bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superior Fidelity and Distinct Editing Outcomes of SaCas9 Compared with SpCas9 in Genome Editing
Authors: Yang Zhi-Xue , Fu Ya-Wen , Zhao Juan-Juan , Zhang Feng , Li Si-Ang , Zhao Mei , Wen Wei , Zhang Lei , Cheng Tao , Zhang Jian-Ping , Zhang Xiao-Bing 
Published: December 2022

Abstract
A series of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 9 (Cas9) systems have been engineered for genome editing. The most widely used Cas9 is SpCas9 from Streptococcus pyogenes and SaCas9 from Staphylococcus aureus. However, a comparison of their detailed gene editing outcomes is still lacking. By characterizing the editing outcomes of 11 sites in human induced pluripotent stem cells (iPSCs) and K562 cells, we found that SaCas9 could edit the genome with greater efficiencies than SpCas9. We also compared the effects of spacer lengths of single-guide RNAs (sgRNAs; 18–21 nt for SpCas9 and 19–23 nt for SaCas9) and found that the optimal spacer lengths were 20 nt and 21 nt for SpCas9 and SaCas9, respectively. However, the optimal spacer length for a particular sgRNA was 18–21 nt for SpCas9 and 21–22 nt for SaCas9. Furthermore, SpCas9 exhibited a more substantial bias than SaCas9 for nonhomologous end–joining (NHEJ) +1 insertion at the fourth nucleotide upstream of the protospacer adjacent motif (PAM), indicating a characteristic of a staggered cut. Accordingly, editing with SaCas9 led to higher efficiencies of NHEJ-mediated double-stranded oligodeoxynucleotide (dsODN) insertion or homology-directed repair (HDR)-mediated adeno-associated virus serotype 6 (AAV6) donor knock-in. Finally, GUIDE-seq analysis revealed that SaCas9 exhibited significantly reduced off-target effects compared with SpCas9. Our work indicates the superior performance of SaCas9 to SpCas9 in transgene integration-based therapeutic gene editing and the necessity to identify the optimal spacer length to achieve desired editing results.
TikTok as a Learning Tool for Archaeology
Authors: Khan Yuhana 
Published: December 2022

OverviewSince its launch, TikTok has become one of the world's most popular social media apps. Once primarily used by teenagers, this app is now used by people of all ages; this shift is largely attributable to the COVID-19 pandemic, when many people transitioned to engaging with others via social media instead of having in-person interactions. Now, anyone who has either the app or access to a web browser can view a plethora of videos, all 10 minutes and under, on any topic. Informational videos about archaeology may not be promoted on everyone's personalized home page—called the For You page (FYP)—but they are easily accessible through the search function. This review will discuss the impact TikTok has on the world of archaeology, with a focus on public engagement, museums, and especially teaching and learning. The social power of this app needs to be acknowledged. Archaeology can introduce the public to snapshots of daily life from the past, a task that fits well with the design of TikTok. This social platform can become a resource to create spaces to learn more, especially through interactive conversations such as in the comments section or response videos.
A TWELVE-HUNDRED-YEAR STABLE OXYGEN ISOTOPE CHRONOLOGY CONSTRUCTED USING SUBFOSSIL WOOD FROM SCHWARZENSEE LAKE, AUSTRIAN ALPS
Authors: Kłusek Marzena , Grabner Michael , Pawlyta Jacek , Pawełczyk Sławomira 
Published: December 2022

ABSTRACTThis study presents a new stable oxygen isotope chronology, covering the years 800–2000 AD, constructed using modern and subfossil wood derived from trees growing around Lake Schwarzensee in Austria. The climatic signal imparted in the chronology is conditioned mainly by the direct influence of environmental factors on the isotopic signature of source water, which in turn is regulated by evaporation and condensation mechanisms. The second driver of stable oxygen isotope is the physiological response of trees to changing weather conditions, most importantly rates of transpiration. The chronology of stable oxygen isotopes corresponds well with both temperature (r = 0.485; p < 0.05) and total precipitation (r = −0.548; p < 0.05) during the growing season (May–September). This mixed signal results from the fact that the relationship between the content of stable oxygen isotopes and the influence of climate is multifactorial. Moreover, the effect exerted by meteorological conditions on stable isotope ratio changes over time. This is most probably linked to interannual variation in climatic and environmental factors.
Risk and Preferences for Government Healthcare Spending: Evidence from the UK COVID-19 Crisis
Authors: Blumenau Jack , Hicks Timothy , Pahontu Raluca L. 
Published: December 2022

AbstractThe onset of the COVID-19 pandemic constituted a large shock to the risk of acquiring a disease that represents a meaningful threat to health. We investigate whether individuals subject to larger increases in objective health risk – operationalized by occupation-based measures of proximity to other people – became more supportive of increased government healthcare spending during the crisis. Using panel data that track UK individuals before (May 2018–December 2019) and after (June 2020) the outbreak of the pandemic, we implement a fixed-effect design that was pre-registered before the key treatment variable was available to us. While individuals in high-risk occupations were more worried about their personal risk of infection and had higher COVID-19 death rates, there is no evidence that increased health risks during COVID-19 shifted either attitudes on government spending on healthcare or broader attitudes relating to redistribution. Our findings are consistent with recent research demonstrating the limited effects of the pandemic on political attitudes.
Updating the distribution range of the maned wolf Chrysocyon brachyurus in Argentina
Authors: Orozco M. Marcela , Caruso Nicolás , Natalini M. Belén , Iaconis Karina , Tittarelli Marcela , Juarez Cecilia P. , Pautasso Andrés , Rosacher Conrado , Gonzalez Ciccia Paula , Soler Lucía 
Published: December 2022

AbstractThe maned wolf Chrysocyon brachyurus, the fourth largest canid, is categorized as Near Threatened on the IUCN Red List. The objectives of this study were to update information on the occurrence of this species in Argentina, compare the current distribution to that previously described for 1988–2008, and indicate the areas in which the species is exposed to particular hazards. We created a database that included 1,051 new records of C. brachyurus for 2009-2021, in addition to records for 1988–2008 that had not been reported previously. We calculated the area of occupancy of the species in Argentina to be 500,000 km2. Most of the new records of C. brachyurus are in the Chaco Seco, Espinal and Pampas ecoregions. Our findings indicate a current area of occupancy 61% higher than that calculated from records for 1988–2008. However the location and frequency of reported threats and the intense environmental transformation that characterizes the areas for which we obtained new records suggest counterintuitive implications for the conservation of the species because of increased human–wildlife interactions. Our study reveals the need for systematic research to improve the understanding of the ecological processes that affect the maned wolf in Argentina, and will aid in the development of conservation strategies for the species.
On Duverger and “Laws of Politics”
Authors: Cuzán Alfred G. 
Published: December 2022

ABSTRACTIn “In Laws of Politics and How to Establish Them,” Erik Weber contends that my arguments for the existence of “five laws of politics” are “inconclusive.” Although the “empirical evidence is impressive,” he avers, the “underlying social mechanisms” responsible for the adduced relationships are missing. Without it, he adds, no empirical relationship rises to the special status of a “law” of politics. Helpfully, Weber did not stop there. Using the example of Duverger’s laws, he suggested ways to close the “argumentative gap.” In this article, I aim to do just that.
Links between early-life contextual factors and later-life cognition and the role of educational attainment
Authors: Palms Jordan D. , Zaheed Afsara B. , Morris Emily P. , Martino Alexa , Meister Lindsey , Sol Ketlyne , Zahodne Laura B. 
Published: December 2022

AbstractObjective:Educational attainment is a well-documented predictor of later-life cognition, but less is known about upstream contextual factors. This study aimed to identify which early-life contextual factors uniquely predict later-life global cognition and whether educational attainment mediates these relationships.Method:Participants were drawn from the Michigan Cognitive Aging Project (N = 485; Mage = 63.51; SDage = 3.13; 50% non-Hispanic Black). Early-life exposures included U.S. region of elementary school (Midwest, South, Northeast), average parental education, household composition (number of adults (1, 2, 3+), number of children), school racial demographics (predominantly White, predominantly Black, diverse), self-reported educational quality, and school type (public/private). Later-life global cognition was operationalized with a factor score derived from a comprehensive neuropsychological battery. Sequential mediation models controlling for sociodemographics estimated total, direct, and indirect effects of early-life contextual factors on cognition through educational attainment (years).Results:Higher educational quality, higher parental education, and attending a private school were each associated with better cognition; attending a predominantly Black or diverse school and reporting three or more adults in the household were associated with lower cognition. After accounting for educational attainment, associations remained for educational quality, school type, and reporting three or more adults in the household. Indirect effects through educational attainment were observed for school region, educational quality, school racial demographics, and parental education.Conclusions:School factors appear to consistently predict later-life cognition more than household factors, highlighting the potential long-term benefits of school-level interventions for cognitive aging. Future research should consider additional mediators beyond educational attainment such as neighborhood resources and childhood adversity.
Ionospheric Oscillations With a Quasi‐Period of ∼6 hr During Intense Magnetic Storms
Authors: Huang Chao‐Song , Zhang Yongliang , Wang Wenbin , Wu Qian , Lin Dong , Qian Liying 
Published: December 2022

AbstractWe study the variations of the topside ionospheric ion density measured by Defense Meteorological Satellite Program satellites during the intense magnetic storm on 7–10 November 2004. It is found for the first time that quasi‐periodic enhancements in the ion density with a period of ∼6 hr occur nearly simultaneously at 0630, 0830, and 0930 local time in the dawn sector during the storm main phase with southward interplanetary magnetic field (IMF). The quasi‐periodic density enhancements extend from the southern subauroral latitudes to the northern subauroral latitudes. In the dusk sector, the topside ion density during the storm main phase is increased at middle latitudes for ∼12 hr but shows decrease or relatively small increase over the magnetic equator, indicating that penetration electric fields dominate the ion density redistribution. Similar quasi‐periodic enhancements in the topside ion density are also observed in the dawn sector during other intense magnetic storms. The solar wind and IMF do not have quasi‐periodic variations in this storm case. Periodic processes in geospace, such as periodic substorms in the magnetosphere, waves and tides in the atmosphere, and traveling ionospheric disturbances, cannot explain the observed periodic enhancements of the ionospheric ion density. We suggest that the magnetosphere‐ionospheric‐thermospheric system may have an intrinsic period of ∼6 hr and that oscillations of the magnetosphere‐ionospheric‐thermospheric system with this period can be excited during intense magnetic storms, although the mechanisms for the generation of the long‐periodic oscillations are not understood.
Thermal Balance and Water Ice Sublimation on the Surface of Hyperactive Comet 103P/Hartley 2
Authors: Yue Yuxian , Liu Jiancen , Wang Xiaohui 
Published: December 2022

AbstractHyperactive comets have attracted attention due to their high water production rate with an unclear mechanism, though some hypotheses have been proposed to explain it. Based on the thermal theories of the comet nuclei, this paper studied a comet surface thermal model considering the sublimation of H2O. In this paper, a method for solving the sublimation rate of water ice by infrared spectroscopy is proposed. The method adopts the assumption of subpixel temperature nonuniformity on the comet nucleus surface and uses the numerical solution of the Fredholm equation. We use the HRI‐IR spectrum (1.05–4.8 μm) data by EPOXI to analyze the pixel‐by‐pixel water sublimation rate of hyperactive comet 103P/Hartley 2. The results show that sublimation exists in most areas of the surface with or without surface roughness, and most of the water production rate (70%–90%) may come from the comet nucleus when Gauss random surface roughness is adopted. According to the sublimation law, it is estimated that the sublimation temperature of water ice on 103P is above 180 K. If the dust‐to‐ice volume ratio is 3:1, the sublimation temperature is about 200–210 K, which indicates that the water ice may sublimate underneath. This may explain why exposed water ice on the surface can hardly be observed while the active fraction of this comet is up to 100%.
Decoding the heterogeneity of Alzheimer’s disease diagnosis and progression using multilayer networks
Authors: Avelar-Pereira Bárbara , Belloy Michael E. , O’Hara Ruth , Hosseini S. M. Hadi ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2022

AbstractAlzheimer’s disease (AD) is a multifactorial and heterogeneous disorder, which makes early detection a challenge. Studies have attempted to combine biomarkers to improve AD detection and predict progression. However, most of the existing work reports results in parallel or compares normalized findings but does not analyze data simultaneously. We tested a multi-dimensional network framework, applied to 490 subjects (cognitively normal [CN] = 147; mild cognitive impairment [MCI] = 287; AD = 56) from ADNI, to create a single model capable of capturing the heterogeneity and progression of AD. First, we constructed subject similarity networks for structural magnetic resonance imaging, amyloid-β positron emission tomography, cerebrospinal fluid, cognition, and genetics data and then applied multilayer community detection to find groups with shared similarities across modalities. Individuals were also followed-up longitudinally, with AD subjects having, on average, 4.5 years of follow-up. Our findings show that multilayer community detection allows for accurate identification of present and future AD (≈90%) and is also able to identify cases that were misdiagnosed clinically. From all MCI participants who developed AD or reverted to CN, the multilayer model correctly identified 90.8% and 88.5% of cases respectively. We observed similar subtypes across the full sample and when examining multimodal data from subjects with no AD pathology (i.e., amyloid negative). Finally, these results were also validated using an independent testing set. In summary, the multilayer framework is successful in detecting AD and provides unique insight into the heterogeneity of the disease by identifying subtypes that share similar multidisciplinary profiles of neurological, cognitive, pathological, and genetics information.
Targeting ubiquitin-specific protease 8 sensitizes anti-programmed death-ligand 1 immunotherapy of pancreatic cancer
Authors: Yang Hanshen , Zhang Xiaozhen , Lao Mengyi , Sun Kang , He Lihong , Xu Jian , Duan Yi , Chen Yan , Ying Honggang , Li Muchun , Guo Chengxiang , Lu Qingsong , Wang Sicheng , Su Wei , Liang Tingbo , Bai Xueli 
Published: December 2022

AbstractProgrammed death-1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1) help tumor cells evade immune surveillance, and are regarded as important targets of anti-tumor immunotherapy. Post-translational modification of PD-L1 has potential value in immunosuppression. Here, we identified that ubiquitin-specific protease 8 (USP8) deubiquitinates PD-L1. Pancreatic cancer tissues exhibited significantly increased USP8 levels compared with those in normal tissues. Clinically, the expression of USP8 showed a significant association with the tumor-node-metastasis stage in multiple patient-derived cohorts of pancreatic cancer. Meanwhile, USP8 deficiency could reduce tumor invasion and migration and tumor size in an immunity-dependent manner, and improve anti-tumor immunogenicity. USP8 inhibitor pretreatment led to reduced tumorigenesis and immunocompetent mice with Usp8 knockdown tumors exhibited extended survival. Moreover, USP8 interacted positively with PD-L1 and upregulated its expression by inhibiting the ubiquitination-regulated proteasome degradation pathway in pancreatic cancer. Combination therapy with a USP8 inhibitor and anti-PD-L1 effectively suppressed pancreatic tumor growth by activation of cytotoxic T-cells and the anti-tumor immunity was mainly dependent on the PD-L1 pathway and CD8 + T cells. Our findings highlight the importance of targeting USP8, which can sensitize PD-L1-targeted pancreatic cancer to immunotherapy and might represent a novel therapeutic strategy to treat patients with pancreatic tumors in the future.
Abrupt termination of vitamin C from ICU patients may increase mortality: secondary analysis of the LOVIT trial
Authors: Hemilä Harri , Chalker Elizabeth 
Published: December 2022

Abstract
Background
The LOVIT trial examined the effect of vitamin C on sepsis patients, and concluded that in adults with sepsis receiving vasopressor therapy in the ICU, those who received 4-day intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. The aim of this study was to determine whether the abrupt termination of vitamin C administration could explain the increased mortality in the vitamin C group.

Methods
We used Cox regression with two time periods to model the distribution of deaths over the first 11 days in the LOVIT trial.

Results
Compared with a uniform difference between vitamin C and placebo groups over the 11-day follow-up period, addition of a separate vitamin C effect starting from day 5 improved the fit of the Cox model (p = 0.026). There was no difference in mortality between the groups during the 4-day vitamin C administration with RR = 0.97 (95% CI: 0.65–1.44). During the week after the sudden termination of vitamin C, there were 57 deaths in the vitamin C group, but only 32 deaths in the placebo group, with RR = 1.9 (95% CI: 1.2–2.9; p = 0.004).

Conclusion
The increased mortality in the vitamin C group in the LOVIT trial is not explained by ongoing vitamin C administration, but by the abrupt termination of vitamin C. The LOVIT trial findings should not be interpreted as evidence against vitamin C therapy for critically ill patients.
National survey of corneal cross-linking (CXL) practice patterns in the United Kingdom during 2019
Authors: Hayes Sally , Jaycock Philip , Rees Nicholas , Figueiredo Francisco C. , O’Brart David P. S. , Meek Keith M. 
Published: December 2022

Abstract
Objective
To provide an insight into trends in corneal cross-linking (CXL) practice in the UK, including criteria for progression of corneal ectasia, identification of patients for CXL, the CXL procedure itself and post-operative management.

Methods
All ophthalmologist members of the UK Cross-linking (UK-CXL) Consortium were invited to complete an online survey about CXL practice for the year 2019. The data collected was anonymised by site and analysed with descriptive statistics.

Results
Responses were received from 16 individual CXL centres (16/38; 42% response rate) and the data represented ~2,000 CXL procedures performed in the UK in 2019. The commonest indication for CXL was progressive keratoconus. Between centres, there were variations in diagnostic evaluation, patient selection for CXL, the CXL procedure and the pre- and post-operative monitoring of patients.

Conclusion
Consistent with the wide number of CXL treatment techniques described in the published literature world-wide, variations in the monitoring of corneal ectasia, indications for CXL, CXL practice and post-CXL follow-up were found to exist between UK-based CXL centres.
Spurious transcription causing innate immune responses is prevented by 5-hydroxymethylcytosine
Authors: Wu Fan , Li Xiang , Looso Mario , Liu Hang , Ding Dong , Günther Stefan , Kuenne Carsten , Liu Shuya , Weissmann Norbert , Boettger Thomas , Atzberger Ann , Kolahian Saeed , Renz Harald , Offermanns Stefan , Gärtner Ulrich , Potente Michael , Zhou Yonggang , Yuan Xuejun , Braun Thomas 
Published: December 2022

AbstractGeneration of functional transcripts requires transcriptional initiation at regular start sites, avoiding production of aberrant and potentially hazardous aberrant RNAs. The mechanisms maintaining transcriptional fidelity and the impact of spurious transcripts on cellular physiology and organ function have not been fully elucidated. Here we show that TET3, which successively oxidizes 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and other derivatives, prevents aberrant intragenic entry of RNA polymerase II pSer5 into highly expressed genes of airway smooth muscle cells, assuring faithful transcriptional initiation at canonical start sites. Loss of TET3-dependent 5hmC production in SMCs results in accumulation of spurious transcripts, which stimulate the endosomal nucleic-acid-sensing TLR7/8 signaling pathway, thereby provoking massive inflammation and airway remodeling resembling human bronchial asthma. Furthermore, we found that 5hmC levels are substantially lower in human asthma airways compared with control samples. Suppression of spurious transcription might be important to prevent chronic inflammation in asthma.