bluuebunny/crossref_metadata_2025 huggingface dataset:
Arguments for One Radio Access Network (OneRAN) mobile infrastructure
Authors: Sheikh Muhammad Usman , Lempiainen Jukka , Jäntti Riku
Published: June 2022

The frequency spectrum is a scarce resource, and is owned and regulated by the state to ensure its efficient and fair utilization. All over the world, a large number of Mobile Network Operators (MNOs) are already involved in either active or passive Radio Access Network (RAN) sharing to maximize cost savings. The aim of this article is to challenge the ownership of individual operator’s infrastructure and present technical arguments for One Radio Access Network (OneRAN) approach for deploying a cellular network. The enormous increase in data traffic and regulatory requirements concerning public safety communications provide the basis for migrating to OneRAN infrastructure. The OneRAN approach provides an opportunity to gain technological benefits and helps in meeting the requirements of critical communication. OneRAN targets to maximize the savings on capital and operational expenses. The main focus of this work is outdoor wide-area coverage i.e., outdoor users in rural areas and on highways, as it is assumed that indoor service provision in the future requires a dedicated indoor solution. For the research work of this article, a measurement campaign was launched and different Key Performance Indicators(KPIs) of Long Term Evolution(LTE) technology for three commercial MNOs of Finland were measured over a 52 km highway from Iittala to Tampere city. The acquired results highlight the gain of OneRAN infrastructure as it enhanced the user quality of experience i.e., user throughput, especially of the critical cell border users, and improved the overall system performance economically. Finally, supportive arguments are presented for having a OneRAN infrastructure specifically over the highways.
Disease Mechanisms of Multiple System Atrophy: What a Parallel Between the Form of Pasta and the Alpha-Synuclein Assemblies Involved in MSA and PD Tells Us
Authors: Melki Ronald
Published: June 2022

Intracellular deposits rich in aggregated alpha-synuclein that appear within the central nervous system are intimately associated to Parkinson’s disease and multiple system atrophy. While it is understandable that the aggregation of proteins, which share no primary structure identity, such as alpha-synuclein and tau protein, leads to different diseases, that of a given protein yielding distinct pathologies is counterintuitive. This short review relates molecular and mechanistic processes to the observed pathological diversity associated to alpha-synuclein aggregation.
Comonotone lower probabilities with robust marginal distributions functions
Authors: Montes Ignacio
Published: June 2022

One of the usual dependence structures between random variables is comononicity, which refers to random variables that increase or decrease simultaneously. Besides the good mathematical properties, comonotonicity has been applied in choice theory under risk or in finance, among many other fields. The problem arises when the marginal distribution functions are only partially known, hence we only know bounds of their values. This can be mathematically modelled using p-boxes, allowing us to build a bridge with the theory of imprecise probabilities. This paper investigates the existence, construction and uniqueness of a joint (imprecise) comonotone model with the given marginal p-boxes. In particular, given that the joint comonotone model is not unique when it exists, we follow the philosophy of the imprecise probability theory and we characterise under which conditions there exists a least-committal comonotone model, called the comonotone natural extension.
Digitalisierung in der Schule: Vorschlag eines systematisierenden Rahmenmodells aus schulpädagogischer Perspektive
Authors: Syring Marcus , Bohl Thorsten , Lachner Andreas
Published: June 2022

Der inflationäre Gebrauch des Begriffes „Digitalisierung“ im Kontext von Schule trägt zu seinem diffusen Verständnis bei. Daher geht der Beitrag der Frage nach, welche Aspekte mit dem Begriff aus schulpädagogischer Perspektive adressiert werden und entwickelt auf Grundlage eines narrativen Reviews ein systematisierendes Rahmenmodell. Die unterschiedlichen Ebenen und Aspekte des Modells werden anhand zentraler Diskurs- und Forschungslinien dargestellt. Chancen des Einsatzes des Modells werden abschließend diskutiert.
Influence of clustering coefficient on network embedding in link prediction
Authors: Robledo Omar F. , Zhan Xiu-Xiu , Hanjalic Alan , Wang Huijuan
Published: June 2022

Multiple network embedding algorithms have been proposed to perform the prediction of missing or future links in complex networks. However, we lack the understanding of how network topology affects their performance, or which algorithms are more likely to perform better given the topological properties of the network. In this paper, we investigate how the clustering coefficient of a network, i.e., the probability that the neighbours of a node are also connected, affects network embedding algorithms’ performance in link prediction, in terms of the AUC (area under the ROC curve). We evaluate classic embedding algorithms, i.e., Matrix Factorisation, Laplacian Eigenmaps and node2vec, in both synthetic networks and (rewired) real-world networks with variable clustering coefficient. Specifically, a rewiring algorithm is applied to each real-world network to change the clustering coefficient while keeping key network properties. We find that a higher clustering coefficient tends to lead to a higher AUC in link prediction, except for Matrix Factorisation, which is not sensitive to the change of clustering coefficient. To understand such influence of the clustering coefficient, we (1) explore the relation between the link rating (probability that a node pair is the missing link) derived from the aforementioned algorithms and the number of common neighbours of the node pair, and (2) evaluate these embedding algorithms’ ability to reconstruct the original training (sub)network. All the network embedding algorithms that we tested tend to assign higher likelihood of connection to node pairs that share an intermediate or high number of common neighbours, independently of the clustering coefficient of the training network. Then, the predicted networks will have more triangles, thus a higher clustering coefficient. As the clustering coefficient increases, all the algorithms but Matrix Factorisation could also better reconstruct the training network. These two observations may partially explain why increasing the clustering coefficient improves the prediction performance.
Implementation and scalability of a digital intervention to reduce depressive symptoms in people with diabetes, hypertension or both in Brazil and Peru: a qualitative study of health system’s stakeholders’ perspectives
Authors: Cavero V. , Toyama M. , Castro H. , Couto M. T. , Brandt L. , Quayle J. , Menezes P. R. , Mohr D. C. , Araya R. , Miranda J. J. , Diez-Canseco F.
Published: June 2022

Two randomized controlled trials (RCTs) in Brazil and Peru demonstrated the effectiveness of CONEMO, a digital intervention supported by trained nurses or nurse assistants (NAs), to reduce depressive symptoms in people with diabetes and/or hypertension. This paper extends the RCTs findings by reflecting on the conditions needed for its wider implementation in routine care services. A qualitative study using semi-structured interviews and content analysis was conducted with nurses/NAs, clinicians, healthcare administrators, and policymakers. Informants reported that CONEMO would be feasible to implement in their health services, but some conditions could be improved before its scale-up: reducing workloads of healthcare workers; raising mental health awareness among clinicians and administrators; being able to inform, deliver and accompany the intervention; assuring appropriate training and supervision of nurses/NAs; and supporting the use of technology in public health services and by patients, especially older ones. We discuss some suggestions on how to overcome these challenges.
Entrapment, Escape, and Elevation from Relationship Violence
Authors: Goodfriend Wind , Simcock Pamela Lassiter
Published: June 2022

How does experiencing intimate partner violence (IPV) affect one's identity, in terms of self-concept and self-esteem? In this Element, the authors propose a novel framework called the E3 Model in which relevant theory and research studies can be organized into three phases: Entrapment, Escape, and Elevation. Entrapment focuses on how people enter and commit to a relationship that later becomes abusive and how experiencing IPV affects the self. Escape explores how victims become survivors as they slowly build the resources needed to leave safely, including galvanizing self-esteem. Finally, Elevation centers on how survivors psychologically rebuild from their experience and become stronger, happier, more hopeful selves. This Element concludes with a discussion of applications of the E3 Model, such as public and legal policy regarding how to best help and support survivors.
The ground states of quasilinear Hénon equation with double weighted critical exponents
Authors: Wang Cong , Su Jiabao
Published: June 2022

We prove the existence of nontrivial ground state solutions of the critical quasilinear Hénon equation $\displaystyle -\Delta _p u=|x|^{\alpha _1}|u|^{p^{*}(\alpha _1)-2}u-|x|^{\alpha _2}|u|^{p^{*}(\alpha _2)-2}u\ \ {\rm in}\ \mathbb {R}^{N}.$ It is a new problem in the sense that the signs of the coefficients of critical terms are opposite.
CEO Selection and Executive Appearance
Authors: Cook Douglas O. , Mobbs Shawn
Published: June 2022

Survey assessments have found limited evidence of benefits of executive attractiveness. We use an objective measure of facial attractiveness that is correlated with survey assessments but less noisy and identify several benefits from executive facial attractiveness previously found in the general population but heretofore empirically elusive among executives. We examine the effect of both measures on executive compensation, promotion to CEO and the corresponding shareholder reaction, and promotion to board chair. The objective measure identifies significantly positive labor market effects for executive attractiveness in all outcomes in contrast to survey assessments of attractiveness that do not correlate with any outcome.
How do the determinants of exclusive breast-feeding change over time? A multi-survey quasi-longitudinal study in Lao People’s Democratic Republic
Authors: Bal Niels , Boulom Sayvisene , van Brakel Kimberly A , Kounnavong Sengchanh , Essink Dirk R
Published: June 2022

Objective:

The current study aimed to assess trends, associated factors and the changes in these factors for exclusive breast-feeding (EBF) over the past two decades in Lao People’s Democratic Republic (Lao PDR).

Design:

The current study used a quasi-longitudinal design. Descriptive analyses were done with correction for complex survey design. Inferential analyses were done for survey years separately using multiple logistic regression. Finally, pooled logistic regression analysis was done using interaction terms to quantify the difference in association per year.

Setting:

The current study used data from all provinces of Lao PDR collected in the years 2000, 2006, 2011/2012 and 2017.

Participants:

Children aged six months or younger from Lao PDR.

Results:

EBF practice was estimated at 19·03 %, 26·87 %, 40·67 % and 44·89 % in the four survey years, respectively. Factors significantly associated with EBF included: region of residence, ethnicity, wealth index and age of child. Region and ethnicity saw significant changes in association, and the South developing positively over time as well as in the Lao-Thai ethnic group. Having had any antenatal visits was not associated with EBF practice, nor did this change over time.

Conclusions:

Our study shows how EBF trends, and factors associated with EBF, changed over time. We applied an easily replicable methodology to assess similar public health phenomena. We argue that such analysis is particularly relevant for transitioning countries. In such rapidly evolving settings, it is crucial to take into account changing underlying factors when assessing and developing public health policy.
God is Green: The Catholic Church's Re-Imagination of Environmental Norms
Authors: Chu Lan T.
Published: June 2022

International discussions regarding the environment have too narrowly focused on contributions by secular actors. The Catholic Church, recognized for its influential role in the democratization processes of the 1990s, also has a long-standing position regarding climate change, yet remains understudied. How can the Church contribute to the international community's debates regarding the environment and climate change? Using the framework of constructivism and Jurgen Habermas' concept of institutional translation, I argue that the Church is a norm entrepreneur that promotes a foreign policy of human/integral ecology. The most recent articulation of this foreign policy is Pope Francis' encyclical Laudato Si’, which was referenced by the Holy See at the 26th UN Climate Change Conference (COP26) in 2021. The Church's participation at COP26 was the latest animation and application of the Church's foreign policy; I examine the Church's efforts to change the narrative on the environment toward a shared, global responsibility.
The Role of Groundwater Withdrawals on River Regulation: Example From the Columbia River Basin
Authors: Eldardiry Hisham , Zhou Tian , Huang Maoyi , Chegwidden Oriana S.
Published: June 2022

The Columbia River Basin (CRB) is heavily regulated by more than 250 dams on its river system while depending significantly on groundwater withdrawals in certain sub‐basins. Neglecting groundwater withdrawals in hydrologic models of the basin could result in inaccurate predictions of its water budget and thus mislead water management decisions in the basin. This study aims to understand the impacts of groundwater pumping on the spatiotemporal patterns of modeling regulated streamflow in the CRB using a modified version of the Variable Infiltration Capacity (VIC) model integrated with a water management component that accounts for groundwater withdrawals, irrigation demands, and reservoir operation (VIC‐GIRR). The VIC‐GIRR simulations showed that considering additional groundwater withdrawals would alleviate the stress of irrigation water deficit in the Snake River Basin with an average reduction of 10 km3/year. Such a reduction in water deficit resulted in slight streamflow increase over the CRB with maximum increase up to 40% during dry period in certain locations. We also note that the implementation of groundwater withdrawal does not, however, improve the overall model performance in long‐term averaged streamflow and storage predictions. Our results highlight the efforts needed to examine additional important processes in representing the interactions between water withdrawals and reservoir operations. Such efforts will aid in better simulation of multi‐reservoir system and improve effectiveness for agricultural productivity, power generation, flood control, and navigation purposes.
Assimilation of Groundwater Level and Soil Moisture Data in an Integrated Land Surface‐Subsurface Model for Southwestern Germany
Authors: Hung Ching Pui , Schalge Bernd , Baroni Gabriele , Vereecken Harry , Hendricks Franssen Harrie‐Jan
Published: June 2022

Integrated terrestrial system models predict the coupled water, energy and biogeochemical cycles. Simulations with these models are affected by uncertainties of model parameters, initial and boundary conditions, atmospheric forcings and the biophysical processes. Data assimilation (DA) can quantify and reduce the uncertainty. This has been tested intensively for single compartment models, but far less for integrated models with multiple compartments. We constructed a virtual reality (VR) with a coupled land surface‐subsurface model under the Terrestrial Systems Modeling Platform, which mimics the Neckar catchment in southern Germany. Soil moisture and groundwater level (GWL) data extracted from the simulated VR are used as measurements to be assimilated with state‐only/state‐hydraulic parameter estimation. Soil moisture DA improves soil moisture characterization in the vertical profile and the neighboring grid cells, with a 40 ∼ 60% reduction of root mean square error (RMSE) over the observation points. In spite of a small ensemble size of 64 members, assimilating soil moisture data improved saturated hydraulic conductivity estimation around the measurement locations. The characterization of evapotranspiration and river discharge only show limited improvements (1% at observation points and less than 0.1% in RMSE at 3 selected gauge locations respectively). GWL DA not only improves the GWL characterization (76 ∼ 88% RMSE reduction at observation locations) but also soil moisture for some cases. In addition, a clear improvement in GWL characterization is observed up to 8 km from the observations, and updating the model states of the saturated zone only instead of the complete domain gives better performance.
Re‐Evaluation of Low Cloud Amount Relationships With Lower‐Tropospheric Stability and Estimated Inversion Strength
Authors: Cutler Lauren , Brunke Michael A. , Zeng Xubin
Published: June 2022

Lower‐tropospheric stability (LTS) and estimated inversion strength (EIS) have a widely accepted relationship with low cloud amount and are key observational foundations for understanding and modeling low‐level stratiform clouds. Using the updated surface‐based and satellite cloud data, we find that low cloud amount is not as strongly correlated with LTS, and not as sensitive to LTS, as established in the past. EIS does not provide a stronger correlation with low cloud amount than LTS over all eight regions (including the midlatitudes). Further analyzing the relationships between LTS and EIS with different types of low clouds, we find that there is a strong correlation of LTS and EIS with stratocumulus only. This explains the weaker correlation of low cloud fraction (including cumulus, stratocumulus, and stratus) to both LTS and EIS. These results also suggest the need to re‐evaluate these relationships in Earth system models.
Hyaluronan synthase 2, a target of miR-200c, promotes carbon tetrachloride-induced acute and chronic liver inflammation via regulation of CCL3 and CCL4
Authors: Kim Sun Myoung , Song Ga Yeon , Shim Aeri , Lee Jee Hyung , Eom Cheol Bin , Liu Cheng , Yang Yoon Mee , Seki Ekihiro
Published: June 2022

Liver fibrosis occurs during wound healing after repeated liver injury and is characterized by extensive extracellular matrix deposition. We previously identified hyaluronan synthase 2 (HAS2) as a driver of liver fibrosis and hepatic stellate cell (HSC) activation. Developing strategies to suppress HSC activation is key to alleviating liver fibrosis, and HAS2 is an attractive candidate for intervention. To gain insight into the molecular function of HAS2, we investigated its posttranscriptional regulation. We found that miR-200c directly targets the 3’ untranslated regions of HAS2. Moreover, miR-200c and HAS2 were inversely expressed in fibrotic human and mouse livers. After establishing the direct interaction between miR-200c and HAS2, we investigated the functional outcome of regulating HAS2 expression in three murine models: CCl4-induced acute liver injury, CCl4-induced chronic liver fibrosis, and bile duct ligation-induced liver fibrosis. Hepatic Has2 expression was induced by acute and chronic CCl4 treatment. In contrast, miR-200c expression was decreased after CCl4 treatment. HSC-specific Has2 deletion reduced the expression of inflammatory markers and infiltration of macrophages in the models. Importantly, hyaluronidase-2 (HYAL2) but not HYAL1 was overexpressed in fibrotic human and murine livers. HYAL2 is an enzyme that can cleave the extracellular matrix component hyaluronan. We found that low-molecular-weight hyaluronan stimulated the expression of inflammatory genes. Treatment with the HA synthesis inhibitor 4-methylumbelliferone alleviated bile duct ligation-induced expression of these inflammatory markers. Collectively, our results suggest that HAS2 is negatively regulated by miR-200c and contributes to the development of acute liver injury and chronic liver inflammation via hyaluronan-mediated immune signaling.
Prognostic accuracy and clinical utility of psychometric instruments for individuals at clinical high-risk of psychosis: a systematic review and meta-analysis
Authors: Oliver Dominic , Arribas Maite , Radua Joaquim , Salazar de Pablo Gonzalo , De Micheli Andrea , Spada Giulia , Mensi Martina Maria , Kotlicka-Antczak Magdalena , Borgatti Renato , Solmi Marco , Shin Jae Il , Woods Scott W. , Addington Jean , McGuire Philip , Fusar-Poli Paolo
Published: June 2022

Accurate prognostication of individuals at clinical high-risk for psychosis (CHR-P) is an essential initial step for effective primary indicated prevention. We aimed to summarise the prognostic accuracy and clinical utility of CHR-P assessments for primary indicated psychosis prevention. Web of Knowledge databases were searched until 1st January 2022 for longitudinal studies following-up individuals undergoing a psychometric or diagnostic CHR-P assessment, reporting transition to psychotic disorders in both those who meet CHR-P criteria (CHR-P + ) or not (CHR-P−). Prognostic accuracy meta-analysis was conducted following relevant guidelines. Primary outcome was prognostic accuracy, indexed by area-under-the-curve (AUC), sensitivity and specificity, estimated by the number of true positives, false positives, false negatives and true negatives at the longest available follow-up time. Clinical utility analyses included: likelihood ratios, Fagan’s nomogram, and population-level preventive capacity (Population Attributable Fraction, PAF). A total of 22 studies (n = 4 966, 47.5% female, age range 12–40) were included. There were not enough meta-analysable studies on CHR-P diagnostic criteria (DSM-5 Attenuated Psychosis Syndrome) or non-clinical samples. Prognostic accuracy of CHR-P psychometric instruments in clinical samples (individuals referred to CHR-P services or diagnosed with 22q.11.2 deletion syndrome) was excellent: AUC = 0.85 (95% CI: 0.81–0.88) at a mean follow-up time of 34 months. This result was driven by outstanding sensitivity (0.93, 95% CI: 0.87–0.96) and poor specificity (0.58, 95% CI: 0.50–0.66). Being CHR-P + was associated with a small likelihood ratio LR + (2.17, 95% CI: 1.81–2.60) for developing psychosis. Being CHR-P- was associated with a large LR- (0.11, 95%CI: 0.06−0.21) for developing psychosis. Fagan’s nomogram indicated a low positive (0.0017%) and negative (0.0001%) post-test risk in non-clinical general population samples. The PAF of the CHR-P state is 10.9% (95% CI: 4.1–25.5%). These findings consolidate the use of psychometric instruments for CHR-P in clinical samples for primary indicated prevention of psychosis. Future research should improve the ability to rule in psychosis risk.
Ultra-rare and common genetic variant analysis converge to implicate negative selection and neuronal processes in the aetiology of schizophrenia
Authors: Akingbuwa Wonuola A. , Hammerschlag Anke R. , Bartels Meike , Nivard Michel G. , Middeldorp Christel M.
Published: June 2022

Both common and rare genetic variants (minor allele frequency >1% and <0.1% respectively) have been implicated in the aetiology of schizophrenia. In this study, we integrate single-cell gene expression data with publicly available Genome-Wide Association Study (GWAS) and exome sequenced data in order to investigate in parallel, the enrichment of common and (ultra-)rare variants related to schizophrenia in several functionally relevant gene-sets. Four types of gene-sets were constructed 1) protein-truncating variant (PTV)-intolerant (PI) genes 2) genes expressed in brain cell types and neurons ascertained from mouse and human brain tissue 3) genes defined by synaptic function and location and 4) intersection genes, i.e., PI genes that are expressed in the human and mouse brain cell gene-sets. We show that common as well as ultra-rare schizophrenia-associated variants are overrepresented in PI genes, in excitatory neurons from the prefrontal cortex and hippocampus, medium spiny neurons, and genes enriched for synaptic processes. We also observed stronger enrichment in the intersection genes. Our findings suggest that across the allele frequency spectrum, genes and genetic variants likely to be under stringent selection, and those expressed in particular brain cell types, are involved in the same biological pathways influencing the risk for schizophrenia.
Functional RECAP (REpair CAPacity) assay identifies homologous recombination deficiency undetected by DNA-based BRCAness tests
Authors: Meijer Titia G. , Nguyen Luan , Van Hoeck Arne , Sieuwerts Anieta M. , Verkaik Nicole S. , Ladan Marjolijn M. , Ruigrok-Ritstier Kirsten , van Deurzen Carolien H. M. , van de Werken Harmen J. G. , Lips Esther H. , Linn Sabine C. , Memari Yasin , Davies Helen , Nik-Zainal Serena , Kanaar Roland , Martens John W. M. , Cuppen Edwin , Jager Agnes , van Gent Dik C.
Published: June 2022

Germline BRCA1/2 mutation status is predictive for response to Poly-[ADP-Ribose]-Polymerase (PARP) inhibitors in breast cancer (BC) patients. However, non-germline BRCA1/2 mutated and homologous recombination repair deficient (HRD) tumors are likely also PARP-inhibitor sensitive. Clinical validity and utility of various HRD biomarkers are under investigation. The REpair CAPacity (RECAP) test is a functional method to select HRD tumors based on their inability to form RAD51 foci. We investigated whether this functional test defines a similar group of HRD tumors as DNA-based tests. An HRD enriched cohort (n = 71; 52 primary and 19 metastatic BCs) selected based on the RECAP test (26 RECAP-HRD; 37%), was subjected to DNA-based HRD tests (i.e., Classifier of HOmologous Recombination Deficiency (CHORD) and BRCA1/2-like classifier). Whole genome sequencing (WGS) was carried out for 38 primary and 19 metastatic BCs. The RECAP test identified all bi-allelic BRCA deficient samples (n = 15) in this cohort. RECAP status partially correlated with DNA-based HRD test outcomes (70% concordance for both RECAP-CHORD and RECAP-BRCA1/2-like classifier). RECAP selected additional samples unable to form RAD51 foci, suggesting that this functional assay identified deficiencies in other DNA repair genes, which could also result in PARP-inhibitor sensitivity. Direct comparison of these HRD tests in clinical trials will be required to evaluate the optimal predictive test for clinical decision making.
Cardiovascular risk of gonadotropin-releasing hormone antagonist versus agonist in men with prostate cancer: an observational study in Taiwan
Authors: Shao Yu-Hsuan Joni , Hong Jian-Hua , Chen Chun-Kai , Huang Chao-Yuan
Published: June 2022

Background

The impact of gonadotropin-releasing hormone (GnRH) antagonist and agonist (GnRHa) treatment on cardiovascular disease (CVD) risk in prostate cancer (PCa) remains inconclusive due to conflicting findings. We compared the effects of GnRH antagonist and GnRHa treatments on CVD risk in patients with PCa and pre-existing CVD, in a Taiwan population-based database.

Methods

We assessed the risk of major adverse CV events (MACE: ischemic heart disease [IHD], stroke, congestive heart failure [CHF] or all cause deaths) and composite CV events (IHD, stroke, CHF or CV deaths) occurring ≥90 days after androgen deprivation therapy (ADT) initiation in patients with PCa after 90 days of treatment with either GnRH antagonist (degarelix; n = 499) or GnRHa (goserelin, leuprolide, triptorelin; n = 15,127). Patients identified with pre-existing CVD had received cardiac therapy for IHD, reported a stroke or CHF within a year before ADT initiation. Adjusted hazard ratios (aHR) and 95% confidence interval (CI) were obtained for MACE and composite CV events risk after adjusting for age, baseline status of diabetes, hypertension and treatments received.

Results

All GnRH antagonist-treated patients showed lower risk of composite CV events than the GnRHa-treated patients. The lower composite CV events risk associated with GnRH antagonist was also observed in patients with metastasis at diagnosis (aHR 0.16; 95% CI, 0.04–0.38; p = 0.013) and those receiving ADT for more than six months (aHR 0.30; 95% CI, 0.16–0.54; p < 0.0001). In patients with pre-existing CVD, the MACE risk was 33% lower (aHR 0.67; 95% CI, 0.46–0.96; p = 0.0299) and composite CV events risk was 84% lower (aHR 0.16; 95% CI, 0.05–0.50; p = 0.0017) in GnRH antagonist-treated than the GnRHa-treated patients.

Conclusions

In patients with PCa and pre-existing CVD, GnRH antagonist use was associated with lower risks for composite CV events and MACE compared with GnRHa.
Identification of cerebrospinal fluid and serum metabolomic biomarkers in first episode psychosis patients
Authors: Shang Pei , Ho Ada Man-Choi , Tufvesson-Alm Maximilian , Lindberg Daniel R. , Grant Caroline W. , Orhan Funda , Eren Feride , Bhat Maria , Engberg Göran , Schwieler Lilly , Fatouros-Bergman Helena , Imbeault Sophie , Iverson Ryan M. , Dasari Surendra , Piehl Fredrik , Cervenka Simon , Sellgren Carl M. , Erhardt Sophie , Choi Doo-Sup
Published: June 2022

Psychotic disorders are currently diagnosed by examining the patient’s mental state and medical history. Identifying reliable diagnostic, monitoring, predictive, or prognostic biomarkers would be useful in clinical settings and help to understand the pathophysiology of schizophrenia. Here, we performed an untargeted metabolomics analysis using ultra-high pressure liquid chromatography coupled with time-of-flight mass spectroscopy on cerebrospinal fluid (CSF) and serum samples of 25 patients at their first-episode psychosis (FEP) manifestation (baseline) and after 18 months (follow-up). CSF and serum samples of 21 healthy control (HC) subjects were also analyzed. By comparing FEP and HC groups at baseline, we found eight CSF and 32 serum psychosis-associated metabolites with non-redundant identifications. Most remarkable was the finding of increased CSF serotonin (5-HT) levels. Most metabolites identified at baseline did not differ between groups at 18-month follow-up with significant improvement of positive symptoms and cognitive functions. Comparing FEP patients at baseline and 18-month follow-up, we identified 20 CSF metabolites and 90 serum metabolites that changed at follow-up. We further utilized Ingenuity Pathway Analysis (IPA) and identified candidate signaling pathways involved in psychosis pathogenesis and progression. In an extended cohort, we validated that CSF 5-HT levels were higher in FEP patients than in HC at baseline by reversed-phase high-pressure liquid chromatography. To conclude, these findings provide insights into the pathophysiology of psychosis and identify potential psychosis-associated biomarkers.
Vapor phase polymerization of Ag QD-embedded PEDOT film with enhanced thermoelectric and antibacterial properties
Authors: Shi Wei , Yao Qin , Donghui Wang , Qu Sanyin , Chen Yanling , Lee Kyu Hyoung , Chen Lidong
Published: June 2022

Nonferric oxidant precursors have the unique advantage of directly polymerizing poly(3,4-ethylenedioxythiophene) (PEDOT)-inorganic composites. However, due to limited solubility and unmatched oxidation potentials, most oxidants only produce powders or porous materials. To obtain high-quality films with improved homogeneity and controllable particle sizes, the oxidants should be adaptable to high-standard PEDOT film fabrication techniques such as vapor phase polymerization (VPP). In this work, we discovered for the first time a nonferric metal salt suitable for the VPP process. With the addition of an Fe(III) salt to stabilize the reaction and adjust the oxidant ratio, micron-thick antibacterial S-PEDOT-Ag quantum dot (QD) composite films with tunable Ag wt% can be synthesized in one facile step. With a low Ag loading of ~0.2 wt%, the film exhibited an optimized power factor of 63.1 μW/mK2, which is among the highest values thus far reported for PEDOT-metal composites. Increase of the Ag(I) concentration in the precursor to a certain level may lead to minor decomposition of the polymer followed by the formation of Ag2S particles.
Electron-phonon interactions in halide perovskites
Authors: Yamada Yasuhiro , Kanemitsu Yoshihiko
Published: June 2022

Strong electron-phonon interactions are frequently considered the origin of the unique electrical and optical properties of lead halide perovskites. Electron-phonon interactions induce the formation of a polaron, which is a charge carrier dressed with a phonon cloud. The details of polaron formation are crucial for carrier transport since polaron formation leads to a larger effective mass of a carrier. Several mechanisms have been proposed regarding the physics of polaron formation in halide perovskites, but the details are still under active debate. While the Fröhlich interaction plays an essential role in ionic crystals, we also need to consider the strong phonon anharmonicity of halide perovskites that may lead to the formation of an unconventional polaron. In this review article, we discuss the uniqueness of perovskite semiconductors from the viewpoint of electron-phonon interactions. We review the experimental results and the proposed models concerning the effective carrier mass and carrier mobility. Finally, we briefly explain two physical phenomena related to strong electron-phonon interactions: strong anti-Stokes photoluminescence and slow hot-carrier cooling.
Extremely confined gap plasmon modes: when nonlocality matters
Authors: Boroviks Sergejs , Lin Zhan-Hong , Zenin Vladimir A. , Ziegler Mario , Dellith Andrea , Gonçalves P. A. D. , Wolff Christian , Bozhevolnyi Sergey I. , Huang Jer-Shing , Mortensen N. Asger
Published: June 2022

Historically, the field of plasmonics has been relying on the framework of classical electrodynamics, with the local-response approximation of material response being applied even when dealing with nanoscale metallic structures. However, when the confinement of electromagnetic radiation approaches atomic scales, mesoscopic effects are anticipated to become observable, e.g., those associated with the nonlocal electrodynamic surface response of the electron gas. Here, we investigate nonlocal effects in propagating gap surface plasmon modes in ultrathin metal–dielectric–metal planar waveguides, exploiting monocrystalline gold flakes separated by atomic-layer-deposited aluminum oxide. We use scanning near-field optical microscopy to directly access the near-field of such confined gap plasmon modes and measure their dispersion relation via their complex-valued propagation constants. We compare our experimental findings with the predictions of the generalized nonlocal optical response theory to unveil signatures of nonlocal damping, which becomes appreciable for few-nanometer-sized dielectric gaps.
A synaptomic analysis reveals dopamine hub synapses in the mouse striatum
Authors: Paget-Blanc Vincent , Pfeffer Marlene E. , Pronot Marie , Lapios Paul , Angelo Maria-Florencia , Walle Roman , Cordelières Fabrice P. , Levet Florian , Claverol Stéphane , Lacomme Sabrina , Petrel Mélina , Martin Christelle , Pitard Vincent , De Smedt Peyrusse Véronique , Biederer Thomas , Perrais David , Trifilieff Pierre , Herzog Etienne
Published: June 2022

Dopamine transmission is involved in reward processing and motor control, and its impairment plays a central role in numerous neurological disorders. Despite its strong pathophysiological relevance, the molecular and structural organization of the dopaminergic synapse remains to be established. Here, we used targeted labelling and fluorescence activated sorting to purify striatal dopaminergic synaptosomes. We provide the proteome of dopaminergic synapses with 57 proteins specifically enriched. Beyond canonical markers of dopamine neurotransmission such as dopamine biosynthetic enzymes and cognate receptors, we validated 6 proteins not previously described as enriched. Moreover, our data reveal the adhesion of dopaminergic synapses to glutamatergic, GABAergic or cholinergic synapses in structures we named “dopamine hub synapses”. At glutamatergic synapses, pre- and postsynaptic markers are significantly increased upon association with dopamine synapses. Dopamine hub synapses may thus support local dopaminergic signalling, complementing volume transmission thought to be the major mechanism by which monoamines modulate network activity.
Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy
Authors: Kuwayama Ryoko , Suzuki Keiichiro , Nakamura Jun , Aizawa Emi , Yoshioka Yoshichika , Ikawa Masahito , Nabatame Shin , Inoue Ken-ichi , Shimmyo Yoshiari , Ozono Keiichi , Kinoshita Taroh , Murakami Yoshiko
Published: June 2022

Inherited glycosylphosphatidylinositol (GPI) deficiency (IGD) is caused by mutations in GPI biosynthesis genes. The mechanisms of its systemic, especially neurological, symptoms are not clarified and fundamental therapy has not been established. Here, we report establishment of mouse models of IGD caused by PIGO mutations as well as development of effective gene therapy. As the clinical manifestations of IGD are systemic and lifelong lasting, we treated the mice with adeno-associated virus for homology-independent knock-in as well as extra-chromosomal expression of Pigo cDNA. Significant amelioration of neuronal phenotypes and growth defect was achieved, opening a new avenue for curing IGDs.
Neuroimaging signatures predicting motor improvement to focused ultrasound subthalamotomy in Parkinson’s disease
Authors: Lin Sue-Jin , Rodriguez-Rojas Rafael , Baumeister Tobias R. , Lenglos Christophe , Pineda-Pardo Jose A. , Máñez-Miró Jorge U. , del Alamo Marta , Martinez-Fernandez Raul , Obeso Jose A. , Iturria-Medina Yasser
Published: June 2022

Subthalamotomy using transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) is a novel and promising treatment for Parkinson’s Disease (PD). In this study, we investigate if baseline brain imaging features can be early predictors of tcMRgFUS-subthalamotomy efficacy, as well as which are the post-treatment brain changes associated with the clinical outcomes. Towards this aim, functional and structural neuroimaging and extensive clinical data from thirty-five PD patients enrolled in a double-blind tcMRgFUS-subthalamotomy clinical trial were analyzed. A multivariate cross-correlation analysis revealed that the baseline multimodal imaging data significantly explain (P < 0.005, FWE-corrected) the inter-individual variability in response to treatment. Most predictive features at baseline included neural fluctuations in distributed cortical regions and structural integrity in the putamen and parietal regions. Additionally, a similar multivariate analysis showed that the population variance in clinical improvements is significantly explained (P < 0.001, FWE-corrected) by a distributed network of concurrent functional and structural brain changes in frontotemporal, parietal, occipital, and cerebellar regions, as opposed to local changes in very specific brain regions. Overall, our findings reveal specific quantitative brain signatures highly predictive of tcMRgFUS-subthalamotomy responsiveness in PD. The unanticipated weight of a cortical-subcortical-cerebellar subnetwork in defining clinical outcome extends the current biological understanding of the mechanisms associated with clinical benefits.
Particulate matters, aldehydes, and polycyclic aromatic hydrocarbons produced from deep-frying emissions: comparisons of three cooking oils with distinct fatty acid profiles
Authors: Chiang Kuang-Mao , Xiu Lili , Peng Chiung-Yu , Lung Shih-Chun Candice , Chen Yu-Cheng , Pan Wen-Harn
Published: June 2022

It is recognized that hazardous emissions produced from frying oils may be related to oil properties, particularly the fatty acid composition. However, investigations have been limited and partial. In this work, the emissions from deep-frying foods with three oils (palm, olive, and soybean oils) with distinct fatty acid profiles were comprehensively examined in a simulated kitchen, and the interrelationship among emitted substances, oil quality parameters, and fatty acids profiles was explored. Firstly, palm oil emitted the highest number concentration of total particle matters ((3895 ± 1796) × 103 #/cm3), mainly in the Aitken mode (20–100 nm). We observed a positive correlation between particle number concentration and levels of palmitic acid, a major saturated fatty acid (SAFA) (rs = 0.73, p < 0.05), and total polar compounds (TPC) (rs = 0.68, p < 0.05) in the fried oil, a degradation marker which was also positively correlated with that of black carbon (BC) (rs = 0.68, p < 0.05). Secondly, soybean oil emitted the highest level of gaseous aldehydes (3636 ± 607 μg/m3), including acrolein, propinoaldehyde, crotonaldehyde, hexanal, and trans-2-heptenal; the total aldehyde concentration were positively correlated with α-linolenic acid (ALA) percentage (rs = 0.78, p < 0.01), while hexanal and trans-2-heptenal were with linoleic acid (LA) (rs = 0.73 and 0.67, p < 0.05). LA and ALA were two major polyunsaturated fatty acids in non-tropical plant oils. Thirdly, palm oil emitted the most particle-bound polycyclic aromatic hydrocarbons (PAHs), and a positive association was discovered between two PAHs and SAFA percentage. Olive oil seems superior to soybean and palm oils with regards to toxic emissions during deep-frying.
A DNA vaccine candidate delivered by an electroacupuncture machine provides protective immunity against SARS-CoV-2 infection
Authors: Tzeng Tsai-Teng , Chai Kit Man , Shen Kuan-Yin , Yu Chia-Yi , Yang Shiu-Ju , Huang Wan-Chun , Liao Hung-Chun , Chiu Fang-Feng , Dou Horng-Yunn , Liao Ching-Len , Chen Hsin-Wei , Liu Shih-Jen
Published: June 2022

A major challenge in the use of DNA vaccines is efficient DNA delivery in vivo. Establishing a safe and efficient electric transfer method is the key to developing rapid DNA vaccines against emerging infectious diseases. To overcome the complexity of designing new electric transfer machines for DNA delivery, a clinically approved electric transfer machine could be considered as an alternative. Here, we report an electroacupuncture machine-based method for DNA vaccine delivery after intramuscular injection of the COVID-19 DNA vaccine. The S gene of SARS-CoV-2 in the pVAX1 plasmid (pSARS2-S) was used as an antigen in this study. We optimized the clinically used electroacupuncture machine settings for efficient induction of the neutralizing antibody titer after intramuscular injection of pSARS2-S in mice. We found that pSARS2-S immunization at 40 Vpp for 3–5 s could induce high neutralizing antibody titers and Th1-biased immune responses. IFN-γ/TNF-α-secreting CD4+ and CD8+ T cells were also observed in the DNA vaccination group but not in the recombinant protein vaccination group. T-cell epitope mapping shows that the major reactive epitopes were located in the N-terminal domain (a.a. 261–285) and receptor-binding domain (a.a. 352–363). Importantly, pSARS2-S immunization in hamsters could induce protective immunity against SARS-CoV-2 challenge in vivo. In the preclinical toxicology study, blood biochemistry, hematology, and DNA persistence analysis reveal that the DNA delivery method is safe. Furthermore, the raised antisera could also cross-neutralize different variants of concern. These findings suggest that DNA vaccination using an electroacupuncture machine is feasible for use in humans in the future.
Parameter identification of a delayed infinite-dimensional heat-exchanger process based on relay feedback and root loci analysis
Authors: Pekař Libor , Song Mengjie , Padhee Subhransu , Dostálek Petr , Zezulka František
Published: June 2022

The focus of this contribution is twofold. The first part aims at the rigorous and complete analysis of pole loci of a simple delayed model, the characteristic function of which is represented by a quasi-polynomial with a non-delay and a delay parameter. The derived spectrum constitutes an infinite set, making it a suitable and simple-enough representative of even high-order process dynamics. The second part intends to apply the simple infinite-dimensional model for relay-based parameter identification of a more complex model of a heating–cooling process with heat exchangers. Processes of this type and construction are widely used in industry. The identification procedure has two substantial steps. The first one adopts the simple model with a low computational effort using the saturated relay that provides a more accurate estimation than the standard on/off test. Then, this result is transformed to the estimation of the initial characteristic equation parameters of the complex infinite-dimensional heat-exchanger model using the exact dominant-pole-loci assignment. The benefit of this technique is that multiple model parameters can be estimated under a single relay test. The second step attempts to estimate the remaining model parameters by various numerical optimization techniques and also to enhance all model parameters via the Autotune Variation Plus relay experiment for comparison. Although the obtained unordinary time and frequency domain responses may yield satisfactory results for control tasks, the identified model parameters may not reflect the actual values of process physical quantities.
Epidemic risk perceptions in Italy and Sweden driven by authority responses to COVID-19
Authors: Raffetti Elena , Mondino Elena , Di Baldassarre Giuliano
Published: June 2022

Understanding public risk perception is an essential step to develop effective measures reducing the spread of disease outbreaks. Here we compare epidemic risk perceptions during two different periods of the COVID-19 pandemic in Italy and Sweden. To this end, we analyzed the results of two nationwide surveys carried out in both countries in two periods characterized by different infection rates: August (N = 4154) and November 2020 (N = 4168). Seven domains of epidemic risk perception were considered: likelihood along with (individual and population) impact, preparedness, and knowledge. The role of the context and period was explored in stratified and formal interaction analyses. In both countries, we found an intensification in epidemic risk perception from August to November 2020. Being male, older and having a higher relative income were associated with a lower perception of the likelihood of epidemics, while excess mortality was marginally related to higher odds. Compared to Sweden, Italy had a higher increase in perception of likelihood and impact, and a concurrent decrease in preparedness and knowledge. The different authority response to the COVID-19 pandemic is associated with a different change over time in risk perception. Regional differences in terms of excess mortality only marginally explained differences in risk perception.