bluuebunny/crossref_metadata_2025_split huggingface dataset:
From the Red Belt to the Bible Belt? Religiosity and Voting in Russia since 2011
Authors: Shcherbak Andrey , Ukhvatova Maria 
Published: June 2022

AbstractThe article explores the relationship between Orthodox religiosity and voting in Russia in 2011–2018. Using the theoretical framework of desecularization from above, which claims that church structures play a key role in the religious renaissance policy, we argue that the rise of the political influence of the ROC (Russian Orthodox Church) may be explained by its capacity for dissemination of traditional values that ultimately results in votes for United Russia and President Vladimir Putin in national elections. This study reveals the emergence of a new area on Russia’s political map—the belt – into Belt, which combines higher levels of Orthodox religiosity and pro-Kremlin voting in national elections. Using multiple empirical strategies we construct an index of religiosity on the regional level and identify the Orthodox Belt regions, test the relationship between Orthodox religiosity and voting in the national elections in 2011–2018, and test the differences in value orientations and electoral support between the Orthodox Belt regions and other ones. Finally, two model regions of the Orthodox Belt—Tambov and Lipetsk—are explored. We conclude that non-Orthodox Belt regions in Russia with higher Orthodox religiosity, conservatism, and loyalty are an emerging trend in Russian political geography.
EUnetHTA’s contribution to the new legal framework for health technology assessment cooperation in Europe
Authors: Imaz-Iglesia Iñaki , Wild Claudia 
Published: June 2022

The history of the European cooperation on health technology assessment (HTA) has reached an important milestone with the adoption of the European HTA Regulation (HTA R) 2021/2282 in Dec 2021 (1). Its publication in the Official Journal of the European Union means a lot to those of us who wish to give HTA a stronger role in supporting health policy in favor of sustainable healthcare systems in Europe. The HTA R was prepared well by the European Commission with an impact assessment on policy options for enhanced EU cooperation on HTA (2) in 2017, followed by 3 years of negotiations with Member States. Now the ratified document stipulates that the European Cooperation on HTA will be based on a legal mandate and no longer stay a voluntary project-based initiative. It also means sustainability, since a permanent Secretariat at the European Commission will be set-up under the HTA R.
5,10-Methylenetetrahydrofolate reductase becomes phosphorylated during meiotic maturation in mouse oocytes
Authors: Young Kyla , Tscherner Allison K. , Zhang Baohua , Meredith Megan , McClatchie Taylor , Trasler Jacquetta M. , Baltz Jay M. 
Published: June 2022

SummaryThe enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) links the folate cycle that produces one-carbon units with the methionine cycle that converts these intoS-adenosylmethionine (SAM), the universal methyl donor for almost all methyltransferases. Previously, MTHFR has been shown to be regulated by phosphorylation, which suppresses its activity. SAM levels have been shown to increase substantially soon after initiation of meiotic maturation of the mouse germinal vesicle (GV) stage oocyte and then decrease back to their original low level in mature second meiotic metaphase (MII) eggs. As MTHFR controls the entry of one-carbon units into the methionine cycle, it is a candidate regulator of the SAM levels in oocytes and eggs.Mthfrtranscripts are expressed in mouse oocytes and preimplantation embryos and MTHFR protein is present at each stage. In mature MII eggs, the apparent molecular weight of MTHFR was increased compared with GV oocytes, which we hypothesized was due to increased phosphorylation. The increase in apparent molecular weight was reversed by treatment with lambda protein phosphatase (LPP), indicating that MTHFR is phosphorylated in MII eggs. In contrast, LPP had no effect on MTHFR from GV oocytes, 2-cell embryos, or blastocysts. MTHFR was progressively phosphorylated after initiation of meiotic maturation, reaching maximal levels in MII eggs before decreasing again after egg activation. As phosphorylation suppresses MTHFR activity, it is predicted that MTHFR becomes inactive during meiotic maturation and is minimally active in MII eggs, which is consistent with the reported changes in SAM levels during mouse oocyte maturation.
Discretion and local health policy implementation: street-level bureaucrats and integrative and complementary therapies in Santos’ local health units
Authors: Macena Ariel , Oliveira Vanessa Elias de 
Published: June 2022

AbstractThis research discusses contextual factors that influence the development of complementary and/or integrative therapies developed by local health units on street-level bureaucracy in Santos. Through a qualitative approach, the research verifies that street-level bureaucracy is free to suggest and implement the aforementioned therapies, even if they do not have formal support of the municipality; however, they need support from their immediate local supervisors so they can adjust and implement the practice’s routine, or the practice might not occur. Additionally, this text also presents guidelines in order to further develop the research.
Vertical Postseismic Deformation of the 2019 Ridgecrest Earthquake Sequence
Authors: Ward Lauren A. , Guns Katherine A. , Smith‐Konter Bridget R. , Xu Xiaohua , Bock Yehuda , Sandwell David T. 
Published: June 2022

AbstractThe 2019 Ridgecrest conjugate Mw6.4 and Mw7.1 events resulted in several meters of strike‐slip and dip‐slip along an intricate rupture, extending from the surface down to 15 km. Now with >2 years of post‐rupture observations, we utilize these results to better understand vertical postseismic deformation from the Ridgecrest sequence and illuminate the emerging significance of vertical earthquake cycle deformation data. We determine the cumulative vertical displacement observed by the continuous GNSS network since Ridgecrest, which requires additional time series analyses to adequately resolve vertical deformation compared to the horizontal. Using a Maxwell‐type viscoelastic relaxation model, with a best fit time‐averaged asthenosphere viscosity of 4e17 Pa·s and a laterally heterogeneous lithosphere, we find that viscoelastic relaxation accounts for a majority of the cumulative vertical deformation at Ridgecrest and strongly controls far‐field observations in all north‐east‐up components. The viscoelastic model alone generally underpredicts deformation from GNSS and the remaining nonviscoelastic displacement is most prominent in the horizontal near‐field (−16 to 19 mm), revealing a deformation pattern matching the coseismic observations. This suggests that multiple deformation mechanisms are contributing to Ridgecrest's postseismic displacement, where afterslip likely dominates the near‐field while viscoelastic relaxation controls the far‐field. Similar deformation at individual GNSS stations has been observed for past earthquakes and additionally reveals long‐term transient viscosity over several years. Moreover, the greater temporal and spatial resolution of the GNSS array for Ridgecrest will help resolve the evolution of deformation for the entire network of observations as regional postseismic deformation persists for the next several years.
Spatial Markov Model for the Prediction of Travel‐Time‐Based Solute Dispersion in Three‐Dimensional Heterogeneous Media
Authors: Cirpka Olaf A. , Stettler Marie‐Madeleine , Dentz Marco 
Published: June 2022

AbstractIn recent years, Spatial Markov Models have gained popularity in simulating solute transport in heterogeneous formations. They describe the transition times of particles between equidistant observation planes by statistical distributions, assuming correlation of the transit times of individual particles between subsequent steps. By this, the approach naturally captures preasymptotic solute dispersion. In this study, we analyze Spatial Markov Models assuming bivariate log‐normal distributions of the particle slowness (i.e., the inverse velocity) in subsequent transitions. The model is fully parameterized by the mean Eulerian velocity, the variance of the log‐slowness, and the correlation coefficient of log‐slowness in subsequent steps. We derive closed‐form expressions for distance‐dependent ensemble dispersion, which is defined in terms of the second‐central moments of the solute breakthrough curves. We relate the coefficients to the properties of the underlying log‐hydraulic conductivity field assuming second‐order stationarity. The results are consistent with linear stochastic theory in the limit of small log‐conductivity variances, while the approach naturally extends to high‐variance cases. We demonstrate the validity of the approach by comparison to three‐dimensional particle‐tracking simulations of advective transport in heterogeneous media with isotropic, exponential correlation structure for log‐conductivity variances up to five. This study contributes to relating solute dispersion to metrics of the porous‐medium structure in cases of strong heterogeneity.
Patterns of activity correlate with symptom severity in major depressive disorder patients
Authors: Spulber S. , Elberling F. , Svensson J. , Tiger M. , Ceccatelli S. , Lundberg J. 
Published: June 2022

AbstractObjective measures, such as activity monitoring, can potentially complement clinical assessment for psychiatric patients. Alterations in rest–activity patterns are commonly encountered in patients with major depressive disorder. The aim of this study was to investigate whether features of activity patterns correlate with severity of depression symptoms (evaluated by Montgomery–Åsberg Rating Scale (MADRS) for depression). We used actigraphy recordings collected during ongoing major depressive episodes from patients not undergoing any antidepressant treatment. The recordings were acquired from two independent studies using different actigraphy systems. Data was quality-controlled and pre-processed for feature extraction following uniform procedures. We trained multiple regression models to predict MADRS score from features of activity patterns using brute-force and semi-supervised machine learning algorithms. The models were filtered based on the precision and the accuracy of fitting on training dataset before undergoing external validation on an independent dataset. The features enriched in the models surviving external validation point to high depressive symptom severity being associated with less complex activity patterns and stronger coupling to external circadian entrainers. Our results bring proof-of-concept evidence that activity patterns correlate with severity of depressive symptoms and suggest that actigraphy recordings may be a useful tool for individual evaluation of patients with major depressive disorder.
Sex-different interrelationships of rs945270, cerebral gray matter volumes, and attention deficit hyperactivity disorder: a region-wide study across brain
Authors: Luo Xingguang , Fang Wenhua , Lin Xiandong , Guo Xiaoyun , Chen Yu , Tan Yunlong , Wang Leilei , Jing Xiaozhong , Wang Xiaoping , Zhang Yong , Yu Ting , Ide Jaime , Cao Yuping , Yang Lingli , Li Chiang-Shan R. 
Published: June 2022

AbstractPrevious genome-wide association studies (GWAS) reported that the allele C of rs945270 of the kinectin 1 gene (KTN1) most significantly increased the gray matter volume (GMV) of the putamen and modestly regulated the risk for attention deficit hyperactivity disorder (ADHD). On the other hand, ADHD is known to be associated with a reduction in subcortical and cortical GMVs. Here, we examined the interrelationships of the GMVs, rs945270 alleles, and ADHD symptom scores in the same cohort of children. With data of rs945270 genotypes, GMVs of 118 brain regions, and ADHD symptom scores of 3372 boys and 3129 girls of the Adolescent Brain Cognition Development project, we employed linear regression analyses to examine the pairwise correlations adjusted for the third of the three traits and other relevant covariates, and examine their mediation effects. We found that the major allele C of rs945270 modestly increased risk for ADHD in males only when controlling for the confounding effects of the GMV of any one of the 118 cerebral regions (0.026 ≤ p ≤ 0.059: Top two: left and right putamen). This allele also significantly increased putamen GMV in males alone (left p = 2.8 × 10−5, and right p = 9.4 × 10−5; α = 2.1 × 10−4) and modestly increased other subcortical and cortical GMVs in both sexes (α < p < 0.05), whether or not adjusted for ADHD symptom scores. Both subcortical and cortical GMVs were significantly or suggestively reduced in ADHD when adjusted for rs945270 alleles, each more significantly in females (3.6 × 10−7 ≤ p < α; Top two: left pallidum and putamen) and males (3.5 × 10−6 ≤ p < α), respectively. Finally, the left and right putamen GMVs reduced 14.0% and 11.7% of the risk effects of allele C on ADHD, and allele C strengthened 4.5% (left) and 12.2% (right) of the protective effects of putamen GMVs on ADHD risk, respectively. We concluded that the rs945270-GMVs-ADHD relationships were sex-different. In males, the major allele C of rs945270 increased risk for ADHD, which was compromised by putamen GMVs; this allele also but only significantly increased putamen GMVs that then significantly protected against ADHD risk. In females, the top two GMVs significantly decreasing ADHD risk were left pallidum and putamen GMVs. Basal ganglia the left putamen in particular play the most critical role in the pathogenesis of ADHD.
Universal protein misfolding intermediates can bypass the proteostasis network and remain soluble and less functional
Authors: Nissley Daniel A. , Jiang Yang , Trovato Fabio , Sitarik Ian , Narayan Karthik B. , To Philip , Xia Yingzi , Fried Stephen D. , O’Brien Edward P. 
Published: June 2022

AbstractSome misfolded protein conformations can bypass proteostasis machinery and remain soluble in vivo. This is an unexpected observation, as cellular quality control mechanisms should remove misfolded proteins. Three questions, then, are: how do long-lived, soluble, misfolded proteins bypass proteostasis? How widespread are such misfolded states? And how long do they persist? We address these questions using coarse-grain molecular dynamics simulations of the synthesis, termination, and post-translational dynamics of a representative set of cytosolic E. coli proteins. We predict that half of proteins exhibit misfolded subpopulations that bypass molecular chaperones, avoid aggregation, and will not be rapidly degraded, with some misfolded states persisting for months or longer. The surface properties of these misfolded states are native-like, suggesting they will remain soluble, while self-entanglements make them long-lived kinetic traps. In terms of function, we predict that one-third of proteins can misfold into soluble less-functional states. For the heavily entangled protein glycerol-3-phosphate dehydrogenase, limited-proteolysis mass spectrometry experiments interrogating misfolded conformations of the protein are consistent with the structural changes predicted by our simulations. These results therefore provide an explanation for how proteins can misfold into soluble conformations with reduced functionality that can bypass proteostasis, and indicate, unexpectedly, this may be a wide-spread phenomenon.
Artificial neural networks enable genome-scale simulations of intracellular signaling
Authors: Nilsson Avlant , Peters Joshua M. , Meimetis Nikolaos , Bryson Bryan , Lauffenburger Douglas A. 
Published: June 2022

AbstractMammalian cells adapt their functional state in response to external signals in form of ligands that bind receptors on the cell-surface. Mechanistically, this involves signal-processing through a complex network of molecular interactions that govern transcription factor activity patterns. Computer simulations of the information flow through this network could help predict cellular responses in health and disease. Here we develop a recurrent neural network framework constrained by prior knowledge of the signaling network with ligand-concentrations as input and transcription factor-activity as output. Applied to synthetic data, it predicts unseen test-data (Pearson correlationr = 0.98) and the effects of gene knockouts (r = 0.8). We stimulate macrophages with 59 different ligands, with and without the addition of lipopolysaccharide, and collect transcriptomics data. The framework predicts this data under cross-validation (r = 0.8) and knockout simulations suggest a role for RIPK1 in modulating the lipopolysaccharide response. This work demonstrates the feasibility of genome-scale simulations of intracellular signaling.
Reliable crystal structure predictions from first principles
Authors: Nikhar Rahul , Szalewicz Krzysztof 
Published: June 2022

AbstractAn inexpensive and reliable method for molecular crystal structure predictions (CSPs) has been developed. The new CSP protocol starts from a two-dimensional graph of crystal’s monomer(s) and utilizes no experimental information. Using results of quantum mechanical calculations for molecular dimers, an accurate two-body, rigid-monomer ab initio-based force field (aiFF) for the crystal is developed. Since CSPs with aiFFs are essentially as expensive as with empirical FFs, tens of thousands of plausible polymorphs generated by the crystal packing procedures can be optimized. Here we show the robustness of this protocol which found the experimental crystal within the 20 most stable predicted polymorphs for each of the 15 investigated molecules. The ranking was further refined by performing periodic density-functional theory (DFT) plus dispersion correction (pDFT+D) calculations for these 20 top-ranked polymorphs, resulting in the experimental crystal ranked as number one for all the systems studied (and the second polymorph, if known, ranked in the top few). Alternatively, the polymorphs generated can be used to improve aiFFs, which also leads to rank one predictions. The proposed CSP protocol should result in aiFFs replacing empirical FFs in CSP research.
Boosting the performance of single-atom catalysts via external electric field polarization
Authors: Pan Yanghang , Wang Xinzhu , Zhang Weiyang , Tang Lingyu , Mu Zhangyan , Liu Cheng , Tian Bailin , Fei Muchun , Sun Yamei , Su Huanhuan , Gao Libo , Wang Peng , Duan Xiangfeng , Ma Jing , Ding Mengning 
Published: June 2022

AbstractSingle-atom catalysts represent a unique catalytic system with high atomic utilization and tunable reaction pathway. Despite current successes in their optimization and tailoring through structural and synthetic innovations, there is a lack of dynamic modulation approach for the single-atom catalysis. Inspired by the electrostatic interaction within specific natural enzymes, here we show the performance of model single-atom catalysts anchored on two-dimensional atomic crystals can be systematically and efficiently tuned by oriented external electric fields. Superior electrocatalytic performance have been achieved in single-atom catalysts under electrostatic modulations. Theoretical investigations suggest a universal “onsite electrostatic polarization” mechanism, in which electrostatic fields significantly polarize charge distributions at the single-atom sites and alter the kinetics of the rate determining steps, leading to boosted reaction performances. Such field-induced on-site polarization offers a unique strategy for simulating the catalytic processes in natural enzyme systems with quantitative, precise and dynamic external electric fields.
YAP inhibits ERα and ER+ breast cancer growth by disrupting a TEAD-ERα signaling axis
Authors: Li Xu , Zhuo Shu , Zhuang Ting , Cho Yong Suk , Wu Guojin , Liu Yuchen , Mu Kun , Zhang Kai , Su Peng , Yang Yingzi , Zhang Cheng Cheng , Zhu Jian , Jiang Jin 
Published: June 2022

AbstractHippo signaling restricts tissue growth by inhibiting the transcriptional effector YAP. Here we uncover a role of Hippo signaling and a tumor suppressor function of YAP in estrogen receptor positive (ER+) breast cancer. We find that inhibition of Hippo/MST1/2 or activation of YAP blocks the ERα transcriptional program and ER+ breast cancer growth. Mechanistically, the Hippo pathway transcription factor TEAD physically interacts with ERα to increase its promoter/enhancer occupancy whereas YAP inhibits ERα/TEAD interaction, decreases ERα occupancy on its target promoters/enhancers, and promotes ERα degradation by the proteasome. Furthermore, YAP inhibits hormone-independent transcription of ERα gene (ESR1). Consistently, high levels of YAP correlate with good prognosis of ER+ breast cancer patients. Finally, we find that pharmacological inhibition of Hippo/MST1/2 impeded tumor growth driven by hormone therapy resistant ERα mutants, suggesting that targeting the Hippo-YAP-TEAD signaling axis could be a potential therapeutical strategy to overcome endocrine therapy resistance conferred by ERα mutants.
Associations between polygenic risk, negative symptoms, and functional connectome topology during a working memory task in early-onset schizophrenia
Authors: Deng Mengjie , Liu Zhening , Zhang Wen , Wu Zhipeng , Cao Hengyi , Yang Jie , Palaniyappan Lena 
Published: June 2022

AbstractWorking memory (WM) deficit in schizophrenia is thought to arise from a widespread neural inefficiency. However, we do not know if this deficit results from the illness-related genetic risk and influence the symptom burden in various domains, especially in patients who have an early onset illness. We used graph theory to examine the topology of the functional connectome in 99 subjects (27 early-onset schizophrenia (EOS), 24 asymptomatic siblings, and 48 healthy subjects) during an n-back task, and calculated their polygenic risk score (PRS) for susceptibility to schizophrenia. Linear regression analysis was used to test associations of the PRS, clinical symptoms, altered connectomic properties, and WM accuracy in EOS. Indices of small-worldness and segregation were elevated in EOS during the WM task compared with the other two groups; these connectomic aberrations correlated with increased PRS and negative symptoms. In patients with higher polygenic risk, WM performance was lower only when both the connectomic aberrations and the burden of negative symptoms were higher. Negative symptoms had a stronger moderating role in this relationship. Our findings suggest that the aberrant connectomic topology is a feature of WM task performance in schizophrenia; this relates to higher polygenic risk score as well as higher burden of negative symptoms. The deleterious effects of polygenic risk on cognition are played out via its effects on the functional connectome, as well as negative symptoms.