bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of early psychosis patients carrying a genetic vulnerability to redox dysregulation: a computational analysis of mechanism-based gene expression profile in fibroblasts
Authors: Giangreco Basilio , Dwir Daniella , Klauser Paul , Jenni Raoul , Golay Philippe , Cleusix Martine , Baumann Philipp S. , Cuénod Michel , Conus Philippe , Toni Nicolas , Do Kim Q. 
Published: March 2023

AbstractIn view of its heterogeneity, schizophrenia needs new diagnostic tools based on mechanistic biomarkers that would allow early detection. Complex interaction between genetic and environmental risk factors may lead to NMDAR hypofunction, inflammation and redox dysregulation, all converging on oxidative stress. Using computational analysis, the expression of 76 genes linked to these systems, known to be abnormally regulated in schizophrenia, was studied in skin-fibroblasts from early psychosis patients and age-matched controls (N = 30), under additional pro-oxidant challenge to mimic environmental stress. To evaluate the contribution of a genetic risk related to redox dysregulation, we investigated the GAG trinucleotide polymorphism in the key glutathione (GSH) synthesizing enzyme, glutamate-cysteine-ligase-catalytic-subunit (gclc) gene, known to be associated with the disease. Patients and controls showed different gene expression profiles that were modulated by GAG-gclc genotypes in combination with oxidative challenge. In GAG-gclc low-risk genotype patients, a global gene expression dysregulation was observed, especially in the antioxidant system, potentially induced by other risks. Both controls and patients with GAG-gclc high-risk genotype (gclcGAG-HR) showed similar gene expression profiles. However, under oxidative challenge, a boosting of other antioxidant defense, including the master regulator Nrf2 and TRX systems was observed only in gclcGAG-HR controls, suggesting a protective compensation against the genetic GSH dysregulation. Moreover, RAGE (redox/inflammation interaction) and AGMAT (arginine pathway) were increased in the gclcGAG-HR patients, suggesting some additional risk factors interacting with this genotype. Finally, the use of a machine-learning approach allowed discriminating patients and controls with an accuracy up to 100%, paving the way towards early detection of schizophrenia.
Fludarabine/TBI 8 Gy versus fludarabine/treosulfan conditioning in patients with AML in first complete remission: a study from the Acute Leukemia Working Party of the EBMT
Authors: Bug Gesine , Labopin Myriam , Niittyvuopio Riitta , Stelljes Matthias , Reinhardt Hans Christian , Hilgendorf Inken , Kröger Nicolaus , Kaare Ain , Bethge Wolfgang , Schäfer-Eckart Kerstin , Verbeek Mareike , Mielke Stephan , Carlson Kristina , Bazarbachi Ali , Spyridonidis Alexandros , Savani Bipin N. , Nagler Arnon , Mohty Mohamad 
Published: March 2023

AbstractThe optimal reduced intensity conditioning (RIC) regimen is a matter of debate. We retrospectively compared conditioning with fludarabine plus fractionated total body irradiation of 8 Gy (FluTBI) and fludarabine plus treosulfan 30, 36 or 42 g/m2 (FluTreo) in 754 patients with AML above the age of 40 years undergoing an allogeneic hematopoietic stem cell transplant (HSCT) in first complete remission (CR). After balancing patient characteristics by propensity score matching of 115 patients in each group, FluTBI was associated with a significantly lower probability of relapse compared to FluTreo (18.3% vs. 34.7%, p = 0.018) which was counteracted by a higher non-relapse mortality (NRM, 16.8% vs. 5.3%, p = 0.02). Thus, overall survival and graft-versus-host disease-free and relapse-free survival at 2 years were similar between groups (OS 66.9% vs. 67.8%, GRFS 50.3% vs. 45.6%). Univariate analysis by age group demonstrated a higher NRM exclusively in patients ≥55 years of age treated with FluTBI compared to FluTreo (27.6% vs. 5.8%, p = 0.02), while a similarly low NRM was observed in patients <55 years in both groups (6.0% vs. 4.7%, p = ns). We conclude that both conditioning regimens are effective and safe, but FluTBI may better be reserved for younger patients below the age of 55 years.
Liquid biopsy on the horizon in immunotherapy of non-small cell lung cancer: current status, challenges, and perspectives
Authors: Yang Ying , Liu Hongyang , Chen Youming , Xiao Nan , Zheng Zhaoyang , Liu Hongchun , Wan Junhu 
Published: March 2023

AbstractNon-small cell lung cancer (NSCLC) is one of the most threatening malignancies to human health and life. In most cases, patients with NSCLC are already at an advanced stage when they are diagnosed. In recent years, lung cancer has made great progress in precision therapy, but the efficacy of immunotherapy is unstable, and its response rate varies from patient to patient. Several biomarkers have been proposed to predict the outcomes of immunotherapy, such as programmed cell death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB). Nevertheless, the detection assays are invasive and demanding on tumor tissue. To effectively predict the outcomes of immunotherapy, novel biomarkers are needed to improve the performance of conventional biomarkers. Liquid biopsy is to capture and detect circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and exosomes in body fluids, such as blood, saliva, urine, pleural fluid and cerebrospinal fluid as samples from patients, so as to make analysis and diagnosis of cancer and other diseases. The application of liquid biopsy provides a new possible solution, as it has several advantages such as non-invasive, real-time dynamic monitoring, and overcoming tumor heterogeneity. Liquid biopsy has shown predictive value in immunotherapy, significantly improving the precision treatment of lung cancer patients. Herein, we review the application of liquid biopsy in predicting the outcomes of immunotherapy in NSCLC patients, and discuss the challenges and future directions in this field.
Structural insights into the mechanism of leptin receptor activation
Authors: Saxton Robert A. , Caveney Nathanael A. , Moya-Garzon Maria Dolores , Householder Karsten D. , Rodriguez Grayson E. , Burdsall Kylie A. , Long Jonathan Z. , Garcia K. Christopher 
Published: March 2023

AbstractLeptin is an adipocyte-derived protein hormone that promotes satiety and energy homeostasis by activating the leptin receptor (LepR)–STAT3 signaling axis in a subset of hypothalamic neurons. Leptin signaling is dysregulated in obesity, however, where appetite remains elevated despite high levels of circulating leptin. To gain insight into the mechanism of leptin receptor activation, here we determine the structure of a stabilized leptin-bound LepR signaling complex using single particle cryo-EM. The structure reveals an asymmetric architecture in which a single leptin induces LepR dimerization via two distinct receptor-binding sites. Analysis of the leptin–LepR binding interfaces reveals the molecular basis for human obesity-associated mutations. Structure-based design of leptin variants that destabilize the asymmetric LepR dimer yield both partial and biased agonists that partially suppress STAT3 activation in the presence of wild-type leptin and decouple activation of STAT3 from LepR negative regulators. Together, these results reveal the structural basis for LepR activation and provide insights into the differential plasticity of signaling pathways downstream of LepR.
Endothelial deletion of PTBP1 disrupts ventricular chamber development
Authors: Liu Hongyu , Duan Ran , He Xiaoyu , Qi Jincu , Xing Tianming , Wu Yahan , Zhou Liping , Wang Lingling , Shao Yujing , Zhang Fulei , Zhou Huixing , Gu Xingdong , Lin Bowen , Liu Yuanyuan , Wang Yan , Liu Yi , Li Li , Liang Dandan , Chen Yi-Han 
Published: March 2023

AbstractThe growth and maturation of the ventricular chamber require spatiotemporally precise synergy between diverse cell types. Alternative splicing deeply affects the processes. However, the functional properties of alternative splicing in cardiac development are largely unknown. Our study reveals that an alternative splicing factor polypyrimidine tract-binding protein 1 (PTBP1) plays a key role in ventricular chamber morphogenesis. During heart development, PTBP1 colocalizes with endothelial cells but is almost undetectable in cardiomyocytes. The endothelial-specific knockout of Ptbp1, in either endocardial cells or pan-endothelial cells, leads to a typical phenotype of left ventricular noncompaction (LVNC). Mechanistically, the deletion of Ptbp1 reduces the migration of endothelial cells, disrupting cardiomyocyte proliferation and ultimately leading to the LVNC. Further study shows that Ptbp1 deficiency changes the alternative splicing of β-arrestin-1 (Arrb1), which affects endothelial cell migration. In conclusion, as an alternative splicing factor, PTBP1 is essential during ventricular chamber development, and its deficiency can lead to congenital heart disease.
The structural basis of the pH-homeostasis mediated by the Cl−/HCO3− exchanger, AE2
Authors: Zhang Qing , Jian Liyan , Yao Deqiang , Rao Bing , Xia Ying , Hu Kexin , Li Shaobai , Shen Yafeng , Cao Mi , Qin An , Zhao Jie , Cao Yu 
Published: March 2023

AbstractThe cell maintains its intracellular pH in a narrow physiological range and disrupting the pH-homeostasis could cause dysfunctional metabolic states. Anion exchanger 2 (AE2) works at high cellular pH to catalyze the exchange between the intracellular HCO3− and extracellular Cl−, thereby maintaining the pH-homeostasis. Here, we determine the cryo-EM structures of human AE2 in five major operating states and one transitional hybrid state. Among those states, the AE2 shows the inward-facing, outward-facing, and intermediate conformations, as well as the substrate-binding pockets at two sides of the cell membrane. Furthermore, critical structural features were identified showing an interlock mechanism for interactions among the cytoplasmic N-terminal domain and the transmembrane domain and the self-inhibitory effect of the C-terminal loop. The structural and cell-based functional assay collectively demonstrate the dynamic process of the anion exchange across membranes and provide the structural basis for the pH-sensitive pH-rebalancing activity of AE2.
Lamella-heterostructured nanoporous bimetallic iron-cobalt alloy/oxyhydroxide and cerium oxynitride electrodes as stable catalysts for oxygen evolution
Authors: Zeng Shu-Pei , Shi Hang , Dai Tian-Yi , Liu Yang , Wen Zi , Han Gao-Feng , Wang Tong-Hui , Zhang Wei , Lang Xing-You , Zheng Wei-Tao , Jiang Qing 
Published: March 2023

AbstractDeveloping robust nonprecious-metal electrocatalysts with high activity towards sluggish oxygen-evolution reaction is paramount for large-scale hydrogen production via electrochemical water splitting. Here we report that self-supported laminate composite electrodes composed of alternating nanoporous bimetallic iron-cobalt alloy/oxyhydroxide and cerium oxynitride (FeCo/CeO2−xNx) heterolamellas hold great promise as highly efficient electrocatalysts for alkaline oxygen-evolution reaction. By virtue of three-dimensional nanoporous architecture to offer abundant and accessible electroactive CoFeOOH/CeO2−xNx heterostructure interfaces through facilitating electron transfer and mass transport, nanoporous FeCo/CeO2−xNx composite electrodes exhibit superior oxygen-evolution electrocatalysis in 1 M KOH, with ultralow Tafel slope of ~33 mV dec−1. At overpotential of as low as 360 mV, they reach >3900 mA cm−2 and retain exceptional stability at ~1900 mA cm−2 for >1000 h, outperforming commercial RuO2 and some representative oxygen-evolution-reaction catalysts recently reported. These electrochemical properties make them attractive candidates as oxygen-evolution-reaction electrocatalysts in electrolysis of water for large-scale hydrogen generation.
A randomized clinical trial for comparing the efficacy of desensitizing toothpastes on the relief of dentin hypersensitivity
Authors: Jang Ji-Hyun , Oh Soram , Kim Hyun-Jung , Kim Duck-Su 
Published: March 2023

AbstractThe 4-week double-blind clinical trial to manage dentin hypersensitivity (DH) using different desensitizing toothpastes was conducted. 53 participants with DH were enrolled in this trial. The participants were randomized into 3 groups: Group N; no active ingredient-containing toothpaste (Pleasia fluoride-free), Group SC; a toothpaste containing strontium chloride (Sensodyne Original), and Group TP; a toothpaste containing tricalcium phosphate (Vussen S). They were instructed to brush their teeth manually for 3 min, 3 times per day for 4 weeks with the allocated toothpastes, and were assessed at baseline (0), 2, and 4 weeks, respectively. Schiff sensitivity score was recorded to 3 different stimuli (air-blast, cold, and acid) at each assessment. Overall DH was also assessed using a visual analog scale (VAS). The longer participants used the toothpastes, the greater reduction in DH in all groups to the three stimuli. Group TP demonstrated significant reduction of DH compared to group N for air-blast and cold stimuli. Group TP showed significantly lower VAS than group N and SC. Tricalcium phosphate containing toothpaste used in this trial was most useful to reduce DH. It can be one of the treatment options that alleviate DH.
Short-term memory capacity analysis of Lu3Fe4Co0.5Si0.5O12-based spin cluster glass towards reservoir computing
Authors: Liao Zhiqiang , Yamahara Hiroyasu , Terao Kenyu , Ma Kaijie , Seki Munetoshi , Tabata Hitoshi 
Published: March 2023

AbstractReservoir computing is a brain heuristic computing paradigm that can complete training at a high speed. The learning performance of a reservoir computing system relies on its nonlinearity and short-term memory ability. As physical implementation, spintronic reservoir computing has attracted considerable attention because of its low power consumption and small size. However, few studies have focused on developing the short-term memory ability of the material itself in spintronics reservoir computing. Among various magnetic materials, spin glass is known to exhibit slow magnetic relaxation that has the potential to offer the short-term memory capability. In this research, we have quantitatively investigated the short-term memory capability of spin cluster glass based on the prevalent benchmark. The results reveal that the magnetization relaxation of Co, Si-substituted Lu3Fe5O12 with spin glass behavior can provide higher short-term memory capacity than ferrimagnetic material without substitution. Therefore, materials with spin glass behavior can be considered as potential candidates for constructing next-generation spintronic reservoir computing with better performance.
Effect of Ag modification on TiO2 and melem/g-C3N4 composite on photocatalytic performances
Authors: Michalska M. , Matějka V. , Pavlovský J. , Praus P. , Ritz M. , Serenčíšová J. , Gembalová L. , Kormunda M. , Foniok K. , Reli M. , Simha Martynková G. 
Published: March 2023

AbstractHere, the comparison of two different semiconductor materials is demonstrated, TiO2 and melem/g-C3N4 composites—modified with balls of approximately 5 nm Ag nanoparticles (NPs) as photocatalysts for the degradation of the model dye acid orange 7 (AO7). The melem molecule synthesized here is one of a series of organic compounds consisting of triazine ring compounds with a structure similar to that of melam and melamine. The photodegradation process of AO7 was carried out to examine all powder materials as a potential photocatalyst. Additionally, two different lamps of wavelengths 368 nm (UV light) and 420 nm (VIS light) were applied to compare the photodegradation tests. A new synthesis route for the acquisition of Ag NPs (Ag content 0.5, 1.0 and 2.5 wt%), based on a wet and low temperature method without the use of reducing reagents was proposed. The best photocatalytic performances under UV and VIS light were obtained for both, TiO2 and melem/g-C3N4 materials (new synthesis route) modified with a very low Ag content—0.5 wt%. The photodegradation activities using UV lamp (3 h, 368 nm irradiation) for samples with 0.5 wt% of Ag: TiO2 and melem/g-C3N4, in excess of 95 and 94%, respectively, were achieved. The highest photoactive materials melem/g-C3N4 with 0.5 and 1 wt% Ag revealed 98% of activity under the VIS lamp after 3 h long irradiation. Our work demonstrates a novel, environmentally acceptable, and cost-effective chemical strategy for preparation of photocatalysts suitable for degradation of organic contaminants in wastewater treatment.
Deep sequencing of microRNAs reveals circadian-dependent microRNA expression in the eyestalks of the Chinese mitten crab Eriocheir sinensis
Authors: Yu Changyue , Huang Zhiwei , Xu Yingkai , Zhang Baoli , Li Yingdong 
Published: March 2023

AbstractMicroRNAs (miRNAs) are small endogenous non-coding RNAs. In crustaceans, miRNAs might be involved in the regulation of circadian rhythms. Many physiological functions of crustaceans including immunity and hormone secretion exhibit circadian rhythms, but it remains unclear whether specific miRNAs contribute to the alteration of crustacean physiological processes under circadian rhythms. This study investigated the mechanisms of miRNA regulation of circadian rhythms in the Chinese mitten crab (Eriocheir sinensis), one of China's most important aquaculture species. We obtained eyestalks from crab specimens at four time points (6:00; 12:00; 18:00; 24:00) during a 24-h period. We identified 725 mature miRNAs, with 23 known miRNAs differentially expressed depending on the time of day. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that the putative target genes for differentially expressed miRNAs were significantly enriched in the immune response and endocrine-related pathways. Numerous putative target genes are involved in the circadian-related pathways and enriched on circadian-control genes. These results suggest that the expression of miRNAs regulates some specific physiological functions in E. sinensis under circadian cycles. We also profiled various putative target genes enriched under the circadian-related pathway. This study performed miRNA expression in the eyestalks of E. sinensis during a 24-h daily cycle, providing insights into the molecular mechanism underlying crustacean circadian rhythms and suggesting miRNAs' role in studying crustacean physiology should not be overlooked.
Perceived difficulty of upwind shouting is a misconception explained by convective attenuation effect
Authors: Pulkki Ville , Daugintis Rapolas , Lähivaara Timo , Öyry Aleksi 
Published: March 2023

AbstractIt is a common thought that in windy conditions the voice of a shouter emanates towards the upwind with lower strength than towards the downwind. Contradicting with this, acoustics literature states that a source emanates with a higher amplitude against the upwind direction in comparison with the downwind direction, which is known as the convective amplification or attenuation effect. This article shows that the discrepancy arises because shouters receive their own voice at their ear canals worse when facing against the upwind direction than in the corresponding down-wind case. When shouting upwind, the ears are situated downwind from the mouth, and the strength of one’s own voice decreases in the ears due to the convective attenuation effect depending on frequency, making the shouter believe that it is more difficult to shout against the wind. This is shown by computational simulations and real measurements using models of a human shouter with simplified geometries.
Environmental-friendly regenerated lignocellulose functionalized cotton fabric to prepare multi-functional degradable membrane for efficient oil–water separation and solar seawater desalination
Authors: Li Jiangyi , Gao Junkai , Fang Jiangyu , Ling Tian , Xia Mengsheng , Cao Xue , Han Zhi , Chen Yan 
Published: March 2023

AbstractFreshwater pollution and shortage have become an imminent problem. Therefore, it is necessary to develop a multi-functional membrane for the production of fresh water. In this work, the regenerated lignocellulose modified cotton fabric was developed as a novel, multi-functional and degradable membrane (LCPT@CF) for efficient oil–water separation and solar steam generation for the first time. The fabrication method has the merits of simple, environmentally friendly and cost effective. The regenerated lignocellulose was adhered on the surface of cotton fabric by tannic acid and polyvinyl alcohol complexes tightly, and the multilayered structures of the LCPT@CF can be formed, which endowed the membranes with underwater superoleophobic property and durability. The underwater superoleophobic property enabled LCPT@CF to purify various kinds of oil-in-water emulsions with a separation efficiency of more than 99.90%. Moreover, benefiting from the excellent photothermal conversion capacity of regenerated lignocellulose, the LCPT@CF achieved high evaporation rate of 1.39 kg m−2 h−1 and favorable evaporation efficiency of 84% under 1 sun illumination, and the LCPT@CF also presented excellent salt-resistance for evaporating seawater for 20 cycles, without salt accumulation. More importantly, the LCPT@CF could be naturally degradable by microorganisms in the natural condition within 3 months, which had outstanding environmental friendliness. These above results demonstrated that the green and efficient LCPT@CF could play great potential in oil–water separation and sewage purification.
Possible correlation of apical localization of MUC1 glycoprotein with luminal A-like status of breast cancer
Authors: Semba Ryoko , Horimoto Yoshiya , Sakata-Matsuzawa Madoka , Ishizuka Yumiko , Denda-Nagai Kaori , Fujihira Haruhiko , Noji Miki , Onagi Hiroko , Ichida Miyu , Miura Hiroyoshi , Watanabe Junichiro , Saito Mitsue , Saito Tsuyoshi , Arakawa Atsushi , Irimura Tatsuro 
Published: March 2023

AbstractAdjuvant chemotherapy has played a major role in the treatment of hormone receptor-positive breast cancer for many years. To better determine which patient subsets need adjuvant chemotherapy, various gene expression analyses have been developed, but cost-effective tools to identify such patients remain elusive. In the present report, we retrospectively investigated immunohistochemical expression and subcellular localization of MUC1 in primary tumors and examined their relationship to tumor malignancy, chemotherapy effect and patient outcomes. We retrospectively examined three patient cohorts with hormone receptor-positive/human epidermal growth factor receptor 2-negative invasive breast cancer: 51 patients who underwent 21-gene expression analysis (multi-gene assay-cohort), 96 patients who received neoadjuvant chemotherapy (neoadjuvant chemotherapy-cohort), and 609 patients whose tumor tissue was used in tissue-microarrays (tissue-microarray-cohort). The immunohistochemical staining pattern of the anti-MUC1 monoclonal antibody, Ma695, was examined in cancer tissues, and subcellular localization was determined as apical, cytoplasmic or negative. In the multi-gene assay-cohort, tumors with apical patterns had the lowest recurrence scores, reflecting lower tumor malignancy, and were significantly lower than MUC1-negative tumors (P = 0.038). In the neoadjuvant chemotherapy-cohort, there was no correlation between MUC1 staining patterns and effects of chemotherapy. Finally, in the tissue-microarray-cohort, we found that patients with apical MUC1 staining patterns had significantly longer disease-free-survival and overall survival than other patterns (P = 0.020 and 0.039, respectively). Our data suggest that an apical MUC1 staining pattern indicates luminal A-likeness. Assessment of the subcellular localization of MUC1 glycoprotein may be useful for identifying patients who can avoid adjuvant chemotherapy.