bluuebunny/crossref_metadata_2025 huggingface dataset:
Social enterprise as a model for change: mapping a global cross-disciplinary framework
Authors: Halsall Jamie P. , Snowden Michael , Clegg Philip , Mswaka Walter , Alderson Maureen , Hyams-Ssekasi Denis , Oberoi Roopinder , Winful Ernest Christian
Published: November 2022

Since the outbreak of COVID-19, social enterprise has experienced a renaissance. In public policy circles, entrepreneurship and innovation are perceived as economic development tools, and in many parts of the world, as catalysts for change that can have a real impact by increasing employment in communities as well as environmental challenges. At a local level, entrepreneurship and innovation enable communities to stay vibrant due to social enterprise organisations offering much-needed goods and services. Social enterprise has been acknowledged as a solution to social inequality and environmental issues in society as it develops new areas of empowerment in local communities. Central to the success of social enterprise is education, training, and the engagement of the higher education sector. Traditionally, entrepreneurship and innovation have fundamentally been entrenched within the business subject area, but have now emerged within other disciplines such as criminology, health and social care, geography, sociology, and politics. The aim of this paper is to map out a new, global, cross-disciplinary framework from a teaching and learning perspective. The authors of this paper call for global empowerment of entrepreneurship education in the higher education sector, using examples from different countries across the world, specifically Ghana, India, and the UK. This paper sets out the vital importance of entrepreneurship in teaching and learning, by showcasing what can be achieved. In this paper, the authors develop and propose a new pedagogical social enterprise model that incorporates and emphasises the ethos of ‘think globally, act locally’ in a sustainability context.
Using camera trap bycatch data to assess habitat use and the influence of human activity on African elephants (Loxodonta africana) in Kasungu National Park, Malawi
Authors: Davis Robert S. , Gentle Louise K. , Mgoola William O. , Stone Emma L. , Uzal Antonio , Yarnell Richard W.
Published: November 2022

African elephants (Loxodonta africana) are increasingly exposed to high levels of human disturbance and are threatened by poaching and human–elephant conflict. As anthropogenic pressures continue to increase, both inside and outside protected areas, understanding elephant behavioural responses to human activity is required for future conservation management. Here, we use bycatch data from camera trap surveys to provide inferences on elephant habitat use and temporal activity in Kasungu National Park (KNP), Malawi. The KNP elephant population has declined by ~ 95% since the late 1970s, primarily because of intensive poaching, and information on elephant ecology and behaviour can assist in the species’ recovery. Using occupancy modelling, we show that proximity to water is the primary driver of elephant habitat use in KNP, with sites closer to water having a positive effect on elephant site use. Our occupancy results suggest that elephants do not avoid sites of higher human activity, while results from temporal activity models show that elephants avoid peak times of human activity and exhibit primarily nocturnal behaviour when using the KNP road network. As key park infrastructure is located near permanent water sources, elephant spatiotemporal behaviour may represent a trade-off between resource utilisation and anthropogenic-risk factors, with temporal partitioning used to reduce encounter rates. Increased law enforcement activity around permanent water sources could help to protect the KNP elephant population during the dry season. Our findings highlight that camera trap bycatch data can be a useful tool for the conservation management of threatened species beyond the initial scope of research.
A New Era of National Guideline Development in Saudi Arabia
Authors: Memish Ziad A. , Alqahtani Abdulrahman S. , Al-Azemi Nahar , Abu Alhamayel Nebras , Saeedi Mohammad , Abuzinada Shatha , Albarakati Rayan G , Natarajan Subramaniasivam , Alvira Ximena , Bilimoria Khushnam , Brunnhuber Klara
Published: November 2022

Saudi Arabia’s ambitious Vision 2030 project was launched in 2016 as a strategy for economic development and national growth, with 11 Vision Realization Programs put in charge of its implementation. The backbone of its Transformation Program for the Health Sector has been the definition of a new Model of Care aiming to deliver 42 coordinated interventions across 6 Systems of Care, with the development of clinical guidelines identified as a key cross-cutting intervention to foster the use of national, evidence-based practices across KSA, reduce care variation, and promote accountable care. This article provides an overview of the history, progress to date, and future outlook of the recently initiated National Guidelines Center in Saudi Arabia, established in collaboration between the Health Holding Company and the Saudi Health Council represented by its National Center for Evidence-based Medicine. The lessons learnt from previous guideline initiatives are grouped under the Center’s design principles of high quality, relevance, practical implementation, and sustainability. Aspects setting the project apart from previous endeavors have been its focus on extensive engagement with key stakeholders in the Saudi guideline ecosystem, the co-development of evidence-based recommendations with aligned key performance measures, and the implementation of guideline recommendations in the clinical workflow via integrated electronic order sets. Nine activity streams aim to enable the Center to take its place among the leading regional and global guideline developing organizations and to optimally support clinicians and patients, Saudi Arabia’s health sector transformation, and the work of guideline communities worldwide.
Helmet Use Among Two-Wheeler Riders’ Road Accident Victims in Benin
Authors: Hounkpè Dos Santos Bella , Kpozehouen Alphonse , Glèlè Ahanhanzo Yolaine , Daddah Donatien , Levêque Alain , Coppieters Yves
Published: November 2022

Background

In Benin, some riders of two-wheeled vehicles still do not wear helmets, the main protection against head injuries in road accidents. The objective of this study is to describe the characteristics of two-wheeled users, and to determine the factors influencing helmet use among this group.

Methods

This is a prospective cross-sectional study of 977 two-wheeled road accident victims from a cohort. Proportions or means were calculated for the different variables. Statistical comparisons were made to test the association with helmet use. Logistic regression modelling was performed to identify factors associated with helmet use.

Results

Among all subjects, 81.1% [CI95% (78.5; 83.4)] wore a helmet. Factors explaining helmet use were female gender (OR = 2.8 [1.3–6.1]), purpose of trip (OR = 1.7 [1.1–2.6]), possession of health insurance (OR = 3.7 [1.3–10, 5]), having been driving for 15–20 years (OR = 2.6 [1.4–4.7]) or more than 20 years (OR = 3.4 [2.0–5.8]), good road conditions (OR = 3.1 [2.0–4.8]), and good visibility (OR = 1.9 [1.3–3.1]).

Conclusion

The factors influencing helmet use are gender, reason for travel, length of time as a driver, possession of health insurance, conditions, and visibility of the road on which the subject are driving. These factors are related to experience and appropriation of the notion of risk, but also related to the environment. To increase helmet use among two-wheelers, helmet awareness should take into account the individual factors found in this study. Enforcement actions should be strengthened, and the quality of the roads improved.
Cholestasis and Pulmonary Hypertension in Neonatal Thyrotoxicosis: A Case Report
Authors: Hantash Ehab Mohamed , Anwar Manar Hany , Naqvi Syeda , Alzubyania Maha Musri , Al Zahrani Abdulrahman Abdullah
Published: November 2022

Neonatal thyrotoxicosis is mostly caused by the transplacental passage of maternal thyroid stimulating hormone (TSH) receptor antibodies (TRAb) to the fetus. Although rare and transient, this condition may be associated with significant morbidity and mortality if not diagnosed and treated in an appropriate and timely manner. Anti-thyroid drugs are the main therapy. Here, we report a preterm newborn that presented with two uncommon presentations of neonatal thyrotoxicosis, cholestasis and pulmonary hypertension that significantly improved following the administration of anti-thyroid medications.
Usability Evaluation of in-Vehicle AR-HUD Interface Applying AHP-GRA
Authors: Yunuo Cheng , Xia Zhong , Min Ye , Liwei Tian
Published: November 2022

Usability is regarded to be a fundamental requirement for in-vehicle HMIs, and usability evaluation reflects the impact of the interface and the acceptance from the users. This study introduced a usability evaluation model of AR-HUD interface by applying grey analytic hierarchy process (AHP). First, based on the ameliorated PSSUQ (Post-Study System Usability Questionnaire), the usability evaluation system was modified and optimized according to the characteristics of AR-HUD. On this basis, the preference weights for evaluation indexes were calculated by AHP and the idea of group decision. Finally, the criteria of usability were integrated into grey relational degree by applying grey relational analysis (GRA) to obtain optimal design. A case study was conducted to demonstrate the applicability of the developed model to the usability evaluation of AR-HUD interface design. According to the existing AR-HUD interface design, 7 dimensions of design elements (A-G) and 18 interface prototypes (S1-S18) were selected by Taguchi orthogonal array test (TOAT). As the results indicated, the grey relational degree of S5 was 0.923, signifying that it was the optimal sample; and the results were also compared with entropy-TOPSIS to verify the feasibility of the proposed method. The grey-based AHP evaluation model can be used to evaluate the usability level of AR-HUD interface effectively, which may help designers achieve insights for design process and samples decision-making.
Prognostic Significance of Admission Lymphocyte-to-Monocyte Ratio in Patients with Spontaneous Intracerebral Hemorrhage: A Retrospective Study
Authors: Qin Jie , Qiu Xingchen , Gong Guangming , Guo Yinan , Lei Lei , Zheng Huaixin , Wang Peng , Xuan Xiaoyan
Published: November 2022

Background

Acute spontaneous intracerebral hemorrhage (sICH) is a morbid and deadly form of stroke. The lymphocyte-to-monocyte ratio (LMR) and systemic immune-inflammation index (SII) are two novel markers of systemic inflammation. We aimed at investigating the predictive value of LMR and SII in patients with sICH.

Methods

We retrospectively evaluated patients who were hospitalized for sICH at the First Affiliated Hospital of Zhengzhou University from September 2019 to July 2020. According to the 3-month modified Rankin Scale (mRS) score, we considered a good prognosis group (mRS: 0–2) and a poor prognosis group (mRS ≥ 3 or death). A logistic regression analysis was used to identify the factors affecting the prognosis at 3 months.

Results

A total of 171 patients with sICH were enrolled. A lower LMR measured at 24 h of admission was an independent predictor of 3-month prognosis (OR: 0.392, 95% CI 0.281–0.547, p < 0.001). A lower GCS score measured at 24 h after admission was an independent predictor of 3-month prognosis (OR: 0.821, 95% CI 0.747–0.902, p = 0.023). A previous heart disease was an independent predictor of 3-month prognosis (OR: 6.307, 95% CI 1.381–30.196, p = 0.021). SII measured at 24 h of admission was not an independent predictor of 3-month prognosis. Combining the results obtained by each indicator, the final curve showed an AUC of 0.850, indicating a satisfactory predictive performance. The receiver operating characteristic curves showed that the sensitivity of LMR was 93.07% (95% CI 86.2–97.2), while the specificity was 52.86% (95% CI 40.6–64.9). The sensitivity of GCS score was 76.77% (95% CI 67.2–84.7), while the specificity was 60.29% (95% CI 47.7–72.05). The sensitivity of SII was 91.09% (95% CI 83.8–95.8), while the specificity was 37.14% (95% CI 25.9–49.5). The DeLong test showed that the predictive value of LMR was higher than SII (p = 0.0001).

Conclusions

In patients with sICH, LMR showed an independent predictive value for anticipating 3-month prognosis.
Active Stokesian dynamics
Authors: Elfring Gwynn J. , Brady John F.
Published: November 2022

Since its development, Stokesian dynamics has been a leading approach for the dynamic simulation of suspensions of particles at arbitrary concentrations with full hydrodynamic interactions. Although developed originally for the simulation of passive particle suspensions, the Stokesian dynamics framework is equally well suited to the analysis and dynamic simulation of suspensions of active particles, as we elucidate here. We show how the reciprocal theorem can be used to formulate the exact dynamics for a suspension of arbitrary active particles, and then show how the Stokesian dynamics method provides a rigorous way to approximate and compute the dynamics of dense active suspensions where many-body hydrodynamic interactions are important.
Business Education in China: Current State and Future Direction
Authors: Lu Xiongwen
Published: November 2022

In this commentary, I expand on Fey's (2022) perspective on the future development of Chinese business schools. In particular, I explore some of the nuances related to Chinese business schools that were not covered by Fey with the goal of continuing this important dialogue.
Who's cheating on your survey? A detection approach with digital trace data
Authors: Munzert Simon , Ramirez-Ruiz Sebastian , Barberá Pablo , Guess Andrew M. , Yang JungHwan
Published: November 2022

In this note, we provide direct evidence of cheating in online assessments of political knowledge. We combine survey responses with web tracking data of a German and a US online panel to assess whether people turn to external sources for answers. We observe item-level prevalence rates of cheating that range from 0 to 12 percent depending on question type and difficulty, and find that 23 percent of respondents engage in cheating at least once across waves. In the US panel, which employed a commitment pledge, we observe cheating behavior among less than 1 percent of respondents. We find robust respondent- and item-level characteristics associated with cheating. However, item-level instances of cheating are rare events; as such, they are difficult to predict and correct for without tracking data. Even so, our analyses comparing naive and cheating-corrected measures of political knowledge provide evidence that cheating does not substantially distort inferences.
CONVIVIAL BED-WETTERS: LUCR. 4.1026–9
Authors: Allen Archibald
Published: November 2022

This note offers a new conjecture on the manuscripts’ puri at Lucr. 4.1026 which would identify more clearly the dreaming bed-wetters as well-wined dinner guests.
Preservation of Membrana Testacea in titanosaurid dinosaur eggshells from the Upper Cretaceous Deccan volcano-sedimentary strata of Central India
Authors: Lourembam Ranjit Singh , Dhiman Harsha , Prasad Guntupalli VR
Published: November 2022

The calcitic eggshell units of amniote eggs are underlain by a soft organic layer, the Membrana Testacea (MT), which has a mesh-like texture consisting of fibrils of organic material. Because of its soft anatomy, the MT is rarely preserved in fossils and only a few fossil reports of MT are known so far. Here we report the preservation of a mineralized MT layer in titanosaur eggshells recovered from a marlstone facies interbedded with the Deccan lava flows exposed near Piplanarayanwar village of Chhindwara District, Madhya Pradesh state in Central India. The MT layer is mesh-like, resembling protein membranes of extant reptiles and the MT reported in titanosaurid eggshells of the Upper Cretaceous Anacleto Formation at Auca Mahuevo, Argentina. The presence of tendrils and fibres of calcite in the MT layer testifies to the fact that the calcium layer represents the original fibrous MT. It also supports the view that fossilization of soft tissues like MT is possible because of the inferred anaerobic conditions that prevailed during the deposition of Piplanarayanwar intertrappean sediments in lacustrine or paludal bodies in a coastal-plain setting.
Idiosyncrasy as a Leading Indicator
Authors: Morck Randall , Yeung Bernard , Zhang Lu Y.
Published: November 2022

Disequilibrating macro shocks affect different firms’ prospects differently, increasing idiosyncratic variation in forward-looking stock returns before affecting economic growth. Consistent with most such shocks from 1947 to 2020 enhancing productivity, increased idiosyncratic stock return variation forecasts next-quarter real GDP growth, industrial production growth, and consumption growth both in-sample and out-of-sample. These effects persist after controlling for other leading economic indicators.
‘You had to be the Detective’: Implementing Workfare in British Employment Services
Authors: Redman Jamie , Fletcher Del Roy , White Richard , Mccarthy Lindsey
Published: November 2022

British employment service delivery has shifted towards a model primed on core ‘workfare’ objectives – that is, enforcing behavioural compliance to work-related duties and expanding participation in work. Nevertheless, significant gaps remain in current knowledge about how workfare is implemented daily by frontline staff. The existing international street-level research on employment service delivery reveals how workers use a range of discretionary practices to achieve workfare objectives. Yet this research largely ignores how, in practice, a key aspect of enforcing behavioural compliance and encouraging work participation is through contending with its opposite – behavioural non-compliance. Analysing 13 interviews with frontline staff, this article contributes to street-level knowledge by revealing the ways managers and workers in British employment services are encouraged to detect and correct variations of claimant non-compliance.
The development and efficacy of a paediatric cardiology fellowship online preparatory course
Authors: Motonaga Kara S. , Sacks Loren , Olson Inger , Balasubramanian Sowmya , Chen Sharon , Peng Lynn , Feinstein Jeffrey A. , Silverman Norman H. , Hanley Frank L. , Axelrod David M. , Krawczeski Catherine D. , Arunamata Alisa , Kwiatkowski David M. , Ceresnak Scott R.
Published: November 2022

Background:

The transition from residency to paediatric cardiology fellowship is challenging due to the new knowledge and technical skills required. Online learning can be an effective didactic modality that can be widely accessed by trainees. We sought to evaluate the effectiveness of a paediatric cardiology Fellowship Online Preparatory Course prior to the start of fellowship.

Methods:

The Online Preparatory Course contained 18 online learning modules covering basic concepts in anatomy, auscultation, echocardiography, catheterisation, cardiovascular intensive care, electrophysiology, pulmonary hypertension, heart failure, and cardiac surgery. Each online learning module included an instructional video with pre-and post-video tests. Participants completed pre- and post-Online Preparatory Course knowledge-based exams and surveys. Pre- and post-Online Preparatory Course survey and knowledge-based examination results were compared via Wilcoxon sign and paired t-tests.

Results:

151 incoming paediatric cardiology fellows from programmes across the USA participated in the 3 months prior to starting fellowship training between 2017 and 2019. There was significant improvement between pre- and post-video test scores for all 18 online learning modules. There was also significant improvement between pre- and post-Online Preparatory Course exam scores (PRE 43.6 ± 11% versus POST 60.3 ± 10%, p < 0.001). Comparing pre- and post-Online Preparatory Course surveys, there was a statistically significant improvement in the participants’ comfort level in 35 of 36 (97%) assessment areas. Nearly all participants (98%) agreed or strongly agreed that the Online Preparatory Course was a valuable learning experience and helped alleviate some anxieties (77% agreed or strongly agreed) related to starting fellowship.

Conclusion:

An Online Preparatory Course prior to starting fellowship can provide a foundation of knowledge, decrease anxiety, and serve as an effective educational springboard for paediatric cardiology fellows.
The Genie and the Lamp: How Can Artificial Intelligence Help Us Find New Case Law?
Authors: Magrath Paul
Published: November 2022

Based on a presentation given at the BIALL Annual Conference in July 2022, this article by Paul Magrath provides an overview of how technology including artificial intelligence (AI) is transforming legal practice and the conduct of litigation, followed by more detailed consideration by way of a case study of ICLR's development of its AI-driven search tool, Case Genie. The article examines the problems that it was designed to solve, particularly the legal researcher's anxiety over ‘unknown unknowns’, and the options for further development of the technology and its application in other areas.
Autoplaying, Unmuting, Attending: (Re)formatting the Twenty-First-Century Digital Sensorium
Authors: HARPER PAULA
Published: November 2022

In this article, I analyse the implications of autoplaying video as a driver of ‘audile techniques’ in the 2010s digital ecosystem – in particular, techniques that respond to the realities of the separability of image and sound, even in media that contain both elements. I then examine a number of strategies through which this audio/visual split has been negotiated, monetized, and creatively bridged by consumers, creators, and corporate personnel – from the creation of new audiovisual genres and aesthetics, to the rise of particular platform pricing models, to the adoption (and, potentially, exploitation) of accessibility features. Ultimately, I seek to show how negotiations of sound and listening factor deeply into contemporary attempts to harness and monetize ‘attention’ as a commodity in a digital economy of platforms, advertisements, and data.
‘Exchanging Cuba for 1 Million YouTube Views’: Technological Precarity, Offline Virality, and ‘Patria y vida’
Authors: LEVINE MIKE
Published: November 2022

For many Cubans, the internet remains an inaccessible destination. The residents of repartimiento districts – Black Cuban residents from outlying districts across Havana – manage the situation through custom solutions that bridge gaps of technological precarity. Utilizing USB drives to share content with one another, artists and music fans have constructed a complex, alternative internet that allows for the peer-to-peer trade of movies, music, and other media. Pirate digital networks such as el paquete semanal and Zapya, for instance, circulate music across the island without the need to rely on costly and unreliable internet infrastructure. Utilizing interviews, physical and digital ethnographies, and theories of viral musicking, I argue that Black Cuban artists and music fans, despite internet scarcity, use alternative networks to generate viral events. In particular, Cubans in 2021 joined in a transnational expression of sonic protest through the popularity of the politically subversive song ‘Patria y vida’, a song that circulated widely through underground, USB-based networks. In this article, I discuss the song's construction, circulation, and role in sounding the J-11 Cuban protests to demonstrate how Black Cuban artists and fans share music through USB-based networks not only to solve gaps in technologically precarious situations, but also to generate powerful moments of viral musicking.
Anitta's ‘Girl from Rio’, Digital Fatigue, and Stereotype
Authors: GOLDSCHMITT K. E.
Published: November 2022

In May 2021, Brazilian pop-funk superstar Anitta released ‘Girl from Rio’. The song was based on the melodic foundation of the bossa nova song ‘The Girl from Ipanema’ that became a huge international hit at the end of the 1960s bossa nova craze. ‘Girl from Rio’ features trap beats on top of the familiar melody with a clear lyrical message that critiques international stereotypes of women from Brazil. When Anitta attempted to capture the US market through TikTok and a high-profile remix, much of her critique disappeared. This article employs the concept of ‘digital fatigue’ to explore how viral musical content loses crucial aspects of its meaning through circulation and endless embodied repetition. By focusing on how the repetition of viral musical media perpetuates stereotypes, it shows how the environment for transnational success requires easy associations to spread.
A MAVEN Case Study of Radial IMF at Mars: Impacts on the Dayside Ionosphere
Authors: Fowler C. M. , Hanley K. G. , McFadden J. , Halekas J. , Schwartz S. J. , Mazelle C. , Chaffin M. , Mitchell D. , Espley J. , Ramstad R. , Dong Y. , Curry S.
Published: November 2022

The solar wind interaction with Mars controls the transfer of energy and momentum from the solar wind into the magnetosphere, ionosphere and atmosphere, driving structure, and dynamics within each. This interaction is highly dependent on the upstream Interplanetary Magnetic Field (IMF) orientation. We use in‐situ plasma measurements made by the Mars Atmosphere and Volatile EvolutioN (MAVEN) mission to identify several prominent features that arise when the IMF is aligned approximately parallel or antiparallel to solar wind flow (conditions known as “radial IMF”). In particular, solar wind protons and alphas are observed to directly penetrate down to periapsis altitudes, while the magnetic barrier forms deep within the dayside ionosphere. The MAVEN observations are consistent with either an ionopause‐like boundary or diamagnetic cavity forming beneath the barrier, as a consequence of the dense cold ionosphere and the absence of significant crustal magnetic fields at this periapsis location. The planetary ions above the magnetic barrier are exposed to solar wind flow and subsequent mass‐loading. The (convective electric field or “ion pickup”) force is weak and highly variable during radial IMF. While wave particle interactions and subsequent wave heating contribute to incorporating the heavy planetary ions into the solar wind flow, the solar wind momentum is not fully deflected around the obstacle and is delivered into the collisional atmosphere. Significant ion heating is observed deep within the dayside ionosphere, and observed ionospheric density and temperature profiles demonstrate that these ion energization mechanisms drive significant erosion and likely escape to space.
Effective Path Length for Estimating Rain Attenuation Over an Earth‐Space Path Using Features of Stratiform and Convective Precipitation at a Tropical Location
Authors: Rakshit Gargi , Maitra Animesh
Published: November 2022

The effective path length (LE) for the rain attenuation estimation over the Earth‐space path depends on rain cell size, rain rate, and rain height which in turn are determined by the types of rain. The present study examines the variation of LE based on the experimental measurements of Ku‐band attenuation and rain rate at a tropical location Kolkata (22°34′N, 88°22′E) in comparison with the ITU‐R. The study also utilizes measurements from a 24‐GHz micro rain Doppler radar to differentiate the precipitation types as stratiform and convective rain on the basis of the presence and absence of a melting layer. Power‐law models of LE in terms of rain rate are proposed for convective and stratiform types of rain. The investigation reveals the physical phenomena behind the variability of LE at low and high rain rates which are associated with stratiform and convective rain respectively. The proposed models provide a significantly better agreement with the experimental data compared to the ITU‐R model and also account for distinguishing features of two types of rain, thus giving a physical basis of the proposed model which is not reflected in the ITU‐R formulations.
The divergent effects of astrocyte ceruloplasmin on learning and memory function in young and old mice
Authors: Li Zhong-Da , Li Haiyan , Kang Shaomeng , Cui Yan-Ge , Zheng Huiwen , Wang Peina , Han Kang , Yu Peng , Chang Yan-Zhong
Published: November 2022

Ceruloplasmin (CP) plays an important role in maintaining iron homeostasis.Cpgene knockout (Cp-/-) mice develop a neurodegenerative disease with aging and show iron accumulation in the brain. However, iron deficiency has also been observed in 3 MCp-/-mice. The use of systemicCpgene knockout is insufficient to reveal specific functions for CP in the central nervous system. Considering recent discoveries that astrocytes synthetize the majority of brain CP, we generated astrocyte conditionalCpknockout (CpGfapcKO) mice, and found that iron contents decreased in the cerebral cortex and hippocampus of young (6 M) and old (18 M)CpGfapcKOmice. Further experiments revealed that 6 MCpGfapcKOmice exhibited impaired learning and memory function, while 18 MCpGfapcKOmice exhibited improved learning and memory function. Our study demonstrates that astrocyticCpdeletion blocks brain iron influx through the blood-brain-barrier, with concomitantly increased iron levels in brain microvascular endothelial cells, resulting in brain iron deficiency and down-regulation of ferritin levels in neurons, astrocytes, microglia and oligodendrocytes. At the young age, the synapse density, synapse-related protein levels, 5-hydroxytryptamine and norepinephrine, hippocampal neurogenesis and myelin formation were all decreased inCpGfapcKOmice. These changes affected learning and memory impairment in youngCpGfapcKOmice. In oldCpGfapcKOmice, iron accumulation with aging was attenuated, and was accompanied by the alleviation of the ROS-MAPK-apoptosis pathway, Tau phosphorylation and β-amyloid aggregation, thus delaying age-related memory decline. Overall, our results demonstrate that astrocyticCpdeletion has divergent effects on learning and memory function via different regulatory mechanisms induced by decreased iron contents in the brain of mice, which may present strategies for the prevention and treatment of dementia.
Altered tRNA processing is linked to a distinct and unusual La protein in Tetrahymena thermophila
Authors: Kerkhofs Kyra , Garg Jyoti , Fafard-Couture Étienne , Abou Elela Sherif , Scott Michelle S. , Pearlman Ronald E. , Bayfield Mark A.
Published: November 2022

Nascent pre-tRNAs are transcribed by RNA polymerase III and immediately bound by La proteins on the UUU-3’OH sequence, using a tandem arrangement of the La motif and an adjacent RNA recognition motif-1 (RRM1), resulting in protection from 3’-exonucleases and promotion of pre-tRNA folding. The Tetrahymena thermophila protein Mlp1 has been previously classified as a genuine La protein, despite the predicted absence of the RRM1. We find that Mlp1 functions as a La protein through binding of pre-tRNAs, and affects pre-tRNA processing in Tetrahymena thermophila and when expressed in fission yeast. However, unlike in other examined eukaryotes, depletion of Mlp1 results in 3’-trailer stabilization. The 3’-trailers in Tetrahymena thermophila are uniquely short relative to other examined eukaryotes, and 5’-leaders have evolved to disfavour pre-tRNA leader/trailer pairing. Our data indicate that this variant Mlp1 architecture is linked to an altered, novel mechanism of tRNA processing in Tetrahymena thermophila.
Chromatin accessibility dynamics dictate renal tubular epithelial cell response to injury
Authors: Cao Xinyi , Wang Jiuchen , Zhang Tianye , Liu Zhiheng , Liu Lijun , Chen Ying , Li Zehua , Zhao Youlu , Yu Qi , Liu Tong , Nie Jing , Niu Yuanjie , Chen Yupeng , Yang Li , Zhang Lirong
Published: November 2022

Renal tubular epithelial cells (TECs) can initiate an adaptive response to completely recover from mild acute kidney injury (AKI), whereas severe injury often leads to persistence of maladaptive repair and progression to kidney fibrosis. Through profiling of active DNA regulatory elements by ATAC-seq, we reveal widespread, dynamic changes in the chromatin accessibility of TECs after ischemia–reperfusion injury. We show that injury-specific domains of regulatory chromatin become accessible prior to gene activation, creating poised chromatin states to activate the consequent gene expression program and injury response. We further identify RXRα as a key transcription factor in promoting adaptive repair. Activation of RXRα by bexarotene, an FDA-approved RXRα agonist, restores the chromatin state and gene expression program to protect TECs against severe kidney injury. Together, our findings elucidate a chromatin-mediated mechanism underlying differential responses of TECs to varying injuries and identify RXRα as a therapeutic target of acute kidney injury.
A p38α-BLIMP1 signalling pathway is essential for plasma cell differentiation
Authors: Wu Jianfeng , Yang Kang , Cai Shaowei , Zhang Xiaohan , Hu Lichen , Lin Fanjia , Wu Su-qin , Xiao Changchun , Liu Wen-Hsien , Han Jiahuai
Published: November 2022

Plasma cells (PC) are antibody-secreting cells and terminal effectors in humoral responses. PCs differentiate directly from activated B cells in response to T cell-independent (TI) antigens or from germinal center B (GCB) cells in T cell-dependent (TD) antigen-induced humoral responses, both of which pathways are essentially regulated by the transcription factor BLIMP1. The p38 mitogen-activated protein kinase isoforms have already been implicated in B cell development, but the precise role of p38α in B cell differentiation is still largely unknown. Here we show that PC differentiation and antibody responses are severely impaired in mice with B cell-specific deletion ofp38α, while B cell development and the GCB cell response are spared. By utilizing aBlimp1reporter mouse model, we show thatp38α-deficiency results in decreased BLIMP1 expression. p38α-driven BLIMP1 up-regulation is required for both TI and TD PCs differentiation. By combining CRISPR/Cas9 screening and other approaches, we identify TCF3, TCF4 and IRF4 as downstream effectors of p38α to control PC differentiation viaBlimp1transcription. This study thus identifies an important signalling pathway underpinning PC differentiation upstream of BLIMP1, and points to a highly specialized and non-redundant role for p38α among p38 isoforms.
Targeting APLN/APJ restores blood-testis barrier and improves spermatogenesis in murine and human diabetic models
Authors: Song Ke , Yang Xinyan , An Geng , Xia Xinyu , Zhao Jiexiang , Xu Xiaoheng , Wan Cong , Liu Tianyuan , Zheng Yi , Ren Shaofang , Wang Mei , Chang Gang , Cronin Shane J. F. , Penninger Josef M. , Jing Tao , Ou Xianghong , Rao Shuan , Liu Zhaoting , Zhao Xiao-Yang
Published: November 2022

Type 2 diabetes mellitus is one of the most prevalent metabolic diseases presenting with systemic pathologies, including reproductive disorders in male diabetic patients. However, the molecular mechanisms that contributing to spermatogenesis dysfunction in diabetic patients have not yet been fully elucidated. Here, we perform STRT-seq to examine the transcriptome of diabetic patients’ testes at single-cell resolution including all major cell types of the testis. Intriguingly, whereas spermatogenesis appears largely preserved, the gene expression profiles of Sertoli cells and the blood-testis barrier (BTB) structure are dramatically impaired. Among these deregulate pathways, the Apelin (APLN) peptide/Apelin-receptor (APJ) axis is hyper-activated in diabetic patients’ testes. Mechanistically, APLN is produced locally by Sertoli cells upon high glucose treatment, which subsequently suppress the production of carnitine and repress the expression of cell adhesion genes in Sertoli cells. Together, these effects culminate in BTB structural dysfunction. Finally, using the small molecule APLN receptor antagonist, ML221, we show that blocking APLN/APJ significantly ameliorate the BTB damage and, importantly, improve functional spermatogenesis in diabetic db/db mice. We also translate and validate these findings in cultured human testes. Our findings identify the APLN/APJ axis as a promising therapeutic target to improve reproduction capacity in male diabetic patients.
Increase in tropical cyclone rain rate with translation speed
Authors: Tu Shifei , Chan Johnny C. L. , Xu Jianjun , Zhong Quanjia , Zhou Wen , Zhang Yu
Published: November 2022

In general, tropical cyclone (TC) rainfall accumulation usually decreases with faster TC translation speed but increases with heavier rain rate. However, how the TC rain rate changes with translation speed is unclear. Here we show that, in all TC basins, the average TC rain rate significantly increases with translation speed. On average, the rain rate in a fast-moving TC is 24% higher than in a slow one. This difference increases with TC intensity, with category 3–5 TCs having a 42% increase while tropical depressions exhibit only a 9% increase. The increase in the average TC rain rate with translation speed is mainly caused by the TC net inflow in the lower troposphere, as well as vertical wind shear. These findings have important implications not only for a deeper understanding of rain rate changes in a translating TC but also for short-term forecasts of TC rainfall and disaster preparedness.
Intelligent certification for quantum simulators via machine learning
Authors: Xiao Tailong , Huang Jingzheng , Li Hongjing , Fan Jianping , Zeng Guihua
Published: November 2022

Quantum simulation is a technology of using controllable quantum systems to study new quantum phases of matter. Certification for quantum simulators is a challenging problem whereas identification and properties estimation are two crucial approaches that can be resorted to. In this work, we propose Ab initio end-to-end machine learning certification protocol briefly named MLCP. The learning protocol is trained with a million-level size of randomized measurement samples without relying on the assistance of quantum tomography. In the light of MLCP, we can identify different types of quantum simulators to observe their distinguishability hardness. We also predict the physical properties of quantum states evolved in quantum simulators such as entanglement entropy and maximum fidelity. The impact of randomized measurement samples on the identification accuracy is analyzed to showcase the potential capability of classical machine learning on quantum simulation results. The entanglement entropy and maximum fidelity with varied subsystem partitions are also estimated with satisfactory precision. This work paves the way for large-scale intelligent certification of quantum simulators and can be extended onto an artificial intelligence center to offer easily accessible services for local quantum simulators in the noisy intermediate-size quantum (NISQ) era.
Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine
Authors: Ong Eugenia Z. , Yee Jia Xin , Ooi Justin S. G. , Syenina Ayesa , de Alwis Ruklanthi , Chen Shiwei , Sim Jean X. Y. , Kalimuddin Shirin , Leong Yan Shan , Chan Yvonne F. Z. , Sekulovich Rose , Sullivan Brian M. , Lindert Kelly , Sullivan Sean B. , Chivukula Pad , Hughes Steven G. , Low Jenny G. , Ooi Eng Eong , Chan Kuan Rong
Published: November 2022

Remarkable potency has been demonstrated for mRNA vaccines in reducing the global burden of the ongoing COVID-19 pandemic. An alternative form of the mRNA vaccine is the self-amplifying mRNA (sa-mRNA) vaccine, which encodes an alphavirus replicase that self-amplifies the full-length mRNA and SARS-CoV-2 spike (S) transgene. However, early-phase clinical trials of sa-mRNA COVID-19 vaccine candidates have questioned the potential of this platform to develop potent vaccines. We examined the immune gene response to a candidate sa-mRNA vaccine against COVID-19, ARCT-021, and compared our findings to the host response to other forms of vaccines. In blood samples from healthy volunteers that participated in a phase I/II clinical trial, greater induction of transcripts involved in Toll-like receptor (TLR) signalling, antigen presentation and complement activation at 1 day post-vaccination was associated with higher anti-S antibody titers. Conversely, transcripts involved in T-cell maturation at day 7 post-vaccination informed the magnitude of eventual S-specific T-cell responses. The transcriptomic signature for ARCT-021 vaccination strongly correlated with live viral vector vaccines, adjuvanted vaccines and BNT162b2 1 day post-vaccination. Moreover, the ARCT-021 signature correlated with day 7 YF17D live-attenuated vaccine transcriptomic responses. Altogether, our findings show that sa-mRNA vaccination induces innate immune responses that are associated with the development of adaptive immunity from other forms of vaccines, supporting further development of this vaccine platform for clinical application.
Quantum affective processes for multidimensional decision-making
Authors: Ho Johnny K. W. , Hoorn Johan F.
Published: November 2022

In modeling the human affective system and applying lessons learned to human–robot interaction, the challenge is to handle ambiguous emotional states of an agency (whether human or artificial), probabilistic decisions, and freedom of choice in affective and behavioral patterns. Moreover, many cognitive processes seem to run in parallel whereas seriality is the standard in conventional computation. Representation of contextual aspects of behavior and processes and of self-directed neuroplasticity are still wanted and so we attempt a quantum-computational construction of robot affect, which theoretically should be able to account for indefinite and ambiguous states as well as parallelism. Our Quantum Coppélia (Q-Coppélia) is a translation into quantum logics of the fuzzy-based Silicon Coppélia system, which simulates the progression of a robot’s attitude towards its user. We show the entire circuitry of the Q-Coppélia framework, aiming at contemporary descriptions of (neuro)psychological processes. Arguably, our work provides a system for simulating and handling affective interactions among various agencies from an understanding of the relations between quantum algorithms and the fundamental nature of psychology.
Serum circulating sirtuin 6 as a novel predictor of mortality after acute ischemic stroke
Authors: Liberale Luca , Ministrini Stefano , Arnold Markus , Puspitasari Yustina M. , Pokorny Thomas , Beer Georgia , Scherrer Natalie , Schweizer Juliane , Christ-Crain Mirjam , Montecucco Fabrizio , Camici Giovanni G. , Katan Kahles Mira
Published: November 2022

In a murine model of acute ischemic stroke, SIRT6 knockdown resulted in larger cerebral infarct size, worse neurological outcome, and higher mortality, indicating a possible neuro-protective role of SIRT6. In this study, we aimed at evaluating the prognostic value of serum SIRT6 levels in patients with acute ischemic stroke (AIS). Serum levels of SIRT6, collected within 72 h from symptom-onset, were measured in 317 consecutively enrolled AIS patients from the COSMOS cohort. The primary endpoint of this analysis was 90-day mortality. The independent prognostic value of SIRT6 was assessed with multivariate logistic and Cox proportional regression models. 35 patients (11%) deceased within 90-day follow-up. After adjustment for established risk factors (age, NIHSS, heart failure, atrial fibrillation, and C reactive protein), SIRT6 levels were negatively associated with mortality. The optimal cut-off for survival was 634 pg/mL. Patients with SIRT6 levels below this threshold had a higher risk of death in multivariable Cox regression. In this pilot study, SIRT6 levels were significantly associated with 90-day mortality after AIS; these results build on previous molecular and causal observations made in animal models. Should this association be confirmed, SIRT6 could be a potential prognostic predictor and therapeutic target in AIS.
Photoacoustic imaging is a novel tool to measure finger artery structure and oxygenation in patients with SSc
Authors: Wilkinson Sarah , Cummings James , Zafar Sakif , Kozar Martin , Manning Joanne , Dinsdale Graham , Berks Michael , Taylor Christopher , Dickinson Mark , Herrick Ariane L. , Murray Andrea K.
Published: November 2022

Systemic sclerosis (SSc)-related digital ischaemia is a major cause of morbidity, resulting from a combination of microvascular and digital artery disease. Photoacoustic imaging offers a newly available, non-invasive method of imaging digital artery structure and oxygenation. The aim of this study was to establish whether photoacoustic imaging could detect and measure vasculopathy in digital arteries, including the level of oxygenation, in patients with SSc and healthy controls. 22 patients with SSc and 32 healthy controls (HC) underwent photoacoustic imaging of the fingers. Vascular volume and oxygenation were assessed across eight fingers at the middle phalanx. In addition, oxygenation change during finger occlusion was measured at the non-dominant ring finger and the vascular network was imaged along the length of one finger for qualitative assessment. There was no statistically significant difference in vascular volume between patients with SSc and HC (mean of eight fingers; SSc, median 118.6 IQR [95.0–130.5] vs. HC 115.6 [97.8–158.9]) mm3. However, baseline oxygenation (mean 8 fingers) was lower in SSc vs. HC (0.373 [0.361–0.381] vs. 0.381 [0.373–0.385] arbitrary sO2 units respectively; p = 0.03). Hyperaemic oxygenation response following occlusion release was significantly lower in SSc compared to HC (0.379 [0.376–0.381] vs. 0.382 [0.377–0.385]; p = 0.03). Whilst vascular volume was similar between groups, digital artery oxygenation was decreased in patients with SSc as compared to HC, indicative of functional deficit. Photoacoustic imaging offers an exciting new method to image the vascular network in patients with SSc and the possibility to capture oxygenation as a functional measure.
Organotypic stromal cells impact endothelial cell transcriptome in 3D microvessel networks
Authors: Curtis Matthew B. , Kelly Natalie , Hughes Christopher C. W. , George Steven C.
Published: November 2022

Endothelial cells line all major blood vessels and serve as integral regulators of many functions including vessel diameter, cellular trafficking, and transport of soluble mediators. Despite similar functions, the phenotype of endothelial cells is highly organ-specific, yet our understanding of the mechanisms leading to organ-level differentiation is incomplete. We generated 3D microvessel networks by combining a common naïve endothelial cell with six different stromal cells derived from the lung, skin, heart, bone marrow, pancreas, and pancreatic cancer. Single cell RNA-Seq analysis of the microvessel networks reveals five distinct endothelial cell populations, for which the relative proportion depends on the stromal cell population. Morphologic features of the organotypic vessel networks inversely correlate with a cluster of endothelial cells associated with protein synthesis. The organotypic stromal cells were each characterized by a unique subpopulation of cells dedicated to extracellular matrix organization and assembly. Finally, compared to cells in 2D monolayer, the endothelial cell transcriptome from the 3D in vitro heart, skin, lung, and pancreas microvessel networks are more similar to the in vivo endothelial cells from the respective organs. We conclude that stromal cells contribute to endothelial cell and microvessel network organ tropism, and create an endothelial cell phenotype that more closely resembles that present in vivo.