah , Sandhu Kieran , Colville Deb , Catran Andrew , Langsford David , Pianta Timothy , Barit David , Ierino Frank , Skene Alison , Mack Heather , Savige Judy 
Published: October 2022

AbstractDrusen are retinal deposits comprising cell debris, immune material and complement that are characteristic of macular degeneration but also found in glomerulonephritis. This was a pilot cross-sectional study to determine how often drusen occurred in IgA glomerulonephritis and their clinical significance. Study participants underwent non-mydriatic retinal photography, and their deidentified retinal images were examined for drusen by two trained graders, who compared central drusen counts, counts ≥ 10 and drusen size with those of matched controls. The cohort comprised 122 individuals with IgA glomerulonephritis including 89 males (73%), 49 individuals (40%) of East Asian or Southern European ancestry, with an overall median age of 54 years (34–64), and median disease duration of 9 years (4–17). Thirty-nine (33%) had an eGFR < 60 ml/min/1.73 m2 and 72 had previously reached kidney failure (61%). Overall mean drusen counts were higher in IgA glomerulonephritis (9 ± 27) than controls (2 ± 7, p < 0.001). Central counts ≥ 10 were also more common (OR = 3.31 (1.42–7.73, p = 0.006), and were associated with longer disease duration (p = 0.03) but not kidney failure (p = 0.31). Larger drusen were associated with more mesangial IgA staining (p = 0.004). Increased drusen counts were also present in IgA glomerulonephritis secondary to Crohn’s disease but not with Henoch-Schonlein purpura. The finding of retinal drusen in IgA glomerulonephritis is consistent with complement activation and represents a model for better understanding glomerular immune deposition and a supporting argument for treatment with anti-complement therapies.
Transmittance properties of one-dimensional metamaterial nanocomposite photonic crystal in GHz range
Authors: Mohamed Aliaa G. , Elsayed Hussein A. , Mehaney Ahmed , Aly Arafa H. , Sabra Walied 
Published: October 2022

AbstractWe have theoretically demonstrated and explored the transmittance characteristics of a one-dimensional binary photonic crystal composed of metamaterial (MM) and nanocomposite (NC) layers. The NC layer was designed from silver nanoparticles (Ag-NPs) in a host material as Yttrium oxide (Y2O3). Using the transfer matrix approach (TMM), the optical properties of a one-dimensional binary periodic structure having MM and NC layers in the Giga Hertz (GHz) range were examined. The filling fractions of nanoparticles have been explored to see their effect on the effective permittivity of NC materials. Furthermore, the transmittance properties of the suggested structure were investigated at various incident angles for the transverse electric (TE) polarization. In addition to that, different parameters, such as the thickness of the MM layer, the permittivity of the host dielectric material, the filling fraction, and the thickness of the NC layer are also taken into account. We also discussed the effect of these parameters on the width of the photonic bandgap (PBG). With the optimum values of the optical parameters of NC layer, this research could open the way for better photonic crystal circuits, splitters, switches and others.