bluuebunny/crossref_metadata_2025 huggingface dataset:
High resolution photocatalytic mapping of SARS-CoV-2 Spike protein-host cell membrane interactions
Authors: Datta Suprama , Tavares Alexander H. , Reyes-Robles Tamara , Ryu Keun Ah , Khan Nazimuddin , Bechtel Tyler J. , Bertoch Jayde M. , White Cory H. , Hazuda Daria J. , Vora Kalpit A. , Hett Erik C. , Fadeyi Olugbeminiyi O. , Oslund Rob C. , Saeed Mohsan , Emili Andrew
Published: September 2022

Identifying protein environments at the virus-host cell interface can improve our understanding of viral entry and pathogenesis. SARS-CoV-2, the virus behind the ongoing COVID-19 pandemic, uses the cell surface ACE2 protein as a major receptor, but the contribution of other cellular proteins in the entry process is unknown. To probe the microenvironment of SARS-CoV-2 Spike-ACE2 protein interactomes on human cells, we developed a photocatalyst-based viral-host protein microenvironment mapping platform (ViraMap) employing iridium photocatalysts conjugated to Spike for visible-light driven proximity labelling on host cells. Application of ViraMap on ACE2-expressing cells captured ACE2, the established co-receptor NRP1, as well as other proteins implicated in host cell entry and immunomodulation. We further investigated these enriched proteins via loss-of-function and over-expression in pseudotype and authentic infection models and observed that the Ig receptor PTGFRN and tyrosine kinase ligand EFNB1 can serve as SARS-CoV-2 entry factors. Our results highlight additional host targets that participate infection and showcase ViraMap for interrogating virus-host cell surface interactomes.
SOGO-SOFI, light-modulated super-resolution optical fluctuation imaging using only 20 raw frames for high-fidelity reconstruction
Authors: Xue Fudong , He Wenting , Peng Dingming , You Hui , Zhang Mingshu , Xu Pingyong
Published: September 2022

Taking advantage of the stochastic photoswitching of genetically encodable reversibly photoswitchable fluorescent proteins (RSFPs), super-resolution optical fluctuation imaging (SOFI) and its variant photochromic stochastic optical fluctuation imaging (pcSOFI) are valuable tools for wide field super- resolution (SR) imaging. Live-cell (pc)SOFI, which requires a small number of original frames to reconstruct an SR image, is prone to structural discontinuity artifacts and low spatial resolution. Herein, we developed a repeated synchronized on- and gradually off-switching SOFI (SOGO-SOFI) that maximized the photoswitching frequency of RSFPs by light modulation and required only 20 frames for high-quality reconstruction. Live-cell SOGO-SOFI imaging of the endoplasmic reticulum (ER) exhibited 10 times higher temporal resolution (100 fps) and fewer artifacts than pcSOFI. Moreover, a combination of SOGO-SOFI with Airyscan further increased the image contrast and the resolution of Airyscan by a factor of 1.5 from 140 nm to 91 nm. The capabilities of SOGO-SOFI were further demonstrated by dual- color imaging of nucleolar proteins in mammalian cells and deep imaging of ER structures in thick brain slices (20.6 µm).
Chorography and conformational dynamism of the Soluble Human Fibrinogen in solution
Authors: Pinelo Jose Emiliano Esparza , Manandhar Pragya , Popovic Grega , Ray Katherine , Nguyen Quoc , Iavarone Anthony T. , Offenbacher Adam R. , Hudson Nathan E. , Sen Mehmet
Published: September 2022

Fibrinogen is a soluble, multi-subunit and multi-domain dimeric protein, which, upon its proteolytic cleavage by thrombin, is converted to insoluble fibrin initiating polymerization that substantially contributes to clot growth. The consentaneous structural view of the soluble form of fibrinogen is relatively straight and rigid-like. However, fibrinogen contains numerous, transiently-accessible “cryptic” epitopes for hemostatic and immunologic proteins, suggesting that fibrinogen exhibits conformational flexibility, which may play functional roles in its temporal and spatial interactions. Hitherto, there has been limited information on the solution structure and internal flexibility of soluble fibrinogen. Here, utilizing an integrative, biophysical approach involving temperature-dependent hydrogen-deuterium exchange mass spectrometry, small angle X-ray scattering, and negative stain electron microscopy, we present a holistic, conformationally dynamic model of human fibrinogen in solution. Our data reveal a high degree of internal flexibility, accommodated by four major and distinct flexible sites along the central axis of the protein. We propose that the fibrinogen structure in solution consists of a complex, conformational landscape with multiple local minima, rather than a single, rigid topology. This is further supported by the location of numerous point mutations that are linked to dysfibrinogenemia, and post-translational modifications, residing near fibrinogen flexions. This work provides a molecular basis for the structural “dynamism” of fibrinogen that is expected to influence the broad swath of functionally diverse macromolecular interactions and fine-tune the structural and mechanical properties of blood clots.
Attention-based GCN Integrates Multi-omics Data for Breast Cancer Subtype Classification and Patient-specific Gene Marker Identification
Authors: Guo Hui , Lv Xiang , Li Yizhou , Li Menglong
Published: September 2022

Breast cancer is a heterogeneous disease and can be divided into several subtypes with unique prognostic and molecular characteristics. Classification of breast cancer subtypes plays an important role in the precision treatment and prognosis of breast cancer. Benefitting from the relation-aware ability of graph convolution network (GCN), we presented a multi-omics integrative method, attention-based GCN, for breast cancer molecular subtype classification using mRNA expression, copy number variation, and DNA methylation multi-omics data. Several attention mechanisms were performed and all exhibited effectiveness in integrating heterogeneous data. Column-wise attention-based GCN outperformed the other baseline methods, achieving AUC of 0.9816, ACC of 0.8743 and MCC of 0.8151 in 5-fold cross validation. Besides, Layer-wise Relevance Propagation (LRP) algorithm was used for interpretation of model decision and could identify patient-specific important biomarkers which were reported to be related to the occurrence and development of breast cancer. Our results highlighted the effectiveness of GCN and attention mechanisms in multi-omics integrative analysis and implement of LRP algorithm could provide biologically reasonable insights into model decision.

Author Summary

Identification of molecular subtype is essential to understanding the pathogenesis of cancer and advancing the development of cancer precision treatment. We have developed a graph convolution network architecture to predict the molecular subtype of breast cancer patients based on multi-omics data. The major difference between our work and other methods is that we have offered a new view for multi-omics data integration with the assistance of graph convolution network. Besides, we adopted an interpretability method to explain the model decision and prioritize the genes for biomarker discovery.
Self-assembly of cellular neighborhoods converts stochastic signaling into sustained olfactory neurogenesis
Authors: Rajan Sriivatsan G. , Lombardo Joseph N. , Nacke Lynne M. , Manuchehrfar Farid , Wong Kaelan , Garcia Jocelyn , Liang Jie , Saxena Ankur
Published: September 2022

Olfactory neurogenesis occurs continuously throughout the lives of vertebrates, including in humans, and relies on the rapid, unceasing differentiation and integration of neurons into a complex multicellular network. The system-wide regulation of this intricate choreography is poorly understood; in particular, it is unclear how progenitor cells convert stochastic fluctuations in cell-cell signaling, over both space and time, into streamlined fate decisions. Here, we track single-cell level multicellular dynamics in the developing zebrafish olfactory epithelium, perturb signaling pathways with temporal specificity, and find that the continuous generation of neurons is driven by the spatially-restricted self-assembly of transient groups of progenitor cells, i.e. cellular neighborhoods. Stochastic modeling and validation of the underlying genetic circuit reveals that neighborhood self-assembly is driven by a tightly regulated bistable toggle switch between Notch signaling and the transcription factor Insulinoma-associated 1a that is responsive to inter-organ retinoic acid signaling. Newly differentiating neurons emerge from neighborhoods and, in response to brain-derived neurotrophic factor signaling, migrate across the olfactory epithelium to take up residence as apically-located, mature sensory neurons. After developmental olfactory neurogenesis is complete, inducing injury results in a robust expansion of neighborhoods, followed by neuroregeneration. Taken together, these findings provide new insights into how stochastic signaling networks spatially pattern and regulate a delicate balance between progenitors and their neuronal derivatives to drive sustained neurogenesis during both development and regeneration.
Excitatory inhibitory imbalance underlies hippocampal atrophy in individuals with 22q11.2 Deletion Syndrome with psychotic symptoms
Authors: Mancini Valentina , Saleh Muhammad G. , Delavari Farnaz , Bagautdinova Joëlle , Eliez Stephan
Published: September 2022

Background

Abnormal neurotransmitter levels have been reported in subjects at high risk for schizophrenia, leading to a shift in the excitatory/inhibitory balance. However, it is unclear if these alterations are predating the onset of clinically relevant symptoms. Our aim was to explore in vivo measures of excitatory/inhibitory balance in 22q11.2 deletion carriers, a population at high genetic risk for psychosis.

Methods

Glx (glutamate + glutamine) and GABA+ concentrations were estimated in the anterior cingulate cortex (ACC), superior temporal gyrus (STG) and hippocampus using a MEGAPRESS sequence and the Gannet toolbox in 52 deletion carriers and 42 controls. T1-weighted images were acquired longitudinally and processed with Freesurfer v.6.0 to extract hippocampal volume. Subgroup analyses were conducted in deletion carriers with psychotic symptoms identified by means of SIPS.

Results

While no differences were found in the ACC, deletion carriers had higher levels of Glx in the hippocampus and STG, and lower levels of GABA+ in the hippocampus compared to controls. We additionally found a higher Glx concentration in the hippocampus of psychotic compared to non-psychotic deletion carriers. Finally, more pronounced hippocampal atrophy and increased functional variability were both significantly associated with increased Glx levels in deletion carriers.

Conclusions

This study provides evidence for an excitatory/inhibitory imbalance in temporal brain structures of deletion carriers, with a further hippocampal Glx increase in individuals with psychotic symptoms that was associated with hippocampal atrophy and abnormal function. These results support theories proposing abnormally enhanced glutamatergic neural transmission as a mechanistic explanation for hippocampal atrophy via excitotoxicity. Overall, our results highlight a central role of glutamate in the hippocampus of individuals at genetic risk for schizophrenia.
Mucosal immunity and antibody anergy in COVID-exposed Covishield vaccinees
Authors: Kannian Priya , Mahanathi Pasuvaraj , Gracemary Arul , Kumarasamy Nagalingeswaran , Challacombe Stephen J.
Published: September 2022

Knowledge is limited on mucosal immunity induction and longitudinal responses to vaccination against SARS-CoV2. Here, we determined serum/salivary antibodies and cytokines after three Covishield vaccine doses. Sera from 205 healthcare workers (HCWs) one-month after first- dose; one-, three- and six-months after second-dose; paired sera and stimulated whole mouth fluid (SWMF) from 10 HCWs one-, three- and six-months after third-dose were tested for anti- spike SARS-CoV2 antibodies by ECLIA and for cytokines by ELISA/cytokine bead arrays. One-month after second-dose, antibodies had increased significantly (6-fold) in COVID-naïve group, but declined (1.5-fold) in those previously exposed to COVID. At one-month after first- dose, IL-10 levels were statistically higher in the previously COVID-exposed group compared to COVID-naïve group (p<0.02). Breakthrough infections were 44% in COVID-naïve group, while re-infections were 27% in COVID-exposed group (p<0.02). Proinflammatory cytokines–IL- 17/IL-21 at one-month after first- and second-doses, and memory cytokines–IL-7/IL-15 at three- and six-months after second-dose were minimal. Antibodies spiked at one-month after third- dose and declined by three- and six-months after third-dose similar to post-second-dose. Paired sera and SWMF at one- and six-months after third-dose lacked adaptive immunity cytokine expression. Innate immunity cytokines (MIG, MCP-1, IL-8, TNF-α, IL-6, IL-1β) showed a declining trend in serum, but were sustained in SWMF. Thus, our findings suggest that first-dose acts as an antibody boost, while second-dose induces antibody anergy in the previously COVID- exposed group. Rapidly declining antibodies and minimal T cell cytokines raises concerns over their durability in subsequent virus exposures. Sustained innate cytokines emanating from the oral mucosa warrant further in-depth explorations.
MAGE enables population level RNAseq driven genotyping and (differential) allelic divergence detection in healthy kidney and carcinoma
Authors: Cedric Stroobandt , Tine Goovaerts , Louis Coussement , Femke De Graeve , Floris Voorthuijzen , Laure Van Steenbergen , Jeroen Galle , Wim Van Criekinge , Tim De Meyer
Published: September 2022

Decreasing sequencing costs have instigated large-scale RNAseq experiments, yet genetic polymorphisms in such data remain poorly exploited. Currently, allele-specific expression (ASE) studies focus almost exclusively on genetic variants explaining expression differences (cis-eQTLs), largely ignoring other ASE effects. The latter are typically associated with higher variance in expression of both copies of a gene, here called Allelic Divergence (AD). We therefore developed an RNAseq-driven population-level beta-binomial mixture model for (differential) AD detection. The model simultaneously enables RNAseq-driven genotyping, which outperforms alternative RNA genotyping methods when applied on healthy kidney data from The Cancer Genome Atlas. Moreover, we identify well-known non-cis-eQTL ASE, e.g. random monoallelic expression of HLA and immunoglobulin genes in healthy kidney, as well as allele-specific aberrations in clear cell kidney carcinoma, including long-range epigenetic silencing of protocadherins, copy-number alterations, and loss of imprinting. These methods are available as the Modeller of Allelic Gene Expression (MAGE) tool suite: https://biobix.github.io/MAGE/.
Bond-length distributions in ionically bonded materials with decomposition by coordination environment
Authors: Sawada Motonari , Iwamoto Ryoga , Kotani Takao , Sakakibara Hirofumi
Published: September 2022

The distributions are analysed of the bond lengths between cations and anions in nitrides, oxides and fluorides for which structural data are available in the Crystallography Open Database (https://www.crystallography.net/cod/). The distributions are decomposed according to analysis of the coordination environments of the cations, which are offered in the tool ChemEnv [Waroquiers, George, Horton, Schenk, Persson, Rignanese, Gonze & Hautier (2020). Acta Cryst. B76, 683–695]. The distributions show how well the concept of ionic radius works. Chemical trends can be observed from the obtained distributions. For example, the bond-length distribution for Sc—O is similar to that for Zr—O. The distributions for Mo—O and V—O show noteworthy similarity. Resources for reproducing all of the results are available at https://github.com/tkotani/CEBond, with additional results for nitrides and fluorides.
Revisiting neutron studies of reentrant spin glasses: the role of small-angle scattering
Authors: Mirebeau Isabelle , Martin Nicolas
Published: September 2022

The application is discussed of neutron methods to the study of reentrant spin glasses (RSGs), close to the transition towards a `canonical' spin glass (SG). The focus is on two emblematic systems, namely Au1−x
Fe
x
and amorphous a-Fe1−x
Mn
x
. A set of experimental results is presented to highlight their peculiar static and dynamic properties. The role of small-angle neutron scattering (SANS) is stressed as an important tool to unravel the structure of these complex systems over mesoscopic length scales. Finally, recent SANS results performed under an applied magnetic field in the region of the RSG → SG transition are presented. They show that vortex-like defects are present in the RSG region up to the critical line and vanish in the SG region. These defects, which develop only in a ferromagnetic medium, could be a key feature to probe the emergence of long-range magnetic order.
Failure analysis of a natural gas transmission X60 steel pipeline
Authors: Ma Yaxin , Zhang Hong , Gao Yifei , Men Zhengxing , He Ling , Cao Jianguo
Published: September 2022

Purpose

This paper aims to investigate the reason for natural gas leakage from transmission pipelines between Linyi and Shouguang in China during sealing tests, explore the failure mechanism and provide a reference for taking reasonable measures to prevent such accidents.

Design/methodology/approach

Failure analysis for the steel pipe has been addressed with different methods, such as microstructure analysis, inclusion analysis, corrosion product analysis, macro- and micro-morphology analyses and bacterially catalyzed experiments.

Findings

Several bulges were observed, especially at the bottom of the steel pipe sample, with the distribution and positioning not related to the weld. The inner surface of the steel pipe was severely corroded, and the oxide scale was flaking in many places. The greatest corrosion area was identified at the bottom of the steel pipe near the gas leakage point. Severe pitting and perforation corrosion in the pipeline were observed, and the main corrosion reaction products were Fe3O4, FeO and FeS. The grain orientation distribution near the crack (coarse grains <101> and fine grains <111> at the microcrack tip) indicates that fine grains may be beneficial in hindering crack propagation.

Originality/value

The principal mechanism for the corrosion failure is supposed to be due to the interaction of chloride ions with the sulfate-reducing microorganisms present and the stress corrosion cracking by chloride and sulfide formed by the sulfate-reducing microorganisms.
Aviation operators (pilots, ATCOs) decision-making process
Authors: Kale Utku , Alharasees Omar , Rohacs Jozsef , Rohacs Daniel
Published: September 2022

Purpose

The purpose of this paper is to investigate and evaluate the subjective decision-making of pilots during final approach with varying degrees of experience for landing and go-around.

Design/methodology/approach

In this research, the “Lorenz Attractor” was modified and used to model the subjective decision-making of pilots during the final approach. For landing and go-around situations, “hesitation frequency” and “decision-making time” were calculated for the subjective decision-making of pilots.

Findings

In this research, the modified Chaotic Lorenz Model was used on MATLAB with varying degrees of experience, namely, student pilots, less-skilled pilots, experienced pilots and well-experienced pilots. Based on the outcomes, the less-skilled pilot needs nearly four times more decision-making time on landing or go-around compared to the well-experienced pilot during the final approach.

Practical implications

Operators (pilots, air traffic controllers) need to make critical and timely decisions in a highly complex work environment, which is influenced by several external elements such as experience level and human factors. According to NASA, 80% of aviation accidents occur due to human errors specifically over the course of the aviation decision-making process in dynamic circumstances. Due to the consequences of this research the operators' training should be redesigned by assisting flight instructors on the weaknesses of pilots.

Originality/value

This research explores the endogenous dynamics of the pilot decision-making process by applying a novel “Chaotic Lorenz Model” on MATLAB. In addition, the operator's total decision time formula was improved by including the decision reviewing time and external factors. Moreover, subjective decision-making model created by the current authors and Wicken's information model were modified to the highly automated systems.
Audit committee characteristics and corporate philanthropic donations before and during COVID-19
Authors: Umar Umar Habibu , Jibril Abubakar Isa , Musa Sulaiman
Published: September 2022

Purpose

This study aims to examine the effects of audit committee attributes on corporate philanthropic donations before and during the COVID-19 pandemic.

Design/methodology/approach

The study targets Nigeria’s listed firms between 2019 and 2020. We hand-collected the data from the available published annual reports of 141 and 128 firms for 2019 and 2020, respectively. Therefore, the authors used a total of 269 firm-year observations for the study. The authors used ordinary least square regression to analyze the data and Tobit regression to establish the robustness of the results.

Findings

The results indicate that the frequency of audit committee meetings has a significant positive relationship with corporate philanthropic donations before and during COVID-19. In the case of audit committee independence, it has only a significant positive relationship with corporate philanthropic donations during the pandemic. However, the findings reveal that audit committee size and foreign directors on the audit committee do not influence corporate philanthropic donations before and during COVID-19.

Research limitations/implications

The study considers audit committee characteristics out of the corporate governance mechanisms that can influence the philanthropic donations of the listed firms in Nigeria over two years from 2019 and 2020.

Practical implications

The findings have practical implications for encouraging the audit committee to support philanthropic donations for the welfare of the poor and the needy, particularly in difficult times like the COVID-19 period. The results could also help regulators and policymakers to provide regulations and policies that can encourage firms to participate actively in philanthropic activities to their best ability.

Social implications

Motivating firms to provide philanthropic donations for the welfare of underprivileged persons could strongly support the government’s effort to minimize the socioeconomic problems caused by COVID-19.

Originality/value

The study contributes to the scant literature that establishes the impact of audit committee attributes on firm philanthropic donations toward helping the poor and the needy in difficult periods.
Take-off, turbulence and turnaround
Authors: Forseth Ulla
Published: September 2022

Purpose

The aim of this paper is to explore the evolving nature of the work of cabin crew in a Scandinavian carrier in three eras, drawing on theories of gender and emotional labour.

Design/methodology/approach

The paper draws on ethnographic data from fieldwork, interviews and documents.

Findings

From being a feminized and temporary occupation for young, upper- and middle-class women in the 1970s, the occupation became a full-time job and with greater diversity of cabin crew. Today there are signs of the job becoming a precarious and temporary one of demanding and devalorized work in a polarized and class-divided labour market. Changing circumstances impact on the emotional labour requirement and terms and conditions at work.

Research limitations/implications

A limitation is that the research design was not initially longitudinal in the sense that the author does not have exactly the same kind of data from each era. The author has, however, been involved in this field for two decades, used multiple methods and interacted with different stakeholders and drew on a unique data material.

Practical implications

The development in aviation is contributing to new discriminatory practices, driving employee conditions downwards and changing the job demands. This development will have practical consequences for the lives and families of cabin crew.

Social implications

The analysis illustrates how work ‘constructs' workers and contributes in creating jobs that are not sustainable for the employees. Intensification of work, insecurity and tougher working conditions also challenge key features in the Nordic model such as proper pay, decent work and a life-long employment. Much indicates that the profession is again becoming a temporary one of demanding work with poor working conditions in a polarized and class-divided labour market.

Originality/value

The research contributes to the literature on emotional labour, gender and the evolving nature of the work of cabin crew. The unique data material, the longitudinal aspect of the research and the focus on a single network carrier are good in charting changes over time.
Financial capability: a systematic conceptual review, extension and synthesis
Authors: Xiao Jing Jian , Huang Jin , Goyal Kirti , Kumar Satish
Published: September 2022

Purpose

This study aims to examine the literature on consumer financial capability. By analyzing the research trends, theories, definitions and themes, the literature on financial capability is synthesized, and agenda for future research is suggested. A framework is presented that portrays the antecedents as well as the outcomes of financial capability and their interlinkages.

Design/methodology/approach

Following a systematic approach, the review is based on 215 articles published during January 2007 and–March 2022, retrieved from Scopus. It presents the definitions and theories of financial capability, publication trends, influential articles, prominent authors, prolific journals and countries publishing on financial capability. Using bibliographic coupling, the intellectual structure of the topic is explored, along with offering a framework through content analysis.

Findings

The bibliographic coupling analysis identifies four major clusters of research themes and capability theory appeared to be the most prominent theory. The synthesis draws upon five conceptual definitions of financial capability. Based on the discussion, in this review, financial capability is defined as an individual ability to apply appropriate financial knowledge, perform desirable financial behaviors and take available financial opportunities for achieving financial well-being. A conceptual framework delineates the synthesized literature and propositions based on this framework and relevant research are proposed. Finally, directions for future research are discussed.

Originality/value

This paper is an attempt to offer a comprehensive synthesis of the scholarship on financial capability and its conceptualization. It further proposes an extensive future research agenda. The study has implications for financial services providers relating to retail bank marketing.
The global impact of management on soil nematode abundances
Authors: White Hannah J.
Published: September 2022

Research Highlight: Li, X., Liu, T., Li, H., Geisen, S., Hu, F., & Liu, M. (2022). Management effects on soil nematode abundance differ among functional groups and land‐use types at a global scale. Journal of Animal Ecology, https://doi.org/10.1111/1365‐2656.13744. Despite the well‐documented decline of aboveground species abundances as a result of land‐use intensification, there has been little attention on the effects of human activities on belowground species abundances. Li et al. analyse nematode data, the most abundant animal on the planet, from across the globe to determine whether their abundances vary between managed and unmanaged habitats. The authors show that, unlike aboveground biodiversity, nematode abundance is higher in managed than unmanaged primary and secondary habitats. Furthermore, responses to land management vary between trophic groups and they do not appear to follow the general hypothesis that higher trophic levels are more vulnerable to human activity than those further down the food chain, except in urban habitats. Finally, Li et al. show that the relationships between environmental predictors and species abundance were weakened (and sometimes reversed) in managed habitats. Together, their results reveal how land‐use management is impacting the trophic composition of soil nematode communities and their relationships with the environment, which has implications for ecosystem functioning.
Debunking Murray‐Darling Basin water trade myths
Authors: Wheeler Sarah Ann
Published: September 2022

Australia, and particularly the Murray–Darling Basin (MDB), has the most mature and adopted water markets globally. Water trading is an important policy tool to deal with water scarcity issues, demonstrating allocative, dynamic and productive efficiency benefits. At the same time, water markets have been controversial in Australia. Markets have been blamed for a range of issues, including claims of unsustainability, inequity, farm bankruptcy, farmer distress and farm exit. This study reviews the MDB water trade literature and finds little evidence to support such myths. Arguably, the biggest misconception is that critics do not separate water markets from the meta‐governance institutional structures that define them. Perceived water market failures are often due to governance issues – not water trade per se. This is not to say that market failure does not exist, it does, and indeed, there are also serious distributional issues that need addressing (e.g., water property entitlements for indigenous stakeholders). As such, water market design and governance need to adapt and evolve as problems arise and the market matures. However, in an era of increasing water scarcity, enabling water trade remains one of the most important instruments available to assist in water sharing, reallocation and farm adaptation to climate change.
Of critical importance: Toward a quantitative probabilistic risk assessment framework for critical infrastructure
Authors: Nas Ivo , Helsloot Ira , Cator Eric
Published: September 2022

Critical comments can be made to the current risk assessment framework for critical infrastructure used in The Netherlands: the Dutch National Risk Assessment (DNRA). The DNRA uses a qualitative approach to risk assessment, based on, for example, ordinal risk scoring and the risk matrix. Even though qualitative risk assessment methods are internationally popular, there is no scientific evidence that a qualitative approach to risk assessment actually works. In the case of the DNRA, the main points of criticisms relate to the usage of a subjective concept of risk, dependency on subjective risk experts, the use of risk matrices and the absence of decision rules. To combat these criticisms, this article proposes a quantitative probabilistic risk assessment framework for critical infrastructure based upon four design principles, that a methodologically justified risk assessment method for critical infrastructure should meet. The proposal made for the quantitative risk assessment framework uses a Bayesian approach, a standardized measure for negligible risk in the form of a yearly mortality probability of 10−6, and Disability Adjusted Life Years to quantify human life years for social cost–benefit analysis. Finally, the proposed quantitative method is demonstrated in a case study.
Association between non‐profit hospital community benefit spending and health outcomes
Authors: Wen Grant , Zare Hossein , Eisenberg Matthew D. , Anderson Gerard
Published: September 2022

Objective

To determine if greater non‐profit hospital spending for community benefits is associated with better health outcomes in the county where they are located.

Data Sources and Study Setting

Community benefit data from IRS Form 990/Schedule H was linked to health outcome data from Area Health Resource Files, Map the Meal Gap, and Medicare claims from the Center for Medicare and Medicaid Services at the county level. Counties with at least one non‐profit hospital in the United States from 2015 to 2019 (N = 5469 across the 5 years) were included.

Study Design

We ran multiple regressions on community benefit expenditures linked with the number of health professionals, food insecurity, and adherence to diabetes and hypertension medication for each county.

Data Collection

The three outcomes were chosen based on prior studies of community benefit and a recent survey sent to 12 health care executives across four regions of the U.S. Data on community benefit expenditures and health outcomes were aggregated at the county level.

Principal Findings

Average hospital community benefit spending in 2019 was $63.6 million per county ($255 per capita). Multivariable regression results did not demonstrate significant associations of total community benefit spending with food insecurity or medication adherence for diabetes. Statistically significant associations with the number of health professionals per 1000 (coefficient, 12.10; SE, 0.32; p < 0.001) and medication adherence for hypertension (marginal effect, 0.27; SE, 0.09; p = 0.003) were identified, but both would require very large increases in community benefit spending to meaningfully improve outcomes.

Conclusions

Despite varying levels of non‐profit hospital community benefit investment across counties, higher community benefit expenditures are not associated with an improvement in the selected health outcomes at the county level. Hospitals can use this information to reassess community benefit strategies, while federal, state, and local governments can use these findings to redefine the measures of community benefit they use to monitor and grant tax exemption.
Evaluation of a non‐pharmacological interdisciplinary pain rehabilitation and functional restoration program for chronic pain in veterans
Authors: Ward Ralph , Rauch Sheila A. M. , Axon Robert Neal , Saenger Michael S.
Published: September 2022

Objective

To conduct a quality improvement evaluation of the Empower Veterans Program (EVP), an interdisciplinary pain rehabilitation/functional restoration program option for functional restoration for high‐impact chronic pain, offered in a large metro‐area Veterans Health Administration (VHA) system.

Data Sources

VHA Corporate Data Warehouse electronic medical record data for patients treated by EVP between 2015 and 2019.

Evaluation Design

This retrospective design first compared EVP patients considered engaged or not engaged in completing treatment in terms of demographic characteristics and post‐treatment changes in clinical measures related to opioid use and mental health. We then compared mortality risk between matched groups of treated and untreated patients with chronic pain and concurrent opioid prescriptions using propensity score matching and Cox proportional hazards methods. “Treated” in the matched groups was defined as any level of EVP participation (i.e., both engaged and not engaged).

Data Collection/Extraction Methods

We first identified 1053 EVP patients with 1 year of pre‐and post‐treatment follow‐time and determined their engagement level. From those with chronic pain and prescription opioids, we matched 237 EVP patients to 375 untreated patients.

Principal Findings

Engaged patients (57.4% of treated patients), were somewhat older than the non‐engaged (mean age 57.1 vs. 53.7, Cohen's D = 0.30), and achieved lower mean PHQ9 depression scores in the post‐treatment year (9.2 vs. 10.6, Cohen's D = 0.20). Participation in EVP was associated with a 65% lower mortality risk among Veterans with chronic pain and opioid use when compared to the untreated patients: (HR: 0.35, 95% CI: 0.17, 0.75).

Conclusions

EVP was associated with a large reduction in mortality risk for Veterans with both chronic pain and opioid use. This result could inform the decision process in a VA station or region when considering providing or expanding access to an interdisciplinary rehabilitation/functional restoration program for chronic pain.
Review article: Ankle intra‐articular haematoma block for reduction of unstable ankle fractures in the emergency department: An integrative review
Authors: Stitt Rebecca , Jull Andrew
Published: September 2022

A review was conducted to assess the efficacy and safety of the intra‐articular haematoma block (IAHB) for manipulation of ankle fractures in ED. Any study investigating the success of IAHB for ankle fracture reduction published in English was sought. Seven databases were searched. The Cochrane Risk of Bias tool was used to quality assess the included studies. Three studies met the inclusion criteria (n = 436 patients). Just one study was a randomised controlled trial (n = 42). The two non‐randomised studies that included the majority of patients were assessed as at high overall risk of bias. The studies reported no significant difference in the overall rate of successful reduction or patient‐reported pain scores between IAHB and procedural sedation groups. A subgroup analysis in one study suggested timelier reduction by 51.4 min (P = 0.01) for fractures involving subluxation when using IAHB, but that more patients with dislocation were reduced on first attempt when using procedural sedation compared to IAHB (74.0% vs 54.8%, P < 0.01). No adverse events were reported from using IAHB, although no study measured events such as joint sepsis or chondrolysis. Findings suggest that IAHB might be safe and effective but the evidence is very limited. High‐quality research is required before IAHB can be considered a routine alternative. However, IAHB could be considered in situations where the risk of procedural sedation outweighs the likely very low risk of chondrolysis.
Molecular diet analysis in mussels and other metazoan filter feeders and an assessment of their utility as natural eDNA samplers
Authors: Weber Sven , Junk Isabelle , Brink Lukas , Wörner Manuel , Künzel Sven , Veith Michael , Teubner Diana , Klein Roland , Paulus Martin , Krehenwinkel Henrik
Published: September 2022

Molecular gut content analysis is a popular tool to study food web interactions and has recently been suggested as an alternative source for DNA‐based biomonitoring. However, the overabundant consumer's DNA often outcompetes that of its diet during PCR. Lineage‐specific primers are an efficient means to reduce consumer amplification while retaining broad specificity for dietary taxa. Here, we designed an amplicon sequencing assay to monitor the eukaryotic diet of mussels and other metazoan filter feeders and explore the utility of mussels as natural eDNA samplers to monitor planktonic communities. We designed several lineage‐specific rDNA primers with broad taxonomic suitability for eukaryotes. The primers were tested using DNA extracts of different limnic and marine mussel species and the results compared to eDNA water samples collected next to the mussel colonies. In addition, we analysed several 25‐year time series samples of mussels from German rivers. Our primer sets efficiently prevent the amplification of mussels and other metazoans. The recovered DNA reflects a broad dietary preference across the eukaryotic tree of life and considerable taxonomic overlap with filtered water samples. We also show the utility of a reversed version of our primers, which prevents amplification of nonmetazoan taxa from complex eukaryote community samples, by enriching fauna associated with the marine brown algae Fucus vesiculosus. Our protocol will enable large‐scale dietary analysis in metazoan filter feeders, facilitate aquatic food web analysis and allow surveying of aquacultures for pathogens. Moreover, we show that mussels and other aquatic filter feeders can serve as complementary DNA source for biomonitoring.
Nuclear war as a predictable surprise
Authors: Rendall Matthew
Published: September 2022

Like asteroids, hundred‐year floods and pandemic disease, thermonuclear war is a low‐frequency, high‐impact threat. In the long run, catastrophe is inevitable if nothing is done − yet each successive government and generation may fail to address it. Drawing on risk perception research, this paper argues that psychological biases cause the threat of nuclear war to receive less attention than it deserves. Nuclear deterrence is, moreover, a ‘front‐loaded good’: its benefits accrue disproportionately to proximate generations, whereas much of the expected cost will be borne in the distant future. Recent surveys indicate that the US and Russian publics assign a surprisingly high likelihood to nuclear war. Nevertheless, earlier research suggests that it is probably not believed to be just around the corner. This, along with the absence of easy solutions, encourages governments and publics to give priority to more pressing concerns. The danger is that the pattern will continue clear up to the point that nuclear war arrives.
Circ_0002476 regulates cell growth, invasion, and mtDNA damage in non–small cell lung cancer by targeting miR‐1182/TFAM axis
Authors: Wang Weijie , Sun Haiting , Ma Xuan , Zhu Ting , Zhang Haina
Published: September 2022

Background

Many circular RNAs (circRNAs) have been identified as potential targets for cancer therapy. However, the role of circ_0002476 in non–small cell lung cancer (NSCLC) progression has not been explored.

Methods

The expression levels of circ_0002476, microRNA (miR)‐1182, and mitochondrial transcription factor A (TFAM) were detected by quantitative real‐time polymerase chain reaction. Cell functions were measured by cell counting kit 8 assay, EdU assay, colony formation assay, flow cytometry and transwell assay. Mitochondrial DNA (mtDNA) damage was assessed by measuring mtDNA copy number and transcript levels of ND1 and ATP6. Protein expression was examined by western blot. The interaction between miR‐1182 and circ_0002476 or TFAM was detected by dual‐luciferase reporter assay and RNA pull‐down assay. Animal experiments were performed to explore circ_0002476 role in vivo. Exosomes (Exs) were extracted and identified by transmission electron microscopy and nanoparticle tracking analysis.

Results

Circ_0002476 was overexpressed in NSCLC tissues and cells. Circ_0002476 knockdown suppressed NSCLC cell proliferation and invasion, while promoted apoptosis and mtDNA damage. Circ_0002476 could sponge miR‐1182, and miR‐1182 inhibitor reversed the influence induced by circ_0002476 knockdown. Moreover, TFAM was targeted by miR‐1182, and miR‐1182 hindered NSCLC cell progression by regulating TFAM. Additionally, circ_0002476 silencing could reduce NSCLC tumor growth by miR‐1182/TFAM. Further analyzed showed that Exs were involved in the transport of circ_0002476 between cells.

Conclusion

Taken together, our findings suggested that circ_0002476 might be a potential molecular target for NSCLC treatment.
Importance of Bmal1 in Alzheimer's disease and associated aging‐related diseases: Mechanisms and interventions
Authors: Fan Rongping , Peng Xuemin , Xie Lei , Dong Kun , Ma Delin , Xu Weijie , Shi Xiaoli , Zhang Shujun , Chen Juan , Yu Xuefeng , Yang Yan
Published: September 2022

With the aging world population, the prevalence of aging‐related disorders is on the rise. Diseases such as Alzheimer's, type 2 diabetes mellitus (T2DM), Parkinson's, atherosclerosis, hypertension, and osteoarthritis are age‐related, and most of these diseases are comorbidities or risk factors for AD; however, our understandings of molecular events that regulate the occurrence of these diseases are still not fully understood. Brain and muscle Arnt‐like protein‐1 (Bmal1) is an irreplaceable clock gene that governs multiple important physiological processes. Continuous research of Bmal1 in AD and associated aging‐related diseases is ongoing, and this review picks relevant studies on a detailed account of its role and mechanisms in these diseases. Oxidative stress and inflammation turned out to be common mechanisms by which Bmal1 deficiency promotes AD and associated aging‐related diseases, and other Bmal1‐dependent mechanisms remain to be identified. Promising therapeutic strategies involved in the regulation of Bmal1 are provided, including melatonin, natural compounds, metformin, d‐Ser2‐oxyntomodulin, and other interventions, such as exercise, time‐restricted feeding, and adiponectin. The establishment of the signaling pathway network for Bmal1 in aging‐related diseases will lead to advances in the comprehension of the molecular and cellular mechanisms, shedding light on novel treatments for aging‐related diseases and promoting aging‐associated brain health.
The impact of implementing patient‐reported measures in routine maternity care: a systematic review
Authors: Chen An , Väyrynen Kirsi , Schmidt Alexandra , Leskelä Riikka‐Leena , Torkki Paulus , Heinonen Seppo , Tekay Aydin , Acharya Ganesh
Published: September 2022

Introduction

While there is growing interest in applying patient‐reported measures (PRMs) in clinical routine, limited collective evidence of the impact of PRMs hinder their widespread use in specific contexts, such as maternity care. Our objective was to synthesize existing emperical evidence on the impact of implementing PRMs in routine maternity care.

Material and methods

We followed the Preferred Reporting Items for Systematic Reviews and Meta‐analyses guidelines (version 2020). We electronically searched six databases for the literature on the implementation of PRMs in maternity care. A multi‐level (woman, clinical, organizational, national and societal) analytic framework for analyzing and synthesizing emperically proven impacts of PRMs was developed. Quality was assessed using the Mixed Method Appraisal Tool. The GRADE‐CERQual approach was used to assess the confidence in the review findings and arguments. The protocol was registered in PROSPERO (CRD42021234501).

Results

Overall, 4971 articles were screened. The emperical evidence, collected from 11 relevant studies, showed that the use of PRMs in routine maternity care could produce positive effects on clinical process (assessment and detection of health problems, clinical visit preparation, resource use, woman–professional communication, decision‐making, woman–professional relationship, and care quality), and health behavior and outcomes (women's health and wellbeing, quality of life, health behavior, experiences and satisfaction with healthcare services), awareness, engagement and self‐management of own health, and disclosure of health issues. The confidence in the review findings was low to moderate due to a limited number of studies, inadequate data and methodological limitations of included studies.

Conclusions

The limited emperical evidence available suggested that the use of PRMs may have positive effects at the individual health level and clinical process level. However, the evidence was not strong enough to provide policy recommendations on the use of PRMs in routine maternity care. This review revealed limitations of currently available research, such as lack of generalizability and narrow scopes in investigating impact. Efforts are needed to improve the quality of research on the use of PRMs in routine maternity care by widening the study population, including different types of PRMs, and considering the effects of PRMs at different levels and domains of healthcare.