bluuebunny/crossref_metadata_2025_split huggingface dataset:
5-HT2A receptor dysregulation in a schizophrenia relevant mouse model of NMDA receptor hypofunction
Authors: Nakao Kazuhito , Singh Mahendra , Sapkota Kiran , Fitzgerald Andrew , Hablitz John J. , Nakazawa Kazu 
Published: April 2022

AbstractBlockade of N-methyl-D-aspartate receptors (NMDAR) is known to augment cortical serotonin 2A receptors (5-HT2ARs), which is implicated in psychosis. However, the pathways from NMDAR hypofunction to 5-HT2AR up-regulation are unclear. Here we addressed in mice whether genetic deletion of the indispensable NMDAR-subunit Grin1 principally in corticolimbic parvalbumin-positive fast-spiking interneurons, could up-regulate 5-HT2ARs leading to cortical hyper-excitability. First, in vivo local-field potential recording revealed that auditory cortex in Grin1 mutant mice became hyper-excitable upon exposure to acoustic click-train stimuli that release 5-HT in the cortex. This excitability increase was reproduced ex vivo where it consisted of an increased frequency of action potential (AP) firing in layer 2/3 pyramidal neurons of mutant auditory cortex. Application of the 5-HT2AR agonist TCB-2 produced similar results. The effect of click-trains was reversed by the 5-HT2AR antagonist M100907 both in vivo and ex vivo. Increase in AP frequency of pyramidal neurons was also reversed by application of Gαq protein inhibitor BIM-46187 and G protein-gated inwardly-rectifying K+ (GIRK) channel activator ML297. In fast-spiking interneurons, 5-HT2AR activation normally promotes GABA release, contributing to decreased excitability of postsynaptic pyramidal neurons, which was missing in the mutants. Moreover, unlike the controls, the GABAA receptor antagonist (+)-bicuculline had little effect on AP frequency of mutant pyramidal neurons, indicating a disinhibition state. These results suggest that the auditory-induced hyper-excitable state is conferred via GABA release deficits from Grin1-lacking interneurons leading to 5-HT2AR dysregulation and GIRK channel suppression in cortical pyramidal neurons, which could be involved in auditory psychosis.
The dental demolition derby: bruxism and its impact - part 1: background
Authors: L. T. Thayer Mark , Ali Rahat 
Published: April 2022

AbstractBruxism may lead to changes or damage to the oral and perioral tissues. Bruxism may occur during sleep or when awake. Many patients will not require active management; however, for some, intervention is required. Control of bruxism may be difficult, if not impossible, but the need exists for preservation of the dentition and quality of life. A prediction of risk to the tissues for the planning of interventions is difficult and relies upon evidence of past damage and assessment of future risks. Treatment options may need to be imaginative and rescuable. This series of papers will review the aetiology of bruxism, its impacts and treatment strategies for persistent bruxers who are at risk of, or suffering, tissue damage.
A stop-gain mutation in GXYLT1 promotes metastasis of colorectal cancer via the MAPK pathway
Authors: Peng Lin , Zhao Min , Liu Tianqi , Chen Jiangbo , Gao Pin , Chen Lei , Xing Pu , Wang Zaozao , Di Jiabo , Xu Qiang , Qu Hong , Jiang Beihai , Su Xiangqian 
Published: April 2022

AbstractGenomic instability plays a key role in the initiation and progression of colorectal cancer (CRC). Although cancer driver genes in CRC have been well characterized, identifying novel genes associated with carcinogenesis and treatment remains challenging because of tumor heterogeneity. Here, we analyzed the genomic alterations of 45 samples from CRC patients in northern China by whole-exome sequencing. In addition to the identification of six well-known CRC driver genes (APC, TP53, KRAS, FBXW7, PIK3CA, and PABPC), two tumor-related genes (MTCH2 and HSPA6) were detected, along with RRP7A and GXYLT1, which have not been previously linked to cancer. GXYLT1 was mutated in 40% (18/45) of the samples in our cohort. Functionally, GXYLT1 promoted migration and invasion in vitro and metastasis in vivo, while the GXYLT1S212* mutant induced significantly greater effect. Furthermore, both GXYLT1 and GXYLT1S212* interacted with ERK2. GXYLT1 induced metastasis via a mechanism involving the Notch and MAPK pathways, whereas the GXYLT1S212* mutant mainly promoted metastasis by activating the MAPK pathway. We propose that GXYLT1 acts as a novel metastasis-associated driver gene and GXYLT1S212* might serve as a potential indicator for therapies targeting the MAPK pathway in CRC.
ODACH: a one-shot distributed algorithm for Cox model with heterogeneous multi-center data
Authors: Luo Chongliang , Duan Rui , Naj Adam C. , Kranzler Henry R. , Bian Jiang , Chen Yong 
Published: April 2022

AbstractWe developed a One-shot Distributed Algorithm for Cox proportional-hazards model to analyze Heterogeneous multi-center time-to-event data (ODACH) circumventing the need for sharing patient-level information across sites. This algorithm implements a surrogate likelihood function to approximate the Cox log-partial likelihood function that is stratified by site using patient-level data from a lead site and aggregated information from other sites, allowing the baseline hazard functions and the distribution of covariates to vary across sites. Simulation studies and application to a real-world opioid use disorder study showed that ODACH provides estimates close to the pooled estimator, which analyzes patient-level data directly from all sites via a stratified Cox model. Compared to the estimator from meta-analysis, the inverse variance-weighted average of the site-specific estimates, ODACH estimator demonstrates less susceptibility to bias, especially when the event is rare. ODACH is thus a valuable privacy-preserving and communication-efficient method for analyzing multi-center time-to-event data.
Deep water pathways in the North Pacific Ocean revealed by Lagrangian particle tracking
Authors: Kawasaki T. , Matsumura Y. , Hasumi H. 
Published: April 2022

AbstractLagrangian particle tracking experiments are conducted to investigate the pathways of deep water in the North Pacific Ocean. The flow field is taken from a state-of-the-art deep circulation simulation. An unprecedented number of particles are tracked to quantify the volume transport and residence time. Half of the North Pacific deep water returns to the Southern Ocean, and its principal pathway is along the western boundary current in the Southwest Pacific Basin in the deep layer. About 30% is exported to the Indian Ocean after upwelling to the shallow layer in the western North Pacific Ocean. The rest is transported to the Arctic Ocean through the Bering Strait or evaporates within the Pacific Ocean. Upwelling of deep water is confined in the western North Pacific Ocean owing to the strong vertical mixing. The mean residence time of deep water in the North Pacific Ocean is estimated to be several hundred years, which is consistent with the observed radiocarbon distribution.
Same-sex competition and sexual conflict expressed through witchcraft accusations
Authors: Peacey Sarah , Campbell Olympia L. K. , Mace Ruth 
Published: April 2022

AbstractThere is significant cross-cultural variation in the sex of individuals most likely to be accused of practising witchcraft. Allegations of witchcraft might be a mechanism for nullifying competitors so resources they would have used become available to others. In this case, who is targeted may result from patterns of competition and conflict (same-sex or male–female) within specific relationships, which are determined by broader socio-ecological factors. Here we examine patterns of sex-specific accusations in historic cases from sub-Saharan Africa (N = 423 accusations). Male ‘witches’ formed the greater part of our sample, and were mostly accused by male blood-relatives and nonrelatives, often in connection to disputes over wealth and status. Accusations of women were mainly from kin by marriage, and particularly from husbands and co-wives. The most common outcomes were that the accused was forced to move, or suffered reputational damage. Our results suggest that competition underlies accusations and relationship patterns may determine who is liable to be accused.
A novel polypeptide-modified fluorescent gold nanoclusters for copper ion detection
Authors: Zhuang Hong , Jiang Xinyu , Wu Sijia , Wang Shujin , Pang Yong , Huang Yanjun , Yan Haiyang 
Published: April 2022

AbstractBiomolecule-functionalized fluorescent gold nanocluster (AuNCs) have attracted a lot of attention due to good biocompatibility, stable physicochemical properties and considerable cost advantages. Inappropriate concentration of Cu2+ may cause a variety of diseases. In this study, AuNCs were synthesized in alkaline aqueous solution using bovine serum albumin (BSA) as a template. And then, the peptide CCYWDAHRDY was coupled to AuNCs. Furthermore, the fluorescence of synthesized CCYWDAHRDY-AuNCs response to Cu2+ was evaluated. As the results shown that the CCYWDAHRDY-AuNCs can sensitively detect Cu2+. After adding Cu2+ to the probe system, the fluorescence of the CCYWDAHRDY-AuNCs was quenched. The detection conditions were at pH 6 and 30 °C for 10 min, the linear relationship between Cu2+ concentration and fluorescence intensity were good in the range of 0.1 ~ 4.2 μmol/L. The regression equation was y = − 105.9x + 693.68, the linear correlation coefficient is 0.997, and the minimum detection limit was 52 nmol/L.
Investigation of crude oil properties impact on wettability alteration during low salinity water flooding using an improved geochemical model
Authors: Ghorbani Maryam , Rashidi Fariborz , Mousavi-Dehghani Ali 
Published: April 2022

AbstractIn low-salinity water flooding (LSWF), modifying the injected brine composition leads to greater oil recovery from carbonate reservoirs. The processes that control improved recovery during LSWF are not totally clear, which could lead to ambiguities in finding optimum brine composition regarding wettability alteration (WA) toward water wetness. One of the methods to determine WA is bound product sum (BPS) calculation using geochemical tools. In the case of wettability improvement, the BPS value of a crude oil-brine-rock (COBR) system should be at its minimum value. In this study, an improved geochemical model is developed, which includes the effects of oil composition (i.e., acid number, base number, and weight percent of nonhydrocarbon components) and physical properties of oil (i.e., density, viscosity, and solution gas-oil ratio) on COBR interactions. The proposed method generates BPS as a function of temperature, pressure, oil and brine composition, and pH for carbonate rocks. The model applicability was validated using several experimental data sets available in the literature. The results of the improved BPS model were in line with the results of contact angle and zeta potential measurements as the major indices of rock wettability. BPS calculations using the available geochemical tools sometimes failed to predict the correct WA trend since they overlooked the impact of oil properties on COBR interactions. The model predictability was also compared with the results of an available geochemical tool, PHREEQC, and the results demonstrate just how important the effect of oil properties and composition inclusion on wettability determination is. The improved BPS approach could be successfully utilized as an optimization tool to optimize the water composition during LSWF for a given COBR system.
Ferroptosis-related lncRNA signature predicts the prognosis and immune microenvironment of hepatocellular carcinoma
Authors: Fang Chongkai , Liu Silin , Feng Kunliang , Huang Chaoyuan , Zhang Ying , Wang Jinan , Lin Hongtong , Wang Junyan , Zhong Chong 
Published: April 2022

AbstractThis study aimed to construct a ferroptosis-related lncRNA signature to probe the prognosis and immune infiltration of HCC patients. The Cancer Genome Atlas (TCGA) database was randomly divided into two parts, with two-thirds training and one-third testing sets. Univariate, multivariate, and least absolute selection operator (LASSO) Cox regression analyses were performed to establish a ferroptosis-related lncRNA signature. The prognostic signature was constructed by 6 ferroptosis-related lncRNAs (PCAT6, MKLN1-AS, POLH-AS1, LINC00942, AL031985.3, LINC00942) shows a promising clinical prediction value in patients with HCC. Patients with high-risk score indicated a poorer prognosis than patients with low-risk score were shown in the training set (p < 0.001) and testing set (p = 0.024). Principal component analysis (PCA) and nomogram were performed to verify the value of the prognostic signature. The area under curves (AUCs) for 1-, 3-, and 5-year survival rates were 0.784, 0.726, 0.699, respectively. Moreover, TCGA revealed that immune cell subpopulations and related functions, including cytolytic activity, MHC class I, type I and type II IFN response, were significantly different between the two risk groups. Immune checkpoints such as PDCD1, CTLA4, CD44, VTCN1 were also abnormally expressed between the two risk groups. This prognostic signature based on the ferroptosis-related lncRNAs may be promising for the clinical prediction of prognosis and immunotherapeutic responses in patients with HCC.
HDAC6 regulates NF-κB signalling to control chondrocyte IL-1-induced MMP and inflammatory gene expression
Authors: Barter Matt J. , Butcher Andrew , Wang Hui , Tsompani Dimitra , Galler Martin , Rumsby Ellen L. , Culley Kirsty L. , Clark Ian M. , Young David A. 
Published: April 2022

AbstractElevated pro-inflammatory signalling coupled with catabolic metalloproteinase expression is a common feature of arthritis, leading to cartilage damage, deterioration of the joint architecture and the associated pain and immobility. Countering these processes, histone deacetylase inhibitors (HDACi) have been shown to suppress matrix metalloproteinase (MMP) expression, block cytokine-induced signalling and reduce the cartilage degradation in animal models of the arthritis. In order to establish which specific HDACs account for these chondro-protective effects an HDAC1-11 RNAi screen was performed. HDAC6 was required for both the interleukin (IL)-1 induction of MMP expression and pro-inflammatory interleukin expression in chondrocytes, implicating an effect on NF-κB signalling. Depletion of HDAC6 post-transcriptionally up-regulated inhibitor of κB (IκB), prevented the nuclear translocation of NF-κB subunits and down-regulated NF-κB reporter activation. The pharmacological inhibition of HDAC6 reduced MMP expression in chondrocytes and cartilage collagen release. This work highlights the important role of HDAC6 in pro-inflammatory signalling and metalloproteinase gene expression, and identifies a part for HDAC6 in the NF-κB signalling pathway. By confirming the protection of cartilage this work supports the inhibition of HDAC6 as a possible therapeutic strategy in arthritis.
Diagnosis of Parkinson's disease by investigating the inhibitory effect of serum components on P450 inhibition assay
Authors: Ihara Kohei , Oguro Ami , Imaishi Hiromasa 
Published: April 2022

AbstractParkinson’s disease (PD) is the second most common neurodegenerative disease, and diagnostic methods and biomarkers for patients without subjective motor symptoms have not yet been established. Previously, we developed a cytochrome P450 inhibition assay that detects alterations in metabolite levels associated with P450s caused by inflammation and exposure to endogenous or exogenous substances. However, it is unknown whether the P450 inhibition assay can be applied in PD diagnosis. Here, we determined whether the P450 inhibition assay can discriminate sera between patients with PD and healthy individuals. The results of the assay revealed that the P450 inhibition assay can discriminate PD with an area under the receiver operating characteristic curve (AUC) value of 0.814–0.914 in rats and an AUC value of 0.910 in humans. These findings demonstrate that the P450 inhibition assay can aid in the future development of liquid biopsy-based diagnostic methods for PD.
Genetic susceptibility to patient-reported xerostomia among long-term oropharyngeal cancer survivors
Authors: Aggarwal Puja , Hutcheson Katherine A. , Yu Robert , Wang Jian , Fuller Clifton D. , Garden Adam S. , Goepfert Ryan P. , Rigert Jillian , Mott Frank E. , Lu Charles , Lai Stephen Y. , Gunn G. Brandon , Chambers Mark S. , Li Guojun , Wu Chih-Chieh , Hanna Ehab Y. , Sturgis Erich M. , Shete Sanjay 
Published: April 2022

AbstractGenetic susceptibility for xerostomia, a common sequela of radiotherapy and chemoradiotherapy for head and neck cancer, is unknown. Therefore, to identify genetic variants associated with moderate to severe xerostomia, we conducted a GWAS of 359 long-term oropharyngeal cancer (OPC) survivors using 579,956 autosomal SNPs. Patient-reported cancer treatment-related xerostomia was assessed using the MD Anderson Symptom Inventory. Patient response was dichotomized as moderate to severe or none to mild symptoms. In our study, 39.2% of OPC survivors reported moderate to severe xerostomia. Our GWAS identified eight SNPs suggestively associated with higher risk of moderate to severe xerostomia in six genomic regions (2p13.3, rs6546481, Minor Allele (MA) = A, ANTXR1, P = 4.3 × 10–7; 5p13.2–p13.1, rs16903936, MA = G, EGFLAM, P = 5.1 × 10–6; 4q21.1, rs10518156, MA = G, SHROOM3, P = 7.1 × 10–6; 19q13.42, rs11882068, MA = G, NLRP9, P = 1.7 × 10–5; 12q24.33, rs4760542, MA = G, GLT1D1, P = 1.8 × 10–5; and 3q27.3, rs11714564, MA = G, RTP1, P = 2.9 × 10–5. Seven SNPs were associated with lower risk of moderate to severe xerostomia, of which only one mapped to specific genomic region (15q21.3, rs4776140, MA = G, LOC105370826, a ncRNA class RNA gene, P = 1.5 × 10–5). Although our small exploratory study did not reach genome-wide statistical significance, our study provides, for the first time, preliminary evidence of genetic susceptibility to xerostomia. Further studies are needed to elucidate the role of genetic susceptibility to xerostomia.
Interaction effects of diabetes and brain-derived neurotrophic factor on suicidal ideation in patients with acute coronary syndrome
Authors: Choi Wonsuk , Kim Ju-Wan , Kang Hee-Ju , Kim Hee Kyung , Kang Ho-Cheol , Lee Ju-Yeon , Kim Sung-Wan , Hong Young Joon , Ahn Youngkeun , Jeong Myung Ho , Stewart Robert , Kim Jae-Min 
Published: April 2022

AbstractAcute coronary syndrome (ACS) is related to an increased risk of suicide. Although both diabetes and the brain-derived neurotrophic factor (BDNF) pathway are closely associated with ACS and suicide, the effects of these factors on suicidal behavior in ACS patients have not been assessed. We investigated the individual and interaction effects of diabetes and BDNF-related markers, namely the serum BDNF (sBDNF) level and the BDNF Val66Met polymorphism, on suicidal ideation (SI) in ACS patients. The presence of diabetes was ascertained, and sBDNF levels and the presence of the BDNF Val66Met polymorphism were measured in 969 patients within 2 weeks after an ACS episode. 711 patients were followed up at 1 year after the ACS episode. SI was assessed using the relevant items of the Montgomery–Åsberg Depression Rating Scale at baseline (acute SI) and the 1-year follow-up (chronic SI). Significant individual effects of low sBDNF levels were found on acute SI. The presence of both diabetes and a low sBDNF level or the BDNF Met/Met genotype was associated with acute SI, with multivariate logistic regression analyses revealing significant interaction effects. The highest frequency of chronic SI was seen in diabetic patients with an sBDNF level in the lowest tertile or with the BDNF Met/Met genotype, although the interaction terms were not statistically significant. Our study suggests that the combination of diabetes and BDNF-related markers, such as the sBDNF level and the BDNF Val66Met polymorphism, might provide a useful predictor of acute SI in ACS patients.
The salmon louse genome may be much larger than sequencing suggests
Authors: Wyngaard Grace A. , Skern-Mauritzen Rasmus , Malde Ketil , Prendergast Rachel , Peruzzi Stefano 
Published: April 2022

AbstractThe genome size of organisms impacts their evolution and biology and is often assumed to be characteristic of a species. Here we present the first published estimates of genome size of the ecologically and economically important ectoparasite, Lepeophtheirus salmonis (Copepoda, Caligidae). Four independent L. salmonis genome assemblies of the North Atlantic subspecies Lepeophtheirus salmonis salmonis, including two chromosome level assemblies, yield assemblies ranging from 665 to 790 Mbps. These genome assemblies are congruent in their findings, and appear very complete with Benchmarking Universal Single-Copy Orthologs analyses finding > 92% of expected genes and transcriptome datasets routinely mapping > 90% of reads. However, two cytometric techniques, flow cytometry and Feulgen image analysis densitometry, yield measurements of 1.3–1.6 Gb in the haploid genome. Interestingly, earlier cytometric measurements reported genome sizes of 939 and 567 Mbps in L. salmonis salmonis samples from Bay of Fundy and Norway, respectively. Available data thus suggest that the genome sizes of salmon lice are variable. Current understanding of eukaryotic genome dynamics suggests that the most likely explanation for such variability involves repetitive DNA, which for L. salmonis makes up ≈ 60% of the genome assemblies.
Multi-objective optimal water resources allocation in the middle and upper reaches of the Huaihe River Basin (China) based on equilibrium theory
Authors: Dong Zengchuan , Zhang Jitao , Zhang Ke , Wang Xinkui , Chen Tian 
Published: April 2022

AbstractIn the river basin water resources allocation (WRA) problem, an unbalanced WRA poses challenges to water resources management departments. Many studies focus on achieving a lower water shortage rate while ignoring the equilibrium relationship among the socio-economic system, water resources system and eco-environmental system, as well as the equilibrium relationship among different regions. In this study, a water resources allocation model(WRAM) based on equilibrium theory is constructed to achieve the balance between different systems and different spaces in a basin. First, the relationship among the water resources system, socio-economic system and eco-environmental system is described. Then, the regional equilibrium index and system equilibrium index are constructed. Finally, the first model based on equilibrium theory is constructed. The results show that: (1) the Pareto Front reflects the contradictory relationship between economic development and environmental sustainability; (2) with the restructuring of industry and cropping, both economic efficiency and water shortage rates improve; (3) the equilibrium of the basin could also be further improved if water resources utilisation is further improved. Therefore, this study improves the existing WRAM, which can be applied to guide the water resources management of river basin.