bluuebunny/crossref_metadata_2025_split huggingface dataset:
The sixth revolution in pediatric vaccinology: immunoengineering and delivery systems
Authors: Soni Dheeraj , Bobbala Sharan , Li Sophia , Scott Evan A. , Dowling David J. 
Published: September 2020

Abstract
Infection is the predominant cause of mortality in early life, and immunization is the most promising biomedical intervention to reduce this burden. However, very young infants fail to respond optimally to most vaccines currently in use, especially neonates. In 2005, Stanley Plotkin proposed that new delivery systems would spur a new revolution in pediatric vaccinology, just as attenuation, inactivation, cell culture of viruses, genetic engineering, and adjuvantation had done in preceding decades. Recent advances in the field of immunoengineering, which is evolving alongside vaccinology, have begun to increasingly influence vaccine formulation design. Historically, the particulate nature of materials used in many vaccine formulations was empiric, often because of the need to stabilize antigens or reduce endotoxin levels. However, present vaccine delivery systems are rationally engineered to mimic the size, shape, and surface chemistry of pathogens, and are therefore often referred to as “pathogen-like particles”. More than a decade from his original assessment, we re-assess Plotkin’s prediction. In addition, we highlight how immunoengineering and advanced delivery systems may be uniquely capable of enhancing vaccine responses in vulnerable populations, such as infants.

Impact

Immunoengineering and advanced delivery systems are leading to new developments in pediatric vaccinology.

Summarizes delivery systems currently in use and development, and prospects for the future.

Broad overview of immunoengineering’s impact on vaccinology, catering to Pediatric Clinicians and Immunologists.
A Core Outcome Set and minimum reporting set for intervention studies in growth restriction in the NEwbOrN: the COSNEON study
Authors: Damhuis Stefanie E. , Bloomfield Frank H. , Khalil Asma , Daly Mandy , Ganzevoort Wessel , Gordijn Sanne J. 
Published: September 2020

Abstract
Background
Different interventions and treatments are available for growth-restricted newborns to improve neonatal and long-term outcomes. Lack of outcome standardization across trials of feeding interventions limits pooled analysis of intervention effects. This study aimed to develop a core outcome set (COS) and minimum reporting set (MRS) for this research field.

Methods
A scoping search identified relevant outcomes and baseline characteristics. These outcomes were presented to two stakeholder groups (lay experience and professional experts) in three rounds of online Delphi surveys. The professional experts were involved in the development of the MRS. All items were rated for their importance on a 5-point Likert scale and re-rated in subsequent rounds after presentation of the results at the group level. During a face-to-face consensus meeting the final COS and MRS were determined.

Results
Forty-seven of 53 experts (89%) who completed the first round completed all three survey rounds. After the consensus meeting, consensus was reached on 19 outcomes and 17 baseline characteristics.

Conclusions
A COS and MRS for feeding interventions in the newborn after growth restriction were developed. Use of these sets will promote uniform reporting of study characteristics and improve data synthesis and meta-analysis of multiple studies.

Impact

Both a COS and MRS for growth restriction in the newborn were developed.

This study provides the first international combined health-care professional and patient consensus on outcomes and baseline characteristics for intervention and treatment studies in growth-restricted newborns.

The use of COS and MRS results in the development of more uniform study protocols, thereby facilitating data synthesis/meta-analysis of multiple studies aiming to optimize treatment and interventions in growth restriction in the newborn.
Cutting out the middle clam: lucinid endosymbiotic bacteria are also associated with seagrass roots worldwide
Authors: Martin Belinda C , Middleton Jen A , Fraser Matthew W , Marshall Ian P G , Scholz Vincent V , Hausl Bertram , Schmidt Hannes 
Published: September 2020

Abstract
Seagrasses and lucinid bivalves inhabit highly reduced sediments with elevated sulphide concentrations. Lucinids house symbiotic bacteria (Ca. Thiodiazotropha) capable of oxidising sediment sulphide, and their presence in sediments has been proposed to promote seagrass growth by decreasing otherwise phytotoxic sulphide levels. However, vast and productive seagrass meadows are present in ecosystems where lucinids do not occur. Hence, we hypothesised that seagrasses themselves host these sulphur-oxidising Ca. Thiodiazotropha that could aid their survival when lucinids are absent. We analysed newly generated and publicly available 16S rRNA gene sequences from seagrass roots and sediments across 14 seagrass species and 10 countries and found that persistent and colonising seagrasses across the world harbour sulphur-oxidising Ca. Thiodiazotropha, regardless of the presence of lucinids. We used fluorescence in situ hybridisation to visually confirm the presence of Ca. Thiodiazotropha on roots of Halophila ovalis, a colonising seagrass species with wide geographical, water depth range, and sedimentary sulphide concentrations. We provide the first evidence that Ca. Thiodiazotropha are commonly present on seagrass roots, providing another mechanism for seagrasses to alleviate sulphide stress globally.
Bridging the membrane lipid divide: bacteria of the FCB group superphylum have the potential to synthesize archaeal ether lipids
Authors: Villanueva Laura , Bastiaan von Meijenfeldt F A , Westbye Alexander B , Yadav Subhash , Hopmans Ellen C , Dutilh Bas E , Sinninghe Damsté Jaap S 
Published: September 2020

Abstract
Archaea synthesize membranes of isoprenoid lipids that are ether-linked to glycerol-1-phosphate (G1P), while Bacteria/Eukarya produce membranes consisting of fatty acids ester-bound to glycerol-3-phosphate (G3P). This dichotomy in membrane lipid composition (i.e., the ‘lipid divide’) is believed to have arisen after the Last Universal Common Ancestor (LUCA). A leading hypothesis is that LUCA possessed a heterochiral ‘mixed archaeal/bacterial membrane’. However, no natural microbial representatives supporting this scenario have been shown to exist today. Here, we demonstrate that bacteria of the Fibrobacteres–Chlorobi–Bacteroidetes (FCB) group superphylum encode a putative archaeal pathway for ether-bound isoprenoid membrane lipids in addition to the bacterial fatty acid membrane pathway. Key genes were expressed in the environment and their recombinant expression in Escherichia coli resulted in the formation of a ‘mixed archaeal/bacterial membrane’. Genomic evidence and biochemical assays suggest that the archaeal-like lipids of members of the FCB group could possess either a G1P or G3P stereochemistry. Our results support the existence of ‘mixed membranes’ in natural environments and their stability over a long period in evolutionary history, thereby bridging a once-thought fundamental divide in biology.
Presynaptic dysfunction in CASK-related neurodevelopmental disorders
Authors: Becker Martin , Mastropasqua Francesca , Reising Jan Philipp , Maier Simon , Ho Mai-Lan , Rabkina Ielyzaveta , Li Danyang , Neufeld Janina , Ballenberger Lea , Myers Lynnea , Moritz Viveka , Kele Malin , Wincent Josephine , Willfors Charlotte , Sitnikov Rouslan , Herlenius Eric , Anderlid Britt-Marie , Falk Anna , Bölte Sven , Tammimies Kristiina 
Published: September 2020

AbstractCASK-related disorders are genetically defined neurodevelopmental syndromes. There is limited information about the effects ofCASKmutations in human neurons. Therefore, we sought to delineateCASK-mutation consequences and neuronal effects using induced pluripotent stem cell-derived neurons from two mutation carriers. One male case with autism spectrum disorder carried a novel splice-site mutation and a female case with intellectual disability carried an intragenic tandem duplication. We show reduction of CASK protein in maturing neurons from the mutation carriers, which leads to significant downregulation of genes involved in presynaptic development and of CASK protein interactors. Furthermore,CASK-deficient neurons showed decreased inhibitory presynapse size as indicated by VGAT staining, which may alter the excitatory–inhibitory (E/I) balance in developing neural circuitries. Using in vivo magnetic resonance spectroscopy quantification of GABA in the male mutation carrier, we further highlight the possibility to validate in vitro cellular data in the brain. Our data show that future pharmacological and clinical studies on targeting presynapses and E/I imbalance could lead to specific treatments forCASK-related disorders.
MT1DP loaded by folate-modified liposomes sensitizes erastin-induced ferroptosis via regulating miR-365a-3p/NRF2 axis in non-small cell lung cancer cells
Authors: Gai Chengcheng , Liu Chuanliang , Wu Xinghan , Yu Mengyu , Zheng Jie , Zhang Weifen , Lv Shijun , Li Wentong 
Published: September 2020

AbstractAlthough ferroptosis has been recognized as a novel antitumoral treatment, high expression of nuclear factor erythroid 2-related factor 2 (NRF2) has been reported to be an antioxidant transcript factor that protects malignant cells from ferroptosis. Previous findings indicated that metallothionein 1D pseudogene (MT1DP), a long noncoding RNA (lncRNA), functioned to aggravate oxidative stress by repressing antioxidation. Here we aimed at assessing whether MT1DP could regulate erastin-induced ferroptosis on non-small cell lung cancer (NSCLC) and elucidating the mechanism. We found that ectopic expression of MT1DP sensitized A549 and H1299 cells to erastin-induced ferroptosis through downregulation of NRF2; in addition, ectopic MT1DP upregulated malondialdehyde (MDA) and reactive oxygen species (ROS) levels, increased intracellular ferrous iron concentration, and reduced glutathione (GSH) levels in cancer cells exposed to erastin, whereas downregulation of MT1DP showed the opposite effect. RNA pulldown assay and dual-luciferase reporter assay confirmed that MT1DP modulated the expression of NRF2 via stabilizing miR-365a-3p. As low solubility of erastin limits its efficient application, we further prepared folate (FA)-modified liposome (FA-LP) nanoparticles for targeted co-delivery of erastin and MT1DP to enhance the bioavailability and the efficiency of the drug/gene combination. Erastin/MT1DP@FA-LPs (E/M@FA-LPs) sensitized erastin-induced ferroptosis with decreased cellular GSH levels and elevated lipid ROS. In vivo analysis showed that E/M@FA-LPs had a favorable therapeutic effect on lung cancer xenografts. In short, our findings identify a novel strategy to elevate erastin-induced ferroptosis in NSCLCs acting through the MT1DP/miR-365a-3p/NRF2 axis.
P53-regulated miR-320a targets PDL1 and is downregulated in malignant mesothelioma
Authors: Costa Caterina , Indovina Paola , Mattioli Eliseo , Forte Iris Maria , Iannuzzi Carmelina Antonella , Luzzi Luca , Bellan Cristiana , De Summa Simona , Bucci Enrico , Di Marzo Domenico , De Feo Marisa , Mutti Luciano , Pentimalli Francesca , Giordano Antonio 
Published: September 2020

AbstractMalignant pleural mesothelioma (MPM) is an aggressive cancer, related to asbestos exposure, which has a dismal prognosis. MPM diagnosis is late and often challenging, suggesting the need to identify more reliable molecular biomarkers. Here, we set out to identify differentially expressed miRNAs in epithelioid, biphasic, and sarcomatoid MPMs versus normal mesothelium and explored specific miRNA contribution to mesothelial tumorigenesis. We screened an LNA™-based miRNA-microrray with 14 formalin-fixed paraffin-embedded (FFPE) MPMs and 6 normal controls. Through real-time qRT-PCR we extended the analysis of a miRNA subset and further investigated miR-320a role through state-of-the-art techniques. We identified 16 upregulated and 32 downregulated miRNAs in MPMs versus normal tissue, including the previously identified potential biomarkers miR-21, miR-126, miR-143, miR-145. We showed in an extended series that miR-145, miR-10b, and miR-320a levels can discriminate tumor versus controls with high specificity and sensitivity. We focused on miR-320a because other family members were found downregulated in MPMs. However, stable miR-320a ectopic expression induced higher proliferation and migration ability, whereas miR-320a silencing reduced these processes, not supporting a classic tumor-suppressor role in MPM cell lines. Among putative targets, we found that miR-320a binds the 3′-UTR of the immune inhibitory receptor ligand PDL1 and, consistently, miR-320a modulation affects PDL1 levels in MPM cells. Finally, we showed that p53 over-expression induces the upregulation of miR-320a, along with miR-200a and miR-34a, both known to target PDL1, and reduces PDL1 levels in MPM cells. Our data suggest that PDL1 expression might be due to a defective p53-regulated miRNA response, which could contribute to MPM immune evasion or tumorigenesis through tumor-intrinsic roles.
The roles of long noncoding RNAs in breast cancer metastasis
Authors: Liu Lingxia , Zhang Yu , Lu Jun 
Published: September 2020

AbstractBreast cancer is the most significant threat to female health. Breast cancer metastasis is the major cause of mortality in breast cancer patients. To fully unravel the molecular mechanisms that underlie the breast cancer cell metastasis is critical for developing strategies to improve survival and prognosis in breast cancer patients. Recent studies have revealed that the long noncoding RNAs (lncRNAs) are involved in breast cancer metastasis through a variety of molecule mechanisms, though the precise functional details of these lncRNAs are yet to be clarified. In the present review, we focus on the functions of lncRNAs in breast cancer invasion and metastasis, with particular emphasis on the functional properties, the regulatory factors, the therapeutic promise, as well as the future challenges in studying these lncRNA.
Quantitative genetic architecture of adaptive phenology traits in the deciduous tree, Populus trichocarpa (Torr. and Gray)
Authors: Richards Thomas J. , Karacic Almir , Apuli Rami-Petteri , Weih Martin , Ingvarsson Pär K. , Rönnberg-Wästljung Ann Christin 
Published: September 2020

AbstractIn a warming climate, the ability to accurately predict and track shifting environmental conditions will be fundamental for plant survival. Environmental cues define the transitions between growth and dormancy as plants synchronise development with favourable environmental conditions, however these cues are predicted to change under future climate projections which may have profound impacts on tree survival and growth. Here, we use a quantitative genetic approach to estimate the genetic basis of spring and autumn phenology in Populus trichocarpa to determine this species capacity for climate adaptation. We measured bud burst, leaf coloration, and leaf senescence traits across two years (2017–2018) and combine these observations with measures of lifetime growth to determine how genetic correlations between phenology and growth may facilitate or constrain adaptation. Timing of transitions differed between years, although we found strong cross year genetic correlations in all traits, suggesting that genotypes respond in consistent ways to seasonal cues. Spring and autumn phenology were correlated with lifetime growth, where genotypes that burst leaves early and shed them late had the highest lifetime growth. We also identified substantial heritable variation in the timing of all phenological transitions (h2 = 0.5–0.8) and in lifetime growth (h2 = 0.8). The combination of additive variation and favourable genetic correlations in phenology traits suggests that populations of cultivated varieties of P. Trichocarpa may have the capability to adapt their phenology to climatic changes without negative impacts on growth.
IL-20 antagonist suppresses PD-L1 expression and prolongs survival in pancreatic cancer models
Authors: Lu Shao-Wei , Pan Hong-Chin , Hsu Yu-Hsiang , Chang Kung-Chao , Wu Li-Wha , Chen Wei-Yu , Chang Ming-Shi 
Published: September 2020

AbstractPancreatic ductal adenocarcinoma (PDAC) and cancer-associated cachexia (CAC) are multifactorial and characterized by dysregulated inflammatory networks. Whether the proinflammatory cytokine IL-20 is involved in the complex networks of PDAC and CAC remains unclear. Here, we report that elevated IL-20 levels in tumor tissue correlate with poor overall survival in 72 patients with PDAC. In vivo, we establish a transgenic mouse model (KPC) and an orthotopic PDAC model and examine the therapeutic efficacy of an anti-IL-20 monoclonal antibody (7E). Targeting IL-20 not only prolongs survival and attenuates PD-L1 expression in both murine models but also inhibits tumor growth and mitigates M2-like polarization in the orthotopic PDAC model. Combination treatment with 7E and an anti-PD-1 antibody shows better efficacy in inhibiting tumor growth than either treatment alone in the orthotopic PDAC model. Finally, 7E mitigates cachexic symptoms in CAC models. Together, we conclude IL-20 is a critical mediator in PDAC progression.
Dual blockade of CD47 and HER2 eliminates radioresistant breast cancer cells
Authors: Candas-Green Demet , Xie Bowen , Huang Jie , Fan Ming , Wang Aijun , Menaa Cheikh , Zhang Yanhong , Zhang Lu , Jing Di , Azghadi Soheila , Zhou Weibing , Liu Lin , Jiang Nian , Li Tao , Gao Tianyi , Sweeney Colleen , Shen Rulong , Lin Tzu-yin , Pan Chong-xian , Ozpiskin Omer M. , Woloschak Gayle , Grdina David J. , Vaughan Andrew T. , Wang Ji Ming , Xia Shuli , Monjazeb Arta M. , Murphy William J. , Sun Lun-Quan , Chen Hong-Wu , Lam Kit S. , Weichselbaum Ralph R. , Li Jian Jian 
Published: September 2020

AbstractAlthough the efficacy of cancer radiotherapy (RT) can be enhanced by targeted immunotherapy, the immunosuppressive factors induced by radiation on tumor cells remain to be identified. Here, we report that CD47-mediated anti-phagocytosis is concurrently upregulated with HER2 in radioresistant breast cancer (BC) cells and RT-treated mouse syngeneic BC. Co-expression of both receptors is more frequently detected in recurrent BC patients with poor prognosis. CD47 is upregulated preferentially in HER2-expressing cells, and blocking CD47 or HER2 reduces both receptors with diminished clonogenicity and augmented phagocytosis. CRISPR-mediated CD47 and HER2 dual knockouts not only inhibit clonogenicity but also enhance macrophage-mediated attack. Dual antibody of both receptors synergizes with RT in control of syngeneic mouse breast tumor. These results provide the evidence that aggressive behavior of radioresistant BC is caused by CD47-mediated anti-phagocytosis conjugated with HER2-prompted proliferation. Dual blockade of CD47 and HER2 is suggested to eliminate resistant cancer cells in BC radiotherapy.
Unique S-scheme heterojunctions in self-assembled TiO2/CsPbBr3 hybrids for CO2 photoreduction
Authors: Xu Feiyan , Meng Kai , Cheng Bei , Wang Shengyao , Xu Jingsan , Yu Jiaguo 
Published: September 2020

AbstractExploring photocatalysts to promote CO2 photoreduction into solar fuels is of great significance. We develop TiO2/perovskite (CsPbBr3) S-scheme heterojunctions synthesized by a facile electrostatic-driven self-assembling approach. Density functional theory calculation combined with experimental studies proves the electron transfer from CsPbBr3 quantum dots (QDs) to TiO2, resulting in the construction of internal electric field (IEF) directing from CsPbBr3 to TiO2 upon hybridization. The IEF drives the photoexcited electrons in TiO2 to CsPbBr3 upon light irradiation as revealed by in-situ X-ray photoelectron spectroscopy analysis, suggesting the formation of an S-scheme heterojunction in the TiO2/CsPbBr3 nanohybrids which greatly promotes the separation of electron-hole pairs to foster efficient CO2 photoreduction. The hybrid nanofibers unveil a higher CO2-reduction rate (9.02 μmol g–1 h–1) comparing with pristine TiO2 nanofibers (4.68 μmol g–1 h–1). Isotope (13CO2) tracer results confirm that the reduction products originate from CO2 source.
Prior knowledge promotes hippocampal separation but cortical assimilation in the left inferior frontal gyrus
Authors: Bein Oded , Reggev Niv , Maril Anat 
Published: September 2020

AbstractAn adaptive memory system rarely learns information tabula rasa, but rather builds on prior knowledge to facilitate learning. How prior knowledge influences the neural representation of novel associations remains unknown. Here, participants associated pairs of faces in two conditions: a famous, highly familiar face with a novel face or two novel faces while undergoing fMRI. We examine multivoxel activity patterns corresponding to individual faces before and after learning. The activity patterns representing members of famous-novel pairs becomes separated in the hippocampus, that is, more distinct from one another through learning, in striking contrast to paired novel faces that become similar. In the left inferior frontal gyrus, however, prior knowledge leads to integration, and in a specific direction: the representation of the novel face becomes similar to that of the famous face after learning, suggesting assimilation of new into old memories. We propose that hippocampal separation might resolve interference between existing and newly learned information, allowing cortical assimilation. Thus, associative learning with versus without prior knowledge relies on radically different computations.
Senescence and entrenchment in evolution of amino acid sites
Authors: Stolyarova A. V. , Nabieva E. , Ptushenko V. V. , Favorov A. V. , Popova A. V. , Neverov A. D. , Bazykin G. A. 
Published: September 2020

AbstractAmino acid propensities at a site change in the course of protein evolution. This may happen for two reasons. Changes may be triggered by substitutions at epistatically interacting sites elsewhere in the genome. Alternatively, they may arise due to environmental changes that are external to the genome. Here, we design a framework for distinguishing between these alternatives. Using analytical modelling and simulations, we show that they cause opposite dynamics of the fitness of the allele currently occupying the site: it tends to increase with the time since its origin due to epistasis (“entrenchment”), but to decrease due to random environmental fluctuations (“senescence”). By analysing the genomes of vertebrates and insects, we show that the amino acids originating at negatively selected sites experience strong entrenchment. By contrast, the amino acids originating at positively selected sites experience senescence. We propose that senescence of the current allele is a cause of adaptive evolution.
An investigation of causal relationships between prediabetes and vascular complications
Authors: Mutie Pascal M. , Pomares-Millan Hugo , Atabaki-Pasdar Naeimeh , Jordan Nina , Adams Rachel , Daly Nicole L. , Tajes Juan Fernandes , Giordano Giuseppe N. , Franks Paul W. 
Published: September 2020

AbstractPrediabetes is a state of glycaemic dysregulation below the diagnostic threshold of type 2 diabetes (T2D). Globally, ~352 million people have prediabetes, of which 35–50% develop full-blown diabetes within five years. T2D and its complications are costly to treat, causing considerable morbidity and early mortality. Whether prediabetes is causally related to diabetes complications is unclear. Here we report a causal inference analysis investigating the effects of prediabetes in coronary artery disease, stroke and chronic kidney disease, complemented by a systematic review of relevant observational studies. Although the observational studies suggest that prediabetes is broadly associated with diabetes complications, the causal inference analysis revealed that prediabetes is only causally related with coronary artery disease, with no evidence of causal effects on other diabetes complications. In conclusion, prediabetes likely causes coronary artery disease and its prevention is likely to be most effective if initiated prior to the onset of diabetes.