bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bayesian causal network modeling suggests adolescent cannabis use accelerates prefrontal cortical thinning
Authors: Owens Max M. , Albaugh Matthew D. , Allgaier Nicholas , Yuan Dekang , Robert Gabriel , Cupertino Renata B. , Spechler Philip A. , Juliano Anthony , Hahn Sage , Banaschewski Tobias , Bokde Arun L. W. , Desrivières Sylvane , Flor Herta , Grigis Antoine , Gowland Penny , Heinz Andreas , Brühl Rüdiger , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Artiges Eric , Nees Frauke , Orfanos Dimitri Papadopoulos , Lemaitre Herve , Paus Tomáš , Poustka Luise , Millenet Sabina , Fröhner Juliane H. , Smolka Michael N. , Walter Henrik , Whelan Robert , Mackey Scott , Schumann Gunter , Garavan Hugh ,   The IMAGEN Consortium, Banaschewski Tobias , Barker Gareth J. , Bokde Arun L. W. , Desrivières Sylvane , Flor Herta , Grigis Antoine , Garavan Hugh , Gowland Penny , Heinz Andreas , Brühl Rüdiger , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Artiges Eric , Nees Frauke , Orfanos Dimitri Papadopoulos , Lemaitre Herve , Paus Tomáš , Poustka Luise , Hohmann Sarah , Millenet Sabina , Fröhner Juliane H. , Smolka Michael N. , Walter Henrik , Whelan Robert , Schumann Gunter 
Published: May 2022

AbstractWhile there is substantial evidence that cannabis use is associated with differences in human brain development, most of this evidence is correlational in nature. Bayesian causal network (BCN) modeling attempts to identify probable causal relationships in correlational data using conditional probabilities to estimate directional associations between a set of interrelated variables. In this study, we employed BCN modeling in 637 adolescents from the IMAGEN study who were cannabis naïve at age 14 to provide evidence that the accelerated prefrontal cortical thinning found previously in adolescent cannabis users by Albaugh et al. [1] is a result of cannabis use causally affecting neurodevelopment. BCNs incorporated data on cannabis use, prefrontal cortical thickness, and other factors related to both brain development and cannabis use, including demographics, psychopathology, childhood adversity, and other substance use. All BCN algorithms strongly suggested a directional relationship from adolescent cannabis use to accelerated cortical thinning. While BCN modeling alone does not prove a causal relationship, these results are consistent with a body of animal and human research suggesting that adolescent cannabis use adversely affects brain development.
CD4+ T cells are required to improve the efficacy of CIK therapy in non-small cell lung cancer
Authors: Liu Shaochuan , Meng Yuan , Liu Liang , Lv Yingge , Yu Wenwen , Liu Ting , Wang Limei , Mu Di , Zhou Qiuru , Liu Min , Ren Yulin , Zhang Dong , Li Baihui , Sun Qian , Ren Xiubao 
Published: May 2022

AbstractAs a widely studied adoptive treatment method, CIK (cytokine-induced killer cells) treatment has shown clinical benefits in many clinical trials on non-small cell lung cancer. As a heterogeneous cell population, however, CIK cells have a strong instability and individual differences in their efficacies, which are collaboratively regulated by the tumor microenvironment and CIK subpopulations. Among them, CD4+ T cells belong to a crucial subgroup of the CIK cell population, and their influence on CIK therapy is still unclear. Herein, we show how CD4+ T cells positively regulate the functions of CD3+CD56+ T and CD3+CD8+ T cells. During this process, we found that Th1/Th17 CD4+ subgroups can induce the phosphorylation of the AKT pathway by secreting IL-17A, and upregulate the expression of T-bet/Eomes transcription factors, thereby restoring the function of CD8+/CD3+CD56+ T cells and reversing the exhaustion of PD-1+Tim-3+ T cells. These findings will provide guidance for the clinical screening of suitable populations for CIK treatment and formulation of strategies for CIK therapy plus immune checkpoint treatment. Based on these findings, we are conducting an open-label phase II study (NCT04836728) is to evaluate the effects of autologous CIKs in combination with PD-1 inhibitor in the first-line treatment of IV NSCLC, and hope to observe patients’ benefits in this clinical trial.
Single-cell characterization of malignant phenotypes and microenvironment alteration in retinoblastoma
Authors: Wu Cheng , Yang Jiaqi , Xiao Wei , Jiang Zehang , Chen Shuxia , Guo Dianlei , Zhang Ping , Liu Chunqiao , Yang Huasheng , Xie Zhi 
Published: May 2022

AbstractRetinoblastoma (RB) is the most common primary intraocular malignancy of childhood. It is known that the tumor microenvironment (TME) regulates tumorigenesis and metastasis. However, how the malignant progression in RB is determined by the heterogeneity of tumor cells and TME remains uncharacterized. Here, we conducted integrative single-cell transcriptome and whole-exome sequencing analysis of RB patients with detailed pathological and clinical measurements. By single-cell transcriptomic sequencing, we profiled around 70,000 cells from tumor samples of seven RB patients. We identified that the major cell types in RB were cone precursor-like (CP-like) and MKI67+ cone precursor (MKI67+ CP) cells. By integrating copy number variation (CNV) analysis, we found that RB samples had large clonal heterogeneity, where the malignant MKI67+ CP cells had significantly larger copy number changes. Enrichment analysis revealed that the conversion of CP-like to MKI67+ CP resulted in the loss of photoreceptor function and increased cell proliferation ability. The TME in RB was composed of tumor-associated macrophages (TAMs), astrocyte-like, and cancer-associated fibroblasts (CAFs). Particularly, during the invasion process, TAMs created an immunosuppressive environment, in which the proportion of TAMs decreased, M1-type macrophage was lost, and the TAMs-related immune functions were depressed. Finally, we identified that TAMs regulated tumor cells through GRN and MIF signaling pathways, while TAMs self-regulated through inhibition of CCL and GALECTIN signaling pathways during the invasion process. Altogether, our study creates a detailed transcriptomic map of RB with single-cell characterization of malignant phenotypes and provides novel molecular insights into the occurrence and progression of RB.
Fluorinated ether electrolyte with controlled solvation structure for high voltage lithium metal batteries
Authors: Zhao Yan , Zhou Tianhong , Ashirov Timur , Kazzi Mario El , Cancellieri Claudia , Jeurgens Lars P. H. , Choi Jang Wook , Coskun Ali 
Published: May 2022

AbstractThe development of new solvents is imperative in lithium metal batteries due to the incompatibility of conventional carbonate and narrow electrochemical windows of ether-based electrolytes. Whereas the fluorinated ethers showed improved electrochemical stabilities, they can hardly solvate lithium ions. Thus, the challenge in electrolyte chemistry is to combine the high voltage stability of fluorinated ethers with high lithium ion solvation ability of ethers in a single molecule. Herein, we report a new solvent, 2,2-dimethoxy-4-(trifluoromethyl)-1,3-dioxolane (DTDL), combining a cyclic fluorinated ether with a linear ether segment to simultaneously achieve high voltage stability and tune lithium ion solvation ability and structure. High oxidation stability up to 5.5 V, large lithium ion transference number of 0.75 and stable Coulombic efficiency of 99.2% after 500 cycles proved the potential of DTDL in high-voltage lithium metal batteries. Furthermore, 20 μm thick lithium paired LiNi0.8Co0.1Mn0.1O2 full cell incorporating 2 M LiFSI-DTDL electrolyte retained 84% of the original capacity after 200 cycles at 0.5 C.
Mobility enhancement in heavily doped semiconductors via electron cloaking
Authors: Zhou Jiawei , Zhu Hangtian , Song Qichen , Ding Zhiwei , Mao Jun , Ren Zhifeng , Chen Gang 
Published: May 2022

AbstractDoping is central for solid-state devices from transistors to thermoelectric energy converters. The interaction between electrons and dopants plays a pivotal role in carrier transport. Conventional theory suggests that the Coulomb field of the ionized dopants limits the charge mobility at high carrier densities, and that either the atomic details of the dopants are unimportant or the mobility can only be further degraded, while experimental results often show that dopant choice affects mobility. In practice, the selection of dopants is still mostly a trial-and-error process. Here we demonstrate, via first-principles simulation and comparison with experiments, that a large short-range perturbation created by selected dopants can in fact counteract the long-range Coulomb field, leading to electron transport that is nearly immune to the presence of dopants. Such “cloaking” of dopants leads to enhanced mobilities at high carrier concentrations close to the intrinsic electron–phonon scattering limit. We show that the ionic radius can be used to guide dopant selection in order to achieve such an electron-cloaking effect. Our finding provides guidance to the selection of dopants for solid-state conductors to achieve high mobility for electronic, photonic, and energy conversion applications.
Transmembrane stem cell factor protein therapeutics enhance revascularization in ischemia without mast cell activation
Authors: Takematsu Eri , Massidda Miles , Auster Jeff , Chen Po-Chih , Im ByungGee , Srinath Sanjana , Canga Sophia , Singh Aditya , Majid Marjan , Sherman Michael , Dunn Andrew , Graham Annette , Martin Patricia , Baker Aaron B. 
Published: May 2022

AbstractStem cell factor (SCF) is a cytokine that regulates hematopoiesis and other biological processes. While clinical treatments using SCF would be highly beneficial, these have been limited by toxicity related to mast cell activation. Transmembrane SCF (tmSCF) has differential activity from soluble SCF and has not been explored as a therapeutic agent. We created novel therapeutics using tmSCF embedded in proteoliposomes or lipid nanodiscs. Mouse models of anaphylaxis and ischemia revealed the tmSCF-based therapies did not activate mast cells and improved the revascularization in the ischemic hind limb. Proteoliposomal tmSCF preferentially acted on endothelial cells to induce angiogenesis while tmSCF nanodiscs had greater activity in inducing stem cell mobilization and recruitment to the site of injury. The type of lipid nanocarrier used altered the relative cellular uptake pathways and signaling in a cell type dependent manner. Overall, we found that tmSCF-based therapies can provide therapeutic benefits without off target effects.
SIMILE enables alignment of tandem mass spectra with statistical significance
Authors: Treen Daniel G. C. , Wang Mingxun , Xing Shipei , Louie Katherine B. , Huan Tao , Dorrestein Pieter C. , Northen Trent R. , Bowen Benjamin P. 
Published: May 2022

AbstractInterrelating small molecules according to their aligned fragmentation spectra is central to tandem mass spectrometry-based untargeted metabolomics. Current alignment algorithms do not provide statistical significance and compounds that have multiple delocalized structural differences and therefore often fail to have their fragment ions aligned. Here we align fragmentation spectra with both statistical significance and allowance for multiple chemical differences using Significant Interrelation of MS/MS Ions via Laplacian Embedding (SIMILE). SIMILE yields spectral alignment inferred structural connections in molecular networks that are not found with cosine-based scoring algorithms. In addition, it is now possible to rank spectral alignments based on p-values in the exploration of structural relationships between compounds and enhance the chemical connectivity that can be obtained with molecular networking.
WAKE-mediated modulation of cVA perception via a hierarchical neuro-endocrine axis in Drosophila male-male courtship behaviour
Authors: Chen Shiu-Ling , Liu Bo-Ting , Lee Wang-Pao , Liao Sin-Bo , Deng Yao-Bang , Wu Chia-Lin , Ho Shuk-Man , Shen Bing-Xian , Khoo Guan-Hock , Shiu Wei-Chiang , Chang Chih-Hsuan , Shih Hui-Wen , Wen Jung-Kun , Lan Tsuo-Hung , Lin Chih-Chien , Tsai Yu-Chen , Tzeng Huey-Fen , Fu Tsai-Feng 
Published: May 2022

AbstractThe nervous and endocrine systems coordinate with each other to closely influence physiological and behavioural responses in animals. Here we show that WAKE (encoded by wide awake, also known as wake) modulates membrane levels of GABAA receptor Resistance to Dieldrin (Rdl), in insulin-producing cells of adult male Drosophila melanogaster. This results in changes to secretion of insulin-like peptides which is associated with changes in juvenile hormone biosynthesis in the corpus allatum, which in turn leads to a decrease in 20-hydroxyecdysone levels. A reduction in ecdysone signalling changes neural architecture and lowers the perception of the male-specific sex pheromone 11-cis-vaccenyl acetate by odorant receptor 67d olfactory neurons. These finding explain why WAKE-deficient in Drosophila elicits significant male-male courtship behaviour.
Regulation of A-to-I RNA editing and stop codon recoding to control selenoprotein expression during skeletal myogenesis
Authors: Noda Yuta , Okada Shunpei , Suzuki Tsutomu 
Published: May 2022

AbstractSelenoprotein N (SELENON), a selenocysteine (Sec)-containing protein with high reductive activity, maintains redox homeostasis, thereby contributing to skeletal muscle differentiation and function. Loss-of-function mutations in SELENON cause severe neuromuscular disorders. In the early-to-middle stage of myoblast differentiation, SELENON maintains redox homeostasis and modulates endoplasmic reticulum (ER) Ca2+ concentration, resulting in a gradual reduction from the middle-to-late stages due to unknown mechanisms. The present study describes post-transcriptional mechanisms that regulate SELENON expression during myoblast differentiation. Part of an Alu element in the second intron of SELENON pre-mRNA is frequently exonized during splicing, resulting in an aberrant mRNA that is degraded by nonsense-mediated mRNA decay (NMD). In the middle stage of myoblast differentiation, ADAR1-mediated A-to-I RNA editing occurs in the U1 snRNA binding site at 5′ splice site, preventing Alu exonization and producing mature mRNA. In the middle-to-late stage of myoblast differentiation, the level of Sec-charged tRNASec decreases due to downregulation of essential recoding factors for Sec insertion, thereby generating a premature termination codon in SELENON mRNA, which is targeted by NMD.
Neural signals regulating motor synchronization in the primate deep cerebellar nuclei
Authors: Okada Ken-ichi , Takeya Ryuji , Tanaka Masaki 
Published: May 2022

AbstractMovements synchronized with external rhythms are ubiquitous in our daily lives. Despite the involvement of the cerebellum, the underlying mechanism remains unclear. In monkeys performing synchronized saccades to periodically alternating visual stimuli, we found that neuronal activity in the cerebellar dentate nucleus correlated with the timing of the next saccade and the current temporal error. One-third of the neurons were active regardless of saccade direction and showed greater activity for synchronized than for reactive saccades. During the transition from reactive to predictive saccades in each trial, the activity of these neurons coincided with target onset, representing an internal model of rhythmic structure rather than a specific motor command. The behavioural changes induced by electrical stimulation were explained by activating different groups of neurons at various strengths, suggesting that the lateral cerebellum contains multiple functional modules for the acquisition of internal rhythms, predictive motor control, and error detection during synchronized movements.
Catalytic asymmetric Tsuji–Trost α−benzylation reaction of N-unprotected amino acids and benzyl alcohol derivatives
Authors: Liu Jian-Hua , Wen Wei , Liao Jian , Shen Qi-Wen , Lin Yao , Wu Zhu-Lian , Cai Tian , Guo Qi-Xiang 
Published: May 2022

AbstractCatalytic asymmetric Tsuji–Trost benzylation is a promising strategy for the preparation of chiral benzylic compounds. However, only a few such transformations with both good yields and enantioselectivities have been achieved since this reaction was first reported in 1992, and its use in current organic synthesis is restricted. In this work, we use N-unprotected amino acid esters as nucleophiles in reactions with benzyl alcohol derivatives. A ternary catalyst comprising a chiral aldehyde, a palladium species, and a Lewis acid is used to promote the reaction. Both mono- and polycyclic benzyl alcohols are excellent benzylation reagents. Various unnatural optically active α-benzyl amino acids are produced in good-to-excellent yields and with good-to-excellent enantioselectivities. This catalytic asymmetric method is used for the formal synthesis of two somatostatin mimetics and the proposed structure of natural product hypoestestatin 1. A mechanism that plausibly explains the stereoselective control is proposed.
A route towards the fabrication of large-scale and high-quality perovskite films for optoelectronic devices
Authors: Rezaee Ehsan , Kutsarov Dimitar , Li Bowei , Bi Jinxin , Silva S. Ravi P. 
Published: May 2022

AbstractHalide perovskite materials have been extensively explored for their unique electrical, optical, magnetic, and catalytic properties. Most notably, solar cells based on perovskite thin films have improved their power conversion efficiency from 3.8% to over 25% during the last 12 years. However, it is still a challenge to develop a perovskite-based ink, suitable for upscaling the fabrication process of high-quality perovskite films with extreme purity, good crystallinity, and complete coverage over the deposition area. This is particularly important if the perovskite films are to be used for the scaled production of optoelectronic devices. Therefore, to make halide perovskites commercially available for various applications, it is vital to develop a reliable and highly robust deposition method, which can then be transferred to industry. Herein, the development of perovskite precursor inks suitable for use at low-temperature and vacuum-free solution-based deposition processes is reported. These inks can be further tailored according to the requirements of the deposition method, i.e., we propose their use with the industrially viable deposition technique called “slot-die coating”. Furthermore, a route for the preparation of low-cost and high-volume manufacturing of perovskite films on both rigid and flexible substrates is suggested in this paper. The presented approach is suitable for the fabrication of any functional layers of perovskites, that can be employed in various scaled applications, and it seeks the potential and the methodology for perovskite film deposition that is scalable to industrial standards.
A novel non-invasive method of measuring microcirculatory perfusion and blood velocity in infants: a pilot study
Authors: Gangaram-Panday Norani H. , te Nijenhuis Louwrina H. , Fine Ilya , Reiss Irwin K. M. , van Weteringen Willem 
Published: May 2022

AbstractCurrent haemodynamic monitoring is mainly aimed at the macrocirculation. Multiple studies have demonstrated the importance of the microcirculation in relation to the patient’s condition and impact of treatment strategies. However, continuous monitoring of the microcirculation is not yet possible in the neonatal field. A novel dynamic light scattering (DLS) sensor technology for continuous monitoring of the microcirculation was investigated in the neonatal population. Thirty-one haemodynamically stable infants were included. Sequential measurements at the forehead, upper extremity, thorax, abdomen and lower extremity were conducted with the DLS sensor. For analyses stable measurements were selected. The DLS parameters, total blood flow (TBF) and relative blood velocity (RBV), were compared between measurement locations. Changes in relative haemodynamic indices (relHIs), indicating the distribution of blood flow in the microcirculatory blood vessels, were associated with heart rate decelerations. Measurements performed at the forehead had significantly lower TBF levels, compared to measurements at other locations. Early changes in relHIs around a heart rate deceleration were recorded a median (IQR) of 22.0 (13.5–27.0) s before the onset. Measurement of the currently unavailable parameters TBF, RBV and relHIs is possible with DLS technology. Validation of the DLS technology is needed for clinical implementation.
Multiple health complaints in preadolescence and hospital contacts during adolescence: a prospective cohort study
Authors: Bernstorff Martin , Rask Charlotte Ulrikka , Rytter Dorte , Hansen Stefan Nygaard , Bech Bodil Hammer 
Published: May 2022

AbstractMultiple health complaints (MHC) is increasing among preadolescents in many countries, but their prognostic effect for individual thriving or societal resource use is scarcely studied. This makes interpreting the significance of this increase challenging. We contribute by examining whether MHC in preadolescence predicts hospital contacts in adolescence by doing a nation-wide population-based cohort-study following preadolescents from the Danish National Birth-Cohort from 2010 to 2018. 96,382 children were invited at age 11. Responses to a modified version of the Health Behaviour in School Children Symptom Checklist (headache, dizziness, stomachache, irritability, feeling nervous, difficulty in getting to sleep and feeling low) was dichotomized into MHC (≥ 2 concurrent symptoms, each with a frequency of at least weekly, yes/no). Hospital contacts were derived from Danish registers from the date of answering the questionnaire to December 31st 2018. Negative binomial regression estimated incidence rate ratios (IRRs) comparing children with MHC to children without. Analyses were further broken down by hospital sector (psychiatric/somatic) and contact type (in-patient/out-patient/emergency room). 47,365 (49.1%) responded. Mean age was 11.2 years, 52% girls. 10.3% of responders reported MHC. For hospital contacts, the unadjusted IRR was 1.74 [95% CI 1.65, 1.83]. Results were robust to adjustment for sociodemographic variables and somatic/psychiatric morbidity diagnosed before baseline, IRR 1.62 [95% CI 1.54–1.71]. In conclusion, MHC in preadolescents are prognostic of hospital contacts. This shows that we cannot ignore MHC, and to prevent potentially unhelpful healthcare use, we must act. Future research should focus on the underlying causes of MHC to understand which changes will be most helpful and thus how to act.
Chiral germanium micro-gears for tuning orbital angular momentum
Authors: Al-Attili Abdelrahman Zaher , Burt Daniel , Li Zuo , Higashitarumizu Naoki , Gardes Frederic , Ishikawa Yasuhiko , Saito Shinichi 
Published: May 2022

AbstractGroup IV light sources with vertical emission and non-zero orbital-angular momentum (OAM) promise to unlock many novel applications. In this report, we demonstrate cylindrically symmetrical germanium micro-gear cavities, fabricated by etching a grating around the circumference of standard micro-disks, with periods ranging from 14 to 22. Photoluminescence (PL) measurements were done to identify the confined whispering-gallery modes (WGM). Finite-difference time-domain (FDTD) simulations were conducted to map the resonant modes to their modal profiles and characteristics. Vertical emission of WGMs with non-zero OAM was demonstrated, with a clear dependence of the OAM order ($$\ell$$
ℓ
) on the WGM azimuthal order and the number of micro-gear grating periods. As the chirality, or the direction of rotation, is not controlled in a symmetrical cavity, we propose introducing staircase or triangular-shaped gear periods resulting in an asymmetry. By choosing the diameter, number of periods, and the asymmetrical direction of the gear-teeth, it is possible to generate OAM signals with certain wavelength, OAM order and chirality.