bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of clinical result acquisition and interpretation on task performance during a simulated pediatric cardiac arrest: a multicentre observational study
Authors: Rizkalla Carol , Garcia-Jorda Dailys , Cheng Adam , Duff Jonathan P. , Gottesman Ronald , Weiss Matthew J. , Koot Deanna A. , Gilfoyle Elaine
Published: May 2022

Purpose

The acquisition and interpretation of clinical results during resuscitations is common; however, this can delay critical clinical tasks, resulting in increased morbidity and mortality. This study aims to determine the impact of clinical result acquisition and interpretation by the team leader on critical task completion during simulated pediatric cardiac arrest before and after team training.

Methods

This is a secondary data analysis of video-recorded simulated resuscitation scenarios conducted during Teams4Kids (T4K) study (June 2011–January 2015); scenarios included cardiac arrest before and after team training. The scenario included either a scripted paper or a phone call delivery of results concurrently with a clinical transition to pulseless ventricular tachycardia. Descriptive statistics and non-parametric tests were used to compare team performance before and after training.

Results

Performance from 40 teams was analyzed. Although the time taken to initiate CPR and defibrillation varied depending on the type of interruption and whether the scenario was before or after team training, these findings were not significantly associated with the leader's behaviour [Kruskal–Wallis test (p > 0.05)]. An exact McNemar’s test determined no statistically significant difference in the proportion of leaders involved or not in interpreting results between and after the training (exact p value = 0.096).

Conclusions

Team training was successful in reducing time to perform key clinical tasks. Although team training modified the way leaders behaved toward the results, this behaviour change did not impact the time taken to start CPR or defibrillate. Further understanding the elements that influence time to critical clinical tasks provides guidance in designing future simulated educational activities, subsequently improving clinical team performance and patient outcomes.
Fourier Analysis
Authors: Körner T. W. , Tao Terence
Published: May 2022

Fourier analysis is a subject that was born in physics but grew up in mathematics. Now it is part of the standard repertoire for mathematicians, physicists and engineers. This diversity of interest is often overlooked, but in this much-loved book, Tom Körner provides a shop window for some of the ideas, techniques and elegant results of Fourier analysis, and for their applications. These range from number theory, numerical analysis, control theory and statistics, to earth science, astronomy and electrical engineering. The prerequisites are few (a reader with knowledge of second- or third-year undergraduate mathematics should have no difficulty following the text), and the style is lively and entertaining. This edition of Körner's 1989 text includes a foreword written by Professor Terence Tao introducing it to a new generation of fans.
Ecotoxicology
Authors: Campbell Peter G. C. , Hodson Peter V. , Welbourn Pamela M. , Wright David A.
Published: May 2022

Ecotoxicology offers a comprehensive overview of the science underpinning the recognition and management of environmental contamination. It describes the toxicology of environmental contaminants, the methods used for assessing their toxicity and ecological impacts, and approaches employed to mitigate pollution and ecological health risks globally. Chapters cover the latest advances in research, including genomics, natural toxins, endocrine disruption and the toxicology of radioactive substances. The second half of the book focuses on applications, such as cradle-to-grave effects of selected industries, legal and economic approaches to environmental regulation, ecological risk assessment, and contaminated site remediation. With short capsules written by invited experts, numerous case studies from around the world and further reading lists, this textbook is designed for advanced undergraduate and graduate one-semester courses. It is also a valuable reference for graduate students and professionals. Online resources for instructors and students are also available.
Cuban Privilege
Authors: Eckstein Susan Eva
Published: May 2022

For over half a century the US granted Cubans, one of the largest immigrant groups in the country, unique entitlements. While other unauthorized immigrants faced detention, deportation, and no legal rights, Cuban immigrants were able to enter the country without authorization, and have access to welfare benefits and citizenship status. This book is the first to reveal the full range of entitlements granted to Cubans. Initially privileged to undermine the Castro-led revolution in the throes of the Cold War, one US President after another extended new entitlements, even in the post-Cold War era. Drawing on unseen archives, interviews, and survey data, Cuban Privilege highlights how Washington, in the process of privileging Cubans, transformed them from agents of US Cold War foreign policy into a politically powerful force influencing national policy. Comparing the exclusionary treatment of neighboring Haitians, the book discloses the racial and political biases embedded within US immigration policy.
The Congressionally Directed Medical Research Programs’ Ovarian Cancer Academy: a new approach to training in biomedical research
Authors: Wyatt Tasha R. , Stepleman Lara , Coleman Taylor , Robinson Leslie , Wylie Karen , Levine Douglas A. , Maihle Nita J.
Published: May 2022

Introduction:

Researchers have begun to change their approach to training in the biomedical sciences through the development of communities of practice (CoPs). CoPs share knowledge across clinical and laboratory contexts to promote the progress of clinical and translational science. The Congressionally Directed Medical Research Programs’ (CDMRP) Ovarian Cancer Academy (OCA) was designed as a virtual CoP to promote interactions among early career investigators (ECIs) and their mentors with the goal of eliminating ovarian cancer.

Methods:

A mixed-methods approach (surveys and interviews) was used to evaluate the effectiveness of the OCA for the eight ECIs and five mentors. Quantitative analysis included internal reliability of scales and descriptive statistics for each measure, as well as paired sample t-tests for Time 1 and Time 2. Qualitative data were analyzed for themes to discern which aspects of the program were useful and where more attention is needed.

Results:

Preliminary analyses reveal several trends, including the importance of training in grant writing to the ECI’s productivity, as well as the value of peer mentorship.

Conclusion:

The results show that the OCA was an innovative and effective way to create a CoP with broad implications for the field of ovarian cancer research, as well as for the future of biomedical research training.
Multiphase large-eddy simulations of human cough jet development and expiratory droplet dispersion
Authors: Lai Xin , Li Shaofan , Yan Jiale , Liu Lisheng , Zhang A-Man
Published: May 2022

Violent respiratory events play critical roles in the transmission of respiratory diseases, such as coughing and sneezing, between infectious and susceptible individuals. In this work, large-scale multiphase flow large-eddy simulations have been performed to simulate the coughing jet from a human's mouth carrying pathogenic or virus-laden droplets by using a weakly compressible smoothed particle hydrodynamics method. We explicitly model the cough jet ejected from a human mouth in the form of a mixture of two-phase fluids based on the cough velocity profile of the exhalation flow obtained from experimental data and the statistics of the droplets’ sizes. The coupling and interaction between the two expiratory phases and ambient surrounding air are examined based on the interaction between the gas particles and droplet particles. First, the results reveal that the turbulence of the cough jet determines the dispersion of the virus-laden droplets, i.e. whether they fly up evolving into aerosols or fall down to the ground. Second, the droplet particles have significant effects on the evolution of the cough jet turbulence; for example, they increase the complexity and butterfly effect introduced by the turbulence disturbance. Our results show that the prediction of the spreading distance of droplet particles often goes beyond the social distancing rules recommended by the World Health Organization, which reminds us of the risks of exposure if we do not take any protecting protocol.
On the role of discrete and continuous modes in a cooled high-speed boundary layer flow
Authors: Saikia B. , Al Hasnine S.M.A. , Brehm C.
Published: May 2022

The disturbance flow field for a Mach$6$flat-plate boundary layer flow with a wall-to-free-stream temperature ratio of$0.5$is studied using direct numerical simulation (DNS), linear stability theory (LST) and biorthogonal decomposition. In the second-mode instability region, the DNS flow field can be reconstructed using a single LST mode, namely$F^+_1$. However, when the supersonic mode emerges, none of the discrete modes nor the continuous branches alone can precisely match the DNS data. A superposition of the pair of discrete supersonic modes$F^\pm _1$and the slow acoustic continuous spectrum is required to reproduce the disturbance amplitude distributions and the amplification rates observed in the DNS. Another finding is that the supersonic mode$F^-_1$, which should be decaying following LST, in actuality is amplified based on the projected DNS data.
Fracture stratigraphy of Mesozoic platform carbonates, Agri Valley, southern Italy
Authors: Manniello C , Agosta F , Todaro S , Cavalcante F , Prosser G
Published: May 2022

The Viggiano Mt. platform carbonates form a layered succession cross-cut by a dense array of pressure solution seams, and five sets of fractures and veins, which together form a sub-seismic structural network associated with polyphasic tectonic evolution. To assess the influence exerted by depositional and diagenetic heterogeneities on fracture geometry, distribution and multiscale properties, we present the results of stratigraphic, petrographic, mineralogical and mesoscale structural analyses conducted at the Viggiano Mountain, southern Italy. Based on rock textures and fossil associations, we documented that the Sinemurian–Pleinsbachian carbonates were deposited in a low-energy open lagoon, the Toarcian carbonates in a ramp setting rimmed by sand shoals, and the Cenomanian carbonates in a medium- to high-energy, lagoonal–tidal setting. Fracture-density (P20) and intensity (P21) values computed after circular scanline measurements show similar trends in both Sinemurian–Pleinsbachian and Toarcian carbonates, consistent with the bed and bed-package heterogeneities acting as efficient mechanical interfaces during incipient faulting. On the other hand, P20 and P21 do not show very similar variations throughout the Cenomanian carbonates due to pronounced bed amalgamation. Throughout the study area, the aforementioned parameters do not vary in proportion to the bed thickness, and show higher values within the coarse-grained carbonate beds. This conclusion is confirmed by results of linear scanline measurements, which focus on the P10 properties of the most common diffuse fracture set. The original results reported in this work are consistent with burial-related, physical–chemical compaction and cementation processes affecting the fracture stratigraphy of the Mesozoic platform carbonates.
An Alternative Institutional Approach to Rules, Organizations, and Development
Authors: Wallis John Joseph
Published: May 2022

In the middle of the nineteenth century, a handful of societies began creating and enforcing impersonal rules, rules that treat everyone the same, on a broad scale. The existing institutional literatures, while appreciating the importance of impersonal rules for the rule of law, have not understood how they contribute to economic and political development through rules that are enforced but not followed: default rules. The conceptual importance of impersonal default rules is drawn out and then applied to better understand both economic and political development in the late nineteenth and early twentieth centuries.
DNA barcoding reveals deep divergent molecular units inPomatomus saltatrix(Perciformes: Pomatomidae): implications for management and global conservation
Authors: Queiroz-Brito Maria Clara G. de , Machado Carolina Barros , Maia Danielle de Jesus Gama , Jacobina Uedson Pereira , Nirchio Mauro , Rotundo Matheus M. , Tubino Rafael de Almeida , Iriarte Pedro Fernández , Haimovici Manuel , Torres Rodrigo Augusto
Published: May 2022

Pomatomus saltatrixis a high-value marine pelagic coastal fish, that is fished throughout subtropical and temperate coastal waters around the world. Despite its large economic potential, there are no global data on its genetic diversity, which could compromise the conservation of the species. The aim of this study was to analyse the genetic-evolutionary structuring of the species, with the intention of evaluating different geneticP. saltatrixstocks that may indicate potential species. Based on 157 Cytochrome C Oxidase Subunit 1 sequences, the molecular delimitation analyses of species (distance and coalescence methods), as well as the haplotype network, found profound geographic structuring related to five distinct units with high and significantFSTpairwise values. The divergence of these molecular units is mostly related to the Pleistocene glacial and interglacial cycles of climatic oscillations. It is hypothesized that one ancestral lineage, adapted to cold water environments, diversified into two lineages, with one more adapted to warmer environments. The high values of global genetic diversity (π = 0.016; h = 0.96) may be related to the existing profound genetic differentiation. Due to the presence of five Molecular Operational Taxonomic Units (MOTUs) within the species it is necessary to employ different regional management strategies. Traits of low haplotype richness and shallow population contraction were identified in the MOTUs V (Venezuela and Brazil) and III (Turkey and Australia), respectively, representing conservation priorities. Other molecular markers, as well as morphological data, should be explored with the aim of defining the taxonomic status ofP. saltatrixstocks.
A philosophical account of repentance
Authors: Oren Noam
Published: May 2022

Repentance is central to the doctrinal philosophies of all major religions. From a theoretical point of view, however, the practice poses significant challenges. As the past cannot be altered, the guilt that obtains from already committed sins appears forever fettered to the sinner. In this article, I explore this conundrum and discuss a number of solutions that have been proposed in religious traditions. I show how these solutions fail to satisfy from both theological and philosophical perspectives. Finally, I propose a novel approach that, I believe, solves the problem.
Intergenerational Learning and Place-making in a Deindustrialized Locality: “Tracks of the Past” in Lanarkshire, Scotland
Authors: Gibbs Ewan , Henderson Susan , Bianchi Victoria
Published: May 2022

This paper contributes to scholarship on the long experience of deindustrialization. It emphasizes contemporary place-making in navigating the much-changed socioeconomic landscapes that the closure of mills, mines, shipyards and factories have left behind. The ‘half-life of deindustrialization' suggests these experiences have been received through understandings of labour and community with origins in the industrial era. ‘Tracks of the Past' was a school-based education project themed around workers' occupation of Caterpillar's earth-moving machinery plant in Lanarkshire, Scotland. The occupation was a response to Caterpillar's shock closure announcement and the loss of 1,200 jobs. It lasted 103 days between January and April 1987 when closure was reluctantly conceded. A Caterpillar Workers Legacy Group (CWLG) commemorated the occupation's thirtieth anniversary. During 2018, academics collaborated with the CWLG to develop a curriculum for a local high school class. ‘Tracks' produced lessons where students engaged with archival sources and physical objects, interviewed members of the CWLG and conducted online research. The ‘learning journey' montages that the students produced combined conversations in 2018 with sources from three decades earlier, often reflecting on the occupation as a historical episode in a highly localised context. Others implicated the closure within an international pattern, linking Caterpillar’s divestment to the actions of multinationals in the contemporary global economy. In neither case did the invocation of the occupation lead to a straightforward translation of the occupation into contemporary workplace justice issues as the CWLG had hoped. However, these results did suggest a creative deployment of the past that rationalised the occupation with reference to contemporary deindustrialized contexts. These findings demonstrate the utility of the half-life through a lingering industrial past, but also demonstrate the need to conceptualise agents or custodians of labour history and challenge the linearity of passing time that an incrementally receding industrial era implicates.
Microhabitat preferences and guild structure of a tropical reptile community from the Western Ghats of India: implications for conservation
Authors: Jins V.J. , Mukherjee Aditi , Arun P.R. , Michael Damian R. , Bhupathy Subramanian
Published: May 2022

Microhabitat characteristics can be used as a proxy to predict the community structure of associated organisms and evaluate their vulnerability to habitat degradation. Microhabitat-specific and ectothermic taxa (like many reptiles) are among the best models to study responses to changing habitats and climate. We examined the niche breadth and guild structure of reptiles from Agasthyamalai Hills in the southern Western Ghats of India based on microhabitat use data. We recorded a total of 47 reptile species from 1,554 observations comprising two major orders and 11 families. Niche breadth analysis revealed that 45% of reptiles are microhabitat specialists, indicating the importance of protecting their habitats with all structural attributes. Cluster analysis grouped reptile species into four major guilds based on microhabitat preferences. The forest floor-dwelling guild was the largest group with 25 species, followed by the semi-arboreal guild with 12 species. The floor-dwelling guild also exhibited both the highest number of microhabitat specialists (n = 11) and globally threatened species (n = 3), highlighting the need for preserving ground cover characteristics such as leaf litter, boulders, and open ground for conserving reptiles in the region. Considering the microhabitat specializations within the community, we recommend a dynamic approach to monitor abundance, diversity, and habitat quality across the Agasthyamalai landscape to better conserve its rich reptile diversity.
Medication-Facilitated Advanced Airway Management with First-Line Use of a Supraglottic Device – A One-Year Quality Assurance Review
Authors: Johnston Bethany J. , Leung Alison K. , Hwang Charles W. , Jones Jason M. , Chowdhury Muhammad Abdul Baker , Buck Alicia , Fitzpatrick Desmond E. , Meurer David A. , Becker Torben K.
Published: May 2022

Introduction:

Airway management is a controversial topic in modern Emergency Medical Services (EMS) systems. Among many concerns regarding endotracheal intubation (ETI), unrecognized esophageal intubation and observations of unfavorable neurologic outcomes in some studies raise the question of whether alternative airway techniques should be first-line in EMS airway management protocols. Supraglottic airway devices (SADs) are simpler to use, provide reliable oxygenation and ventilation, and may thus be an alternative first-line airway device for paramedics. In 2019, Alachua County Fire Rescue (ACFR; Alachua, Florida USA) introduced a novel protocol for advanced airway management emphasizing first-line use of a second-generation SAD (i-gel) for patients requiring medication-facilitated airway management (referred to as “rapid sequence airway” [RSA] protocol).

Study Objective:

This was a one-year quality assurance review of care provided under the RSA protocol looking at compliance and first-pass success rate of first-line SAD use.

Methods:

Records were obtained from the agency’s electronic medical record (EMR), searching for the use of the RSA protocol, advanced airway devices, or either ketamine or rocuronium. If available, hospital follow-up data regarding patient condition and emergency department (ED) airway exchange were obtained.

Results:

During the first year, 33 advanced airway attempts were made under the protocol by 23 paramedics. Overall, compliance with the airway device sequence as specified in the protocol was 72.7%. When ETI was non-compliantly used as first-line airway device, the first-pass success rate was 44.4% compared to 87.5% with adherence to first-line SAD use. All prehospital SADs were exchanged in the ED in a delayed fashion and almost exclusively per physician preference alone. In no case was the SAD exchanged for suspected dislodgement evidenced by lack of capnography.

Conclusion:

First-line use of a SAD was associated with a high first-pass attempt success rate in a real-life cohort of prehospital advanced airway encounters. No SAD required emergent exchange upon hospital arrival.
Estimating prevalence of child and youth mental disorder and mental health-related service contacts: a comparison of survey data and linked administrative health data
Authors: Duncan L. , Georgiades K. , Wang L. , Edwards J. , Comeau J.
Published: May 2022

Aims

Prevalence estimates of child and youth mental disorder and mental health-related service contacts are needed for policy formulation, research, advocacy and resource allocation. Our aim is to compare prevalence estimates of child and youth mental disorder and mental health-related service contacts derived from general population survey data v. linked administrative health data.

Methods

Provincially representative 2014 Ontario Child Health Study data were linked to administrative health records for 5563 children and youth aged 4–17 in Ontario. Emotional disorders (mood and anxiety) and attention-deficit/hyperactivity disorder were assessed using a standardised diagnostic interview in the survey and using diagnostic codes in administrative health data. Physician-based mental health-related service contacts were assessed using parent self-reports from the survey and administrative data related to mental health-related diagnostic codes. Prevalence estimates were calculated and compared based on one-sample z-tests and ratios of survey data to administrative data-based prevalence. Sensitivity, specificity and agreement between classifications were compared using κ. Prevalence estimates were calculated by age, sex and geography sub-groups and consistent group differences across data source were counted.

Results

Disorder prevalence and service contact estimates were significantly higher in survey data in all cases, except for mood disorder. Ratios of survey data to administrative data-based prevalence varied, ranging from 0.80 (mood) to 11.01 (attention-deficit/hyperactivity disorder). Specificity was high (0.98–1.00), sensitivity was low (0.07–0.41) and agreement ranged from slight (κ = 0.13) to moderate (κ = 0.46). Out of 18 sub-group difference comparisons, half were non-significant in either data source. In the remaining nine comparisons, the only significant differences between groups that were consistent across data source were for sex-based differences (attention-deficit/hyperactivity disorder and service contacts). There were no consistent age- or geography-based differences in prevalence across data sources.

Conclusions

Our findings suggest that conclusions drawn about prevalence, service contacts and sub-group differences in these estimates are dependent on data source. Further research is needed to understand who and what is being captured by each source. Researchers should conduct data linkage where possible to access and compare multiple sources of information.
Primärqualifizierende Pflegestudiengänge aus Sicht Studierender
Authors: Großmann Daniel , Olden Daria , Dorin Lena , Meng Michael , Peters Miriam , Reuschenbach Bernd
Published: May 2022

Zusammenfassung. Hintergrund: Das Pflegeberufegesetz schafft erstmals einen konkreten Rahmen für die akademische Pflegeausbildung in Deutschland. Die primärqualifizierenden Pflegestudiengänge starteten 2020 und werden von einer Befragung Studierender begleitet. Fragestellung/Ziel: Der Beitrag stellt Ergebnisse der ersten Befragungswelle (2021) zur Sicht der Studierenden dar. Es werden Herausforderungen und Nachsteuerungsbedarfe der hochschulischen Primärqualifizierung analysiert und Lösungsansätze entwickelt. Methode: Die Online-Erhebung ist als längsschnittliche Kohortenstudie mit drei Messzeitpunkten konzipiert (2021, 2022, 2023). Es erfolgt eine deskriptive Ergebnisdatenanalyse der ersten Befragungswelle mit N = 57 Studierenden. Ergebnisse: Das primärqualifizierende Pflegestudium wird insgesamt gut bewertet (Gesamtnote 2,32), doch kommt ein Drittel (35,85%) zu eher kritischen Gesamteinschätzungen. Anpassungsbedarfe sieht jede/r zweite Studierende bei der Finanzierung des Studiums. Das Lernen in der Praxis entspricht oft nicht den Erwartungen der Studierenden. 86% der Befragten berichten, dass die Einsatzorte unzureichend über die Qualifikation der Studierenden informiert sind. Schlussfolgerungen: Die Studienfinanzierung, dabei insbesondere die Vergütung der Praxiseinsätze, stellen kurzfristig zu lösende Regelungslücken dar. Beim Lernen in der Praxis zeigt sich Bedarf nach einer besser auf die akademische Pflegeausbildung ausgerichteten Praxisanleitung. Damit geht die Notwendigkeit einer genaueren Definition späterer Tätigkeitsfelder und Stellenprofile einher.
Groundwater Flow May Contribute to Submarine Permafrost Thaw
Authors: Lee Jack
Published: May 2022

New, detailed surveys from the Beaufort Sea reveal a seafloor depression the size of a city block associated with permafrost thaw and likely influenced by the movement of groundwater below.
Divergence-degenerate spatial multiplexing towards future ultrahigh capacity, low error-rate optical communications
Authors: Wan Zhensong , Shen Yijie , Wang Zhaoyang , Shi Zijian , Liu Qiang , Fu Xing
Published: May 2022

Spatial mode (de)multiplexing of orbital angular momentum (OAM) beams is a promising solution to address future bandwidth issues, but the rapidly increasing divergence with the mode order severely limits the practically addressable number of OAM modes. Here we present a set of multi-vortex geometric beams (MVGBs) as high-dimensional information carriers for free-space optical communication, by virtue of three independent degrees of freedom (DoFs) including central OAM, sub-beam OAM, and coherent-state phase. The novel modal basis set has high divergence degeneracy, and highly consistent propagation behaviors among all spatial modes, capable of increasing the addressable spatial channels by two orders of magnitude than OAM basis as predicted. We experimentally realize the tri-DoF MVGB mode (de)multiplexing and data transmission by the conjugated modulation method, demonstrating lower error rates caused by center offset and coherent background noise, compared with OAM basis. Our work provides a potentially useful basis for the next generation of large-scale dense data communication.
TGF-β1/SH2B3 axis regulates anoikis resistance and EMT of lung cancer cells by modulating JAK2/STAT3 and SHP2/Grb2 signaling pathways
Authors: Wang Li-Na , Zhang Zi-Teng , Wang Li , Wei Hai-Xiang , Zhang Tao , Zhang Li-Ming , Lin Hang , Zhang Heng , Wang Shao-Qiang
Published: May 2022

The pathogenesis of lung cancer, the most common cancer, is complex and unclear, leading to limited treatment options and poor prognosis. To provide molecular insights into lung cancer development, we investigated the function and underlying mechanism of SH2B3 in the regulation of lung cancer. We indicated SH2B3 was diminished while TGF-β1 was elevated in lung cancer tissues and cells. Low SH2B3 level was correlated with poor prognosis of lung cancer patients. SH2B3 overexpression suppressed cancer cell anoikis resistance, proliferation, migration, invasion, and EMT, while TGF-β1 promoted those processes via reducing SH2B3. SH2B3 bound to JAK2 and SHP2 to repress JAK2/STAT3 and SHP2/Grb2/PI3K/AKT signaling pathways, respectively, resulting in reduced cancer cell anoikis resistance, proliferation, migration, invasion, and EMT. Overexpression of SH2B3 suppressed lung cancer growth and metastasis in vivo. In conclusion, SH2B3 restrained the development of anoikis resistance and EMT of lung cancer cells via suppressing JAK2/STAT3 and SHP2/Grb2/PI3K/AKT signaling cascades, leading to decreased cancer cell proliferation, migration, and invasion.
circ-Pank1 promotes dopaminergic neuron neurodegeneration through modulating miR-7a-5p/α-syn pathway in Parkinson’s disease
Authors: Liu Qing , Li Qiyao , Zhang Runjiao , Wang Hongfang , Li Yibo , Liu Ziyu , Xie Wenmeng , Geng Dandan , Wang Lei
Published: May 2022

Circular RNA (circRNA) is a type of non-coding RNA that is widely expressed in mammals. It is highly conserved and abundantly expressed in the brain. Here, we report the regulatory role of circRNA derived from the pantothenate kinase 1 (Pank1) gene (circ-Pank1) in Parkinson’s disease (PD). Circ-Pank1 is highly expressed in the substantia nigra (SN) of PD model mice treated with rotenone and in the MN9D cell model of dopaminergic neurons. The circ-Pank1 knockdown ameliorated dopaminergic neuron damage and locomotor dysfunction after the treatment with rotenone. We found that circ-Pank1 could adsorb miR-7a-5p and upregulate the expression of α-synuclein (α-syn), which is a molecular hallmark closely related to PD. The inhibition of miR-7a-5p reversed the circ-Pank1 knockdown-induced amelioration of dopaminergic neuron injury. In conclusion, circ-Pank1 is overexpressed in PD and enhances the locomotor dysfunction via the miR-7a-5p/α-syn signaling axis. We revealed the functional role of circRNAs in the progression of PD and provided a potential target for noncoding RNAs in delaying the progression of PD.
METTL3-mediated macrophage exosomal NEAT1 contributes to hepatic fibrosis progression through Sp1/TGF-β1/Smad signaling pathway
Authors: Shu Bo , Zhang Rui-Zhi , Zhou Ying-Xia , He Chao , Yang Xin
Published: May 2022

Hepatic fibrosis (HF) is caused by chronic hepatic injury and is characterized by hepatic stellate cells (HSCs) activation. Studies focusing on the function of exosomes derived from macrophages in HF progression are limited. This study aims to identify the roles of exosomal NEAT1 derived from macrophages on HF and the underlying mechanisms. Our studies showed that METTL3 targeted and enhanced NEAT1 expression in macrophages. Exosomal NEAT1 originating from LPS-treated macrophages promoted HSCs proliferation and migration, and induced the expression of fibrotic proteins including collagen I, α-SMA, and fibronectin. Macrophage exosomal NEAT1 contributed to HSCs activation by sponging miR-342. MiR-342 directly targeted Sp1 and suppressed its downstream TGF-β1/Smad signaling pathway, which eventually led to the inhibition of HSCs activation. Depletion of NEAT1 in the macrophage exosomes inhibited HF progression both in vitro and in vivo. Altogether, our study proved that silence of NEAT1 in the macrophage exosomes exerted protective roles against HF through the miR-342/Sp1/TGF-β1/Smad signaling pathway, suggesting a potential therapeutic target in HF treatment.
International collaboration for the development of clinical guidelines in low and middle-income countries: case study on the development of a national framework and clinical guidelines for diabetic retinopathy in Ghana
Authors: Mwangi Nyawira , Amissah-Arthur Kwesi Nyan , Braimah Imoro Zeba , Sarfo-Kantanka Osei , Akpalu Josephine , Akrofi Bridgid , Boadi-Kusi Samuel Bert , Atiase Yacoba , Yorke Ernest , Gichangi Michael , Faal Hannah , Addy James
Published: May 2022

Background

Diabetic retinopathy is a leading cause of blindness in many countries across the world. Ghana has seen a rise in diabetic retinopathy and is working on various strategies to prevent blindness. Clinical guidelines are seen as a promising strategy for improving quality and reducing cost of care. Little is known about the processes of collaborative guideline development in the African context.

Methods

This case study discusses the process of developing clinical guidelines for diabetic retinopathy in Ghana via a collaboration with the Kenya team that had previously developed guidelines for Kenya.

Results

The main lesson learnt was the ability to overcome challenges. The main output achieved was the draft national framework, guidelines and training slides on the guidelines.

Conclusion

Horizontal international collaboration can aid development of clinical guidelines.
RNA supply drives physiological granule assembly in neurons
Authors: Bauer Karl E. , Bargenda Niklas , Schieweck Rico , Illig Christin , Segura Inmaculada , Harner Max , Kiebler Michael A.
Published: May 2022

Membraneless cytoplasmic condensates of mRNAs and proteins, known as RNA granules, play pivotal roles in the regulation of mRNA fate. Their maintenance fine-tunes time and location of protein expression, affecting many cellular processes, which require complex protein distribution. Here, we report that RNA granules—monitored by DEAD-Box helicase 6 (DDX6)—disassemble during neuronal maturation both in cell culture and in vivo. This process requires neuronal function, as synaptic inhibition results in reversible granule assembly. Importantly, granule assembly is dependent on the RNA-binding protein Staufen2, known for its role in RNA localization. Altering the levels of free cytoplasmic mRNA reveals that RNA availability facilitates DDX6 granule formation. Specifically depleting RNA from DDX6 granules confirms RNA as an important driver of granule formation. Moreover, RNA is required for DDX6 granule assembly upon synaptic inhibition. Together, this data demonstrates how RNA supply favors RNA granule assembly, which not only impacts subcellular RNA localization but also translation-dependent synaptic plasticity, learning, and memory.
Shape and structural relaxation of colloidal tactoids
Authors: Almohammadi Hamed , Khadem Sayyed Ahmad , Bagnani Massimo , Rey Alejandro D. , Mezzenga Raffaele
Published: May 2022

Facile geometric-structural response of liquid crystalline colloids to external fields enables many technological advances. However, the relaxation mechanisms for liquid crystalline colloids under mobile boundaries remain still unexplored. Here, by combining experiments, numerical simulations and theory, we describe the shape and structural relaxation of colloidal liquid crystalline micro-droplets, called tactoids, where amyloid fibrils and cellulose nanocrystals are used as model systems. We show that tactoids shape relaxation bears a universal single exponential decay signature and derive an analytic expression to predict this out of equilibrium process, which is governed by liquid crystalline anisotropic and isotropic contributions. The tactoids structural relaxation shows fundamentally different paths, with first- and second-order exponential decays, depending on the existence of splay/bend/twist orientation structures in the ground state. Our findings offer a comprehensive understanding on dynamic confinement effects in liquid crystalline colloidal systems and may set unexplored directions in the development of novel responsive materials.
Frequency modulation of a bacterial quorum sensing response
Authors: Bettenworth Vera , van Vliet Simon , Turkowyd Bartosz , Bamberger Annika , Wendt Heiko , McIntosh Matthew , Steinchen Wieland , Endesfelder Ulrike , Becker Anke
Published: May 2022

In quorum sensing, bacteria secrete or release small molecules into the environment that, once they reach a certain threshold, trigger a behavioural change in the population. As the concentration of these so-called autoinducers is supposed to reflect population density, they were originally assumed to be continuously produced by all cells in a population. However, here we show that in the α-proteobacterium Sinorhizobium meliloti expression of the autoinducer synthase gene is realized in asynchronous stochastic pulses that result from scarcity and, presumably, low binding affinity of the key activator. Physiological cues modulate pulse frequency, and pulse frequency in turn modulates the velocity with which autoinducer levels in the environment reach the threshold to trigger the quorum sensing response. We therefore propose that frequency-modulated pulsing in S. meliloti represents the molecular mechanism for a collective decision-making process in which each cell’s physiological state and need for behavioural adaptation is encoded in the pulse frequency with which it expresses the autoinducer synthase gene; the pulse frequencies of all members of the population are then integrated in the common pool of autoinducers, and only once this vote crosses the threshold, the response behaviour is initiated.
BMP4 drives primed to naïve transition through PGC-like state
Authors: Yu Shengyong , Zhou Chunhua , He Jiangping , Yao Zhaokai , Huang Xingnan , Rong Bowen , Zhu Hong , Wang Shijie , Chen Shuyan , Wang Xialian , Cai Baomei , Zhao Guoqing , Chen Yuhan , Xiao Lizhan , Liu He , Qin Yue , Guo Jing , Wu Haokaifeng , Zhang Zhen , Zhang Man , Zhao Xiaoyang , Lan Fei , Wang Yixuan , Chen Jiekai , Cao Shangtao , Pei Duanqing , Liu Jing
Published: May 2022

Multiple pluripotent states have been described in mouse and human stem cells. Here, we apply single-cell RNA-seq to a newly established BMP4 induced mouse primed to naïve transition (BiPNT) system and show that the reset is not a direct reversal of cell fate but goes through a primordial germ cell-like cells (PGCLCs) state. We first show that epiblast stem cells bifurcate into c-Kit+ naïve and c-Kit− trophoblast-like cells, among which, the naïve branch undergoes further transition through a PGCLCs intermediate capable of spermatogenesis in vivo. Mechanistically, we show that DOT1L inhibition permits the transition from primed pluripotency to PGCLCs in part by facilitating the loss of H3K79me2 from Gata3/6. In addition, Prdm1/Blimp1 is required for PGCLCs and naïve cells, while Gata2 inhibits PGC-like state by promoting trophoblast-like fate. Our work not only reveals an alternative route for primed to naïve transition, but also gains insight into germ cell development.
Intermolecular 2+2 imine-olefin photocycloadditions enabled by Cu(I)-alkene MLCT
Authors: Flores Daniel M. , Neville Michael L. , Schmidt Valerie A.
Published: May 2022

2 + 2 Photocycloadditions are idealized, convergent construction approaches of 4-membered heterocyclic rings, including azetidines. However, methods of direct excitation are limited by the unfavorable photophysical properties of imines and electronically unbiased alkenes. Here, we report copper-catalyzed photocycloadditions of non-conjugated imines and alkenes to produce a variety of substituted azetidines. Design principles allow this base metal-catalyzed method to achieve 2 + 2 imine-olefin photocycloaddition via selective alkene activation through a coordination-MLCT pathway supported by combined experimental and computational mechanistic studies.
Defect-gradient-induced Rashba effect in van der Waals PtSe2 layers
Authors: Jo Junhyeon , Kim Jung Hwa , Kim Choong H. , Lee Jaebyeong , Choe Daeseong , Oh Inseon , Lee Seunghyun , Lee Zonghoon , Jin Hosub , Yoo Jung-Woo
Published: May 2022

Defect engineering is one of the key technologies in materials science, enriching the modern semiconductor industry and providing good test-beds for solid-state physics. While homogenous doping prevails in conventional defect engineering, various artificial defect distributions have been predicted to induce desired physical properties in host materials, especially associated with symmetry breakings. Here, we show layer-by-layer defect-gradients in two-dimensional PtSe2 films developed by selective plasma treatments, which break spatial inversion symmetry and give rise to the Rashba effect. Scanning transmission electron microscopy analyses reveal that Se vacancies extend down to 7 nm from the surface and Se/Pt ratio exhibits linear variation along the layers. The Rashba effect induced by broken inversion symmetry is demonstrated through the observations of nonreciprocal transport behaviors and first-principles density functional theory calculations. Our methodology paves the way for functional defect engineering that entangles spin and momentum of itinerant electrons for emerging electronic applications.
A new class of bilayer kagome lattice compounds with Dirac nodal lines and pressure-induced superconductivity
Authors: Shi Mengzhu , Yu Fanghang , Yang Ye , Meng Fanbao , Lei Bin , Luo Yang , Sun Zhe , He Junfeng , Wang Rui , Jiang Zhicheng , Liu Zhengtai , Shen Dawei , Wu Tao , Wang Zhenyu , Xiang Ziji , Ying Jianjun , Chen Xianhui
Published: May 2022

Kagome lattice composed of transition-metal ions provides a great opportunity to explore the intertwining between geometry, electronic orders and band topology. The discovery of multiple competing orders that connect intimately with the underlying topological band structure in nonmagnetic kagome metals AV3Sb5 (A = K, Rb, Cs) further pushes this topic to the quantum frontier. Here we report a new class of vanadium-based compounds with kagome bilayers, namely AV6Sb6 (A = K, Rb, Cs) and V6Sb4, which, together with AV3Sb5, compose a series of kagome compounds with a generic chemical formula (Am-1Sb2m)(V3Sb)n (m = 1, 2; n = 1, 2). Theoretical calculations combined with angle-resolved photoemission measurements reveal that these compounds feature Dirac nodal lines in close vicinity to the Fermi level. Pressure-induced superconductivity in AV6Sb6 further suggests promising emergent phenomena in these materials. The establishment of a new family of layered kagome materials paves the way for designer of fascinating kagome systems with diverse topological nontrivialities and collective ground states.
A deep learning model and human-machine fusion for prediction of EBV-associated gastric cancer from histopathology
Authors: Zheng Xueyi , Wang Ruixuan , Zhang Xinke , Sun Yan , Zhang Haohuan , Zhao Zihan , Zheng Yuanhang , Luo Jing , Zhang Jiangyu , Wu Hongmei , Huang Dan , Zhu Wenbiao , Chen Jianning , Cao Qinghua , Zeng Hong , Luo Rongzhen , Li Peng , Lan Lilong , Yun Jingping , Xie Dan , Zheng Wei-Shi , Luo Junhang , Cai Muyan
Published: May 2022

Epstein–Barr virus-associated gastric cancer (EBVaGC) shows a robust response to immune checkpoint inhibitors. Therefore, a cost-efficient and accessible tool is needed for discriminating EBV status in patients with gastric cancer. Here we introduce a deep convolutional neural network called EBVNet and its fusion with pathologists for predicting EBVaGC from histopathology. The EBVNet yields an averaged area under the receiver operating curve (AUROC) of 0.969 from the internal cross validation, an AUROC of 0.941 on an external dataset from multiple institutes and an AUROC of 0.895 on The Cancer Genome Atlas dataset. The human-machine fusion significantly improves the diagnostic performance of both the EBVNet and the pathologist. This finding suggests that our EBVNet could provide an innovative approach for the identification of EBVaGC and may help effectively select patients with gastric cancer for immunotherapy.
Inhibition mechanism of the chloride channel TMEM16A by the pore blocker 1PBC
Authors: Lam Andy K. M. , Rutz Sonja , Dutzler Raimund
Published: May 2022

TMEM16A, a calcium-activated chloride channel involved in multiple cellular processes, is a proposed target for diseases such as hypertension, asthma, and cystic fibrosis. Despite these therapeutic promises, its pharmacology remains poorly understood. Here, we present a cryo-EM structure of TMEM16A in complex with the channel blocker 1PBC and a detailed functional analysis of its inhibition mechanism. A pocket located external to the neck region of the hourglass-shaped pore is responsible for open-channel block by 1PBC and presumably also by its structural analogs. The binding of the blocker stabilizes an open-like conformation of the channel that involves a rearrangement of several pore helices. The expansion of the outer pore enhances blocker sensitivity and enables 1PBC to bind at a site within the transmembrane electric field. Our results define the mechanism of inhibition and gating and will facilitate the design of new, potent TMEM16A modulators.
Different hotspot p53 mutants exert distinct phenotypes and predict outcome of colorectal cancer patients
Authors: Hassin Ori , Nataraj Nishanth Belugali , Shreberk-Shaked Michal , Aylon Yael , Yaeger Rona , Fontemaggi Giulia , Mukherjee Saptaparna , Maddalena Martino , Avioz Adi , Iancu Ortal , Mallel Giuseppe , Gershoni Anat , Grosheva Inna , Feldmesser Ester , Ben-Dor Shifra , Golani Ofra , Hendel Ayal , Blandino Giovanni , Kelsen David , Yarden Yosef , Oren Moshe
Published: May 2022

The TP53 gene is mutated in approximately 60% of all colorectal cancer (CRC) cases. Over 20% of all TP53-mutated CRC tumors carry missense mutations at position R175 or R273. Here we report that CRC tumors harboring R273 mutations are more prone to progress to metastatic disease, with decreased survival, than those with R175 mutations. We identify a distinct transcriptional signature orchestrated by p53R273H, implicating activation of oncogenic signaling pathways and predicting worse outcome. These features are shared also with the hotspot mutants p53R248Q and p53R248W. p53R273H selectively promotes rapid CRC cell spreading, migration, invasion and metastasis. The transcriptional output of p53R273H is associated with preferential binding to regulatory elements of R273 signature genes. Thus, different TP53 missense mutations contribute differently to cancer progression. Elucidation of the differential impact of distinct TP53 mutations on disease features may make TP53 mutational information more actionable, holding potential for better precision-based medicine.
Lipid droplet degradation by autophagy connects mitochondria metabolism to Prox1-driven expression of lymphatic genes and lymphangiogenesis
Authors: Meçe Odeta , Houbaert Diede , Sassano Maria-Livia , Durré Tania , Maes Hannelore , Schaaf Marco , More Sanket , Ganne Maarten , García-Caballero Melissa , Borri Mila , Verhoeven Jelle , Agrawal Madhur , Jacobs Kathryn , Bergers Gabriele , Blacher Silvia , Ghesquière Bart , Dewerchin Mieke , Swinnen Johan V. , Vinckier Stefan , Soengas María S. , Carmeliet Peter , Noël Agnès , Agostinis Patrizia
Published: May 2022

Autophagy has vasculoprotective roles, but whether and how it regulates lymphatic endothelial cells (LEC) homeostasis and lymphangiogenesis is unknown. Here, we show that genetic deficiency of autophagy in LEC impairs responses to VEGF-C and injury-driven corneal lymphangiogenesis. Autophagy loss in LEC compromises the expression of main effectors of LEC identity, like VEGFR3, affects mitochondrial dynamics and causes an accumulation of lipid droplets (LDs) in vitro and in vivo. When lipophagy is impaired, mitochondrial ATP production, fatty acid oxidation, acetyl-CoA/CoA ratio and expression of lymphangiogenic PROX1 target genes are dwindled. Enforcing mitochondria fusion by silencing dynamin-related-protein 1 (DRP1) in autophagy-deficient LEC fails to restore LDs turnover and lymphatic gene expression, whereas supplementing the fatty acid precursor acetate rescues VEGFR3 levels and signaling, and lymphangiogenesis in LEC-Atg5−/− mice. Our findings reveal that lipophagy in LEC by supporting FAO, preserves a mitochondrial-PROX1 gene expression circuit that safeguards LEC responsiveness to lymphangiogenic mediators and lymphangiogenesis.