bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulated heme biosynthesis increases obstructive sleep apnea severity: a pathway-based Mendelian randomization study
Authors: Wang Heming , Kurniansyah Nuzulul , Cade Brian E. , Goodman Matthew O. , Chen Han , Gottlieb Daniel J. , Gharib Sina A. , Purcell Shaun M. , Lin Xihong , Saxena Richa , Zhu Xiaofeng , Durda Peter , Tracy Russel , Liu Yongmei , Taylor Kent D. , Johnson W. Craig , Gabriel Stacey , Smith Joshua D. , Aguet François , Ardlie Kirstin , Blackwell Tom , Reiner Alexander P. , Rotter Jerome I. , Rich Stephen S. ,   TOPMed Sleep Traits Working Group, Ayas Najib , Burkardt Deepika , Cade Brian , Chen Han , Clarkson-Townsend Danielle , Dutta Joyita , Ekunwe Lynette , Floyd Caitlin , Gharib Sina , Goodman Matthew , Gottlieb Daniel , Granot-Hershkovitz Einat , Hale Lauren , Hanly Patrick , Heemann Scott , Hsiung Chao , Huang Tianyi , Justice Anne , Keenan Brendan , Lane Jacqueline , Liang Jingjing , Lin Xihong , Liu Jiayan , Lorincz-Comi Noah , Magalang Ulysses , Mazzotti Diego R. , Mei Hao , Mikulla Julie , Miller Amy , Moafi-Madani Miremad , Ngo Debby , O’Connell Jeff , Ochs-Balcom Heather , Pack Allan , Patel Sanjay , Purcell Shaun , Redline Susan , Saxena Richa , Soemedi Rachel , Sofer Tamar , Sul Jae Hoon , Sunyaev Shamil , Tchio Cynthia , Wang Heming , Wilson Ava , Xia Lluvia , Zhang Man , Zhou Hufeng , Zhu Xiaofeng , Redline Susan , Sofer Tamar 
Published: January 2022

AbstractObstructive sleep apnea (OSA) is a common disorder associated with increased risk of cardiovascular disease and mortality. Iron and heme metabolism, implicated in ventilatory control and OSA comorbidities, was associated with OSA phenotypes in recent admixture mapping and gene enrichment analyses. However, its causal contribution was unclear. In this study, we performed pathway-level transcriptional Mendelian randomization (MR) analysis to investigate the causal relationships between iron and heme related pathways and OSA. In primary analysis, we examined the expression level of four iron/heme Reactome pathways as exposures and four OSA traits as outcomes using cross-tissue cis-eQTLs from the Genotype-Tissue Expression portal and published genome-wide summary statistics of OSA. We identify a significant putative causal association between up-regulated heme biosynthesis pathway with higher sleep time percentage of hypoxemia (p = 6.14 × 10–3). This association is supported by consistency of point estimates in one-sample MR in the Multi-Ethnic Study of Atherosclerosis using high coverage DNA and RNA sequencing data generated by the Trans-Omics for Precision Medicine project. Secondary analysis for 37 additional iron/heme Gene Ontology pathways did not reveal any significant causal associations. This study suggests a causal association between increased heme biosynthesis and OSA severity.
Identification of type of threading dislocation causing reverse leakage in GaN p–n junctions after continuous forward current stress
Authors: Narita Tetsuo , Kanechika Masakazu , Kojima Jun , Watanabe Hiroki , Kondo Takeshi , Uesugi Tsutomu , Yamaguchi Satoshi , Kimoto Yasuji , Tomita Kazuyoshi , Nagasato Yoshitaka , Ikeda Satoshi , Kosaki Masayoshi , Oka Tohru , Suda Jun 
Published: January 2022

AbstractPower devices are operated under harsh conditions, such as high currents and voltages, and so degradation of these devices is an important issue. Our group previously found significant increases in reverse leakage current after applying continuous forward current stress to GaN p–n junctions. In the present study, we identified the type of threading dislocations that provide pathways for this reverse leakage current. GaN p–n diodes were grown by metalorganic vapor phase epitaxy on freestanding GaN(0001) substrates with threading dislocation densities of approximately 3 × 105 cm−2. These diodes exhibited a breakdown voltage on the order of 200 V and avalanche capability. The leakage current in some diodes in response to a reverse bias was found to rapidly increase with continuous forward current injection, and leakage sites were identified by optical emission microscopy. Closed-core threading screw dislocations (TSDs) were found at five emission spots based on cross-sectional transmission electron microscopy analyses using two-beam diffraction conditions. The Burgers vectors of these dislocations were identified as [0001] using large-angle convergent-beam electron diffraction. Thus, TSDs for which b = 1c are believed to provide current leakage paths in response to forward current stress.
Gastric cancer cell death analyzed by live cell imaging of spheroids
Authors: Alzeeb George , Arzur Danielle , Trichet Valérie , Talagas Matthieu , Corcos Laurent , Le Jossic-Corcos Catherine 
Published: January 2022

AbstractGastric cancer (GC) is the third cause of cancer-related mortality worldwide and is often diagnosed at advanced stages of the disease. This makes the development of more comprehensive models and efficient treatments crucial. One option is based on repurposing already marketed drugs as adjuvants to chemotherapy. Accordingly, we have previously developed the combination of docetaxel and the cholesterol-lowering drug, lovastatin, as a powerful trigger of HGT-1 human GC cells’ apoptosis using 2D cultures. Because 3D models, known as spheroids, are getting recognized as possibly better suited than 2Ds in toxicological research, we aimed to investigate the efficacy of this drug combination with such a model. We established monocellular spheroids from two human (GC) cell lines, HGT-1 and AGS, and bicellular spheroids from these cells mixed with cancer-associated fibroblasts. With these, we surveyed drug-induced cytotoxicity with MTT assays. In addition, we used the Incucyte live imaging and analysis system to follow spheroid growth and apoptosis. Taken together, our results showed that the lovastatin + docetaxel combination was an efficient strategy to eliminate GC cells grown in 2D or 3D cultures, lending further support in favor of repurposing lovastatin as an adjuvant to taxane-based anticancer treatment.
Reference intervals for coagulation parameters in non-pregnant and pregnant women
Authors: Fu Mengyu , Liu Junjie , Xing Jinfang , Dai Yanpeng , Ding Yanzi , Dong Kainan , Zhang Xuewei , Yuan Enwu 
Published: January 2022

AbstractEstablished reference intervals (RIs) of coagulation parameters generally based on the general population are not applicable to specific women. In order to accurately evaluate the coagulation status of non-pregnant women and pregnant women, specific RIs should be established. Our study recruited 465 non-pregnant women and 1972 pregnant women aged 20–45 years. Eight tests including antithrombin (AT), protein C (PC), free protein S (fPS), lupus anticoagulant (LA), D-dimer, fibrin/fibrinogen degradation products (FDP), coagulation factor VII (FVII), and factor VIII (FVIII) were performed on ACL TOP automated coagulation instrument. The RIs for these tests were established in non-pregnant and pregnant women at different gestational weeks. Compared to the non-pregnant group, the medians of AT and fPS were lower, while the medians of PC, LA normalized ratio, D-dimer, FDP, FVII, and FVIII were higher. During pregnancy, AT and fPS activity showed a decreasing trend, with the increase of gestational age. PC activity, LA normalized ratio, D-dimer concentrations, FDP concentrations, FVII, and FVIII activity presented an increasing trend, with the increase of gestational age. The non-pregnant women-specific RIs and the gestational age-specific RIs of AT, PC, fPS, LA normalized ratio, D-dimer, FDP, FVII, and FVIII needed to be established for accurate clinical diagnoses.
Effects of working memory load on frontal connectivity in children with autism spectrum disorder: a fNIRS study
Authors: Han Yvonne M. Y. , Chan Ming-Chung , Chan Melody M. Y. , Yeung Michael K. , Chan Agnes S. 
Published: January 2022

AbstractIndividuals with autism spectrum disorder (ASD) perform poorly in working memory (WM) tasks, with some literature suggesting that their impaired performance is modulated by WM load. While some neuroimaging and neurophysiological studies have reported altered functional connectivity during WM processing in individuals with autism, it remains largely unclear whether such alterations are moderated by WM load. The present study aimed to examine the effect of WM load on functional connectivity within the prefrontal cortex (PFC) in ASD using functional near-infrared spectroscopy (fNIRS). Twenty-two children with high-functioning ASD aged 8–12 years and 24 age-, intelligent quotient (IQ)-, sex- and handedness-matched typically developing (TD) children performed a number n-back task with three WM loads (0-back, 1-back, and 2-back). Hemodynamic changes in the bilateral lateral and medial PFC during task performance were monitored using a multichannel NIRS device. Children with ASD demonstrated slower reaction times, specifically during the “low load” condition, than TD children. In addition, the ASD and TD groups exhibited differential load-dependent functional connectivity changes in the lateral and medial PFC of the right but not the left hemisphere. These findings indicate that WM impairment in high-functioning ASD is paralleled by load-dependent alterations in right, but not left, intrahemispheric connectivity during WM processing in children with ASD. A disruption of functional neural connections that support different cognitive processes may underlie poor performance in WM tasks in ASD.
The dynamic gut microbiota of zoophilic members of the Anopheles gambiae complex (Diptera: Culicidae)
Authors: Singh Ashmika , Allam Mushal , Kwenda Stanford , Khumalo Zamantungwa T. H. , Ismail Arshad , Oliver Shüné V. 
Published: January 2022

AbstractThe gut microbiota of mosquitoes plays a critical role in the life history of the animal. There is a growing body of research characterising the gut microbiota of a range of mosquito species, but there is still a paucity of information on some members of the Anopheles gambiae complex. In this study, the gut microbiota of four laboratory strains were characterised. SENN (Anopheles arabiensis—insecticide susceptible major vector), SENN DDT (Anopheles arabiensis—insecticide resistant major vector), MAFUS (Anopheles merus—minor vector) and SANGWE (Anopheles quadriannulatus—non-vector) were used in this study. The microbiota of fourth instar larvae, 3-day old, 15-day old non-blood fed and 15-day old blood fed females were characterised by MALDI-TOF mass spectroscopy and 16 s rRNA gene sequencing by next generation sequencing. The four strains differed in species richness but not diversity. The major vectors differ in β-diversity from that of the minor and non-vectors. There was no difference in α- or β-diversity in 15 non-blood fed females and 15-day old females that had 3 blood meals before day 15. These differences may be related to a mixture of the effect of insecticide resistance phenotype as well as a potential relationship to vector competence to a limited extent. Bacterial diversity is affected by species and age. There is also a potential relationship between the differences in gut microbiota and capacity to transmit parasites. This genetic background of the mosquitoes, however, play a major role, and must be considered in this relationship.
Microstructure of unsaturated loess and its influence on strength characteristics
Authors: Wei Ya-zhi , Yao Zhi-hua , Chong Xiao-lei , Zhang Jian-hua , Zhang Jun 
Published: January 2022

AbstractPrevious studies have shown that structure has a significant influence on the mechanical deformation of unsaturated loess, but there is little published information focused on the influence mechanism of microstructure and mesostructure on the mechanical properties of loess. In this paper, the unsaturated undisturbed loess and its remolded loess under the same physical condition were taken as the research objects. The unsaturated triaxial shear tests with constant suction and net confining pressure were carried out, and the microstructure differences between the two are compared by using SEM and CT scanning to reveal the influence of structure on strength characteristics. The test results show that the cohesion and internal friction angle of undisturbed loess are greater than those of remolded loess. The angle of undisturbed soil particles is obvious, and the particles are bracket contact with good cementation. The remolded loess particles are close to round shape, and the particles are inlaid contact with destroyed cementation. The average radius of undisturbed soil is higher than that of remolded soil, indicating that there are bracket pores in undisturbed soil, but the bracket structure and macropores are deformed during shear deformation, and good structural and cementation ensure the strength of loess specimens.
Characterization of a novel non-steroidal glucocorticoid receptor agonist optimized for topical treatment
Authors: Eirefelt Stefan , Stahlhut Martin , Svitacheva Naila , Carnerup Martin A. , Da Rosa Joel Mauricio Correa , Ewald David Adrian , Marstrand Troels T. , Krogh-Madsen Mikkel , Dünstl Georg , Dack Kevin Neil , Ollerstam Anna , Norsgaard Hanne 
Published: January 2022

AbstractGlucocorticoids (GCs) are commonly used topical treatments for skin diseases but are associated with both local and systemic side effects. In this study, we describe a selective non-steroidal glucocorticoid receptor (GR) agonist for topical use, LEO 134310, which is rapidly deactivated in the blood resulting in low systemic exposure and a higher therapeutic index in the TPA-induced skin inflammation mouse model compared with betamethasone valerate (BMV) and clobetasol propionate (CP). Selectivity of LEO 134310 for GR was confirmed within a panel of nuclear receptors, including the mineralocorticoid receptor (MR), which has been associated with induction of skin atrophy. Topical treatment with LEO 134310 in minipigs did not result in any significant reduction in epidermal thickness in contrast to significant epidermal thinning induced by treatment with BMV and CP. Thus, the profile of LEO 134310 may potentially provide an effective and safer treatment option for skin diseases compared with currently used glucocorticoids.
Intranasal calcitonin gene-related peptide administration impairs fear memory retention in mice through the PKD/p-HDAC5/Npas4 pathway
Authors: Hashikawa-Hobara Narumi , Yoneyama Yoshikazu , Fujiwara Kyoushiro , Hashikawa Naoya 
Published: January 2022

AbstractThe calcitonin gene-related peptide (CGRP) suppresses fear memory retention in mice. Although intracerebroventricular administration of CGRP alters the fear memory processes, making it a promising therapeutic strategy for post-traumatic stress disorder (PTSD), direct brain injection into patients is not practical. Therefore, we propose that intranasal application may be an effective way to deliver CGRP to the brain. This study tested whether CGRP nasal administration exerts the same effect as intracerebroventricular administration using C57BL6J mice. The amount of CGRP in the cerebrospinal fluid and hippocampus 30 min after nasal administration of CGRP was significantly higher when compared with saline. Intranasal CGRP also elicited photophobic behaviors similar to intracerebroventricular injection. Moreover, intranasal CGRP decreased fear memory retention but did not affect reactivation and extinction of fear memory. We found intranasal CGRP significantly increased the expression of protein kinase D (PKD), phosphorylated histone deacetylase 5 (p-HDAC5) and neuronal PAS domain protein 4 (Npas4) in the hippocampus. CGRP-mediated impairment of fear memory and Npas4 expression increases were attenuated significantly by the CGRP receptor antagonist BIBN4096. Together, our data demonstrate that intranasal CGRP delivery activates the PKD/p-HDAC5/Npas4 pathway, decreases fear memory retention.
Ependymoma associated protein Zfta is expressed in immature ependymal cells but is not essential for ependymal development in mice
Authors: Herranz-Pérez Vicente , Nakatani Jin , Ishii Masaki , Katada Toshiaki , García-Verdugo Jose Manuel , Ohata Shinya 
Published: January 2022

AbstractThe fusion protein of uncharacterised zinc finger translocation associated (ZFTA) and effector transcription factor of tumorigenic NF-κB signalling, RELA (ZFTA-RELA), is expressed in more than two-thirds of supratentorial ependymoma (ST-EPN-RELA), but ZFTA’s expression profile and functional analysis in multiciliated ependymal (E1) cells have not been examined. Here, we showed the mRNA expression of mouse Zfta peaks on embryonic day (E) 17.5 in the wholemount of the lateral walls of the lateral ventricle. Zfta was expressed in the nuclei of FoxJ1-positive immature E1 (pre-E1) cells in E18.5 mouse embryonic brain. Interestingly, the transcription factors promoting ciliogenesis (ciliary TFs) (e.g., multicilin) and ZFTA-RELA upregulated luciferase activity using a 5′ upstream sequence of ZFTA in cultured cells. Zftatm1/tm1 knock-in mice did not show developmental defects or abnormal fertility. In the Zftatm1/tm1 E1 cells, morphology, gene expression, ciliary beating frequency and ependymal flow were unaffected. These results suggest that Zfta is expressed in pre-E1 cells, possibly under the control of ciliary TFs, but is not essential for ependymal development or flow. This study sheds light on the mechanism of the ZFTA-RELA expression in the pathogenesis of ST-EPN-RELA: Ciliary TFs initiate ZFTA-RELA expression in pre-E1 cells, and ZFTA-RELA enhances its own expression using positive feedback.
Innovative composite tool use by Goffin’s cockatoos (Cacatua goffiniana)
Authors: Osuna-Mascaró Antonio J. , Mundry Roger , Tebbich Sabine , Beck Sarah R. , Auersperg Alice M. I. 
Published: January 2022

AbstractComposite tool use (using more than one tool simultaneously to achieve an end) has played a significant role in the development of human technology. Typically, it depends on a number of specific and often complex spatial relations and there are thus very few reported cases in non-human animals (e.g., specific nut-cracking techniques in chimpanzees and capuchin monkeys). The innovative strategies underlying the innovation and spread of tool manufacture and associative tool use (using > 1 tools) across tool using animals is an important milestone towards a better understanding of the evolution of human technology. We tested Goffin’s cockatoos on a composite tool problem, the ‘Golf Club Task’, that requires the use of two objects in combination (one used to control the free movement of a second) to get a reward. We demonstrate that these parrots can innovate composite tool use by actively controlling the position of the end effector and movement of both objects involved in a goal directed manner. The consistent use of different techniques by different subjects highlights the innovative nature of the individual solutions. To test whether the solution could be socially transmitted, we conducted a second study, which provided only tentative evidence for emulative learning. To our knowledge, this indicates that the cognitive preconditions for composite tool use have also evolved outside the primate lineage.
Planar ultrasonic transducer based on a metasurface piezoelectric ring array for subwavelength acoustic focusing in water
Authors: Hur Shin , Choi Hyunggyu , Yoon Gil Ho , Kim Nam Woon , Lee Duck-Gyu , Kim Yong Tae 
Published: January 2022

AbstractThe development of a new ultrasonic transducer capable of improved focusing performance has become a necessity to overcome the limitations of conventional ultrasonic transducer technology. In this study, we designed and optimized a metasurface piezoelectric ring device, and using multiphysics finite element analysis, we examined the performance of a planar ultrasonic transducer consisting of this device, a matching layer, a backing layer, and housing in producing a needle-like subwavelength focusing beam in water. For practical experiments, a metasurface piezoelectric ring device was fabricated using a laser ablation process. Subsequently, using a pulse-echo test, we found that the − 6 dB bandwidth of a planar ultrasonic transducer with a center frequency of 1.0 MHz was 37.5%. In addition, the results of an ultrasonic-focusing performance test showed that the full width at half-maximum of the axial subwavelength focusing beam was 0.78λ, and the full lateral width at half-maximum of the subwavelength lateral focusing beam was 7.03λ at a distance of 10.89λ. The needle-like focused ultrasonic beam technology implemented with a piezoelectric ring array based new planar ultrasound transducer is expected to be used in high-resolution imaging devices or medical ultrasound focusing devices in the future.
Sodium–calcium exchanger isoform-3 targeted Withania somnifera (L.) Dunal therapeutic intervention ameliorates cognition in the 5xFAD mouse model of Alzheimer’s disease
Authors: Afewerky Henok Kessete , Li Hao , Zhang Tongmei , Li Xinyan , Mahaman Yacoubou Abdoul Razak , Duan Limin , Qin Pengwei , Zheng Jiequn , Pei Lei , Lu Youming 
Published: January 2022

AbstractThe third isoform of the Na+–Ca2+ exchanger (NCX3) is crucial for a physiological fine-tuning of the Ca2+ fluxes in excitable tissues. In this view, the NCX3 accounts for the aberrant Ca2+ influx seen during neuronal excitotoxicity, such as in Alzheimer’s disease (AD). However, little is known about NCX3 regulation and functional properties. Withania somnifera (L.) Dunal (W. somnifera), a traditional indigenous plant widely recognized for having numerous medicinal values, was undertaken to determine its potential therapeutic benefit against aggregated Aβ1–42-induced NCX3 dysregulation and the thereof cognition impairment in 5xFAD mice. The undertaken sourced dried roots of authenticated W. somnifera physicochemical compositional tests satisfied standards of pharmacognostic quality, and further phytochemical analysis of the roots methanol extract revealed the roots constitute several antioxidants. Following an intra-gastric gavage administration of synthesized W. somnifera roots methanolic extract from postnatal day 30 (P30) to P75, in vivo cognitional studies and then neurochemical examinations of the NCX3 expression level, Aβ plaque deposition, and antioxidant activities in the AD-associated brain regions of 4-month-old 5xFAD mice suggests that the oxidative stress normalizing effects of W. somnifera constituents, operating on the NCX3, may have a therapeutic role in the improvement of cognition in AD.