bluuebunny/crossref_metadata_2025 huggingface dataset:
Augmented Respiratory–Sympathetic Coupling and Hemodynamic Response to Acute Mild Hypoxia in Female Rodents With Chronic Kidney Disease
Authors: Saha Manash , Sun Qi-Jian , Hildreth Cara M. , Burke Peter G. R. , Phillips Jacqueline K.
Published: May 2021

Carotid body feedback and hypoxia may serve to enhance respiratory–sympathetic nerve coupling (respSNA) and act as a driver of increased blood pressure. Using the Lewis polycystic kidney (LPK) rat model of chronic kidney disease, we examined respSNA in adult female rodents with CKD and their response to acute hypoxia or hypercapnia compared to Lewis control animals. Under urethane anesthesia, phrenic nerve activity, splanchnic sympathetic nerve activity (sSNA), and renal sympathetic nerve activity (rSNA) were recorded under baseline conditions and during mild hypoxic or hypercapnic challenges. At baseline, tonic SNA and blood pressure were greater in female LPK rats versus Lewis rats (all P < 0.05) and respSNA was at least two-fold larger [area under the curve (AUC), sSNA: 7.8 ± 1.1 vs. 3.4 ± 0.7 μV s, rSNA: 11.5 ± 3 vs. 4.8 ± 0.7 μV s, LPK vs. Lewis, both P < 0.05]. Mild hypoxia produced a larger pressure response in LPK [Δ mean arterial pressure (MAP) 30 ± 6 vs. 12 ± 6 mmHg] and augmented respSNA (ΔAUC, sSNA: 8.9 ± 3.4 vs. 2 ± 0.7 μV s, rSNA: 6.1 ± 1.2 vs. 3.1 ± 0.7 μV s, LPK vs. Lewis, all P ≤ 0.05). In contrast, central chemoreceptor stimulation produced comparable changes in blood pressure and respSNA (ΔMAP 13 ± 3 vs. 9 ± 5 mmHg; respSNA ΔAUC, sSNA: 2.5 ± 1 vs. 1.3 ± 0.7 μV s, rSNA: 4.2 ± 0.9 vs. 3.5 ± 1.4 μV s, LPK vs. Lewis, all P > 0.05). These results demonstrate that female rats with CKD exhibit heightened respSNA coupling at baseline that is further augmented by mild hypoxia, and not by hypercapnia. This mechanism may be a contributing driver of hypertension in this animal model of CKD.
Impact of Orthodontic Forces on Plasma Levels of Markers of Bone Turnover and Inflammation in a Rat Model of Buccal Expansion
Authors: Danz Jan C. , Kantarci Alpdogan , Bornstein Michael M. , Katsaros Christos , Stavropoulos Andreas
Published: May 2021

Plasma levels of protein analytes might be markers to predict and monitor the kinetics of bone and tissue remodeling, including maximization of orthodontic treatment stability. They could help predict/prevent and/or diagnose possible adverse effects such as bone dehiscences, gingival recession, or root resorption. The objective of this study was to measure plasma levels of markers of bone turnover and inflammation during orthodontic force application in a rat model of orthodontic expansion. Two different orthodontic forces for bilateral buccal expansion of the maxillary arches around second and third molars were applied in 10 rats equally distributed in low-force (LF) or conventional force (CF) groups. Four rats served as the control group. Blood samples were collected at days 0, 1, 2, 3, 6, 13, 21, and 58. Longitudinal concentrations of osteoprotegerin (OPG), soluble receptor activator of nuclear factor kappaB ligand (sRANKL), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor α (TNF), and parathyroid hormone (PTH) were determined in blood samples by a multiplex immunoassay. CF and LF resulted in a significantly maxillary skeletal expansion while the CF group demonstrated significantly higher expansion than the LF group in the long term. Bone turnover demonstrated a two-phase response. During the “early phase” (up to 6 days of force application), LF resulted in more sRANKL expression and increased sRANKL/OPG ratio than the CF and control animals. There was a parallel increase in PTH levels in the early phase in response to LF. During the “late phase” (6–58 days), the markers of bone turnover were stable in both groups. IL-4, IL-6, and IL-10 levels did not significantly change the test groups throughout the study. These results suggest that maxillary expansion in response to different orthodontic forces follows different phases of bone turnover that may be force specific.
Effect of ω-3 Polyunsaturated Fatty Acids-Derived Bioactive Lipids on Metabolic Disorders
Authors: Duan Jinjie , Song Yayue , Zhang Xu , Wang Chunjiong
Published: May 2021

Arachidonic acid (ARA) is an important ω-6 polyunsaturated fatty acid (PUFA), and docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and n-3 docosapentaenoic acid (n-3 DPA) are three well-known ω-3 PUFAs. These fatty acids can be metabolized into a number of bioactive lipids. Eicosanoids derived from ARA have drawn great attention because of their important and complex biofunctions. Although EPA, DHA and n-3 DPA have also shown powerful biofunctions, we have fewer studies of metabolites derived from them than those from ARA. Recently, growing research has focused on the bioaction of ω-3 PUFA-derived metabolites, which indicates their great potential for treating metabolic disorders. Most of the functional studies of these bioactive lipids focused on their anti-inflammatory effects. However, several studies elucidated their direct effects on pancreatic β cells, hepatocytes, adipocytes, skeletal muscle cells, and endothelial cells. These researches revealed the importance of studying the functions of metabolites derived from ω-3 polyunsaturated fatty acids other than themselves. The current review summarizes research into the effects of ω-3 PUFA-derived oxylipins on metabolic disorders, including diabetes, non-alcoholic fatty liver disease, adipose tissue dysfunction, and atherosclerosis.
Cardiac Natriuretic Peptide Profiles in Chronic Hypertension by Single or Sequentially Combined Renovascular and DOCA-Salt Treatments
Authors: Cerrudo Carolina S. , Cavallero Susana , Rodríguez Fermepín Martín , González Germán E. , Donato Martín , Kouyoumdzian Nicolás M. , Gelpi Ricardo J. , Hertig Cecilia M. , Choi Marcelo R. , Fernández Belisario E.
Published: May 2021

The involvement of natriuretic peptides was studied during the hypertrophic remodeling transition mediated by sequential exposure to chronic hemodynamic overload. We induced hypertension in rats by pressure (renovascular) or volume overload (DOCA-salt) during 6 and 12 weeks of treatment. We also studied the consecutive combination of both models in inverse sequences: RV 6 weeks/DS 6 weeks and DS 6 weeks/RV 6 weeks. All treated groups developed hypertension. Cardiac hypertrophy and left ventricular ANP gene expression were more pronounced in single DS than in single RV groups. BNP gene expression was positively correlated with left ventricular hypertrophy only in RV groups, while ANP gene expression was positively correlated with left ventricular hypertrophy only in DS groups. Combined models exhibited intermediate values between those of single groups at 6 and 12 weeks. The latter stimulus associated to the second applied overload is less effective than the former to trigger cardiac hypertrophy and to increase ANP and BNP gene expression. In addition, we suggest a correlation of ANP synthesis with volume overload and of BNP synthesis with pressure overload-induced hypertrophy after a prolonged treatment. Volume and pressure overload may be two mechanisms, among others, involved in the differential regulation of ANP and BNP gene expression in hypertrophied left ventricles. Plasma ANP levels reflect a response to plasma volume increase and volume overload, while circulating BNP levels seem to be regulated by cardiac BNP synthesis and ventricular hypertrophy.
BayCANN: Streamlining Bayesian Calibration With Artificial Neural Network Metamodeling
Authors: Jalal Hawre , Trikalinos Thomas A. , Alarid-Escudero Fernando
Published: May 2021

Purpose:Bayesian calibration is generally superior to standard direct-search algorithms in that it estimates the full joint posterior distribution of the calibrated parameters. However, there are many barriers to using Bayesian calibration in health decision sciences stemming from the need to program complex models in probabilistic programming languages and the associated computational burden of applying Bayesian calibration. In this paper, we propose to use artificial neural networks (ANN) as one practical solution to these challenges.

Methods:Bayesian Calibration using Artificial Neural Networks (BayCANN) involves (1) training an ANN metamodel on a sample of model inputs and outputs, and (2) then calibrating the trained ANN metamodel instead of the full model in a probabilistic programming language to obtain the posterior joint distribution of the calibrated parameters. We illustrate BayCANN using a colorectal cancer natural history model. We conduct a confirmatory simulation analysis by first obtaining parameter estimates from the literature and then using them to generate adenoma prevalence and cancer incidence targets. We compare the performance of BayCANN in recovering these “true” parameter values against performing a Bayesian calibration directly on the simulation model using an incremental mixture importance sampling (IMIS) algorithm.

Results:We were able to apply BayCANN using only a dataset of the model inputs and outputs and minor modification of BayCANN's code. In this example, BayCANN was slightly more accurate in recovering the true posterior parameter estimates compared to IMIS. Obtaining the dataset of samples, and running BayCANN took 15 min compared to the IMIS which took 80 min. In applications involving computationally more expensive simulations (e.g., microsimulations), BayCANN may offer higher relative speed gains.

Conclusions:BayCANN only uses a dataset of model inputs and outputs to obtain the calibrated joint parameter distributions. Thus, it can be adapted to models of various levels of complexity with minor or no change to its structure. In addition, BayCANN's efficiency can be especially useful in computationally expensive models. To facilitate BayCANN's wider adoption, we provide BayCANN's open-source implementation in R and Stan.
Association Between Aneurysmal Haemodynamics and Device Microstructural Characteristics After Flow-Diversion Treatments With Dual Stents of Different Sizes: A Numerical Study
Authors: Zhang Mingzi , Tupin Simon , Li Yujie , Ohta Makoto
Published: May 2021

Objectives

Treating intracranial aneurysms with flow-diverting stents sometimes requires deployment of a second device. Herein we quantify the sizing effects of devices in dual-stent treatments upon the final stent microstructure and the post-treatment aneurysmal haemodynamics.

Methods

Fifteen sidewall ICA aneurysm geometries were included. Using a virtual stenting technique, we implanted either one or two stents for each aneurysm treatment considered, with each stent specified as one of two different sizes, yielding a total of two single-stent and fouir dual-stent treatment scenarios for each aneurysm. Three stent microstructural parameters and nine aneurysmal haemodynamic parameters were quantified and systematically compared across the 90 treatment scenarios.

Results

Deployment of a second stent further reduced the aneurysmal inflow rate (IR) and energy loss (EL) by, respectively, 14 ± 11% (p = 0.001) and 9 ± 12% (p = 0.056), relative to the untreated condition. Sizing effects of the earlier-deployed stent led to largest differences of 6.9% for the final IR reduction and 11.1% for the EL, whereas sizing effects from the later-deployed stent were minor (≤2.1%). The change in stent pore size was the only microstructural parameter demonstrating a strong correlation with the reduction in the post-treatment aneurysmal haemodynamics, in terms of the IR (r = 0.50, p < 0.001) and pressure drop (r = 0.63, p < 0.001).

Conclusion

Size of the earlier-deployed stent has substantial effects on the final haemodynamic outcomes after dual-stent treatment. The average pore size of stent wires at the aneurysm orifice shows promise as a potential index for predicting the efficacy of flow-diversion treatments.
Heart Rate Variability and Clinical Features as Predictors of Atrial Fibrillation Recurrence After Catheter Ablation: A Pilot Study
Authors: Saiz-Vivo Javier , Corino Valentina D. A. , Hatala Robert , de Melis Mirko , Mainardi Luca T.
Published: May 2021

Single-procedure catheter ablation success rate is as low as 52% in atrial fibrillation (AF) patients. This study evaluated the feasibility of using clinical data and heart rate variability (HRV) features extracted from an implantable cardiac monitor (ICM) to predict recurrences in patients prior to undergoing catheter ablation for AF. HRV-derived features were extracted from the 500 beats preceding the AF onset and from the first 2 min of the last AF episode recorded by an ICM of 74 patients (67% male; 57 ± 12 years; 26% non-paroxysmal AF; 57% AF recurrence) before undergoing their first AF catheter ablation. Two types of classification algorithm were studied to predict AF recurrence: single classifiers including support vector machines, classification and regression trees, and K-nearest neighbor classifiers as well as ensemble classifiers. The sequential forward floating search algorithm was used to select the optimum feature set for each classification method. The optimum weighted voting method, which used an optimum combination of the single classifiers, was the best overall classifier (accuracy = 0.82, sensitivity = 0.76, and specificity = 0.87). Clinical and HRV features can be used to predict rhythm outcome using an ensemble classifier which would enable a more effective pre-ablation patient triage that could reduce the economic and personal burden of the procedure by increasing the success rate of first catheter ablation.
Genome-Wide Identification Reveals That Nicotiana benthamiana Hypersensitive Response (HR)-Like Lesion Inducing Protein 4 (NbHRLI4) Mediates Cell Death and Salicylic Acid-Dependent Defense Responses to Turnip Mosaic Virus
Authors: Wu Xinyang , Lai Yuchao , Rao Shaofei , Lv Lanqing , Ji Mengfei , Han Kelei , Weng Jiajia , Lu Yuwen , Peng Jiejun , Lin Lin , Wu Guanwei , Chen Jianping , Yan Fei , Zheng Hongying
Published: May 2021

Hypersensitive response (HR)-like cell death is an important mechanism that mediates the plant response to pathogens. In our previous study, we reported that NbHIR3s regulate HR-like cell death and basal immunity. However, the host genes involved in HR have rarely been studied. Here, we used transcriptome sequencing to identify Niben101Scf02063g02012.1, an HR-like lesion inducing protein (HRLI) in Nicotiana benthamiana that was significantly reduced by turnip mosaic virus (TuMV). HRLIs are uncharacterized proteins which may regulate the HR process. We identified all six HRLIs in N. benthamiana and functionally analyzed Niben101Scf02063g02012.1, named NbHRLI4, in response to TuMV. Silencing of NbHRLI4 increased TuMV accumulation, while overexpression of NbHRLI4 conferred resistance to TuMV. Transient overexpression of NbHRLI4 caused cell death with an increase in the expression of salicylic acid (SA) pathway genes but led to less cell death level and weaker immunity in plants expressing NahG. Thus, we have characterized NbHRLI4 as an inducer of cell death and an antiviral regulator of TuMV infection in a SA-mediated manner.
Interaction of OsRopGEF3 Protein With OsRac3 to Regulate Root Hair Elongation and Reactive Oxygen Species Formation in Rice (Oryza sativa)
Authors: Kim Eui-Jung , Hong Woo-Jong , Tun Win , An Gynheung , Kim Sun-Tae , Kim Yu-Jin , Jung Ki-Hong
Published: May 2021

Root hairs are tip-growing cells that emerge from the root epidermis and play a role in water and nutrient uptake. One of the key signaling steps for polar cell elongation is the formation of Rho-GTP by accelerating the intrinsic exchange activity of the Rho-of-plant (ROP) or the Rac GTPase protein; this step is activated through the interaction with the plant Rho guanine nucleotide exchange factor (RopGEFs). The molecular players involved in root hair growth in rice are largely unknown. Here, we performed the functional analysis of OsRopGEF3, which is highly expressed in the root hair tissues among the OsRopGEF family genes in rice. To reveal the role of OsRopGEF3, we analyzed the phenotype of loss-of-function mutants of OsRopGEF3, which were generated using the CRISPR-Cas9 system. The mutants had reduced root hair length and increased root hair width. In addition, we confirmed that reactive oxygen species (ROS) were highly reduced in the root hairs of the osropgef3 mutant. The pairwise yeast two-hybrid experiments between OsRopGEF3 and OsROP/Rac proteins in rice revealed that the OsRopGEF3 protein interacts with OsRac3. This interaction and colocalization at the same subcellular organelles were again verified in tobacco leaf cells and rice root protoplasts via bimolecular functional complementation (BiFC) assay. Furthermore, among the three respiratory burst oxidase homolog (OsRBOH) genes that are highly expressed in rice root hair cells, we found that OsRBOH5 can interact with OsRac3. Our results demonstrate an interaction network model wherein OsRopGEF3 converts the GDP of OsRac3 into GTP, and OsRac3-GTP then interacts with the N-terminal of OsRBOH5 to produce ROS, thereby suggesting OsRopGEF3 as a key regulating factor in rice root hair growth.
New Insights Into Lignification via Network and Multi-Omics Analyses of Arogenate Dehydratase Knock-Out Mutants in Arabidopsis thaliana
Authors: Hixson Kim K. , Marques Joaquim V. , Wendler Jason P. , McDermott Jason E. , Weitz Karl K. , Clauss Therese R. , Monroe Matthew E. , Moore Ronald J. , Brown Joseph , Lipton Mary S. , Bell Callum J. , Paša-Tolić Ljiljana , Davin Laurence B. , Lewis Norman G.
Published: May 2021

Multiple Arabidopsis arogenate dehydratase (ADT) knock-out (KO) mutants, with phenotypes having variable lignin levels (up to circa 70% reduction), were studied to investigate how differential reductions in ADTs perturb its overall plant systems biology. Integrated “omics” analyses (metabolome, transcriptome, and proteome) of wild type (WT), single and multiple ADT KO lines were conducted. Transcriptome and proteome data were collapsed into gene ortholog (GO) data, with this allowing for enzymatic reaction and metabolome cross-comparisons to uncover dominant or likely metabolic biosynthesis reactions affected. Network analysis of enzymes–highly correlated to stem lignin levels–deduced the involvement of novel putative lignin related proteins or processes. These included those associated with ribosomes, the spliceosome, mRNA transport, aminoacyl tRNA biosynthesis, and phosphorylation. While prior work helped explain lignin biosynthesis regulation at the transcriptional level, our data here provide support for a new hypothesis that there are additional post-transcriptional and translational level processes that need to be considered. These findings are anticipated to lead to development of more accurate depictions of lignin/phenylpropanoid biosynthesis models in situ, with new protein targets identified for further biochemical analysis and/or plant bioengineering. Additionally, using KEGG defined functional categorization of proteomics and transcriptomics analyses, we detected significant changes to glucosinolate, α-linolenic acid, nitrogen, carotenoid, aromatic amino acid, phenylpropanoid, and photosynthesis-related metabolic pathways in ADT KO mutants. Metabolomics results also revealed that putative carotenoid and galactolipid levels were generally increased in amount, whereas many glucosinolates and phenylpropanoids (including flavonoids and lignans) were decreased in the KO mutants.
The Cyclophilin ROC3 Regulates ABA-Induced Stomatal Closure and the Drought Stress Response of Arabidopsis thaliana
Authors: Liu Huiping , Shen Jianlin , Yuan Chao , Lu Dongxue , Acharya Biswa R. , Wang Mei , Chen Donghua , Zhang Wei
Published: May 2021

Drought causes a major constraint on plant growth, development, and crop productivity. Drought stress enhances the synthesis and mobilization of the phytohormone abscisic acid (ABA). Enhanced cellular levels of ABA promote the production of reactive oxygen species (ROS), which in turn induce anion channel activity in guard cells that consequently leads to stomatal closure. Although Cyclophilins (CYPs) are known to participate in the biotic stress response, their involvement in guard cell ABA signaling and the drought response remains to be established. The Arabidopsis thaliana gene ROC3 encodes a CYP. Arabidopsis roc3 T-DNA mutants showed a reduced level of ABA-activated S-type anion currents, and stomatal closure than wild type (WT). Also, roc3 mutants exhibited rapid loss of water in leaf than wild type. Two complementation lines of roc3 mutants showed similar stomatal response to ABA as observed for WT. Both complementation lines also showed similar water loss as WT by leaf detached assay. Biochemical assay suggested that ROC3 positively regulates ROS accumulation by inhibiting catalase activity. In response to ABA treatment or drought stress, roc3 mutant show down regulation of a number of stress responsive genes. All findings indicate that ROC3 positively regulates ABA-induced stomatal closure and the drought response by regulating ROS homeostasis and the expression of various stress-activated genes.
Overexpression of a SOC1-Related Gene Promotes Bud Break in Ecodormant Poplars
Authors: Gómez-Soto Daniela , Ramos-Sánchez José M. , Alique Daniel , Conde Daniel , Triozzi Paolo M. , Perales Mariano , Allona Isabel
Published: May 2021

Perennial species in the boreal and temperate regions are subject to extreme annual variations in light and temperature. They precisely adapt to seasonal changes by synchronizing cycles of growth and dormancy with external cues. Annual dormancy–growth transitions and flowering involve factors that integrate environmental and endogenous signals. MADS-box transcription factors have been extensively described in the regulation of Arabidopsis flowering. However, their participation in annual dormancy–growth transitions in trees is minimal. In this study, we investigate the function of MADS12, a Populus tremula × alba SUPPRESSOR OF CONSTANS OVEREXPRESSION 1 (SOC1)-related gene. Our gene expression analysis reveals that MADS12 displays lower mRNA levels during the winter than during early spring and mid-spring. Moreover, MADS12 activation depends on the fulfillment of the chilling requirement. Hybrid poplars overexpressing MADS12 show no differences in growth cessation and bud set, while ecodormant plants display an early bud break, indicating that MADS12 overexpression promotes bud growth reactivation. Comparative expression analysis of available bud break-promoting genes reveals that MADS12 overexpression downregulates the GIBBERELLINS 2 OXIDASE 4 (GA2ox4), a gene involved in gibberellin catabolism. Moreover, the mid-winter to mid-spring RNAseq profiling indicates that MADS12 and GA2ox4 show antagonistic expression during bud dormancy release. Our results support MADS12 participation in the reactivation of shoot meristem growth during ecodormancy and link MADS12 activation and GA2ox4 downregulation within the temporal events that lead to poplar bud break.
Biochemical and Functional Characterization of GALT8, an Arabidopsis GT31 β-(1,3)-Galactosyltransferase That Influences Seedling Development
Authors: Narciso Joan Oñate , Zeng Wei , Ford Kris , Lampugnani Edwin R. , Humphries John , Austarheim Ingvild , van de Meene Allison , Bacic Antony , Doblin Monika S.
Published: May 2021

Arabinogalactan-proteins (AGPs) are members of the hydroxyproline-rich glycoprotein (HRGP) superfamily, a group of highly diverse proteoglycans that are present in the cell wall, plasma membrane as well as secretions of almost all plants, with important roles in many developmental processes. The role of GALT8 (At1g22015), a Glycosyltransferase-31 (GT31) family member of the Carbohydrate-Active Enzyme database (CAZy), was examined by biochemical characterization and phenotypic analysis of a galt8 mutant line. To characterize its catalytic function, GALT8 was heterologously expressed in tobacco leaves and its enzymatic activity tested. GALT8 was shown to be a β-(1,3)-galactosyltransferase (GalT) that catalyzes the synthesis of a β-(1,3)-galactan, similar to the in vitro activity of KNS4/UPEX1 (At1g33430), a homologous GT31 member previously shown to have this activity. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) confirmed the products were of 2-6 degree of polymerisation (DP). Previous reporter studies showed that GALT8 is expressed in the central and synergid cells, from whence the micropylar endosperm originates after the fertilization of the central cell of the ovule. Homozygous mutants have multiple seedling phenotypes including significantly shorter hypocotyls and smaller leaf area compared to wild type (WT) that are attributable to defects in female gametophyte and/or endosperm development. KNS4/UPEX1 was shown to partially complement the galt8 mutant phenotypes in genetic complementation assays suggesting a similar but not identical role compared to GALT8 in β-(1,3)-galactan biosynthesis. Taken together, these data add further evidence of the important roles GT31 β-(1,3)-GalTs play in elaborating type II AGs that decorate AGPs and pectins, thereby imparting functional consequences on plant growth and development.
Economic Policy Uncertainty and Financial Innovation: Is There Any Affiliation?
Authors: Jia Zeng , Mehta Ahmed Muneeb , Qamruzzaman Md. , Ali Majid
Published: May 2021

The impetus of this study is to gauge the nexus between economic policy uncertainty (EPU) and financial innovation in Brazil, Russia, India, China, and South Africa (BRIC) nations for the period from 2004M1 to 2018M12. This study utilizes both the linear and non-linear autoregressive distributed lag (ARDL) models to evaluate the long-run and the short-run association between EPU and financial innovation; furthermore, the causal effects are investigated by following the non-Granger casualty framework. The results of long-run cointegration, i.e., the test statistics of modified F-test (FPSS), standard Wald test (WPSS), and tBDM, reject the null hypothesis and establish the presence of the long-run association between EPU and financial innovation. Conversely, long-run asymmetry cointegration revealed the test statistics of FPSS, WPSS, and tBDM in non-linear estimation. Furthermore, both in the long run and short run, the Wald test results disclose asymmetric effects running from EPU to financial innovation. In regards to the asymmetric impact of EPU on financial innovation, this study documents that the positive and negative shocks in EPU are negatively linked with financial innovation in the long run but are insignificant for short-run effects. Besides, financial innovation measured by R&D investment exhibits a positive linkage with shocks in EPU, implying that uncertainty induces innovation in the economy. Referring to causality effects, this study divulges the feedback hypothesis, i.e., bidirectional causality prevails between EPU and financial innovation in all sample countries.
The Effects of Familial Social Support Relationships on Identity Meaning in Older Adults: A Longitudinal Investigation
Authors: Toyoshima Aya , Nakahara Jun
Published: May 2021

This study aimed to examine whether social support promotes identity meaning among older adults. We hypothesized that when two spouses exchange social support, their sense of marital identity is enhanced. Among older adults, parental identity may be more strongly enhanced when parents provide social support to their children rather than receive social support from them. We conducted a longitudinal survey of 355 older adults (240 men and 115 women aged >60 years), who were assessed four times over 2 years. First, we confirmed the relationship between social support and identity meaning using an autoregressive path model. Second, we examined the effect of social support on the trajectory of role identities in a growth curve model. The intercepts of receiving support and providing support were significantly associated with the intercept of marital identity. In addition, the intercept of identity meaning for parents correlated with the intercept of providing support to their children but not with that of receiving support from their children. Social support between family members promotes role identities in family relationships. In particular, providing support to children correlates with parental roles which connect to subjective well-being.
Compulsory Interventions in Severe and Persistent Mental Illness: A Survey on Attitudes Among Psychiatrists in Switzerland
Authors: Stoll Julia , Hodel Martina A. , Riese Florian , Irwin Scott A. , Hoff Paul , Biller-Andorno Nikola , Trachsel Manuel
Published: May 2021

Background: Some psychiatric patients develop severe and persistent mental illness (SPMI), which, for a variety of reasons, can be therapy-refractory. Sometimes, treatment is not considered helpful by the patients themselves and does not improve their subjective quality of life. Furthermore, many SPMI patients experience compulsory interventions such as seclusion, restraint, or treatment against their will, which can cause harm.

Methods: In a cross-sectional survey of 1,311 German-speaking psychiatrists in Switzerland, participants were asked about the care of SPMI patients in general, and about their attitudes with regard to compulsory interventions in particular, using three case vignettes of patients with severe and persistent anorexia nervosa, schizophrenia and depression.

Results: Out of 1,311 contacted psychiatrists, 457 (34.9%) returned the completed survey. In general, 91.0% found it important or very important to respect SPMI patients' autonomy in decision making. However, based on three different clinical case vignettes, 36.8% of psychiatrists would act against the wishes of the patient with severe and persistent schizophrenia, 34.1% against the wishes of the patient with severe and persistent depression, and 21.1% against the wishes of the patient with severe and persistent anorexia nervosa, although all patients were stated to have preserved decision-making capacity. With regard to the case vignettes, 41.1% considered compulsory interventions leading to a temporary reduction of quality of life acceptable in the patient with severe and persistent schizophrenia, 39.4% in the patient with severe and persistent depression, and 25.6% in the patient with severe and persistent anorexia nervosa, although it was stated in all three case vignettes that two independent experts ascribed the patients decision-making capacity regarding their illness and further treatment.

Conclusions: Many psychiatrists in our sample found themselves in an ethical dilemma between autonomy and the provision of medical care. While most respondents respect the autonomy of SPMI patients, many saw the need to perform compulsory interventions even though it was clearly and prominently stated that two independent psychiatrists had ascribed the patients in the case vignettes decision-making capacity. Further examination of these conflicting views is warranted, perhaps along with the development of guidelines for such situations.
Genetic and Metabolite Variability in One-Carbon Metabolism Applied to an Insulin Resistance Model in Patients With Schizophrenia Receiving Atypical Antipsychotics
Authors: Ward Kristen M. , Burghardt Kyle , Kraal A. Zarina , Jaeger Andrew , Yeomans Larisa , McHugh Cora , Karnovsky Alla , Stringer Kathleen A. , Ellingrod Vicki L.
Published: May 2021

Background: Patients with schizophrenia are at high risk of pre-mature mortality due to cardiovascular disease (CVD). Our group has completed studies in pharmacogenomics and metabolomics that have independently identified perturbations in one-carbon metabolism as associated with risk factors for CVD in this patient population. Therefore, this study aimed to use genetic and metabolomic data to determine the relationship between folate pharmacogenomics, one-carbon metabolites, and insulin resistance as measured using the homeostatic model assessment for insulin resistance (HOMA-IR) as a marker of CVD.

Methods: Participants in this pilot analysis were on a stable atypical antipsychotic regimen for at least 6 months, with no diabetes diagnosis or use of antidiabetic medications. Participant samples were genotyped for MTHFR variants rs1801131 (MTHFR A1298C) and rs1801133 (MTHFR C677T). Serum metabolite concentrations were obtained with NMR. A least squares regression model was used to predict log(HOMA-IR) values based on the following independent variables: serum glutamate, glycine, betaine, serine, and threonine concentrations, and carrier status of the variant alleles for the selected genotypes.

Results: A total of 67 participants were included, with a median age of 47 years old (IQR 42–52), 39% were female, and the median BMI was 30.3 (IQR 26.3–37.1). Overall, the model demonstrated an ability to predict log(HOMA-IR) values with an adjusted R2 of 0.44 and a p-value of < 0.001. Glutamate, threonine, and carrier status of the MTHFR 1298 C or MTHFR 677 T allele were positively correlated with log(HOMA-IR), whereas glycine, serine, and betaine concentrations trended inversely with log(HOMA-IR). All factors included in this final model were considered as having a possible effect on predicting log(HOMA-IR) as measured with a p-value < 0.1.

Conclusions: Presence of pharmacogenomic variants that decrease the functional capacity of the MTHFR enzyme are associated with increased risk for cardiovascular disease, as measured in this instance by log(HOMA-IR). Furthermore, serine, glycine, and betaine concentrations trended inversely with HOMA-IR, suggesting that increased presence of methyl-donating groups is associated with lower measures of insulin resistance. Ultimately, these results will need to be replicated in a significantly larger population.
Case Report: Severe Adolescent Major Depressive Syndrome Turns Out to Be an Unusual Case of Anti-NMDA Receptor Encephalitis
Authors: Moldavski Alexander , Wenz Holger , Lange Bettina E. , Rohleder Cathrin , Leweke F. Markus
Published: May 2021

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a neuroinflammatory condition mediated by autoantibodies against the GluN1 subunit of the receptor. Clinically, it is characterized by a complex neuropsychiatric presentation with rapidly progressive psychiatric symptoms, cognitive deficits, seizures, and abnormal movements. Isolated psychiatric manifestations of anti-NMDAR encephalitis are rare and usually dominated by psychotic symptoms. We present a case of an 18-year-old female high school student—without a previous history of psychiatric disorders—with a rapid onset severe depressive syndrome. Surprisingly, we found pleocytosis and anti-NMDAR autoantibodies in the cerebrospinal fluid (CSF), despite an otherwise unremarkable diagnostic workup, including blood test, clinical examination, and cranial magnetic resonance imaging (MRI). After intravenous immunoglobulins treatment, a complete remission of the initial symptoms was observed. In a follow-up 5 years later, the young woman did not experience any relapse or sequelae. Anti-NMDAR encephalitis can present in rare cases as an organic disorder with major depressive symptoms without distinct concomitant psychotic or neurological symptoms. A clinical presentation such as a rapid onset of symptoms, distinct disturbance in the thought process, restlessness, and cognitive deficits should prompt screening for NMDAR- and other neural autoantibodies to rule out this rare but debilitating pathology.
Understanding Adolescents' Perceptions of Diarrhea: A Formative Research Study of a Visual Scale to Measure Self-Reported Diarrhea in Low-Resource Settings
Authors: Gold-Watts Anise , Aamodt Geir , Gandhimathi Subramanian , Sudha Rajamani , Bastien Sheri
Published: May 2021

Introduction: Although water, sanitation, and hygiene interventions are effective in reducing diarrhea, there are methodological issues regarding the research tools used to evaluate their health impact. Moreover, there is limited research on individuals' subjective interpretations of diarrheal illness which may introduce further limitations in relying on self-reported data. Therefore, we conducted a study that aims to understand adolescents' perceptions of diarrheal illness in rural Tamil Nadu, India. Next, we wish to explore the acceptability of the Bristol Stool Form Scale to assess self-reported diarrhea in water, sanitation, and hygiene interventions involving adolescent participants in low-resource settings.

Materials and Methods: The study was conducted as part of the formative research phase in the cultural adaptation of Project SHINE, a school-based educational water, sanitation, and hygiene intervention in Thirumalaikodi, Tamil Nadu, India. A convergent parallel mixed-methods study design with a purposive sampling strategy was used. Qualitative data included 10 in-depth interviews with student participants aged 13–14. Quantitative data were collected through interviewer-administered face-to-face surveys (n = 14) and one-week stool diaries (n = 14). Each data set was analyzed separately and compiled during the interpretation of the findings.

Results: Across all data sets, diarrhea was reported to be perceived as unhealthy and an irregular occurrence among participants. Participants also reported diarrheal-taboos, local methods to cure or control diarrhea, and discussed how diarrheal illness can lead to absenteeism or withdrawal from school and social activities. Moreover, participants were able to understand and answer questions about their stool using the Bristol Stool Form Scale, suggesting that is an acceptable tool.

Discussion: Visual tools demonstrate promise in improving self-reported diarrheal illness among adolescents in low-resource settings in India. However, until we address diarrhea-related taboos it will be difficult to address methodological issues in the assessment and reporting of diarrheal illness among adolescents.
Association Between Rare Earth Element Cerium and the Risk of Oral Cancer: A Case-Control Study in Southeast China
Authors: He Baochang , Wang Jing , Lin Jing , Chen Jinfa , Zhuang Zhaocheng , Hong Yihong , Yan Lingjun , Lin Lisong , Shi Bin , Qiu Yu , Pan Lizhen , Zheng Xiaoyan , Liu Fengqiong , Chen Fa
Published: May 2021

Cerium (Ce), the most abundant of rare earth elements in the earth's crust, has received much health concerns due to its wide application in industry, agriculture, and medicine. The current study aims to evaluate whether there is an association between Ce exposures and the risk of developing oral cancer. Serum Ce level of 324 oral cancer patients and 650 matched healthy controls were measured by inductively coupled plasma mass spectrometry. Association between Ce level and the risk of oral cancer was estimated with an unconditional logistic regression model. Serum Ce concentrations in the oral cancer patients and controls were 0.57 (0.21–3.02) μg/L and 2.27 (0.72–4.26) μg/L, respectively. High level of Ce was associated with a decreased risk of oral cancer (OR: 0.60, 95% CI: 0.43–0.84). Stronger inverse associations between high level of Ce and oral cancer risk were observed among those with smoking (OR: 0.46, 95% CI: 0.27–0.79), drinking (OR: 0.50, 95% CI: 0.26–0.96), limited intake of leafy vegetables (OR: 0.40, 95% CI: 0.22–0.71) and fish (OR: 0.52, 95% CI: 0.33–0.83). There were significant multiplicative interactions between Ce level and alcohol drinking or intake of leafy vegetables and fish (all Pinteraction <0.05). This preliminary case-control study suggests an inverse association between high serum Ce level and the risk of oral cancer. Further prospective studies with a larger sample size are needed to confirm the findings.
Your Eyes Do Not Lie! Dissecting Humor Effects in Health Messages Using Eye Tracker Technology
Authors: Brigaud Emmanuelle , Lafont Alex , Blanc Nathalie
Published: May 2021

In the past decade, humor in scientific research has become more and more popular providing an increase of data identifying the context in which humor is a promising communication strategy in preventive health messages. To avoid the limits of declarative responses usually recorded in past studies, eye tracker technology offers the possibility to assess and dissect the effects of humor on visual attention. In this brief report, we first attempt to extend the results of previous studies by recording eye movements while participants were exposed to humorous and nonhumorous print health ads dealing with tobacco and alcohol consumption. A secondary purpose is specifically to test the visual attention French women devoted to humorous tobacco preventive ads, the worrying results of recent studies urging to find a way to improve tobacco preventive campaigns. Based on three complementary eye-tracking measures (i.e., total dwell time, fixation count, and revisits), the results showed that humorous health messages were scanned longer and more frequently and revisited more often compared to nonhumorous ones. In addition, humor appeared to reduce smokers' avoidance of preventive tobacco messages. The different pattern of visual exploration confirms that humor is a good strategy to grab attention even of individuals who are involved in the health topic addressed. In short, this paper argues for introducing lightness into a very serious subject, health communication, based on the analysis of eye movement evidence.
Minimally Invasive Dentistry: Parent/Carer Perspectives on Atraumatic Restorative Treatments and Dental General Anaesthesia to the Management of Early Childhood Caries
Authors: Arrow Peter , Forrest Helen , Piggott Susan
Published: May 2021

Introduction: Parents of children treated under dental general anaesthesia (DGA) have reported feelings of concern and anxiety. This study elicited the views of parents/carers (P/C) of children with early childhood caries (ECC) who participated in a randomised trial (core study) which tested the effectiveness of care under DGA or care using alternative minimally invasive Atraumatic Restorative Treatment and the Hall Technique approaches (ART/HT).

Methods: P/C of children treated using the ART/HT (test) approach or care under a DGA (control) were interviewed. Focus group semi-structured interviews with P/C were undertaken in community facilities. The transcripts were read and inductively coded into domains to identify emergent themes. The codes were entered into NVivo software to assist data management and were further refined into broad themes.

Results: Seven grouped interviews with 14 participants were conducted and one test participant provided a written response. Four groups with eight test participants; two groups with four control participants; and one combined group with one test and one control participant were interviewed. Five broad themes emerged after thematic analysis: (1) Impacts on the child and the family; (2) Child-/family-centred care; (3) Timeliness of care; (4) Affordable care; (5) Accessible care. Impacts were related to that of the effects of the disease, and of the care for the disease. Child-centred/family-centred care (CCC) was a source of appreciation by P/C of both groups when it was experienced. Frustration at the lack of timely care of their child's treatment needs, coupled with the perceived expensiveness of care and difficulties in physically getting to the location for a specialist consultation was expressed by P/Cs in the study.

Discussion: The use of the ART/HT enabled the establishment of a relationship between the clinical team and the child and P/C which was central to the delivery of CCC. P/Cs in the DGA arm of the study expressed dissatisfaction more often with the issues of timely care, cost of care and accessibility of care. P/C of both groups were equally satisfied with the treatment, where treatment had been received in a timely, child-centred manner.

Conclusion: The findings suggest that minimally invasive approaches which facilitated CCC are acceptable alternative options to the DGA and should be considered for the management of ECC.

Australian New Zealand Clinical Trials Registry: ACTRN12616001124426.
Cannabis Use Is Associated With Recurrence After Primary Spontaneous Pneumothorax
Authors: Wakefield Connor J. , Seder Christopher W. , Arndt Andrew T. , Geissen Nicole , Liptay Michael J. , Karush Justin M.
Published: May 2021

Purpose: Primary spontaneous pneumothorax (PSP) is a frequently encountered entity that carries a high rate of recurrence. The current study aims to investigate if cannabis use at time of initial PSP is associated with disease recurrence.

Methods: Patients presenting with PSP between 2010 and 2018 at a single institution were identified. Exclusion criteria included secondary pneumothorax, severe chronic lung disease, lung cancer, and lost to follow-up. Patients were compared relative to their cannabis usage with Fisher's exact test, Wilcoxon rank-sum test, and logistic regression.

Results: Overall, 67 patients (53 male) met inclusion criteria with a median body mass index (BMI) of 21.5 kg/m2 (IQR 19.1–25.2) and age of 34 years (IQR 22–53). Initial treatment consisted of chest tube in 42 patients (63%), video-assisted thoracoscopic surgery wedge resection in 19 patients (28%), and observation in 6 patients (9%). Cannabis users (n = 28; 42%) had a higher rate of tobacco use (79 vs. 38%; p = 0.005), lower BMI [21.0 kg/m2 (IQR 18.3–23.1) vs. 22.2 kg/m2 (IQR 19.9–28.6), p = 0.037], and were more likely to require intervention at first presentation compared with non-marijuana users. Cannabis use was associated with PSP recurrence when adjusting for tobacco use, BMI, and height (OR 1.85, 95% CI 1.38–18.3, p = 0.014).

Conclusion: There is a high rate of cannabis usage in patients presenting with PSP. Cannabis usage is associated with PSP recurrence and eventual need for operative intervention.
Anterior Inferior Cerebellar Aneurysm Treated by Aneurysm Resection and Intracranial Artery Anastomosis in situ: A Case Report and Literature Review
Authors: Huang Chaojue , Qin Shixing , Huang Wei , Yu Yongjia
Published: May 2021

Background: Anterior inferior cerebellar artery (AICA) aneurysms are relatively rare in clinical practice, accounting for <1% of all intracranial arteries. After the diagnosis and location are confirmed by angiography, magnetic resonance, and other imaging examinations, interventional, or surgical treatment is often used, but some complex aneurysms require reconstructive surgery.

Case Description: An 8-year-old male child was admitted to the hospital due to sudden disturbance of consciousness for 2 weeks. The head CT showed hematocele in the ventricular system with subarachnoid hemorrhage in the basilar cistern and annular cistern. On admission, he was conscious, answered correctly, had a soft neck, limb muscle strength was normal, and had no cranial nerves or nervous system abnormalities. A preoperative examination showed the right side of the anterior distal arteries class under the circular wide neck aneurysm, the distal anterior inferior cerebellar artery supplying a wide range of blood to the cerebellum, the ipsilateral posterior inferior cerebellar artery absent, and the aneurysm close to the VII, VIII nerves. The aneurysm was successfully treated by aneurysm resection and intracranial artery anastomosis in situ of a2 AICA-a2 AICA.

Conclusions: AICA aneurysms are relatively rare; in this case, a complex wide-necked aneurysm was successfully treated by aneurysm resection and anastomosis in situ of a2 AICA-a2 AICA. This case can provide a reference for the surgical treatment of complex anterior cerebellar aneurysms.