bluuebunny/crossref_metadata_2025_split huggingface dataset:
Market efficiency of cryptocurrency: evidence from the Bitcoin market
Authors: Yi Eojin , Yang Biao , Jeong Minhyuk , Sohn Sungbin , Ahn Kwangwon 
Published: March 2023

AbstractThis study examines whether the Bitcoin market satisfies the (weak-form) efficient market hypothesis using a quantum harmonic oscillator, which provides the state-specific probability density functions that capture the superimposed Gaussian and non-Gaussian states of the log return distribution. Contrasting the mixed evidence from a variance ratio test, the high probability allocated to the ground state suggests a near-efficient Bitcoin market. Findings imply that as Bitcoin evolves into an efficient market, speculators might encounter difficulty in exploiting profitable trading strategies. Furthermore, when policymakers initiate tight regulations to control the market, they should closely monitor market efficiency as an index of price distortion.
Clinical variations of polypoidal choroidal vasculopathy: A cohort study from Japan and the USA
Authors: Fukuyama Hisashi , BouGhanem Ghazi , Moir John , Skondra Dimitra , Gomi Fumi , Fawzi Amani A. 
Published: March 2023

AbstractWe describe the clinical characteristics of treatment-naïve polypoidal choroidal vasculopathy (PCV) in three tertiary clinic settings in 2 cities (Chicago in the USA and Nishinomiya in Japan). This cohort study was a retrospective, multicenter, consecutive case series. A total of 126 patients with treatment-naïve PCV—46 in Chicago and 80 in Nishinomiya—were identified. The proportion of PCV in patients with neovascular age-related macular degeneration was lower in Chicago (10.8% vs. 36.9%). Patients in Chicago had a significantly higher prevalence of soft drusen (50.0% vs 25.0%, p = 0.006) and intra-retinal cyst (37.0% vs 15.0%, p = 0.008), and a significantly lower prevalence of pachyvessels (41.3% vs 62.5%, p = 0.03). At baseline, presenting vision for patients in Chicago was worse than in Nishinomiya (mean log MAR: 0.609 vs. 0.312, p < 0.001). Ninety-five eyes were followed for more than one year. The Nishinomiya group received a higher rate of combination therapy (61.0%) compared to the Chicago group (5.3%). Vision and central foveal thickness at month 12 were significantly improved from baseline in both Chicago (p = 0.009 and p = 0.01) and Nishinomiya groups (both p < 0.001). Our study highlights interesting differences in the proportion of PCV, clinical findings and treatment responses of PCV, that need to be further evaluated in larger, epidemiologic cohorts.
The maternal brain is more flexible and responsive at rest: effective connectivity of the parental caregiving network in postpartum mothers
Authors: Orchard Edwina R. , Voigt Katharina , Chopra Sidhant , Thapa Tribikram , Ward Phillip G. D. , Egan Gary F. , Jamadar Sharna D. 
Published: March 2023

AbstractThe field of neuroscience has largely overlooked the impact of motherhood on brain function outside the context of responses to infant stimuli. Here, we apply spectral dynamic causal modelling (spDCM) to resting-state fMRI data to investigate differences in brain function between a group of 40 first-time mothers at 1-year postpartum and 39 age- and education-matched women who have never been pregnant. Using spDCM, we investigate the directionality (top–down vs. bottom–up) and valence (inhibition vs excitation) of functional connections between six key left hemisphere brain regions implicated in motherhood: the dorsomedial prefrontal cortex, ventromedial prefrontal cortex, posterior cingulate cortex, parahippocampal gyrus, amygdala, and nucleus accumbens. We show a selective modulation of inhibitory pathways related to differences between (1) mothers and non-mothers, (2) the interactions between group and cognitive performance and (3) group and social cognition, and (4) differences related to maternal caregiving behaviour. Across analyses, we show consistent disinhibition between cognitive and affective regions suggesting more efficient, flexible, and responsive behaviour, subserving cognitive performance, social cognition, and maternal caregiving. Together our results support the interpretation of these key regions as constituting a parental caregiving network. The nucleus accumbens and the parahippocampal gyrus emerging as ‘hub’ regions of this network, highlighting the global importance of the affective limbic network for maternal caregiving, social cognition, and cognitive performance in the postpartum period.
Eye-movement indices of arousal predict ADHD and comorbid externalizing symptoms over a 2-year period
Authors: Kleberg Johan Lundin , Frick Matilda A. , Brocki Karin C. 
Published: March 2023

AbstractAttention-deficit/hyperactivity disorder (ADHD) follows a variable course across childhood. Disrupted arousal has been hypothesized to underlie core symptoms as well as comorbid internalizing and externalizing conditions. The current study examined eye-movement and pupil-dilation metrics indexing arousal as longitudinal predictors of ADHD, externalizing, and internalizing symptoms over a 2-year period. Participants aged 8–13 years (N = 54, 30% with a diagnosis of ADHD) completed a modified version of the gap-overlap task including arousal-inducing auditory warning signals. Parents rated symptoms at the time of testing and at 2 years follow-up. Phasic alerting (reaction-time reduction after alerting cues) is an index of arousal. Here, larger phasic alerting effects predicted higher ADHD-symptom levels 2 years later. Blunted pupil-dilation responses predicted externalizing symptoms at T2, controlling for ADHD and externalizing at T1. Our results support the theory that ADHD is associated with altered arousal. Blunted arousal reactivity may be a longitudinal risk factor for externalizing problems in children with ADHD symptoms.
Optimizing human α-galactosidase for treatment of Fabry disease
Authors: Hallows William C. , Skvorak Kristen , Agard Nick , Kruse Nikki , Zhang Xiyun , Zhu Yu , Botham Rachel C. , Chng Chinping , Shukla Charu , Lao Jessica , Miller Mathew , Sero Antoinette , Viduya Judy , Ismaili Moulay Hicham Alaoui , McCluskie Kerryn , Schiffmann Raphael , Silverman Adam P. , Shen Jin-Song , Huisman Gjalt W. 
Published: March 2023

AbstractFabry disease is caused by a deficiency of α-galactosidase A (GLA) leading to the lysosomal accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids. Fabry patients experience significant damage to the heart, kidney, and blood vessels that can be fatal. Here we apply directed evolution to generate more stable GLA variants as potential next generation treatments for Fabry disease. GLAv05 and GLAv09 were identified after screening more than 12,000 GLA variants through 8 rounds of directed evolution. Both GLAv05 and GLAv09 exhibit increased stability at both lysosomal and blood pH, stability to serum, and elevated enzyme activity in treated Fabry fibroblasts (19-fold) and GLA–/–podocytes (10-fold). GLAv05 and GLAv09 show improved pharmacokinetics in mouse and non-human primates. In a Fabry mouse model, the optimized variants showed prolonged half-lives in serum and relevant tissues, and a decrease of accumulated Gb3 in heart and kidney. To explore the possibility of diminishing the immunogenic potential of rhGLA, amino acid residues in sequences predicted to bind MHC II were targeted in late rounds of GLAv09 directed evolution. An MHC II-associated peptide proteomics assay confirmed a reduction in displayed peptides for GLAv09. Collectively, our findings highlight the promise of using directed evolution to generate enzyme variants for more effective treatment of lysosomal storage diseases.
The perspectives of UK personnel towards current killing practices for laboratory rodents
Authors: Clarkson Jasmine M. , Leach Matthew C. , McKeegan Dorothy E. F. , Martin Jessica E. 
Published: March 2023

AbstractRodents are the predominant species used for scientific research and must be humanely killed upon completion of the work. In the UK this is regulated by Schedule 1 of the Animals Scientific Procedures Act 1986, which lists permitted methodologies considered capable of humane killing, including overdose of an anaesthetic, exposure to carbon dioxide (CO2) gas, dislocation of the neck and concussion of the brain by striking the cranium. Although all are permitted, operator motivations behind method selection and individual operator preference remain unknown. The views of 219 laboratory animal personnel on institutional availability and use of Schedule 1 killing methods for laboratory rodents were obtained. Only 10% of participants reported that all four methods were available at their institution with 57.5% of respondents preferring cervical dislocation. For CO2, only 18.6% of participants reported using the recommended flow rate, while 45.5% did not know the flow rate employed. We highlight the urgent requirement for the development of quality-controlled training programmes, to improve knowledge and confidence in the selection and application of killing methods. We advocate for continuous review of killing practices to ensure best practice is reflected in legislation and achieve optimal protection of the welfare of laboratory rodents during killing.
Identification and gene expression analysis of serine proteases and their homologs in the Asian corn borer Ostrinia furnacalis
Authors: Yang Lei , Xu Xiaoli , wei Wei , Chen Xiaoyun , Peng Cheng , Wang Xiaofu , Xu Junfeng 
Published: March 2023

AbstractSerine proteases (SPs) and their homologs (SPHs) are among the best-characterized gene families. They are involved in several physiological processes, including digestion, embryonic development and immunity. In the current study, a total of 177 SPs-related genes were characterized in the genome of Ostrinia furnacalis. The activation site of SPs/SPHs and enzyme specificity of SPs were identified, and the findings showed that most of the SPs analyzed possessed trypsin substrate specificity. Several SPs/SPHs with similar simple gene structures had tandem repeat-like distributions on the scaffold, indicated that gene expansion has occurred in this large family. Furthermore, we constructed 30 RNA sequencing libraries including four with developmental stage and four middle larval stage tissues to study the transcript levels of these genes. Differentially upregulated and downregulated genes were obtained via data analysis. More than one-quarter of the genes were specifically identified as highly expressed in the midgut in compared to the other three tissues evaluated. In the current study, the domain structure, gene location and phylogenetic relationship of genes in O. furnacalis were explored. Orthologous comparisons of SPs/SPHs between model insects and O. furnacalis indicated their possible functions. This information provides a basis for understanding the functional roles of this large family.
Evaluation of a point-of-care haemozoin assay (Gazelle device) for rapid detection of Plasmodium knowlesi malaria
Authors: Tan Angelica F. , Thota Priyaleela , Sakam Sitti Saimah Binti , Lew Yao Long , Rajahram Giri S. , William Timothy , Barber Bridget E. , Kho Steven , Anstey Nicholas M. , Bell David , Grigg Matthew J. 
Published: March 2023

AbstractPlasmodium knowlesi is the major cause of zoonotic malaria in Southeast Asia. Rapid and accurate diagnosis enables effective clinical management. A novel malaria diagnostic tool, Gazelle (Hemex Health, USA) detects haemozoin, a by-product of haem metabolism found in all Plasmodium infections. A pilot phase refined the Gazelle haemozoin identification algorithm, with the algorithm then tested against reference PCR in a larger cohort of patients with P. knowlesi mono-infections and febrile malaria-negative controls. Limit-of-detection analysis was conducted on a subset of P. knowlesi samples serially diluted with non-infected whole blood. The pilot phase of 40 P. knowlesi samples demonstrated 92.5% test sensitivity. P. knowlesi-infected patients (n = 203) and febrile controls (n = 44) were subsequently enrolled. Sensitivity and specificity of the Gazelle against reference PCR were 94.6% (95% CI 90.5–97.3%) and 100% (95% CI 92.0–100%) respectively. Positive and negative predictive values were 100% and 98.8%, respectively. In those tested before antimalarial treatment (n = 143), test sensitivity was 96.5% (95% CI 92.0–98.9%). Sensitivity for samples with ≤ 200 parasites/µL (n = 26) was 84.6% (95% CI 65.1–95.6%), with the lowest parasitaemia detected at 18/µL. Limit-of-detection (n = 20) was 33 parasites/µL (95% CI 16–65%). The Gazelle device has the potential for rapid, sensitive detection of P. knowlesi infections in endemic areas.
Water cycle changes in reanalyses: a complementary framework
Authors: Vargas Godoy Mijael Rodrigo , Markonis Yannis 
Published: March 2023

AbstractClimate reanalyses complement traditional surface-based measurements and offer unprecedented coverage over previously inaccessible or unmonitored regions. Even though these have improved the quantification of the global water cycle, their varying performances and uncertainties limit their applicability. Herein, we discuss how a framework encompassing precipitation, evaporation, their difference, and their sum could further constrain uncertainty by unveiling discrepancies otherwise overlooked. Ahead, we physically define precipitation plus evaporation to describe the global water cycle fluxes in four reanalysis data sets (20CR v3, ERA-20C, ERA5, and NCEP1). Among them, we observe four different responses to the temperature increase between 1950–2010, with ERA5 showing the best agreement with the water cycle acceleration hypothesis. Our results show that implementing the framework proposed can improve the evaluation of reanalyses’ performance and enhance our understanding of the water cycle changes on a global scale.
Satureja khuzistanica Jamzad essential oil and pure carvacrol attenuate TBI-induced inflammation and apoptosis via NF-κB and caspase-3 regulation in the male rat brain
Authors: Abbasloo Elham , Amiresmaili Sedigheh , Shirazpour Sara , Khaksari Mohammad , Kobeissy Firas , Thomas Theresa Currier 
Published: March 2023

AbstractTraumatic brain injury (TBI) causes progressive dysfunction that induces biochemical and metabolic changes that lead to cell death. Nevertheless, there is no definitive FDA-approved therapy for TBI treatment. Our previous immunohistochemical results indicated that the cost-effective natural Iranian medicine, Satureja khuzistanica Jamzad essential oil (SKEO), which consists of 94.16% carvacrol (CAR), has beneficial effects such as reducing neuronal death and inflammatory markers, as well as activating astrocytes and improving neurological outcomes. However, the molecular mechanisms of these neuroprotective effects have not yet been elucidated. This study investigated the possible mechanisms involved in the anti-inflammatory and anti-apoptotic properties of SKEO and CAR after TBI induction. Eighty-four male Wistar rats were randomly divided into six groups: Sham, TBI, TBI + Vehicle, TBI + CAR (100 and 200 mg/kg), and TBI + SKEO (200 mg/kg) groups. After establishing the “Marmarou” weight drop model, diffuse TBI was induced in the rat brain. Thirty minutes after TBI induction, SKEO & CAR were intraperitoneally injected. One day after TBI, injured rats exhibited significant brain edema, neurobehavioral dysfunctions, and neuronal apoptosis. Western blot results revealed upregulation of the levels of cleaved caspase-3, NFκB p65, and Bax/Bcl-2 ratio, which was attenuated by CAR and SKEO (200 mg/kg). Furthermore, the ELISA results showed that CAR treatment markedly prevents the overproduction of the brain pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-6. Moreover, the neuron-specific enolase (NSE) immunohistochemistry results revealed the protective effect of CAR and SKEO on post-TBI neuronal death. The current study revealed that the possible neuroprotective mechanisms of SKEO and CAR might be related to (at least in part) modulating NF-κB regulated inflammation and caspase-3 protein expression. It also suggested that CAR exerts more potent protective effects than SKEO against TBI. Nevertheless, the administration of SKEO and CAR may express a novel therapeutic approach to ameliorate TBI-related secondary phase neuropathological outcomes.
Precise control of liposome size using characteristic time depends on solvent type and membrane properties
Authors: Choi Sunghak , Kang Bongsu , Yang Eunhye , Kim Keesung , Kwak Moon Kyu , Chang Pahn-Shick , Jung Ho-Sup 
Published: March 2023

AbstractControlling the sizes of liposomes is critical in drug delivery systems because it directly influences their cellular uptake, transportation, and accumulation behavior. Although hydrodynamic focusing has frequently been employed when synthesizing nano-sized liposomes, little is known regarding how flow characteristics determine liposome formation. Here, various sizes of homogeneous liposomes (50–400 nm) were prepared according to flow rate ratios in two solvents, ethanol, and isopropyl alcohol (IPA). Relatively small liposomes formed in ethanol due to its low viscosity and high diffusivity, whereas larger, more poly-dispersed liposomes formed when using IPA as a solvent. This difference was investigated via numerical simulations using the characteristic time factor to predict the liposome size; this approach was also used to examine the flow characteristics inside the microfluidic channel. In case of the liposomes, the membrane rigidity also has a critical role in determining their size. The increased viscosity and packing density of the membrane by addition of cholesterol confirmed by fluorescence anisotropy and polarity lead to increase in liposome size (40–530 nm). However, the interposition of short-chain lipids de-aligned the bilayer membrane, leading to its degradation; this decreased the liposome size. Adding short-chain lipids linearly decreased the liposome size (130–230 nm), but at a shallower gradient than that of cholesterol. This analytical study expands the understanding of microfluidic environment in the liposome synthesis by offering design parameters and their relation to the size of liposomes.
Heat shock protein A2 is a novel extracellular vesicle-associated protein
Authors: Sojka Damian Robert , Abramowicz Agata , Adamiec-Organiściok Małgorzata , Karnas Elżbieta , Mielańczyk Łukasz , Kania Daria , Blamek Sławomir , Telka Ewa , Scieglinska Dorota 
Published: March 2023

Abstract70-kDa Heat Shock Proteins (HSPA/HSP70) are chaperones playing a central role in the proteostasis control mechanisms. Their basal expression can be highly elevated as an adaptive response to environmental and pathophysiological stress conditions. HSPA2, one of poorly characterised chaperones of the HSPA/HSP70 family, has recently emerged as epithelial cells differentiation-related factor. It is also commonly expressed in cancer cells, where its functional significance remains unclear. Previously, we have found that proteotoxic stress provokes a decrease in HSPA2 levels in cancer cells. In the present study we found that proteasome inhibition-related loss of HSPA2 from cancer cells neither is related to a block in the gene transcription nor does it relate to increased autophagy-mediated disposals of the protein. Proteotoxic stress stimulated extracellular release of HSPA2 in extracellular vesicles (EVs). Interestingly, EVs containing HSPA2 are also released by non-stressed cancer and normal cells. In human urinary EVs levels of HSPA2 were correlated with the levels of TSG101, one of the main EVs markers. We conclude that HSPA2 may constitute basic components of EVs. Nevertheless, its specific role in EVs and cell-to-cell communication requires further investigation.
Development of the multi-directional ablation process using the femtosecond laser to create a pattern on the lateral side of a 3D microstructure
Authors: Ha Cheol Woo , Son Yong 
Published: March 2023

AbstractTwo-photon stereolithography (TPS) is widely used for the fabrication of various three–dimensional (3D) structures with sub-micron fabrication resolution in a single fabrication process. However, TPS is unsuitable for microstructures with fine-hole patterns. The laser ablation process can be easily drilled, or made holes in various materials. However, in the case of laser ablation, the focal plane of the laser is fixed, which is limited to the processing plane. In this study, a multidirectional ablation process is studied to apply laser ablation to various processing planes of a 3D microstructure fabricated by the TPS process. A 3D hybrid fabrication process with the advantages of both TPS and laser ablation is expected to improve the fabrication efficiency. The 3D hybrid process is proposed based on a single laser source. The microstructure is fabricated using TPS, and the multi-directional ablation process creates a hole in the lateral side of the 3D microstructure. To develop the multidirectional ablation process, the reflecting mirror system should be designed to adaptably rotate the laser focal plane and guide the laser path for the target process plane. Through various examples, we demonstrate the ability of the multi-directional ablation process with various examples.
Relative contributions of internal variability and external forcing to the inter-decadal transition of climate patterns in East Asia
Authors: Huang Fang , Xu Zhongfeng , Guo Weidong , Feng Jinming , Chen Liang , Zheng Hui , Fu Congbin 
Published: March 2023

AbstractThe annual precipitation in North China and South China shows a dipole pattern with a clear inter-decadal transition around the late 1970s. However, the relative contribution of internal variability and external forcing to this inter-decadal transition is still unclear. Here, we separate internal variability from the externally forced climate response through a set of dynamical downscaling simulations with lateral boundary conditions derived from reanalysis data and a large ensemble mean of the CMIP5 historical simulations. We find that internal variability accounts for about 65 and 55% of the inter-decadal transition of the annual precipitation in South and North China, respectively. By contrast, external forcing accounts for about 70% of the warming trend in eastern China over the second half of the 20th century. This study highlights the differential response of regional precipitation and air temperature to internal variability and external forcing over eastern China on an inter-decadal timescale.
Defining incidence and complications of fibrolamellar liver cancer through tiered computational analysis of clinical data
Authors: Zack Travis , Losert Kurt P. , Maisel Samantha M. , Wild Jennifer , Yaqubie Amin , Herman Michael , Knox Jennifer J. , Mayer Robert J. , Venook Alan P. , Butte Atul , O’Neill Allison F. , Abou-Alfa Ghassan K. , Gordan John D. 
Published: March 2023

AbstractThe incidence and biochemical consequences of rare tumor subtypes are often hard to study. Fibrolamellar liver cancer (FLC) is a rare malignancy affecting adolescents and young adults. To better characterize the incidence and biochemical consequences of this disease, we combined a comprehensive analysis of the electronic medical record and national payer data and found that FLC incidence is likely five to eight times higher than previous estimates. By employing unsupervised learning on clinical laboratory data from patients with hyperammonemia, we find that FLC-associated hyperammonemia mirrors metabolic dysregulation in urea cycle disorders. Our findings demonstrate that advanced computational analysis of rich clinical datasets can provide key clinical and biochemical insights into rare cancers.