bluuebunny/crossref_metadata_2025 huggingface dataset:
Who’s striking, and who’s not? Avoiding and acknowledging bias in youth climate activism research
Authors: Feldman Hannah R.
Published: February 2022

The School Strike 4 Climate is a timely opportunity for education and research sectors to support youth stories in climate change policy, and foster impactful relationships between researchers, teachers and students. But much research in this space has inherent selection biases where youth representation in research is limited by place (such as attendance at a protest), snowball sampling (often within already engaged groups) or through education channels (such as private or independent schools), ultimately leading to unrepresentative response samples. This comment explores the challenges and opportunities for equitable inclusion of teenage voices in environmental research, including some practical approaches (such as inclusion of public schools) to ensure more diverse samples are represented. Implications for how the existing body of research should be viewed is discussed, highlighting an existing lack of representation of students that do not overtly engage with climate activism or School Strikes.
Not Worth the Wait: Why the Long-Awaited Regulations Under the AHRA Don’t Address Egg Donor Concerns
Authors: Hammond Kathleen
Published: February 2022

The Assisted Human Reproduction Act seeks to protect egg donors’ health and well-being and prevent trade in their reproductive capabilities. In order to fulfill these objectives, the Act prohibits the buying and selling of ova, and only allows for egg donors to be reimbursed for their expenses. However, no regulations setting out what expenses can be reimbursed were promulgated. Sixteen years later, these long-awaited regulations finally came into force in June 2020. In this study, I rely on data from interviews with sixteen egg donors in order to assess how the new regulations might help or hinder concerns that egg donors have with how egg transactions are regulated in Canada. I argue that the new regulations might hinder, more than help with, addressing current concerns related to egg transactions in Canada. The most likely result is that they will not change the current state of affairs.
The Challenges of Nurse Redeployment and Opportunities for Leadership During COVID-19 Pandemic
Authors: Ballantyne Helen , Achour Nebil
Published: February 2022

Objective:

Literature has previously shown that healthcare staff redeployment has been widely implemented to build capacity, with little focus on nurses. This study aims to manage redeployment more effectively by capturing and scrutinizing nurses’ redeployment experiences.

Methods:

A cross-sectional short and structured interview was conducted. Data was analyzed using Braun and Clarkes 6 Step Thematic Analysis approach.

Results:

55 interviews were conducted predominantly from women (85%, N = 47), over the age of 45 years (45%, N = 25), who were in the role of Specialist Nurse or Staff Nurse (78%, N = 43). 5 critical themes emerged: willingness to work in redeployed role, poor communication, stress and anxiety, feelings of being unsupported and abandoned, and positive experiences despite challenging circumstances.

Conclusion:

Nurses in redeployed roles were susceptible to stress and anxiety and were seeking dedicated leadership as they worked during a pandemic with the additional challenge of unfamiliar workspaces and colleagues. Nurses play a major role in the resilience of healthcare service, which cannot be achieved without a comprehensive resilience strategy. Healthcare organisations are required to develop strategies, policies, and enforcement measures to ensure that their staff are well empowered and protected not just during potential redeployment but also in their daily operations.
Acquisition of carbapenem-resistant gram-negative bacilli among intensive care unit (ICU) patients with no previous use of carbapenems: Indirect population impact of antimicrobial use
Authors: Oliveira Juliana da Silva , Sampaio Natalie Carlos Ferreira Melo , Leite Gabriela Silveira , Pereira Milena Aparecida Del Masso , Fortaleza Carlos Magno Castelo Branco
Published: February 2022

Objective:

To measure the impact of exposure to patients using carbapenem on the acquisition of carbapenem-resistant gram-negative bacilli (CR-GNB) among patients not using carbapenems.

Design:

An ecological study and a cohort study.

Setting:

Two medical surgical intensive care units (ICUs) in inner Brazil.

Participants:

Patients admitted to 2 ICUs from 2013 through 2018 to whom carbapenem was not prescribed.

Methods:

In the ecologic study, the monthly use of carbapenems (days of therapy [DOT] per 1,000 patient days) was tested for linear correlation with the 2-month moving average of incidence CR-GNB among patients to whom carbapenem was not prescribed. In the cohort study, those patients were addressed individually for risk factors (demographics, invasive interventions, use of antimicrobials) for acquisition of CR-GNB, including time at risk and the “carbapenem pressure,” described as the aggregate DOT among other ICU patients during time at risk. The analysis was performed in univariate and multivariable Poisson regression models.

Results:

The linear regression model revealed an association of total carbapenem use and incidence of CR-GNB (coefficient, 0.04; 95% confidence interval [CI], 0.02–0.06; P = .001). In the cohort model, the adjusted rate ratio (RR) for carbapenem DOT was 1.009 (95% CI, 1.001–1.018; P = .03). Other significant risk factors were mechanical ventilation and the previous use of ceftazidime (with or without avibactam).

Conclusions:

Every additional DOT of total carbapenem use increased the risk of CR-GNB acquisition by patients not using carbapenems by nearly 1%. We found evidence for a population (“herd effect”-like) impact of antimicrobial use in the ICUs.
Examining drivers of coronavirus disease 2019 (COVID-19) vaccine hesitancy among healthcare workers
Authors: Swann Mandy C. , Bendetson Jesse , Johnson Alexis , Jatta Maimuna , Schleupner Charles J. , Baffoe-Bonnie Anthony
Published: February 2022

Objective:

To assess characteristics and perceptions associated with vaccine hesitancy among healthcare workers to increase coronavirus disease 2019 (COVID-19) vaccine uptake in this population.

Design:

Cross-sectional quantitative survey.

Setting:

A not-for-profit healthcare system in southwestern Virginia.

Participants:

A convenience sample of 2,720 employees of a not-for-profit healthcare system.

Methods:

Between March 15 and 29, 2021, we conducted an Internet-based survey. Our questionnaire assessed sociodemographic and work-related characteristics, vaccine experience and intentions, agreement with vaccine-related perceptions, the most important reasons for getting or not getting vaccinated, and trusted sources of information about COVID-19. We used χ2analyses to assess the relationship between vaccine hesitancy and both HCW characteristics and vaccine-related perceptions.

Results:

Overall, 18% of respondents were classified as vaccine hesitant. Characteristics significantly associated with hesitancy included Black race, younger age, not having a high-risk household member, and prior personal experience with COVID-19 illness. Vaccine hesitancy was also significantly associated with many vaccine-related perceptions, including concerns about short-term and long-term side effects and a belief that the vaccines are not effective. Among vaccine-acceptant participants, wanting to protect others and wanting to help end the pandemic were the most common reasons for getting vaccinated. Personal physicians were cited most frequently as trusted sources of information about COVID-19 among both vaccine-hesitant and vaccine-acceptant respondents.

Conclusions:

Educational interventions to decrease vaccine hesitancy among healthcare workers should focus on alleviating safety concerns, emphasizing vaccine efficacy, and appealing to a sense of duty. Such interventions should target younger adult audiences. Personal physicians may also be an effective avenue for reducing hesitancy among their patients through patient-centered discussions.
Captured Courts and Legitimized Autocrats: Transforming Kazakhstan’s Constitutional Court
Authors: Webb Williams Nora , Hanson Margaret
Published: February 2022

Contemporary dictators routinely co-opt institutions crucial for democratic governance. Although an extensive literature examines why and how aspiring autocrats bring elections and parties under their control, constitutions—and the judicial or quasi-judicial bodies charged with interpreting constitutions—are often assumed to reflect the existing balance of power. But following regime change, constitutional courts’ power of review makes them integral for establishing political supremacy. We detail how President Nursultan Nazarbayev of Kazakhstan captured the Constitutional Court via its transformation into the Constitutional Council. The uncertainty and upheaval of the post-Soviet collapse created opportunities for formal institutional changes that made the court susceptible to executive capture. Nazarbayev subsequently used the council rulings to lay claim to democratic and constitutional legitimacy in a clear example of authoritarian constitutionalism. To trace the process of capture and legitimation, we examine key court rulings throughout the president’s tenure using a database of Constitutional Council decisions.
The improvement of parturition duration by high intake of dietary fibre in late gestation is associated with gut microbiota and metabolome in sows
Authors: Liu Yang , Jiang Pingping , Chen Nan , Jiang Yannan , Zhang Ruinan , Fang Zhengfeng , Lin Yan , Xu Shengyu , Feng Bin , Zhuo Yong , Wu De , Theil Peter Kappel , Che Lianqiang
Published: February 2022

Prolonged parturition duration has been widely demonstrated to be a risk factor for incidence of stillbirth. This study evaluated the supply of dietary fibre on the parturition duration, gut microbiota and metabolome using sows as a model. A total of 40 Yorkshire sows were randomly given diet containing normal level of dietary fibre (NDF, 17·5 % dietary fibre) or high level of dietary fibre (HDF, 33·5 % dietary fibre). Faecal microbiota profiled with 16S rRNA amplicon sequencing, SCFA and metabolome in the faeces and plasma around parturition were compared between the dietary groups. Correlation analysis was conducted to further explore the potential associations between specific bacterial taxa and metabolites. Results showed that HDF diet significantly improved the parturition process as presented by the shorter parturition duration. HDF diet increased the abundance of the phyla Bacteroidetes and Synergistetes and multiple genera. Except for butyrate, SCFA levels in the faeces and plasma of sows at parturition were elevated in HDF group. The abundances of fifteen and twelve metabolites in the faeces and plasma, respectively, markedly differ between HDF and NDF sows. These metabolites are involved in energy metabolism and bacterial metabolism. Correlation analysis also showed associations between specific bacteria taxa and metabolites. Collectively, our study indicates that the improvement of parturition duration by high fibre intake in late gestation is associated with gut microbiota, production of SCFA and other metabolites, potentially serving for energy metabolism.
Perception of animal welfare and its certification system by Brazilian consumers and dairy farmers
Authors: Comin Vinicius Cardoso , Karsburg Helena Fagundes , Souza Bruna Maria Salotti de , Almeida Henrique Meiroz de Souza , Neira Ligia Maria , Rossi Gabriel Augusto Marques
Published: February 2022

The practices adopted in dairy farms can positively or negatively affect the perception of consumers. To meet consumer expectations and improve the productivity of dairy farms, a welfare certification system has recently been initiated in Brazil. In this research communication we describe the perceptions of Brazilian consumers and farmers regarding the implementation of welfare certification systems and the most common practices that affect animal welfare on dairy farms. For this purpose, two semi-structured questionnaires were used: one applied to 409 consumers and the other to 158 dairy farmers. The results demonstrate that consumers are concerned with the adoption of welfare practices in animal husbandry at dairy farms, mainly on topics related to movement restriction and cow-calf separation. Thus, the majority of consumers state that they are willing to pay more for welfare-certified dairy products. In addition, most dairy farmers are interested in adopting a welfare certification system, especially if it could add value to the raw milk sold to industries. Veterinarians and animal scientists are important for disseminating animal welfare recommendations, and the consequences of its improper adoption need to be emphasized. Finally, dairy farms need improvements regarding environmental hygiene, thermal conditions, animal husbandry, health, and milking processes. In conclusion, consumers and farmers are interested in welfare systems and their certification, and there is a need for stakeholders to make welfare certification a reality in the Brazilian dairy supply chain.
Impact of parasitic infection on mental health and illness in humans in Africa: a systematic review
Authors: Lampard-Scotford Alexandra R. , McCauley Angela , Kuebel Julius Arthur , Ibbott Rachel , Mutapi Francisca
Published: February 2022

A growing body of research implicates inflammation as a potential pathway in the aetiology and pathophysiology of some mental illnesses. A systematic review was conducted to determine the association between parasitic infection and mental illnesses in humans in Africa and reviewed the state of the evidence available. The search focused on publications from Africa documenting the relationship between parasites from two parasite groups, helminths and protozoans, and four classifications of mental illness: mood affective disorders, neurotic and stress-related disorders, schizotypal disorders and unspecified mental illnesses. In the 26 reviewed papers, the prevalence of mental illness was significantly higher in people with parasitic infection compared to those without infection, i.e., 58.2% vs 41.8% (P < 0.001). An overall odds ratio found that the association of having a mental illness when testing positive for a parasitic infection was four times that of people without infection. Whilst the study showed significant associations between parasite infection and mental illness, it also highlights gaps in the present literature on the pathophysiology of mental illness in people exposed to parasite infection. This study highlighted the importance of an integrated intervention for parasitic infection and mental illness.
Design of a customized humanoid robot with coevolution of body morphology and its locomotion
Authors: Zhang Jiwen , Shi Xunlei , Fu Chenglong , Liu Li , Chen Ken
Published: February 2022

An important goal for humanoid robots is to achieve fast, flexible and stable walking. In previous research, the structure and walking algorithms evolved separately, resulting in a slow evolution speed and lack of an initial design basis. This paper proposes comprehensively considering body morphology and walking patterns, exploring the relationship between them and their influence on the motion ability. The method parameterizes the body morphology and walking patterns. Then a response surface model is established to describe the complex relationship between these parameters and finally obtain the optimized parameters, which provides a reference for the structural design and gait generation.
The prevalence of hepatitis B virus infection in Bangladesh: a systematic review and meta-analysis
Authors: Banik Sujan , Datta Anamika , Ghosh Antara , Ghosh Kanak Yadab , Debi Hoimonti
Published: February 2022

Despite the availability of an effective vaccine, hepatitis B virus (HBV) infection is one of the major public health problems worldwide, mostly in developing countries. This systematic review and meta-analysis were performed to estimate the pooled prevalence of HBV infection in Bangladesh. We systematically searched various electronic databases to retrieve relevant studies published until April 2021. A total of 15 studies were met the inclusion criteria and included in the meta-analysis. The pooled estimated prevalence of HBV infection in the general population of Bangladesh from 1995 to 2017 was 4.0% [95% confidence interval (CI) 3.0–5.1]. The results of subgroup analysis revealed that the prevalence of hepatitis B was higher in females than males [odds ratio (OR) 1.20, 95% CI 0.48–2.97, P = 0.70], people of age <25 years had a higher prevalence than people of age >25 years (OR 1.25, 95% CI 0.72–2.17, P = 0.42) and married people had a higher prevalence than unmarried/single people (OR 2.16, 95% CI 1.51–3.10, P < 0.0001). The Egger's test statistics (P = 0.584), Begg and Mazumdar's rank correlation test (P = 0.054) indicated the absence of publication bias. This study analysis reported a low intermediate prevalence of HBV infection (4%) in Bangladesh, which is currently higher than the global prevalence of HBV infection (3.5%).
Investigating seasonal patterns in enteric infections: a systematic review of time series methods
Authors: Simpson Ryan B. , Kulinkina Alexandra V. , Naumova Elena N.
Published: February 2022

Foodborne and waterborne gastrointestinal infections and their associated outbreaks are preventable, yet still result in significant morbidity, mortality and revenue loss. Many enteric infections demonstrate seasonality, or annual systematic periodic fluctuations in incidence, associated with climatic and environmental factors. Public health professionals use statistical methods and time series models to describe, compare, explain and predict seasonal patterns. However, descriptions and estimates of seasonal features, such as peak timing, depend on how researchers define seasonality for research purposes and how they apply time series methods. In this review, we outline the advantages and limitations of common methods for estimating seasonal peak timing. We provide recommendations improving reporting requirements for disease surveillance systems. Greater attention to how seasonality is defined, modelled, interpreted and reported is necessary to promote reproducible research and strengthen proactive and targeted public health policies, intervention strategies and preparedness plans to dampen the intensity and impacts of seasonal illnesses.
The effects of MALL training on preservice and in-service EFL teachers’ perceptions and use of mobile technology
Authors: Hafour Marwa F.
Published: February 2022

Owing to the anytime-anywhere-anyhow nature of mobile learning, together with the ubiquity of affordably priced mobile phones, learning has become a mobigital practice, as termed by Şad and Göktaş (2014). Consequently, language teaching/learning is gradually shifting from computer-assisted language learning to mobile-assisted language learning (MALL). In response, the current study examined the impact of MALL training on preservice and in-service EFL teachers’ perceptions and use of mobile technology (MT). For this purpose, two groups of preservice (N = 33) and in-service (N = 31) EFL teachers were randomly selected and exposed to MALL training. The pretest-posttest experimental mixed-methods design was used as a framework for collecting and analyzing both quantitative and qualitative data (using closed- and open-ended-question surveys). Quantitative results revealed that both preservice and in-service teachers had similar perceptions of MT before and after training. The only exception is that, after training, in-service teachers were more interested in MT than preservice teachers. However, both groups demonstrated an overall (and subfactor) improvement in their perceptions after MT training, except for their perceived ease of use. In-service teachers’ use also improved after training and, due to the yielded positive correlation, their perceptions were a significant predictor of use. Qualitative findings showed that in-service teachers used MT more in listening and speaking (for synchronous communication) than in reading and writing, selecting social media and translation apps as the least useful ones. Moreover, they regarded technical and digital literacy problems as the ones most challenging to the use of MT.
Rainfall shocks and fertilizer use: a district level study of India
Authors: Bora Kaushik
Published: February 2022

In the context of climate change and increasing occurrences of extreme events, it is essential to understand farmers' responses to weather shocks and adaptations. This paper uses a panel dataset of 311 selected Indian districts ranging from 1966 to 2009 to investigate how application of chemical fertilizers varies in response to rainfall shocks. Two rainfall shock measures are constructed based on deviation in rainfall from the normal, a categorical measure of rainfall shock; and another, a continuous index of negative rainfall deviation. Based on a panel fixed effect regression, the study finds no apparent reduction in the level of fertilizer use in negative rainfall shock years. However, with a one-year lagged rainfall shock, a reduction in fertilizer application rate is observed for the continuous drought index. Further, exposure to higher intensity droughts in the previous year leads to an increase in the amount of fertilizer application in the current year.
Improvisation through Performance-installation
Authors: Richards John , Shaw Tim
Published: February 2022

This article builds on Richards’s work to formulate an understanding of the emerging practice of performance-installation, which embraces sound art, DIY electronic music and maker culture. A number of key points are addressed in this formulation: making/unmaking and ‘public making’; the assembling/disassembling of sonic devices and artefacts in the performance space; sound ‘through’ materials and materials at hand; and site and architectural features as material. In addition, readymade actions, illustrated by George Brecht’s The Cabinet, and the relationship between audience and performer are also presented. The article continues by outlining practice undertaken by the authors comprising two UK tours: ‘Sacrificial Floors’, 2018 with Tetsuya Umeda; and ‘Points of Failure’, 2020. Derek Bailey’s idea of ‘instrumental impulse’ is extended to include the concepts of expanded and reduced instruments that encompass ‘instrument as object’ and ‘raw material as instrument’. ‘Instrument’ is also viewed as a distributed mesh-like structure in which collective improvisation may occur. Borrowing from Ingold, ‘wayfaring’ is used to describe improvising with materials found ‘along the way’. Silent actions, uncontrollable instruments, unstable systems, performative failures, reimagined affordance of objects, ‘playing with resource’ and ‘improvising inside electronics’ are all addressed in relation to performance-installation. Finally, the authors explore the idea of ‘virtuosity in listening’, and question sonic autonomy and self-expression in improvisation and how ‘attending to sound’ can be an active part of improvised performance.
Asia’s oceanic Anthropocene: How political elites and global offshore oil development moved Asian marine spaces into the new epoch
Authors: Huebner Stefan
Published: February 2022

The Anthropocene epoch, characterized by human-caused planetary-scale transformations like climate change and ocean acidification, today is usually associated with the period beginning in the mid-twentieth century. Taking an oceanic perspective on the Anthropocene in Asia, the article argues that oceanic and terrestrial energy regimes synchronized since the 1950s when, for the first time in history, oceanic ghost acres turned marine spaces into a major fuel source. Despite global connections between offshore oil regions located in North America, Asia, and other places going back to the late nineteenth century, Asia’s contingent offshore oil field locations and their physical geographies, combined with political factors, inhibited large-scale offshore drilling before the 1950s. These characteristics of marine spaces meant that Asian political elites and their developmentalist agendas became the guiding force in exploring offshore fields, a process that was hardly dominated by corporate capitalism or structural choice limitations due to the legacies of colonialism.
Why IR scholars should care about quantum theory, part II: critics in the PITs
Authors: Wendt Alexander
Published: February 2022

Part II responds to some of my critics' substantive concerns about QMASS. However, to sharpen that discussion I first introduce the idea of classical and quantum physical instantiation tests or ‘PITs’. PITs are a thought experiment taking advantage of the causal closure of physics. To encourage critical self-reflection on the usually tacit ontological assumptions of our theories, PITs invite social scientists to translate their mostly qualitative, folk psychological arguments into physical descriptions, meeting classical and quantum constraints respectively, to see which feels more appropriate to the case at hand. With this diagnostic tool in hand, the paper addresses criticisms of QMASS in five areas: (1) the threat of physics reductionism; (2) the potential for epistemic repression stemming from the realist nature of QMASS’ argument; (3) doubts that a quantum approach can support a genuine notion of human freedom; (4) the place of ethics and normativity in social and international life; and (5) implications for graduate methods training and quantum pedagogy more generally.
High-resolution fabrication of nanopatterns by multistep iterative miniaturization of hot-embossed prestressed polymer films and constrained shrinking
Authors: Sayed Shady , Selvaganapathy P. Ravi
Published: February 2022

The fabrication of nanostructures and nanopatterns is of crucial importance in microelectronics, nanofluidics, and the manufacture of biomedical devices and biosensors. However, the creation of nanopatterns by means of conventional nanofabrication techniques such as electron beam lithography is expensive and time-consuming. Here, we develop a multistep miniaturization approach using prestressed polymer films to generate nanopatterns from microscale patterns without the need of complex nanolithography methods. Prestressed polymer films have been used as a miniaturization technique to fabricate features with a smaller size than the initial imprinted features. However, the height of the imprinted features is significantly reduced after the thermal shrinking of the prestressed films due to the shape memory effect of the polymer, and as a result, the topographical features tend to disappear after shrinking. We have developed a miniaturization approach that controls the material flow and maintains the shrunken patterns by applying mechanical constraints during the shrinking process. The combination of hot embossing and constrained shrinking makes it possible to reduce the size of the initial imprinted features even to the nanoscale. The developed multistep miniaturization approach allows using the shrunken pattern as a master for a subsequent miniaturization cycle. Well-defined patterns as small as 100 nm are fabricated, showing a 10-fold reduction in size from the original master. The developed approach also allows the transfer of the shrunken polymeric patterns to a silicon substrate, which can be used as a functional substrate for many applications or directly as a master for nanoimprint lithography.
Insulinopathies of the brain? Genetic overlap between somatic insulin-related and neuropsychiatric disorders
Authors: Fanelli Giuseppe , Franke Barbara , De Witte Ward , Ruisch I. Hyun , Haavik Jan , van Gils Veerle , Jansen Willemijn J. , Vos Stephanie J. B. , Lind Lars , Buitelaar Jan K. , Banaschewski Tobias , Dalsgaard Søren , Serretti Alessandro , Mota Nina Roth , Poelmans Geert , Bralten Janita
Published: February 2022

The prevalence of somatic insulinopathies, like metabolic syndrome (MetS), obesity, and type 2 diabetes mellitus (T2DM), is higher in Alzheimer’s disease (AD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD). Dysregulation of insulin signalling has been implicated in these neuropsychiatric disorders, and shared genetic factors might partly underlie this observed multimorbidity. We investigated the genetic overlap between AD, ASD, and OCD with MetS, obesity, and T2DM by estimating pairwise global genetic correlations using the summary statistics of the largest available genome-wide association studies for these phenotypes. Having tested these hypotheses, other potential brain “insulinopathies” were also explored by estimating the genetic relationship of six additional neuropsychiatric disorders with nine insulin-related diseases/traits. Stratified covariance analyses were then performed to investigate the contribution of insulin-related gene sets. Significant negative genetic correlations were found between OCD and MetS (rg = −0.315, p = 3.9 × 10−8), OCD and obesity (rg = −0.379, p = 3.4 × 10−5), and OCD and T2DM (rg = −0.172, p = 3 × 10−4). Significant genetic correlations with insulin-related phenotypes were also found for anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), major depressive disorder, and schizophrenia (p < 6.17 × 10−4). Stratified analyses showed negative genetic covariances between AD, ASD, OCD, ADHD, AN, bipolar disorder, schizophrenia and somatic insulinopathies through gene sets related to insulin signalling and insulin receptor recycling, and positive genetic covariances between AN and T2DM, as well as ADHD and MetS through gene sets related to insulin processing/secretion (p < 2.06 × 10−4). Overall, our findings suggest the existence of two clusters of neuropsychiatric disorders, in which the genetics of insulin-related diseases/traits may exert divergent pleiotropic effects. These results represent a starting point for a new research line on “insulinopathies” of the brain.
RIPK1-RIPK3 mediates myocardial fibrosis in type 2 diabetes mellitus by impairing autophagic flux of cardiac fibroblasts
Authors: Qiao Shigang , Hong Lei , Zhu Yongming , Zha Jun , Wang An , Qiu Jia , Li Wei , Wang Chen , An Jianzhong , Zhang Huiling
Published: February 2022

Receptor-interacting protein kinase 1 (RIPK1) and 3 (RIPK3) are critical regulators of programmed necrosis or necroptosis. However, the role of the RIPK1/RIPK3 signaling pathway in myocardial fibrosis and related diabetic cardiomyopathy is still unclear. We hypothesized that RIPK1/RIPK3 activation mediated myocardial fibrosis by impairing the autophagic flux. To this end, we established in vitro and in vivo models of type 2 diabetes mellitus with high glucose fat (HGF) medium and diet respectively. HGF induced myocardial fibrosis, and impaired cardiac diastolic and systolic function by activating the RIPK1/RIPK3 pathway, which increased the expression of autophagic related proteins such as LC3-II, P62 and active-cathepsin D. Inhibition of RIPK1 or RIPK3 alleviated HGF-induced death and fibrosis of cardiac fibroblasts by restoring the impaired autophagic flux. The autophagy blocker neutralized the effects of the RIPK1 inhibitor necrostatin-1 (Nec-1) and RIPK3 inhibitor GSK872 (GSK). RIPK1/RIPK3 inhibition respectively decreased the levels of RIPK3/p-RIPK3 and RIPK1/p-RIPK1. P62 forms a complex with RIPK1-RIPK3 and promotes the binding of RIPK1 and RIPK3, silencing of RIPK1 decreased the association of RIPK1 with P62 and the binding of P62 to LC3. Furthermore, inhibition of both kinases in combination with a low dose of Nec-1 and GSK in the HGF-treated fibroblasts significantly decreased cell death and fibrosis, and restored the autophagic flux. In the diabetic rat model, Nec-1 (1.65 mg/kg) treatment for 4 months markedly alleviated myocardial fibrosis, downregulated autophagic related proteins, and improved cardiac systolic and diastolic function. In conclusion, HGF induces myocardial fibrosis and cardiac dysfunction by activating the RIPK1-RIPK3 pathway and by impairing the autophagic flux, which is obviated by the pharmacological and genetic inhibition of RIPK1/RIPK3.
Synthetic virions reveal fatty acid-coupled adaptive immunogenicity of SARS-CoV-2 spike glycoprotein
Authors: Staufer Oskar , Gupta Kapil , Hernandez Bücher Jochen Estebano , Kohler Fabian , Sigl Christian , Singh Gunjita , Vasileiou Kate , Yagüe Relimpio Ana , Macher Meline , Fabritz Sebastian , Dietz Hendrik , Cavalcanti Adam Elisabetta Ada , Schaffitzel Christiane , Ruggieri Alessia , Platzman Ilia , Berger Imre , Spatz Joachim P.
Published: February 2022

SARS-CoV-2 infection is a major global public health concern with incompletely understood pathogenesis. The SARS-CoV-2 spike (S) glycoprotein comprises a highly conserved free fatty acid binding pocket (FABP) with unknown function and evolutionary selection advantage1,2. Deciphering FABP impact on COVID-19 progression is challenged by the heterogenous nature and large molecular variability of live virus. Here we create synthetic minimal virions (MiniVs) of wild-type and mutant SARS-CoV-2 with precise molecular composition and programmable complexity by bottom-up assembly. MiniV-based systematic assessment of S free fatty acid (FFA) binding reveals that FABP functions as an allosteric regulatory site enabling adaptation of SARS-CoV-2 immunogenicity to inflammation states via binding of pro-inflammatory FFAs. This is achieved by regulation of the S open-to-close equilibrium and the exposure of both, the receptor binding domain (RBD) and the SARS-CoV-2 RGD motif that is responsible for integrin co-receptor engagement. We find that the FDA-approved drugs vitamin K and dexamethasone modulate S-based cell binding in an FABP-like manner. In inflammatory FFA environments, neutralizing immunoglobulins from human convalescent COVID-19 donors lose neutralization activity. Empowered by our MiniV technology, we suggest a conserved mechanism by which SARS-CoV-2 dynamically couples its immunogenicity to the host immune response.
All-optical dissipative discrete time crystals
Authors: Taheri Hossein , Matsko Andrey B. , Maleki Lute , Sacha Krzysztof
Published: February 2022

Time crystals are periodic states exhibiting spontaneous symmetry breaking in either time-independent or periodically-driven quantum many-body systems. Spontaneous modification of discrete time-translation symmetry in periodically-forced physical systems can create a discrete time crystal (DTC) constituting a state of matter possessing properties like temporal rigid long-range order and coherence, which are inherently desirable for quantum computing and information processing. Despite their appeal, experimental demonstrations of DTCs are scarce and significant aspects of their behavior remain unexplored. Here, we report the experimental observation and theoretical investigation of DTCs in a Kerr-nonlinear optical microcavity. Empowered by the self-injection locking of two independent lasers with arbitrarily large frequency separation simultaneously to two same-family cavity modes and a dissipative Kerr soliton, this versatile platform enables realizing long-awaited phenomena such as defect-carrying DTCs and phase transitions. Combined with monolithic microfabrication, this room-temperature system paves the way for chip-scale time crystals supporting real-world applications outside sophisticated laboratories.
Local and global crosstalk among heterochromatin marks drives DNA methylome patterning in Arabidopsis
Authors: To Taiko Kim , Yamasaki Chikae , Oda Shoko , Tominaga Sayaka , Kobayashi Akie , Tarutani Yoshiaki , Kakutani Tetsuji
Published: February 2022

Transposable elements (TEs) are robustly silenced by multiple epigenetic marks, but dynamics of crosstalk among these marks remains enigmatic. In Arabidopsis, TEs are silenced by cytosine methylation in both CpG and non-CpG contexts (mCG and mCH) and histone H3 lysine 9 methylation (H3K9me). While mCH and H3K9me are mutually dependent for their maintenance, mCG and mCH/H3K9me are independently maintained. Here, we show that establishment, rather than maintenance, of mCH depends on mCG, accounting for the synergistic colocalization of these silent marks in TEs. When mCG is lost, establishment of mCH is abolished in TEs. mCG also guides mCH in active genes, though the resulting mCH/H3K9me is removed thereafter. Unexpectedly, targeting efficiency of mCH depends on relative, rather than absolute, levels of mCG within the genome, suggesting underlying global negative controls. We propose that local positive feedback in heterochromatin dynamics, together with global negative feedback, drive robust and balanced DNA methylome patterning.
Structural basis of neuropeptide Y signaling through Y1 receptor
Authors: Park Chaehee , Kim Jinuk , Ko Seung-Bum , Choi Yeol Kyo , Jeong Hyeongseop , Woo Hyeonuk , Kang Hyunook , Bang Injin , Kim Sang Ah , Yoon Tae-Young , Seok Chaok , Im Wonpil , Choi Hee-Jung
Published: February 2022

Neuropeptide Y (NPY) is highly abundant in the brain and involved in various physiological processes related to food intake and anxiety, as well as human diseases such as obesity and cancer. However, the molecular details of the interactions between NPY and its receptors are poorly understood. Here, we report a cryo-electron microscopy structure of the NPY-bound neuropeptide Y1 receptor (Y1R) in complex with Gi1 protein. The NPY C-terminal segment forming the extended conformation binds deep into the Y1R transmembrane core, where the amidated C-terminal residue Y36 of NPY is located at the base of the ligand-binding pocket. Furthermore, the helical region and two N-terminal residues of NPY interact with Y1R extracellular loops, contributing to the high affinity of NPY for Y1R. The structural analysis of NPY-bound Y1R and mutagenesis studies provide molecular insights into the activation mechanism of Y1R upon NPY binding.
Humoral and cellular responses after a third dose of SARS-CoV-2 BNT162b2 vaccine in patients with lymphoid malignancies
Authors: Re Daniel , Seitz-Polski Barbara , Brglez Vesna , Carles Michel , Graça Daisy , Benzaken Sylvia , Liguori Stéphane , Zahreddine Khaled , Delforge Margaux , Bailly-Maitre Béatrice , Verrière Benjamin , Chamorey Emmanuel , Barrière Jérôme
Published: February 2022

Patients with hematological malignancies have impaired immune response after two doses of BNT162b2 (Pfizer/BioNTech) vaccine against SARS-CoV-2. Here, in this observational study (registration number HDH F20210324145532), we measure SARS-CoV-2 anti-Spike antibodies, neutralizing antibodies and T-cell responses after immune stimulation with a third dose (D3) of the same vaccine in patients with chronic lymphocytic leukemia (n = 13), B cell non-Hodgkin lymphoma (n = 14), and multiple myeloma (n = 16)). No unexpected novel side effects are reported. Among 25 patients with positive anti-S titers before D3, 23 (92%) patients increase their anti-S and neutralizing antibody titer after D3. All 18 (42%) initially seronegative patients remain negative. D3 increases the median IFN-γ secretion in the whole cohort and induces IFN-γ secretion in a fraction of seronegative patients. Our data thus support the use of a third vaccine dose amongst patients with lymphoid malignancies, even though some of them will still have vaccine failure.
Antibody responses and correlates of protection in the general population after two doses of the ChAdOx1 or BNT162b2 vaccines
Authors: Wei Jia , Pouwels Koen B. , Stoesser Nicole , Matthews Philippa C. , Diamond Ian , Studley Ruth , Rourke Emma , Cook Duncan , Bell John I. , Newton John N. , Farrar Jeremy , Howarth Alison , Marsden Brian D. , Hoosdally Sarah , Jones E. Yvonne , Stuart David I. , Crook Derrick W. , Peto Tim E. A. , Walker A. Sarah , Eyre David W. ,   the COVID-19 Infection Survey team, Thomas Tina , Ayoubkhani Daniel , Black Russell , Felton Antonio , Crees Megan , Jones Joel , Lloyd Lina , Sutherland Esther , Pritchard Emma , Vihta Karina-Doris , Doherty George , Kavanagh James , Chau Kevin K. , Hatch Stephanie B. , Ebner Daniel , Ferreira Lucas Martins , Christott Thomas , Dejnirattisai Wanwisa , Mongkolsapaya Juthathip , Cameron Sarah , Tamblin-Hopper Phoebe , Wolna Magda , Brown Rachael , Cornall Richard , Screaton Gavin , Lythgoe Katrina , Bonsall David , Golubchik Tanya , Fryer Helen , Cox Stuart , Paddon Kevin , James Tim , House Thomas , Robotham Julie , Birrell Paul , Jordan Helena , Sheppard Tim , Athey Graham , Moody Dan , Curry Leigh , Brereton Pamela , Jarvis Ian , Godsmark Anna , Morris George , Mallick Bobby , Eeles Phil , Hay Jodie , VanSteenhouse Harper , Lee Jessica , White Sean , Evans Tim , Bloemberg Lisa , Allison Katie , Pandya Anouska , Davis Sophie , Conway David I. , MacLeod Margaret , Cunningham Chris
Published: February 2022

Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination. However, antibody trajectories and the associated duration of protection after a second vaccine dose remain unclear. In this study, we investigated anti-spike IgG antibody responses and correlates of protection after second doses of ChAdOx1 or BNT162b2 vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United Kingdom general population. In 222,493 individuals, we found significant boosting of anti-spike IgG by the second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Older individuals and males had lower peak levels with BNT162b2 but not ChAdOx1, whereas declines were similar across ages and sexes with ChAdOX1 or BNT162b2. Prior infection significantly increased antibody peak level and half-life with both vaccines. Anti-spike IgG levels were associated with protection from infection after vaccination and, to an even greater degree, after prior infection. At least 67% protection against infection was estimated to last for 2–3 months after two ChAdOx1 doses, for 5–8 months after two BNT162b2 doses in those without prior infection and for 1–2 years for those unvaccinated after natural infection. A third booster dose might be needed, prioritized to ChAdOx1 recipients and those more clinically vulnerable.
A FAIR and AI-ready Higgs boson decay dataset
Authors: Chen Yifan , Huerta E. A. , Duarte Javier , Harris Philip , Katz Daniel S. , Neubauer Mark S. , Diaz Daniel , Mokhtar Farouk , Kansal Raghav , Park Sang Eon , Kindratenko Volodymyr V. , Zhao Zhizhen , Rusack Roger
Published: February 2022

To enable the reusability of massive scientific datasets by humans and machines, researchers aim to adhere to the principles of findability, accessibility, interoperability, and reusability (FAIR) for data and artificial intelligence (AI) models. This article provides a domain-agnostic, step-by-step assessment guide to evaluate whether or not a given dataset meets these principles. We demonstrate how to use this guide to evaluate the FAIRness of an open simulated dataset produced by the CMS Collaboration at the CERN Large Hadron Collider. This dataset consists of Higgs boson decays and quark and gluon background, and is available through the CERN Open Data Portal. We use additional available tools to assess the FAIRness of this dataset, and incorporate feedback from members of the FAIR community to validate our results. This article is accompanied by a Jupyter notebook to visualize and explore this dataset. This study marks the first in a planned series of articles that will guide scientists in the creation of FAIR AI models and datasets in high energy particle physics.
Whole genome sequences of 234 indigenous African chickens from Ethiopia
Authors: Gheyas Almas , Vallejo-Trujillo Adriana , Kebede Adebabay , Dessie Tadelle , Hanotte Olivier , Smith Jacqueline
Published: February 2022

Indigenous chickens predominate poultry production in Africa. Although preferred for backyard farming because of their adaptability to harsh tropical environments, these populations suffer from relatively low productivity compared to commercial lines. Genome analyses can unravel the genetic potential of improvement of these birds for both production and resilience traits for the benefit of African poultry farming systems. Here we report whole-genome sequences of 234 indigenous chickens from 24 Ethiopian populations distributed under diverse agro-climatic conditions. The data represents over eight terabytes of paired-end sequences from the Ilumina HiSeqX platform with an average coverage of about 57X. Almost 99% of the sequence reads could be mapped against the chicken reference genome (GRCg6a), confirming the high quality of the data. Variant calling detected around 15 million SNPs, of which about 86% are known variants (i.e., present in public databases), providing further confidence on the data quality. The dataset provides an excellent resource for investigating genetic diversity and local environmental adaptations with important implications for breed improvement and conservation purposes.
Thinking out loud, an open-access EEG-based BCI dataset for inner speech recognition
Authors: Nieto Nicolás , Peterson Victoria , Rufiner Hugo Leonardo , Kamienkowski Juan Esteban , Spies Ruben
Published: February 2022

Surface electroencephalography is a standard and noninvasive way to measure electrical brain activity. Recent advances in artificial intelligence led to significant improvements in the automatic detection of brain patterns, allowing increasingly faster, more reliable and accessible Brain-Computer Interfaces. Different paradigms have been used to enable the human-machine interaction and the last few years have broad a mark increase in the interest for interpreting and characterizing the “inner voice” phenomenon. This paradigm, called inner speech, raises the possibility of executing an order just by thinking about it, allowing a “natural” way of controlling external devices. Unfortunately, the lack of publicly available electroencephalography datasets, restricts the development of new techniques for inner speech recognition. A ten-participant dataset acquired under this and two others related paradigms, recorded with an acquisition system of 136 channels, is presented. The main purpose of this work is to provide the scientific community with an open-access multiclass electroencephalography database of inner speech commands that could be used for better understanding of the related brain mechanisms.
A holistic genome dataset of bacteria, archaea and viruses of the Pearl River estuary
Authors: Xu Bu , Li Fuyan , Cai Lanlan , Zhang Rui , Fan Lu , Zhang Chuanlun
Published: February 2022

Estuaries are one of the most important coastal ecosystems. While microbiomes and viromes have been separately investigated in some estuaries, few studies holistically deciphered the genomes and connections of viruses and their microbial hosts along an estuarine salinity gradient. Here we applied deep metagenomic sequencing on microbial and viral communities in surface waters of the Pearl River estuary, one of China’s largest estuaries with strong anthropogenic impacts. Overall, 1,205 non-redundant prokaryotic genomes with ≥50% completeness and ≤10% contamination, and 78,502 non-redundant viral-like genomes were generated from samples of three size fractions and five salinity levels. Phylogenomic analysis and taxonomy classification show that majority of these estuarine prokaryotic and viral genomes are novel at species level according to public databases. Potential connections between the microbial and viral populations were further investigated by host-virus matching. These combined microbial and viral genomes provide an important complement of global marine genome datasets and should greatly facilitate our understanding of microbe-virus interactions, evolution and their implications in estuarine ecosystems.