bluuebunny/crossref_metadata_2025 huggingface dataset:
Research informatics and the COVID-19 pandemic: Challenges, innovations, lessons learned, and recommendations
Authors: Bookman Richard J. , Cimino James J. , Harle Christopher A. , Kost Rhonda G. , Mooney Sean , Pfaff Emily , Rojevsky Svetlana , Tobin Jonathan N. , Wilcox Adam , Tsinoremas Nick F.
Published: March 2021

The recipients of NIH’s Clinical and Translational Science Awards (CTSA) have worked for over a decade to build informatics infrastructure in support of clinical and translational research. This infrastructure has proved invaluable for supporting responses to the current COVID-19 pandemic through direct patient care, clinical decision support, training researchers and practitioners, as well as public health surveillance and clinical research to levels that could not have been accomplished without the years of ground-laying work by the CTSAs. In this paper, we provide a perspective on our COVID-19 work and present relevant results of a survey of CTSA sites to broaden our understanding of the key features of their informatics programs, the informatics-related challenges they have experienced under COVID-19, and some of the innovations and solutions they developed in response to the pandemic. Responses demonstrated increased reliance by healthcare providers and researchers on access to electronic health record (EHR) data, both for local needs and for sharing with other institutions and national consortia. The initial work of the CTSAs on data capture, standards, interchange, and sharing policies all contributed to solutions, best illustrated by the creation, in record time, of a national clinical data repository in the National COVID-19 Cohort Collaborative (N3C). The survey data support seven recommendations for areas of informatics and public health investment and further study to support clinical and translational research in the post-COVID-19 era.
Challenges and lessons learned for institutional review board procedures during the COVID-19 pandemic
Authors: Ford Daniel E. , Johnson Ann , Nichols Jason J. , Rothwell Erin , Dubinett Steve , Naeim Arash
Published: March 2021

The COVID-19 pandemic changed the clinical research landscape in America. The most urgent challenge has been to rapidly review protocols submitted by investigators that were designed to learn more about or intervene in COVID-19. International Review Board (IRB) offices developed plans to rapidly review protocols related to the COVID-19 pandemic. An online survey was conducted with the IRB Directors at Clinical and Translational Science Awards (CTSA) institutions as well as two focus groups. Across the CTSA institutions, 66% reviewed COVID-19 protocols across all their IRB committees, 22% assigned protocols to just one committee, and 10% created a new committee for COVID-19 protocols. Fifty-two percent reported COVID-19 protocols were reviewed much faster, 41% somewhat faster, and 7% at the same speed as other protocols. Three percent reported that the COVID-19 protocols were reviewed with much better quality, 32% reported slightly better quality, and 65% reported the reviews were of the same quality as similar protocols before the COVID-19 pandemic. IRBs were able to respond to the emergent demand for reviewing COVID-19 protocols. Most of the increased review capacity was due to extra effort by IRB staff and members and not changes that will be easily implemented across all research going forward.
How Do Mainstream Parties ‘Become’ Mainstream, and Pariah Parties ‘Become’ Pariahs? Conceptualizing the Processes of Mainstreaming and Pariahing in the Labelling of Political Parties
Authors: Moffitt Benjamin
Published: March 2021

How does a political party become ‘mainstream’? And what makes some parties receive arguably the opposite designation – ‘pariah party’? This conceptual article examines the processes by which parties’ mainstream or pariah status must be constructed, negotiated and policed, not only by political scientists in the pursuit of case selection, but by several actors actively involved in the political process, including media actors and political parties themselves. It explains how these actors contribute to these processes of ‘mainstreaming’ and ‘pariahing’, considers their motivations and provides illustrative examples of how such processes take place. As such, the article moves beyond the literature on the ways in which mainstream parties seek to deal with or respond to threats from a variety of pariah parties, instead paying attention to how those parties have been constructed as pariahs in the first place, and how these processes simultaneously contribute to the maintenance of mainstream party identities.
The Roles of Settler Canadians within Decolonization: Re-evaluating Invitation, Belonging and Rights
Authors: Leblanc Deanne Aline Marie
Published: March 2021

This article, grounded within the argument that liberal citizenship and recognition-based approaches to decolonization are inappropriate responses to Indigenous calls to decolonize, proposes an alternative approach premised on re-evaluating non-Indigenous understandings of invitation, belonging and rights within the Canadian settler state. I suggest that non-Indigenous peoples consider themselves “foreigners” in need of invitation onto Indigenous lands and that, ascolonial denizens, non-Indigenous Canadians take up an ethos that encourages them to re-evaluate their lives and relations with Indigenous peoples, Indigenous lands and the settler state. Such re-evaluations would encourage settlers to question the sovereignty of the state and their daily relations, as well as encourage them to place responsibilities to others above inwardly focused rights. I contend that identifying and acting upon such an ethos can provide a way through which non-Indigenous peoples can appropriately and seriously meet Indigenous peoples’ calls for change.
Fulfilling Campaign Promises or Following Public Opinion: Does the Size of the Majority Matter?
Authors: Coulombe Maxime , Blais André , Alfaro Maria-Alexis , Carbonaro Sofia , Trinque Tristan
Published: March 2021

We perform a survey experiment on the issue of immigration. People are presented with a situation where public opinion is at odds with the election promise. In our control group, no information is given about public opinion. In the treatment groups, respondents are told that 55 per cent or 80 per cent of the people are against the project. When respondents are informed about the election promise but are not told about public opinion, 64 per cent say that the party should fulfill its promise. That percentage drops to 51 per cent when people are informed that a slight majority (55 per cent) are opposed to the project and to 42 per cent when they are told that a strong majority (80 per cent) are opposed. Citizens thus believe that politicians should pay attention not only to the majority view but also to the size of that majority.
Situating the Global Compact on Refugees in Africa: Will it Make a Difference to the Lives of Refugees “Languishing in Camps”?
Authors: Khan Fatima , Sackeyfio Cecile
Published: March 2021

The protection of refugees languishing in camps in Africa has posed a challenge for the international community for far too long. The OAU Refugee Convention does not reflect refugee rights or provide a durable solution for refugees in host states. Over the last 50 years there have been multiple attempts to resolve what remains one of the greatest challenges facing Africa. Each resolution has clarified the steps required to enhance the situation for those most affected and to provide solutions for refugee-hosting countries in need of strategic policies and funding. This article considers recent developments in refugee law since the adoption of the New York Declaration. It specifically evaluates the benefit of the Global Compact on Refugees (GCR) for African states and the refugees they host. Furthermore, because the OAU convention is the first refugee convention to make international solidarity (ie burden-sharing) a state obligation, the article assesses how the GCR builds on the convention.
The Protection of Internally Displaced Children in Africa: A Doctrinal Analysis of Article 23(4) of the African Children's Charter
Authors: Adeola Romola , Mezmur Benyam D
Published: March 2021

This article considers the protection of, and assistance for, internally displaced children (IDCs) in Africa. Internal displacement has become one of Africa's most pressing human rights challenges. Over the last decade, millions of persons have been internally displaced on the continent by conflict, disaster and other causes. Children are one of the most affected categories of persons, given the implications of displacement for them. Article 23(4) of the African Charter on the Rights and Welfare of the Child incorporates specific protection for IDCs. This article examines the protection of IDCs in the context of this regional framework. It argues that, while article 23(4) requires that both refugee children and IDCs should be accorded the same protection from a rights-based perspective, it also requires that the protection of IDCs should be construed with reference to the Kampala Convention, which is the most recent applicable regional regime governing internal displacement.
Influence of colony traits on ectoparasite infestation in birds breeding in mixed-species colonies
Authors: Gameiro João , Veiga Jesús , Valera Francisco , Palmeirim Jorge M. , Catry Inês
Published: March 2021

Coloniality in birds is often associated with an increase in parasite burden, but whether the co-occurrence of several host species influences the prevalence and abundance of ectoparasites and their relationship with colony size or density remains poorly known. Here, we studied mixed-species breeding colonies formed after the provision of artificial breeding structures for restoring the lesser kestrel (Falco naumanni) population in Portugal, to investigate the influence of colony traits on ectoparasite infestation. We sampled four groups of ectoparasites (carnid flies, haematophagous mites, louse flies and chewing lice) in four hosts: lesser kestrels, European rollers (Coracias garrulus), feral pigeons (Columba livia) and spotless starlings (Sturnus unicolor). Each host species had a distinct infracommunity of ectoparasites, regardless of colony traits such as size, density or host richness. The abundance of the most common ectoparasite,Carnus hemapterus, was influenced by colony composition – number of nests of each host species – rather than by colony size or density, with its abundance being diluted with increasing numbers of less suitable hosts such as starlings. The increased contact between multiple species of hosts in breeding colonies may complexify host–parasite interactions and challenge our current knowledge on the ecological relationships between host sociality and parasitism.
Association between live childhood vaccines and COVID-19 outcomes: a national-level analysis
Authors: Ogimi Chikara , Qu Pingping , Boeckh Michael , Bender Ignacio Rachel A. , Zangeneh Sahar Z.
Published: March 2021

We investigated whether countries with higher coverage of childhood live vaccines [BCG or measles-containing-vaccine (MCV)] have reduced risk of coronavirus disease 2019 (COVID-19)-related mortality, while accounting for known systems differences between countries. In this ecological study of 140 countries using publicly available national-level data, higher vaccine coverage, representing estimated proportion of people vaccinated during the last 14 years, was associated with lower COVID-19 deaths. The associations attenuated for both vaccine variables, and MCV coverage became no longer significant once adjusted for published estimates of the Healthcare access and quality index (HAQI), a validated summary score of healthcare quality indicators. The magnitude of association between BCG coverage and COVID-19 death rate varied according to HAQI, and MCV coverage had little effect on the association between BCG and COVID-19 deaths. While there are associations between live vaccine coverage and COVID-19 outcomes, the vaccine coverage variables themselves were strongly correlated with COVID-19 testing rate, HAQI and life expectancy. This suggests that the population-level associations may be further confounded by differences in structural health systems and policies. Cluster randomised studies of booster vaccines would be ideal to evaluate the efficacy of trained immunity in preventing COVID-19 infections and mortality in vaccinated populations and on community transmission.
The Nrf2 inhibitor brusatol has a protective role in a rat model of oxygen-induced retinopathy of prematurity
Authors: Liang Xiuying , Wang Ruifen
Published: March 2021

Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been testified to be involved in the development of retinopathy of prematurity (ROP), which can cause childhood visual impairment. Whether brusatol, an Nrf2 inhibitor, could be utilized to treat ROP was unknown. The oxygen-induced retinopathy rat model was established to mimic ROP, which was further intravitreal administrated with brusatol. Vessel morphology and microglial activation in the retina were assessed with histology analysis. The relative expression levels of angiogenesis and inflammation-related molecules were detected with Western blot and real-time polymerase chain reaction methods. Intravitreal brusatol administration could alleviate both angiogenesis and microgliosis induced by hyperoxia, along with down-regulation of vascular endothelial growth factor, vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, cluster of differentiation molecule 11B, tumor necrosis factor alpha, inducible nitric oxide synthase, glial fibrillary acidic protein, and IBA-1 expression. It was further revealed that Nrf2 and heme oxygenease-1 were diminished by brusatol administration. The results demonstrate the potential of intravitreal brusatol deliver to treat ROP with down-regulation of angiogenesis and microgliosis.
Management of chronic kidney disease: perspectives of Brazilian primary care physicians
Authors: Delatorre Thatiane , Romão Elen A. , Mattos Augustus T. R. de , Ferreira Janise B. B.
Published: March 2021

Aim:

To investigate primary care physicians’ knowledge of and attitudes toward care for chronic kidney disease patients.

Background:

In Brazil, care for chronic kidney disease, a global public health problem, is provided by the Brazilian National Health System, which is organized around primary care. The study aimed to investigate the knowledge and attitudes of primary care physicians about the management of chronic kidney disease.

Method:

This research is based on quantitative and qualitative data. The participants were 92 physicians from 81 primary care units located in eight cities of the São Paulo/Brazil health region, who answered a self-administered questionnaire.

Findings:

Only 59% and 58% of the physicians recognized smoking and obesity, respectively, as risk factors for chronic kidney disease. Health appointments and drug therapy predominated as disease prevention strategies and less than 30% mentioned multiprofessional care and health education groups. For early diagnosis, isolated serum creatinine was the most used test and 64.6% stated they classified the disease stages. Exclusive follow-up in primary care decreased from 79% in stage 1 to 19.5% in stage 3B and the patients’ monitoring in the healthcare network varied from 8.7% in stage 1 to 70.6% in stages 4 and 5ND, suggesting early referrals and lack of referral at the necessary stages. Access to information on the referred patient was, predominantly, through the patient’s report and 74% of the physicians did not have matrix support regarding chronic kidney disease.

Conclusion:

The study showed that the healthcare teams need to update their knowledge and procedures to be able to provide a comprehensive and efficient approach to treating chronic kidney disease in primary care.
Assessment of professional bereavement: The development and validation of the Professional Bereavement Scale
Authors: Chen Chuqian , Chow Amy Yin Man
Published: March 2021

Objectives

To develop and validate Professional Bereavement Scale (PBS), a specific measurement tool for professional bereavement experiences.

Methods

An online cross-sectional survey collected data from 563 physicians and nurses from urban hospitals in Mainland China. Item consistency analysis, component factor analysis, exploratory factor analysis, and confirmatory factor analysis were run to develop and validate the scale. Correlational analysis was conducted to evaluate the psychometric property of the scale.

Results

Two subscales of the PBS were developed: the 17-item Short-term Bereavement Reactions Subscale (PBS–SBR) and the 15-item Accumulated Global Changes Subscale (PBS–AGC). Four factors, namely, frustration and trauma, guilt, grief, and being moved, are involved in PBS–SBR. Five factors are involved in PBS–AGC, which are new insights, more acceptance of limitations, more death-related anxiety, less influenced by patient deaths, and better coping with patient deaths. Both subscales have good content validity, construct validity, and criterion validity, as well as satisfactory internal consistency and split-half reliability.

Significance of results

PBS is a specific assessment tool for professional bereavement which is clearly defined, comprehensive, rigorously tested, and generalizable to different professional caregivers from various departments. Unveiled constructs illustrate that professional bereavement experiences contain a professional dimension in addition to a personal dimension both in an event-specific and a global perspective, which distinguishes them from familial bereavement experiences.
Risk factors of post-traumatic stress disorder 10 years after Wenchuan earthquake: a population-based case–control study
Authors: Lu Bingqing , Zeng Wenqi , Li Zhuyue , Wen Jin
Published: March 2021

Aims

To investigate the prevalence of post-traumatic stress disorder (PTSD) symptoms in the hard-hit areas 10 years after the Wenchuan earthquake, and explore the risk factors of long-term PTSD among Wenchuan earthquake survivors.

Methods

A matched case–control study was conducted. The involving participants were from the hard-hit areas 10 years after the Wenchuan earthquake. The collected information includes demographic characteristics, socioeconomic status, behaviour habits, earthquake exposure, perceived social support, physical health and mental health. Mental health status was measured using the PTSD Checklist-Civilian Version (PCL-C). Respondents with PCL-C score ⩾38 were classified as cases, and then the cases and controls were matched based on age (±3 years) and community location according to a ratio of 1:3.

Results

We obtained 86 cases and 258 controls. After controlling for confounding factors, it was found that lower income (OR 2.42; 95% CI 1.16–5.03), chronic diseases (OR 3.00; 95% CI 1.31–6.88) and death of immediate families in the earthquake (OR 7.30; 95% CI 2.36–22.57) were significantly associated with long-term PTSD symptoms.

Conclusion

Even 10 years after the Wenchuan earthquake, the survivors in the hard-hit areas still suffered from severe mental trauma. Low income, chronic diseases and death of immediate families in the earthquakes are significantly associated with long-term PTSD symptoms. Interventions by local governments and health institutions to address these risk factors should be undertaken to promote the health of survivors.
Evidenzbasierte Indikation für Protonenpumpeninhibitoren – Erfahrungsbericht aus einer hausärztlichen Gruppenpraxis
Authors: Gerber Tonia , Zeller Andreas
Published: March 2021

Zusammenfassung. Über das Ausmass von nicht evidenzbasierten Protonenpumpeninhibitoren(PPI)-Verschreibungen im hausärztlichen Setting in der Schweiz ist wenig bekannt. Eine Empfehlung zur Langzeittherapie wurde im Jahr 2014 in die «Top-5-Liste» von «smarter medicine» für die ambulante Innere Medizin aufgenommen. Die Beobachtungsstudie erfasste in einer Praxis mit sechs Hausärzten retrospektiv über drei Monate den Anteil von Patientinnen und Patienten ohne evidenzbasierte Indikation für eine PPI-Einnahme. Von 2225 analysierten Patientinnen und Patienten nahmen 11,1 % (n = 248) einen PPI ein. Der prozentuale Anteil ohne klare evidenzbasierte Indikation betrug 46,8 %. Annähernd jeder zweite wies keine klare evidenzbasierte Indikation für eine PPI-Einnahme auf. Die erhobenen Resultate könnten einen Anreiz für Hausärztinnen und Hausärzte sein, bei der Verschreibung eines PPI eine gerechtfertigte Indikation zu überdenken, dies auch im Sinne von «smarter medicine».
COVID-19 und Kopfschmerzen
Authors: Pohl Heiko , Gantenbein Andreas R.
Published: March 2021

Zusammenfassung. Kopfschmerzen sind ein häufiges Symptom einer COVID-19-Infektion und werden typischerweise als bilateral lokalisiert, frontal betont, drückend und mittelstark bis stark beschrieben. Die Unterscheidung von primären Kopfschmerzerkrankungen gelingt in der Regel durch die systematische Suche nach «Red Flags»; meist werden die Kopfschmerzen von Fieber, Husten oder erhöhten Entzündungsparametern im Blut begleitet. Früher geäusserte Bedenken gegen den Einsatz von Ibuprofen zur symptomatischen Kopfschmerztherapie bei Patientinnen und Patienten mit COVID-19 werden durch prospektive Studien nicht unterstützt. Während das Tragen von Masken sehr oft zu Kopfschmerzen führt, die wahrscheinlich durch Kompression sensibler Nerven ausgelöst werden, wirkt sich der Lockdown in der Regel positiv auf eine vorbestehende Migräne aus. Die Behandlung von Betroffenen mit primären Kopfschmerzen wird durch Quarantäneregeln erschwert, weshalb viele Zentren auf virtuelle Konsultationen setzen.
Computerized Adaptive Testing for Sleep Disorders
Authors: She Menghua , Li Yaling , Tu Dongbo , Cai Yan
Published: March 2021

Abstract. Background: As more and more people suffer from sleep disorders, the need to develop an efficient, inexpensive, and accurate assessment tool for screening sleep disorders has become more urgent. Aim: The aim of the current study was to develop a system allowing computerized adaptive testing for sleep disorders (CAT-SD). Methods: A large sample ( N = 1,304) was recruited to construct an item bank for CAT-SD and to investigate the psychometric characteristics of CAT-SD. First, analyses of unidimensionality, model fit, item fit, item discrimination parameters, and differential item functioning (DIF) were conducted to construct a final item pool to meet the requirements of item response theory measurement. Then, a simulated CAT study with real data was performed to investigate the psychometric characteristics of CAT-SD, including the reliability, validity, and predictive utility (sensitivity and specificity). Results: The final unidimensional item bank of the CAT-SD had good item fit, high discrimination, and no DIF. Moreover, it had acceptable reliability, validity, and predictive utility. Limitations: Non-statistical assembly constraints, execution environment, construction of item bank, criterion-related validity, and predictive utility (sensitivity and specificity) of CAT-SD, and sample representativeness are discussed. Conclusions: The CAT-SD could be used as an effective and accurate assessment tool for measuring the sleep disorders in individuals and offers a novel approach to the screening of sleep disorders utilizing psychological scales.
CSES High Precision Magnetometer Data Products and Example Study of an Intense Geomagnetic Storm
Authors: Yang Yanyan , Zhou Bin , Hulot Gauthier , Olsen Nils , Wu Yingyan , Xiong Chao , Stolle Claudia , Zhima Zeren , Huang Jianping , Zhu Xinghong , Pollinger Andreas , Cheng Bingjun , Magnes Werner , Zhao Xudong , Shen Xuhui
Published: March 2021

Providing accurate measurement of the magnetic field intensity and its vector components is one of the primary objectives of the China Seismo‐Electromagnetic Satellite (CSES). The high precision magnetometer (HPM) payload assembled on CSES is designed to achieve this goal. In this study, the data format, naming convention, and content of the CSES HPM Level 2 scientific data products are introduced, as a reference for users who are interested in this data set. In particular, flags for potential magnetic field disturbances from the platform and payloads are discussed. Possible scientific applications are also outlined. A preliminary validation of the data is conducted through comparison with magnetic data from the ESA’s Swarm constellation, and the result demonstrates that the HPM data of CSES are of good quality. Taking the intense geomagnetic storm that occurred on August 25–26, 2018 as an example, the magnetic field variations and the expansion of the field‐aligned currents (FACs) during this storm are discussed. We finally show that the CSES HPM data can be used to derive a satellite‐derived index equivalent to the Dst index, which agrees well to the index during this event. Our analysis thus suggests a high scientific potential of the HPM data.
Integrating Arctic Plant Functional Types in a Land Surface Model Using Above‐ and Belowground Field Observations
Authors: Sulman Benjamin N. , Salmon Verity G. , Iversen Colleen M. , Breen Amy L. , Yuan Fengming , Thornton Peter E.
Published: March 2021

Accurate simulations of high‐latitude ecosystems are critical for confident Earth system model (ESM) projections of carbon cycle feedbacks to global climate change. Land surface model components of ESMs, including the E3SM Land Model (ELM), simulate vegetation growth and ecosystem responses to changing climate and atmospheric CO2 concentrations by grouping heterogeneous vegetation into like sets of plant functional types (PFTs). Many such models represent high‐latitude vegetation using only two PFTs (shrub and grass), thereby missing the diversity of vegetation growth forms and functional traits in the Arctic. Here, we use field observations of biomass and leaf traits across a gradient of plant communities on the Seward Peninsula in northwest Alaska to replace the original ELM configuration for the first time with nine Arctic‐specific PFTs. The newly developed PFTs include: (1) nonvascular mosses and lichens, (2) deciduous and evergreen shrubs of various height classes, including an alder PFT, (3) graminoids, and (4) forbs. Improvements relative to the original model configuration included greater belowground biomass allocation, persistent fine roots and rhizomes of nonwoody plants, and better representation of variability in total plant biomass across sites with varying plant communities and depth to bedrock. Simulations through 2100 using the RCP8.5 climate scenario and constant PFT fractional areas showed alder‐dominated plant communities gaining more biomass and lichen‐dominated communities gaining less biomass compared to default PFTs. Our results highlight how representing the diversity of arctic vegetation and confronting models with measurements from varied plant communities improves the representation of arctic vegetation in terrestrial ecosystem models.
Late Cretaceous–Recent Low‐Temperature Cooling History and Tectonic Analysis of the Zuni Mountains, West‐Central New Mexico
Authors: Thacker Jacob O. , Kelley Shari A. , Karlstrom Karl E.
Published: March 2021

Laramide tectonic models are testable with spatiotemporal constraints. The Colorado Plateau portion of the orogen, however, lacks detailed information on deformation timing. Herein, we analyze the Zuni Mountains, a Colorado Plateau Laramide arch, with apatite thermochronology, stratigraphic analysis, and thermal calculations to constrain and interpret its low‐temperature and tectonic history. Results show 2.9–3.6 km of pre‐exhumation burial by Late Cretaceous time that was sufficient to reset apatite (U‐Th)/He and apatite fission track dates after Pennsylvanian–Permian Ancestral Rocky Mountains exhumation. Low thermal conductivity of fine‐grained sediments was instrumental in facilitating sufficient temperatures to reset dates. Cooling histories of samples were structurally controlled. Forward and inverse models suggest ca. 80–45 Ma moderate to rapid cooling on the southwest flank and range crest of the arch, while the northeast flank displays 80–55 Ma slow cooling, very slow 55–20 Ma cooling and/or reheating, and post‐20 Ma rapid cooling. Northeast flank protracted cooling likely resulted from burial during backlimb tilting of the arch. Onset of exhumation was ca. 80 Ma, similar to 80–75 Ma onset of localized subsidence in San Juan Basin and 80–77 Ma onset of exhumation on the Nacimiento arch, but somewhat earlier than commonly considered for Colorado Plateau Laramide arches. In the regional context, our results support an easterly sweep of deformation driven by Farallon flat‐slab processes, and argues against prior suggestions for synchronous onset of Colorado Plateau Laramide deformation. Timing of post‐20 Ma cooling is most consistent with mantle‐driven epeirogenic uplift rather than Oligocene geotherm relaxation.
Sea Cucumbers: The Excremental Heroes of Coral Reef Ecosystems
Authors: Thomasy Hannah
Published: March 2021

Drone surveillance reveals just how big a contribution sea cucumbers make to reef habitats.
Pancreatic cancer induces muscle wasting by promoting the release of pancreatic adenocarcinoma upregulated factor
Authors: Yoo Wonbeak , Choi Hyunji , Son Young Hoon , Lee Jaemin , Jo Seongyea , Jung Dana , Kim Yeon Jeong , Koh Sang Seok , Yang Yong Ryoul , Kwon Eun-Soo , Lee Kwang-Pyo , Noh Kyung Hee , Kim Kyung Won , Ko Yousun , Jun Eunsung , Kim Song Cheol , Kim Seokho
Published: March 2021

Cancer cachexia is a highly debilitating condition characterized by weight loss and muscle wasting that contributes significantly to the morbidity and mortality of pancreatic cancer. The factors that induce cachexia in pancreatic cancer are largely unknown. We previously showed that pancreatic adenocarcinoma upregulated factor (PAUF) secreted by pancreatic cancer cells is responsible for tumor growth and metastasis. Here, we analyzed the relation between pancreatic cancer-derived PAUF and cancer cachexia in mice and its clinical significance. Body weight loss and muscle weight loss were significantly higher in mice with Panc-1/PAUF tumors than in those with Panc-1/Mock tumors. Direct administration of rPAUF to muscle recapitulated tumor-induced atrophy, and a PAUF-neutralizing antibody abrogated tumor-induced muscle wasting in Panc-1/PAUF tumor-bearing mice. C2C12 myotubes treated with rPAUF exhibited rapid inactivation of Akt-Foxo3a signaling, resulting in Atrogin1/MAFbx upregulation, myosin heavy chain loss, and muscle atrophy. The neutrophil-to-lymphocyte ratio and body weight loss were significantly higher in pancreatic cancer patients with high PAUF expression than in those with low PAUF expression. Analysis of different pancreatic cancer datasets showed that PAUF expression was significantly higher in the pancreatic cancer group than in the nontumor group. Analysis of The Cancer Genome Atlas data found associations between high PAUF expression or a high DNA copy number and poor overall survival. Our data identified tumor-secreted circulating PAUF as a key factor of cachexia, causing muscle wasting in mice. Neutralizing PAUF may be a useful therapeutic strategy for the treatment of pancreatic cancer-induced cachexia.
Social networks strongly predict the gut microbiota of wild mice
Authors: Raulo Aura , Allen Bryony E , Troitsky Tanya , Husby Arild , Firth Josh A , Coulson Tim , Knowles Sarah C L
Published: March 2021

The mammalian gut teems with microbes, yet how hosts acquire these symbionts remains poorly understood. Research in primates suggests that microbes can be picked up via social contact, but the role of social interactions in non-group-living species remains underexplored. Here, we use a passive tracking system to collect high resolution spatiotemporal activity data from wild mice (Apodemus sylvaticus). Social network analysis revealed social association strength to be the strongest predictor of microbiota similarity among individuals, controlling for factors including spatial proximity and kinship, which had far smaller or nonsignificant effects. This social effect was limited to interactions involving males (male-male and male-female), implicating sex-dependent behaviours as driving processes. Social network position also predicted microbiota richness, with well-connected individuals having the most diverse microbiotas. Overall, these findings suggest social contact provides a key transmission pathway for gut symbionts even in relatively asocial mammals, that strongly shapes the adult gut microbiota. This work underlines the potential for individuals to pick up beneficial symbionts as well as pathogens from social interactions.
Correction: Autophagy buffers Ras-induced genotoxic stress enabling malignant transformation in keratinocytes primed by human papillomavirus
Authors: Cararo-Lopes Eduardo , Dias Matheus H. , da Silva Marcelo S. , Zeidler Julianna D. , Vessoni Alexandre T. , Reis Marcelo S. , Boccardo Enrique , Armelin Hugo A.
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41419-021-03564-4
An interaction between PRRT2 and Na+/K+ ATPase contributes to the control of neuronal excitability
Authors: Sterlini Bruno , Romei Alessandra , Parodi Chiara , Aprile Davide , Oneto Michele , Aperia Anita , Valente Pierluigi , Valtorta Flavia , Fassio Anna , Baldelli Pietro , Benfenati Fabio , Corradi Anna
Published: March 2021

Mutations in PRoline Rich Transmembrane protein 2 (PRRT2) cause pleiotropic syndromes including benign infantile epilepsy, paroxysmal kinesigenic dyskinesia, episodic ataxia, that share the paroxysmal character of the clinical manifestations. PRRT2 is a neuronal protein that plays multiple roles in the regulation of neuronal development, excitability, and neurotransmitter release. To better understand the physiopathology of these clinical phenotypes, we investigated PRRT2 interactome in mouse brain by a pulldown-based proteomic approach and identified α1 and α3 Na+/K+ ATPase (NKA) pumps as major PRRT2-binding proteins. We confirmed PRRT2 and NKA interaction by biochemical approaches and showed their colocalization at neuronal plasma membrane. The acute or constitutive inactivation of PRRT2 had a functional impact on NKA. While PRRT2-deficiency did not modify NKA expression and surface exposure, it caused an increased clustering of α3-NKA on the plasma membrane. Electrophysiological recordings showed that PRRT2-deficiency in primary neurons impaired NKA function during neuronal stimulation without affecting pump activity under resting conditions. Both phenotypes were fully normalized by re-expression of PRRT2 in PRRT2-deficient neurons. In addition, the NKA-dependent afterhyperpolarization that follows high-frequency firing was also reduced in PRRT2-silenced neurons. Taken together, these results demonstrate that PRRT2 is a physiological modulator of NKA function and suggest that an impaired NKA activity contributes to the hyperexcitability phenotype caused by PRRT2 deficiency.
Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies
Authors: Yan Renhong , Wang Ruoke , Ju Bin , Yu Jinfang , Zhang Yuanyuan , Liu Nan , Wang Jia , Zhang Qi , Chen Peng , Zhou Bing , Li Yaning , Shen Yaping , Zhang Shuyuan , Tian Long , Guo Yingying , Xia Lu , Zhong Xinyue , Cheng Lin , Ge Xiangyang , Zhao Juanjuan , Wang Hong-Wei , Wang Xinquan , Zhang Zheng , Zhang Linqi , Zhou Qiang
Published: March 2021

Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus disease 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disrupting proper interaction between the receptor binding domain (RBD) of the viral spike (S) protein and the receptor angiotensin converting enzyme 2 (ACE2). However, the structural basis for their potent neutralizing activity remains unclear. Here, we report cryo-EM structures of the ten most potent nAbs in their native full-length IgG-form or in both IgG-form and Fab-form bound to the trimeric S protein of SARS-CoV-2. The bivalent binding of the full-length IgG is found to associate with more RBDs in the “up” conformation than the monovalent binding of Fab, perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein. Comparison of a large number of nAbs identified common and unique structural features associated with their potent neutralizing activities. This work provides a structural basis for further understanding the mechanism of nAbs, especially through revealing the bivalent binding and its correlation with more potent neutralization and the shedding of S1 subunit.
Short-term prediction of preeclampsia using the sFlt-1/PlGF ratio: a subanalysis of pregnant Japanese women from the PROGNOSIS Asia study
Authors: Ohkuchi Akihide , Saito Shigeru , Yamamoto Tatsuo , Minakami Hisanori , Masuyama Hisashi , Kumasawa Keiichi , Yoshimatsu Jun , Nagamatsu Takeshi , Dietl Angela , Grill Sonja , Hund Martin
Published: March 2021

Two prospective multicenter studies demonstrated that a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio cutoff of ≤38 can rule out preeclampsia within 1 week with a negative predictive value (NPV) of 99.3% (PROGNOSIS) and 98.6% (PROGNOSIS Asia). We report a subanalysis of the Japanese cohort from the PROGNOSIS Asia study. Pregnant women with suspected preeclampsia between gestational weeks 18 + 0 days and 36 + 6 days were enrolled at eight Japanese sites. Primary objectives: Assess the performance of the Elecsys® sFlt-1/PlGF ratio cutoff ≤38 to rule out preeclampsia within 1 week and of the cutoff >38 to rule in preeclampsia within 4 weeks. Key secondary objectives: Prediction of maternal and fetal adverse outcomes (MAOs/FAOs) and their relationship with duration of pregnancy. Of 192 women enrolled, 180 (93.8%)/175 (91.1%) were evaluable for primary/combined endpoint analyses. Overall preeclampsia prevalence was 13.3%. A sFlt-1/PlGF ratio of ≤38 provided an NPV of 100% (95% confidence interval [CI], 97.5–100) for ruling out preeclampsia within 1 week, and a ratio of >38 provided a positive predictive value of 32.4% (95% CI, 18.0–49.8) for ruling in preeclampsia within 4 weeks. The area under the curve for the prediction of preeclampsia/maternal/fetal adverse outcomes within 1 week was 94.2% (95% CI, 89.3–97.8). After adjusting for gestational age and final preeclampsia status, Cox regression indicated a 2.8-fold greater risk of imminent delivery for women with a sFlt-1/PlGF ratio >38 versus ≤38. This subanalysis of Japanese women with suspicion of preeclampsia showed high predictive value for a Elecsys sFlt-1/PlGF ratio cutoff of 38 for short-term prediction of preeclampsia.
Long-distance electron transfer in a filamentous Gram-positive bacterium
Authors: Yang Yonggang , Wang Zegao , Gan Cuifen , Klausen Lasse Hyldgaard , Bonné Robin , Kong Guannan , Luo Dizhou , Meert Mathijs , Zhu Chunjie , Sun Guoping , Guo Jun , Ma Yuxin , Bjerg Jesper Tataru , Manca Jean , Xu Meiying , Nielsen Lars Peter , Dong Mingdong
Published: March 2021

Long-distance extracellular electron transfer has been observed in Gram-negative bacteria and plays roles in both natural and engineering processes. The electron transfer can be mediated by conductive protein appendages (in short unicellular bacteria such as Geobacter species) or by conductive cell envelopes (in filamentous multicellular cable bacteria). Here we show that Lysinibacillus varians GY32, a filamentous unicellular Gram-positive bacterium, is capable of bidirectional extracellular electron transfer. In microbial fuel cells, L. varians can form centimetre-range conductive cellular networks and, when grown on graphite electrodes, the cells can reach a remarkable length of 1.08 mm. Atomic force microscopy and microelectrode analyses suggest that the conductivity is linked to pili-like protein appendages. Our results show that long-distance electron transfer is not limited to Gram-negative bacteria.
dCas9 regulator to neutralize competition in CRISPRi circuits
Authors: Huang Hsin-Ho , Bellato Massimo , Qian Yili , Cárdenas Pablo , Pasotti Lorenzo , Magni Paolo , Del Vecchio Domitilla
Published: March 2021

CRISPRi-mediated gene regulation allows simultaneous control of many genes. However, highly specific sgRNA-promoter binding is, alone, insufficient to achieve independent transcriptional regulation of multiple targets. Indeed, due to competition for dCas9, the repression ability of one sgRNA changes significantly when another sgRNA becomes expressed. To solve this problem and decouple sgRNA-mediated regulatory paths, we create a dCas9 concentration regulator that implements negative feedback on dCas9 level. This allows any sgRNA to maintain an approximately constant dose-response curve, independent of other sgRNAs. We demonstrate the regulator performance on both single-stage and layered CRISPRi-based genetic circuits, zeroing competition effects of up to 15-fold changes in circuit I/O response encountered without the dCas9 regulator. The dCas9 regulator decouples sgRNA-mediated regulatory paths, enabling concurrent and independent regulation of multiple genes. This allows predictable composition of CRISPRi-based genetic modules, which is essential in the design of larger scale synthetic genetic circuits.
Ligand assisted growth of perovskite single crystals with low defect density
Authors: Liu Ye , Zheng Xiaopeng , Fang Yanjun , Zhou Ying , Ni Zhenyi , Xiao Xun , Chen Shangshang , Huang Jinsong
Published: March 2021

A low defect density in metal halide perovskite single crystals is critical to achieve high performance optoelectronic devices. Here we show the reduction of defect density in perovskite single crystals grown by a ligand-assisted solution process with 3‐(decyldimethylammonio)‐propane‐sulfonate inner salt (DPSI) as an additive. DPSI ligands anchoring with lead ions on perovskite crystal surfaces not only suppress nucleation in solution, but also regulate the addition of proper ions to the growing surface, which greatly enhances the crystal quality. The grown CH3NH3PbI3 crystals show better crystallinity and a 23-fold smaller trap density of 7 × 1010 cm−3 than the optimized control crystals. The enhanced material properties result in significantly suppressed ion migration and superior X-ray detection sensitivity of CH3NH3PbI3 detectors of (2.6 ± 0.4) × 106 µC Gy−1air cm−2 for 60 kVp X-ray and the lowest detectable dose rate reaches (5.0 ± 0.7) nGy s−1, which enables reduced radiation dose to patients in medical X-ray diagnostics.
Antibody-guided in vivo imaging of Aspergillus fumigatus lung infections during antifungal azole treatment
Authors: Henneberg Sophie , Hasenberg Anja , Maurer Andreas , Neumann Franziska , Bornemann Lea , Gonzalez-Menendez Irene , Kraus Andreas , Hasenberg Mike , Thornton Christopher R. , Pichler Bernd J. , Gunzer Matthias , Beziere Nicolas
Published: March 2021

Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of immunocompromised humans, caused by the opportunistic fungal pathogen Aspergillus fumigatus. Inadequacies in current diagnostic procedures mean that early diagnosis of the disease, critical to patient survival, remains a major clinical challenge, and is leading to the empiric use of antifungal drugs and emergence of azole resistance. A non-invasive procedure that allows both unambiguous detection of IPA and its response to azole treatment is therefore needed. Here, we show that a humanised Aspergillus-specific monoclonal antibody, dual labelled with a radionuclide and fluorophore, can be used in immunoPET/MRI in vivo in a neutropenic mouse model and 3D light sheet fluorescence microscopy ex vivo in the infected mouse lungs to quantify early A. fumigatus lung infections and to monitor the efficacy of azole therapy. Our antibody-guided approach reveals that early drug intervention is critical to prevent complete invasion of the lungs by the fungus, and demonstrates the power of molecular imaging as a non-invasive procedure for tracking IPA in vivo.
Author Correction: Quantum non-demolition measurement of a many-body Hamiltonian
Authors: Yang Dayou , Grankin Andrey , Sieberer Lukas M. , Vasilyev Denis V. , Zoller Peter
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22105-3
Orbital structure of the effective pairing interaction in the high-temperature superconducting cuprates
Authors: Mai Peizhi , Balduzzi Giovanni , Johnston Steven , Maier Thomas A.
Published: March 2021

The nature of the effective interaction responsible for pairing in the high-temperature superconducting cuprates remains unsettled. This question has been studied extensively using the simplified single-band Hubbard model, which does not explicitly consider the orbital degrees of freedom of the relevant CuO2 planes. Here, we use a dynamical cluster quantum Monte Carlo approximation to study the orbital structure of the pairing interaction in the three-band Hubbard model, which treats the orbital degrees of freedom explicitly. We find that the interaction predominately acts between neighboring copper orbitals, but with significant additional weight appearing on the surrounding bonding molecular oxygen orbitals. By explicitly comparing these results to those from the simpler single-band Hubbard model, our study provides strong support for the single-band framework for describing superconductivity in the cuprates.
Bacteria-host transcriptional response during endothelial invasion by Staphylococcus aureus
Authors: Grønnemose Rasmus Birkholm , Garde Christian , Wassmann Claes Søndergaard , Klitgaard Janne Kudsk , Nielsen Ronni , Mandrup Susanne , Mattsson Andreas Holm , Andersen Thomas Emil
Published: March 2021

Staphylococcus aureus is the cause of serious vascular infections such as sepsis and endocarditis. These infections are notoriously difficult to treat, and it is believed that the ability of S. aureus to invade endothelial cells and persist intracellularly is a key mechanism for persistence despite ongoing antibiotic treatment. Here, we used dual RNA sequencing to study the simultaneous transcriptional response of S. aureus and human endothelial cells during in vitro infections. We revealed discrete and shared differentially expressed genes for both host and pathogen at the different stages of infection. While the endothelial cells upregulated genes involved in interferon signalling and antigen presentation during late infection, S. aureus downregulated toxin expression while upregulating genes related to iron scavenging. In conclusion, the presented data provide an important resource to facilitate functional investigations into host–pathogen interaction during S. aureus invasive infection and a basis for identifying novel drug target sites.