bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic Review and Meta-Analysis of Endovascular Therapy Effectiveness for Unruptured Saccular Intracranial Aneurysms
Authors: Pineda-Castillo Sergio A. , Jones Evan R. , Laurence Keely A. , Thoendel Lauren R. , Cabaniss Tanner L. , Zhao Yan D. , Bohnstedt Bradley N. , Lee Chung-Hao 
Published: July 2023

ABSTRACTBackgroundCurrently, endovascular treatment of intracranial aneurysms (ICAs) is limited by low complete occlusion rates. The advent of novel endovascular technology has expanded the applicability of endovascular therapy; however, the superiority of novel embolic devices over the traditional Guglielmi detachable coils (GDCs) is still debated. We performed a systematic review of literature that reported the Raymond-Roy occlusion classifications (RROC) rates of modern endovascular devices to determine their immediate and long-term occlusion effectiveness for the treatment of unruptured saccular ICAs.MethodsA search was conducted using electronic databases (PUBMED, Cochrane,ClinicalTrials.gov, Web of Science). We retrieved studies published between 2000-2022 reporting immediate and long-term RROC rates of subjects treated with different endovascular ICA therapies. We extracted demographic information of the treated patients and their reported angiographic RROC rates.ResultsA total of 80 studies from 15 countries were included for data extraction. RROC rates determined from angiogram were obtained for 21,331 patients (72.5% females, pooled mean age: 58.2 (95% CI: 56.8-59.6), harboring 22,791 aneurysms. The most frequent aneurysm locations were the internal carotid artery (46.4%, 95% CI: 41.9%-50.9%), the anterior communicating artery (26.4%, 95% CI: 22.5%-30.8%), the middle cerebral artery (24.5%, 95% CI:19.2%-30.8%) and the basilar tip (14.4%, 95% CI:11.3%-18.3%). The RROC rates were analyzed for GDCs, the Woven EndoBridge (WEB), and flow diverters. The immediate complete occlusion (RROC-I) rate was the highest in balloon-assisted coiling (73.9%, 95% CI: 65.0%-81.2%) and the lowest in the WEB (27.8%, 95% CI:13.2%-49.2%). The long-term complete occlusion probability was homogenous in all analyzed devices.ConclusionsWe observed that the coil-based endovascular therapy provides acceptable rates of complete occlusion, where the balloon-assisted coils provide greater probability of immediate complete occlusion. Out of the analyzed devices, the WEB exhibited the shortest time to achieve >90% probability of long-term complete occlusion (∼18 months). Overall, the GDCs remain thegold standardfor endovascular treatment of unruptured saccular aneurysms.
Common infections and neuroimaging markers of dementia in three UK cohort studies
Authors: Green Rebecca E , Sudre Carole H , Warren-Gash Charlotte , Butt Julia , Waterboer Tim ,   the Insight 46 study team, Hughes Alun D , Schott Jonathan M , Richards Marcus , Chaturvedi Nish , Williams Dylan M 
Published: July 2023

AbstractIntroductionWe aimed to investigate associations between common infections and neuroimaging markers of dementia risk (brain volume, hippocampal volume, white matter lesions) across three population-based studies.MethodsWe tested associations between serology measures (pathogen serostatus, cumulative burden, continuous antibody responses) and outcomes using linear regression, including adjustments for total intracranial volume and scanner/clinic information (basic model), age, sex, ethnicity, education, socioeconomic position, alcohol, BMI, and smoking (fully adjusted model). Interactions between serology measures and APOE genotype were tested. Findings were meta-analysed across cohorts (Nmain=2632; NAPOE-interaction=1810).ResultsSeropositivity to JC virus associated with smaller brain volumes in basic models (ß=-3.89ml[-5.81,-1.97],padjusted<0.05); these were largely attenuated in fully adjusted models (ß=-1.59ml[-3.55,0.36], p=0.11). No other relationships were robust to multiple testing correction and sensitivity analyses, but several suggestive associations were observed.DiscussionWe did not find clear evidence for relationships between common infections and markers of dementia risk. Some suggestive findings warrant testing for replication.
AAV-mediated Delivery of Plakophilin-2a Arrests Progression of Arrhythmogenic Right Ventricular Cardiomyopathy in Murine Hearts: Preclinical Evidence Supporting Gene Therapy in Humans
Authors: van Opbergen Chantal JM , Narayanan Bitha , Sacramento Chester B , Stiles Katie M , Mishra Vartika , Frenk Esther , Ricks David , Chen Grace , Zhang Mingliang , Yarabe Paul , Schwartz Jonathan , Delmar Mario , Herzog Chris D , Cerrone Marina 
Published: July 2023

ABSTRACTBackgroundPathogenic variants in plakophilin-2 (PKP2) cause arrhythmogenic right ventricular cardiomyopathy (ARVC), a disease characterized by life-threatening arrhythmias and progressive cardiomyopathy leading to heart failure. No effective medical therapy is available to prevent and/or arrest the disease. We tested the hypothesis that AAV-mediated delivery of the humanPKP2gene to an adult mammalian heart deficient in PKP2 can arrest disease progression and significantly prolong survival.MethodsExperiments were carried out using a cardiac-specific, tamoxifen (TAM)-activated PKP2 knockout murine model (PKP2-cKO). The potential therapeutic, AAVrh.74-PKP2a (RP-A601), is a recombinant AAVrh.74 gene therapy viral vector encoding the human PKP2 variant A (PKP2a). AAVrh.74-PKP2a was delivered to adult mice by a single tail vein injection either before or after TAM-activated PKP2-cKO. PKP2 expression was confirmed by molecular and histopathologic analyses. Cardiac function and disease progression were monitored by survival analyses, echocardiography and electrocardiography.ResultsConsistent with prior findings, loss of PKP2 expression caused 100% mortality within 50 days after TAM injection. In contrast, AAVrh.74-PKP2a-mediated PKP2a expression resulted in 100% survival for more than 5 months (at study termination). Echocardiographic analysis revealed that AAVrh.74-PKP2a prevented right ventricle dilation, arrested left ventricle functional decline, and mitigated arrhythmia burden. Molecular and histological analysis showed AAVrh.74-PKP2a– mediated transgene mRNA and protein expression and appropriate PKP2 localization at the cardiomyocyte intercalated disc. Importantly, therapeutic benefit was shown in mice receiving AAVrh.74-PKP2aafterdisease onset.ConclusionThese preclinical data demonstrate the potential for AAVrh.74-PKP2a (RP-A601) as a therapeutic for PKP2-related ARVC in both early and more advanced stages of disease.
The Integrated Stress Response effector GADD34 is repurposed by neurons to promote stimulus-induced translation
Authors: Oliveira Mauricio M. , Mohamed Muhaned , Elder Megan K. , Banegas-Morales Keylin , Mamcarz Maggie , Lu Emily H. , Golhan Ela A.N. , Navrange Nishika , Chatterjee Snehajyoti , Abel Ted , Klann Eric 
Published: July 2023

SummaryNeuronal protein synthesis is required for long-lasting plasticity and long-term memory consolidation. Dephosphorylation of eukaryotic initiation factor 2α is one of the key translational control events that is required to increasede novoprotein synthesis that underlies long-lasting plasticity and memory consolidation. Here, we interrogate the molecular pathways of translational control that are triggered by stimulation of neurons with brain-derived neurotrophic factor (BDNF), which results in eIF2α dephosphorylation andde novoprotein synthesis. Primary rodent neurons exposed to BDNF displayed elevated translation, but not transcription, of GADD34, which facilitates eIF2α dephosphorylation and subsequentde novoprotein synthesis. Furthermore, GADD34 requires G-actin generated by cofilin to dephosphorylate eIF2α and enhance protein synthesis. Finally, GADD34 is required for the BDNF-induced translation of synaptic plasticity-related proteins. Overall, we provide evidence that neurons repurpose GADD34, an effector of the Integrated Stress Response, as an orchestrator of rapid increases in eIF2-dependent translation in response to plasticity-inducing stimuli.
Polo-like kinase 1 regulates immune synapse assembly and cytotoxic T cell function by driving microtubule dynamics
Authors: Zevolini Fabrizia , Onnis Anna , Khazen Roxana , Müller Sabina , Marotta Giuseppe , Valitutti Salvatore , Finetti Francesca , Baldari Cosima T 
Published: July 2023

AbstractElimination of virally infected or tumoral cells is mediated by cytotoxic T cells (CTL). Upon antigen recognition CTLs assemble a specialized signaling and secretory domain at the interface with their target, the immune synapse (IS). During IS formation CTLs acquire a transient polarity, marked by re-orientation of the centrosome and microtubule cytoskeleton toward the IS, thus directing the transport and delivery of the lytic granules to the target cell. Based on the implication of the kinase Aurora-A in CTL function we hypothesized that its substrate, the mitotic regulator Polo-like kinase 1 (PLK1), may participate in CTL IS assembly. We demonstrate that PLK1 is phosphorylated upon TCR triggering and polarizes to the IS. PLK1 silencing or inhibition results in impaired IS assembly and function, as witnessed by defective synaptic accumulation of TCRs as well as compromised centrosome and lytic granule polarization to the IS, resulting in impaired target cell killing. This function is achieved by coupling early signaling to microtubule dynamics, a function pivotal for CTL-mediated cytotoxicity. These results identify PLK1 as a new player in CTL IS assembly and function.Summary statementThe mitotic kinase Polo-like kinase 1 promotes centrosome polarization to the immune synapse in cytotoxic T cells by coupling TCR signaling to microtubule dynamics
Extracellular vesicle-mediated release of bis(monoacylglycerol)phosphate is regulated by LRRK2 and Glucocerebrosidase activity
Authors: Meneses-Salas Elsa , Arnold Marianna , Castellá Moises , Hsieh Frank , Fernández-Santiago Ruben , Ezquerra Mario , Garrido Alicia , Martí María-José , Enric Carlos , Pfeffer Suzanne R. , Merchant Kalpana , Lu Albert 
Published: July 2023

ABSTRACTThe endo-lysosomal phospholipid, bis(monoacylglycerol)phosphate (BMP), is aberrantly elevated in the urine of Parkinson’s patients with mutations in genes encoding leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GCase). Because BMP resides on and regulates the biogenesis of endo-lysosomal intralumenal membranes that become extracellular vesicles (EVs) upon release, we hypothesized that elevated urinary BMP may be driven by increased exocytosis of BMP-enriched EVs. To test this hypothesis, we analyzed BMP metabolism and EV-associated release of BMP in wild type (WT) and R1441G LRRK2-expressing mouse embryonic fibroblast (MEF) cells. Using immunofluorescence microscopy and transmission electron microscopy we detected structural alterations in endo-lysosomes and antibody-accessible BMP pool, indicating that mutant LRRK2 affects endolysosomal homeostasis. Biochemical analyses of isolated EV fractions confirmed the effect on endo-lysosomes by showing an increase in LAMP2-positive EVs in mutant cells, which was partially restored by LRRK2 kinase inhibition but further augmented by GCase inhibition. Using mass spectrometry, we detected an overall increase in total di-22:6-BMP and total di-18:1-BMP in cell lysates from mutant LRRK2 MEFs compared to WT cells. Inhibition of LRRK2 kinase partially restored cellular BMP levels, whereas inhibition of GCase further increased the BMP content. In isolated EVs from LRRK2 mutant cells, LRRK2 inhibition decreased BMP content whereas GCase inhibition tended to increase it. Using metabolic labeling experiments, we demonstrated that the increase in cellular BMP content is not due to an increase in BMP synthesis, even though we observed an increase in BMP synthesizing enzyme, CLN5, in LRRK2 mutant MEFs and patient-derived fibroblasts. Finally, pharmacological modulators of EV release confirmed that BMP release is associated with EV secretion. Together, these results establish LRRK2 as a regulator of BMP levels in cells and its release through EVs, with GCase activity further modulating this process in LRRK2 mutant cells. Mechanistic insights from these studies have implications for the potential use of BMP-positive EVs as a biomarker for Parkinson’s disease and associated treatments.
Multiscale entropy analysis of combined EEG-fNIRS measurement in preterm neonates
Authors: Semeia Lorenzo , Nourhashemi Mina , Mahmoudzadeh Mahdi , Wallois Fabrice , Sippel Katrin , Preissl Hubert 
Published: July 2023

AbstractIn nature, biological systems such as the human brain are characterized by complex and non-linear dynamics. One way of quantifying signal complexity is Multiscale Entropy (MSE), which is suitable for structures with long-range correlation at different time scales. In developmental neuroscience, MSE can be taken as an index of brain maturation, and can differentiate between healthy and pathological development. In our current work, we explored the developmental trends of MSE on the basis of 30 simultaneous EEG – fNIRS recordings in premature infants between 27 and 34 weeks of gestational age (wGA). To explore potential factors impacting MSE, we determined the relation between MSE and the EEG Power Spectrum Density (PSD) and Spontaneous Activity Transients (SATs). As a result, via wGA, the MSE calculated on the EEG increases, thus reflecting the maturational processes in the brain networks, whereas in the fNIRS, MSE decreases, which might indicate a maturation of the brain blood supply. Moreover, we propose that the EEG power in the beta band (13-30 Hz) might be the main contributor to MSE in the EEG. Finally, we highlight the importance of SATs in determining MSE as calculated from the fNIRS recordings.HighlightsBiological systems show complex and non-linear dynamics. With Multiscale Entropy (MSE) we studied simultaneous EEG-fNIRS in premature infants. MSE in the EEG increases over gestational age, MSE in the fNIRS decreases. EEG power spectrum density and spontaneous activity transients contribute to MSE.
High throughput PRIME editing screens identify functional DNA variants in the human genome
Authors: Ren Xingjie , Yang Han , Nierenberg Jovia L. , Sun Yifan , Chen Jiawen , Beaman Cooper , Pham Thu , Nobuhara Mai , Takagi Maya Asami , Narayan Vivek , Li Yun , Ziv Elad , Shen Yin 
Published: July 2023

AbstractDespite tremendous progress in detecting DNA variants associated with human disease, interpreting their functional impact in a high-throughput and base-pair resolution manner remains challenging. Here, we develop a novel pooled prime editing screen method, PRIME, which can be applied to characterize thousands of coding and non-coding variants in a single experiment with high reproducibility. To showcase its applications, we first identified essential nucleotides for a 716 bpMYCenhancer via PRIME-mediated saturation mutagenesis. Next, we applied PRIME to functionally characterize 1,304 non-coding variants associated with breast cancer and 3,699 variants from ClinVar. We discovered that 103 non-coding variants and 156 variants of uncertain significance are functional via affecting cell fitness. Collectively, we demonstrate PRIME capable of characterizing genetic variants at base-pair resolution and scale, advancing accurate genome annotation for disease risk prediction, diagnosis, and therapeutic target identification.
The h-current controls cortical recurrent network activity through modulation of dendrosomatic communication
Authors: Shu Yousheng , Hasenstaub Andrea , McCormick David A. 
Published: July 2023

AbstractA fundamental feature of the cerebral cortex is the ability to rapidly turn on and off maintained activity within ensembles of neurons through recurrent excitation balanced by inhibition. Here we demonstrate that reduction of the h-current, which is especially prominent in pyramidal cell dendrites, strongly increases the ability of local cortical networks to generate maintained recurrent activity. Reduction of the h-current resulted in hyperpolarization and increase in input resistance of both the somata and apical dendrites of layer 5 pyramidal cells, while strongly increasing the dendrosomatic transfer of low (<20 Hz) frequencies, causing an increased responsiveness to dynamic clamp-induced recurrent network-like activity injected into the dendrites and substantially increasing the duration of spontaneous Up states. We propose that modulation of the h-current may strongly control the ability of cortical networks to generate recurrent persistent activity and the formation and dissolution of neuronal ensembles.
Design differences explain variation in results between randomized trials and their non-randomized emulations
Authors: Heyard Rachel , Held Leonhard , Schneeweiss Sebastian , Wang Shirley V 
Published: July 2023

ABSTRACTObjectivesWhile randomized controlled trials (RCTs) are considered a standard for evidence on the efficacy of medical treatments, non-randomized real-world evidence (RWE) studies using data from health insurance claims or electronic health records can provide important complementary evidence. The use of RWE to inform decision-making has been questioned because of concerns regarding confounding in non-randomized studies and the use of secondary data. RCT-DUPLICATE was a demonstration project that emulated the design of 32 RCTs with non-randomized RWE studies. We sought to explore how emulation differences relate to variation in results between the RCT-RWE study pairs.MethodsWe include all RCT-RWE study pairs from RCT-DUPLICATE where the measure of effect was a hazard ratio and use exploratory meta-regression methods to explain differences and variation in the effect sizes between the results from the RCT and the RWE study. The considered explanatory variables are related to design and population differences.ResultsMost of the observed variation in effect estimates between RCT-RWE study pairs in this sample could be explained by three emulation differences in the meta-regression model: (i) in-hospital start of treatment (not observed in claims data), (ii) discontinuation of certain baseline therapies at randomization (not part of clinical practice), (iii) delayed onset of drug effects (missed by short medication persistence in clinical practice).ConclusionsThis analysis suggests that a substantial proportion of the observed variation between results from RCTs and RWE studies can be attributed to design emulation differences.What is already known on this topicReal-world evidence (RWE) studies can complement randomized controlled trials (RCT) by providing insights on the effectiveness of a medical treatment in clinical practice. Concerns about confounding have limited the use of RWE studies in clinical practice and policy decisions.What this study addsA large share of the observed variation in results between RCT-RWE study pairs could be explained by design emulation differences.
The evaluation of target markets for hazelnut exports with the classification approach of potential market alternatives
Authors: Baki Rahmi 
Published: July 2023

PurposeThe aim of the proposed classification approach of potential market alternatives (CAPMA) is to provide exporting countries with a framework for identifying potential market opportunities for their products or services.Design/methodology/approachIn today's global market conditions, with competition increasing daily, companies, businesses and states must seek new markets at the national and international level. Target market selection is a strategic process that directly affects the success of an organization and can lead to important results in the short and long term. The process requires systematic research and digitization of data to analyse target markets.FindingsThe study tested the proposed approach by analysing Turkey's potential markets for hazelnut exports and identifying new target markets. A significant part of Turkey's hazelnut exporting is confined to the European geography of Turkey, the leading country in hazelnut production and export. Twenty potential markets were evaluated on the basis of 11 criteria, and feasible alternatives were categorized into four classes. The study revealed that the USA, India, the United Kingdom and Japan were in the category of markets with the greatest potential for increasing exports (Dimension 1).Originality/valueThis study has developed a novel approach that allows the comparison of the current market situation with potential market outcomes and creates an accurate classification of target markets.
Sectoral risk contagion and quantile network connectedness on Chinese stock sectors after the COVID-19 outbreak
Authors: Gao Yang , Zheng Wanqi , Wang Yaojun 
Published: July 2023

PurposeThis study aims to explore the risk spillover effects among different sectors of the Chinese stock market after the outbreak of COVID-19 from both Internet sentiment and price fluctuations.Design/methodology/approachThe authors develop four indicators used for risk contagion analysis, including Internet investors and news sentiments constructed by the FinBERT model, together with realized and jump volatilities yielded by high-frequency data. The authors also apply the time-varying parameter vector autoregressive (TVP-VAR) model-based and the tail-based connectedness framework to investigate the interdependence of tail risk during catastrophic events.FindingsThe empirical analysis provides meaningful results related to the COVID-19 pandemic, stock market conditions and tail behavior. The results show that after the outbreak of COVID-19, the connectivity between risk spillovers in China's stock market has grown, indicating the increased instability of the connected system and enhanced connectivity in the tail. The changes in network structure during COVID-19 pandemic are not only reflected by the increased spillover connectivity but also by the closer relationships between some industries. The authors also found that major public events could significantly impact total connectedness. In addition, spillovers and network structures vary with market conditions and tend to exhibit a highly connected network structure during extreme market status.Originality/valueThe results confirm the connectivity between sentiments and volatilities spillovers in China's stock market, especially in the tails. The conclusion further expands the practical application and theoretical framework of behavioral finance and also lays a theoretical basis for investors to focus on the practical application of volatility prediction and risk management across stock sectors.
FinTech and firm’s cash holdings: evidence from China
Authors: Ullah Irfan , Zeb Aurang 
Published: July 2023

Purpose
This study aims to empirically explore the nexus between FinTech and a firm’s cash holdings.

Design/methodology/approach
A panel data regression analysis is conducted on a sample of A-listed firms registered on the Shenzhen and Shanghai Stock Exchanges from 2011 to 2019. To address simultaneity issues in the study, the authors use various endogeneity tests, including lag of independent variables, generalized method of moments and two-stage least squares estimation.

Findings
Results reveal that FinTech has a significantly negative effect on a firm’s cash holdings, suggesting that FinTech development improves cash management by alleviating agency costs and reducing financial constraints. The findings remain consistent across different FinTech measures and alternative cash holding proxies, demonstrating that FinTech serves as a corporate governance mechanism.

Practical implications
The findings suggest that FinTech disciplines corporate managers and alleviates agency problems regarding cash holdings.

Originality/value
This study suggests that FinTech determines a firm’s cash holdings.