bluuebunny/crossref_metadata_2025 huggingface dataset:
Lifting generic points
Authors: DOWNAROWICZ TOMASZ , WEISS BENJAMIN
Published: February 2024

Let
$(X,T)$
and
$(Y,S)$
be two topological dynamical systems, where
$(X,T)$
has the weak specification property. Let
$\xi $
be an invariant measure on the product system
$(X\times Y, T\times S)$
with marginals
$\mu $
on X and
$\nu $
on Y, with
$\mu $
ergodic. Let
$y\in Y$
be quasi-generic for
$\nu $
. Then there exists a point
$x\in X$
generic for
$\mu $
such that the pair
$(x,y)$
is quasi-generic for
$\xi $
. This is a generalization of a similar theorem by T. Kamae, in which
$(X,T)$
and
$(Y,S)$
are full shifts on finite alphabets.
Characteristics and suppression of beam distortion in a high repetition rate nanosecond stimulated Brillouin scattering phase conjugation mirror
Authors: Chen Yifu , Tan Bowen , Jin Duo , Chen Bin , Bai Zhenxu , Wang Kun , Wang Yulei , Lü Zhiwei
Published: February 2024

The stimulated Brillouin scattering phase conjugation mirror (SBS-PCM) based on liquid media is widely used in high-power laser systems due to its robust thermal load capacity, high energy conversion efficiency and improved beam quality. Nevertheless, with an increase in the pump repetition rate, thermally-induced blooming and optical breakdown can emerge, leading to distortions in the Stokes beam. In this study, we delved into the thermal effects in liquid SBS-PCMs employing hydrodynamic analysis, establishing a relationship between beam profile distortion and the thermal convection field. We calculated the temperature and convection velocity distribution based on the pump light parameters and recorded the corresponding beam profiles. The intensities of the beam profiles were modulated in alignment with the convection directions, reaching a velocity peak of 2.85 mm/s at a pump pulse repetition rate of 250 Hz. The residual sum of squares (RSS) was employed to quantify the extent of beam profile distortion relative to a Gaussian distribution. The RSS escalated to 7.8, in contrast to 0.7 of the pump light at a pump pulse repetition rate of 500 Hz. By suppressing thermal convection using a high-viscosity medium, we effectively mitigated beam distortion. The RSS was reduced to 0.7 at a pump pulse repetition rate of 500 Hz, coinciding with a twentyfold increase in viscosity, thereby enhancing the beam quality. By integrating hydrodynamic analysis, we elucidated and mitigated distortion with targeted solutions. Our research offers an interdisciplinary perspective on studying thermal effects and contributes to the application of SBS-PCMs in high-repetition-rate laser systems by unveiling the mechanism of photothermal effects.
The beer garden state: Neolocalism and clustering of craft breweries in New Jersey
Authors: Fouad Geoffrey , Scott Robert H.
Published: February 2024

This paper investigates the growth and clustering of craft breweries in New Jersey. We compiled a historical dataset from 1995 to 2020 that allows us to measure the degree of geographic clustering among craft breweries in New Jersey. The number of craft breweries in New Jersey grew 491% from 2012 to 2020 (from 22 to 130 craft breweries). An impetus for this growth was that New Jersey enacted legislation in 2012 that made opening and operating a craft brewery in the state more economically viable. Our analysis finds that craft breweries in New Jersey are clustering in specific parts of the state and that this is likely due to co-location benefits such as building a culture of craft beer that drives innovation, knowledge sharing, customer sharing, and a thicker labor market. While distinct craft beer clusters have formed in New Jersey, we find there is still significant opportunity for growth. Our analysis confirms this using data on planned craft brewery openings to measure changes in the size and density of clusters and where, in New Jersey, new clusters are likely to form.
Spatial standardization of taxon occurrence data—a call to action
Authors: Antell Gawain T. , Benson Roger B. J. , Saupe Erin E.
Published: February 2024

The fossil record is spatiotemporally heterogeneous: taxon occurrence data have patchy spatial distributions, and this patchiness varies through time. Large-scale quantitative paleobiology studies that fail to account for heterogeneous sampling coverage will generate uninformative inferences at best and confidently draw wrong conclusions at worst. Explicitly spatial methods of standardization are necessary for analyses of large-scale fossil datasets, because nonspatial sample standardization, such as diversity rarefaction, is insufficient to reduce the signal of varying spatial coverage through time or between environments and clades. Spatial standardization should control both geographic area and dispersion (spread) of fossil localities. In addition to standardizing the spatial distribution of data, other factors may be standardized, including environmental heterogeneity or the number of publications or field collecting units that report taxon occurrences. Using a case study of published global Paleobiology Database occurrences, we demonstrate strong signals of sampling; without spatial standardization, these sampling signatures could be misattributed to biological processes. We discuss practical issues of implementing spatial standardization via subsampling and present the new R package divvy to improve the accessibility of spatial analysis. The software provides three spatial subsampling approaches, as well as related tools to quantify spatial coverage. After reviewing the theory, practice, and history of equalizing spatial coverage between data comparison groups, we outline priority areas to improve related data collection, analysis, and reporting practices in paleobiology.
THE PROBLEM OF LANGUAGE IN ENNODIUS OF PAVIA
Authors: Hernández Lobato Jesús
Published: February 2024

This paper analyses the metaliterary statements that pervade the oeuvre of Ennodius of Pavia (a.d. 474–521) in order to reconstruct his underlying conception of language: its nature, power, function, limitations, and dangers. This new perspective provides a more nuanced insight into the paradoxical poetics of the author as well as his final renunciation to literature after his appointment as bishop of Pavia.
Lost needle in the oral cavity: can the nightmare be just a bad dream?
Authors: Rodríguez-Alcalá Laura , Valderrama-Penagos Johanna Ximena , O'Connor-Garcia St Ernesto , O'Connor-Reina Carlos
Published: February 2024

Objective

The loss of a scalpel or a needle during surgery can threaten the health of the patient and lead to additional costs, and radiographical assistance during surgery has been the only recovery method. This study evaluates the efficacy of a metal detector compared with conventional radiology for recovering a needle lost in the oropharynx during surgery.

Method

Different fragment sizes of needles normally used in pharyngoplasty were embedded at different locations and depths in a lamb's head. Three experienced and three junior otolaryngologists searched for the needle fragments using a metal detector and conventional radiology.

Results

All fragments were found with each method, but the mean searching time was 90 per cent shorter with the metal detector.

Conclusion

A metal detector can be a useful tool for locating needles that break during ENT surgery, as it requires less time than conventional radiology and avoids exposing patients to radiation.
Immunization of cattle with a Rhipicephalus microplus chitinase peptide containing predicted B-cell epitopes reduces tick biological fitness
Authors: Perez-Soria María Martina Esperanza , López-Díaz Daniel Gustavo , Jiménez-Ocampo Rafael , Aguilar-Tipacamú Gabriela , Ueti Massaro W. , Mosqueda Juan
Published: February 2024

Rhipicephalus microplus, the cattle fever tick, is the most important ectoparasite impacting the livestock industry worldwide. Overreliance on chemical treatments for tick control has led to the emergence of acaricide-resistant ticks and environmental contamination. An immunological strategy based on vaccines offers an alternative approach to tick control. To develop novel tick vaccines, it is crucial to identify and evaluate antigens capable of generating protection in cattle. Chitinases are enzymes that degrade older chitin at the time of moulting, therefore allowing interstadial metamorphosis. In this study, 1 R. microplus chitinase was identified and its capacity to reduce fitness in ticks fed on immunized cattle was evaluated. First, the predicted amino acid sequence was determined in 4 isolates and their similarity was analysed by bioinformatics. Four peptides containing predicted B-cell epitopes were designed. The immunogenicity of each peptide was assessed by inoculating 2 cattle, 4 times at 21 days intervals, and the antibody response was verified by indirect ELISA. A challenge experiment was conducted with those peptides that were immunogenic. The chitinase gene was successfully amplified and sequenced, enabling comparison with reference strains. Notably, a 99.32% identity and 99.84% similarity were ascertained among the sequences. Furthermore, native protein recognition was demonstrated through western blot assays. Chitinase peptide 3 reduced the weight and oviposition of engorged ticks, as well as larvae viability, exhibiting a 71% efficacy. Therefore, chitinase 3 emerges as a viable vaccine candidate, holding promise for its integration into a multiantigenic vaccine against R. microplus.
Cross-cultural validation of the revised Green et al., paranoid thoughts scale
Authors: Schlier Björn , Lincoln Tania M. , Kingston Jessica L. , So Suzanne H. , Gaudiano Brandon A. , Morris Eric M. J. , Ellett Lyn
Published: February 2024

Background

With efforts increasing worldwide to understand and treat paranoia, there is a pressing need for cross-culturally valid assessments of paranoid beliefs. The recently developed Revised Green et al., Paranoid Thoughts Scale (R-GPTS) constitutes an easy to administer self-report assessment of mild ideas of reference and more severe persecutory thoughts. Moreover, it comes with clinical cut-offs for increased usability in research and clinical practice. With multiple translations of the R-GPTS already available and in use, a formal test of its measurement invariance is now needed.

Methods

Using data from a multinational cross-sectional online survey in the UK, USA, Australia, Germany, and Hong Kong (N = 2510), we performed confirmatory factory analyses on the R-GPTS and tested for measurement invariance across sites.

Results

We found sufficient fit for the two-factor structure (ideas of reference, persecutory thoughts) of the R-GPTS across cultures. Measurement invariance was found for the persecutory thoughts subscale, indicating that it does measure the same construct across the tested samples in the same way. For ideas of reference, we found no scalar invariance, which was traced back to (mostly higher) item intercepts in the Hong Kong sample.

Conclusion

We found sufficient invariance for the persecutory thoughts scale, which is of substantial practical importance, as it is used for the screening of clinical paranoia. A direct comparison of the ideas of reference sum-scores between cultures, however, may lead to an over-estimation of these milder forms of paranoia in some (non-western) cultures.
Association of psychiatric disorders with clinical diagnosis of long COVID in US veterans
Authors: Nishimi Kristen , Neylan Thomas C. , Bertenthal Daniel , Seal Karen H. , O'Donovan Aoife
Published: February 2024

Background

Psychiatric disorders may be a risk factor for long COVID, broadly defined as COVID-19 conditions continuing three months post-acute infection. In US Veterans with high psychiatric burden, we examined associations between psychiatric disorders and clinical diagnosis of long COVID.

Methods

We conducted a retrospective cohort study using health records from VA patients with a positive SARS-CoV-2 test from February 2020 to February 2023. Generalized linear models estimated associations between any psychiatric disorder and likelihood of subsequent diagnosis with long COVID (i.e. two or more long COVID clinical codes). Models were adjusted for socio-demographic, medical, and behavioral factors. Secondary models examined individual psychiatric disorders and age-stratified associations.

Results

Among 660 217 VA patients with positive SARS-CoV-2 tests, 56.3% had at least one psychiatric disorder diagnosis and 1.4% were diagnosed with long COVID. Individuals with any psychiatric disorder had higher risk for long COVID diagnosis in models adjusted for socio-demographic factors, vaccination status, smoking, and medical comorbidities (relative risk, RR = 1.28, 95% CI 1.21–1.35), with the strongest associations in younger individuals. Considering specific disorders, depressive, anxiety, and stress-related disorders were associated with increased risk for long COVID diagnoses (RRs = 1.36–1.48), but associations were in the opposite direction for substance use and psychotic disorders (RRs = 0.78–0.88).

Conclusions

Psychiatric disorder diagnoses were associated with increased long COVID diagnosis risk in VA patients, with the strongest associations observed in younger individuals. Improved surveillance, treatment, and prevention for COVID-19 and its long-term sequelae should be considered for individuals with psychiatric conditions.
Neuroadaptive Bayesian optimisation can allow integrative design spaces at the individual level in the social and behavioural sciences… and beyond
Authors: Haartsen Rianne , Gui Anna , Jones Emily J. H.
Published: February 2024

Almaatouq et al. propose an integrative experiment design space combined with large samples for scientific advancement. We argue recent innovative designs combining closed-loop experiment designs and Bayesian optimisation allow for integrative experiments at an individual level during a single session, circumventing the necessity for large samples. This method can be applied across disciplines, including developmental and clinical research.
Replies to commentaries on beyond playing 20 questions with nature
Authors: Almaatouq Abdullah , Griffiths Thomas L. , Suchow Jordan W. , Whiting Mark E. , Evans James , Watts Duncan J.
Published: February 2024

Commentaries on the target article offer diverse perspectives on integrative experiment design. Our responses engage three themes: (1) Disputes of our characterization of the problem, (2) skepticism toward our proposed solution, and (3) endorsement of the solution, with accompanying discussions of its implementation in existing work and its potential for other domains. Collectively, the commentaries enhance our confidence in the promise and viability of integrative experiment design, while highlighting important considerations about how it is used.
Clinical isolate characteristics and demographics of patients with C.jejuni and C.coli infections in Northern Israel, 2015–2021
Authors: Tsafrir Ofri , Rohana Hanan , Bousani Lior , Orsan Khatib , Abozaid Said , Azrad Maya , Peretz Avi
Published: February 2024

C.coli is a significant cause of foodborne gastroenteritis worldwide, with the majority of cases attributed to C.jejuni. Although most clinical laboratories do not typically conduct antimicrobial susceptibility testing for C.coli, the rise in resistant strains has underscored the necessity for such testing and epidemiological surveillance. The current study presents clinical isolate characteristics and demographics of 221 patients with C.coli (coli and jejuni) infections in Northern Israel, between 2015 and 2021. Clinical and demographic data were collected from patient medical records. Susceptibility to erythromycin, tetracycline, ciprofloxacin, and gentamicin was assessed using the standard E-test. No significant correlations were found between bacterial species and patient ethnicity, patient gender, or duration of hospitalization. In contrast, significant differences were found between infecting species and patient age and age subgroup (P < 0.001). Furthermore, erythromycin resistance was observed in only 0.5% of the study population, while resistance to ciprofloxacin, tetracycline, and gentamicin was observed in 95%, 93%, and 2.3% of the population, respectively. The presented study underscores the need for routine surveillance of C.coli antibiotic resistance.
Immune response to SARS-CoV-2 variants after immunization with different vaccines in Mexico
Authors: Garay Erika , Whelan Sean P. J. , DuBois Rebecca M. , O’Rourke Sara M. , Salgado-Escobar Angel Eduardo , Muñoz-Medina José Esteban , Arias Carlos F. , López Susana
Published: February 2024

There is limited information on the antibody responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subjects from developing countries with populations having a high incidence of co-morbidities. Here, we analysed the immunogenicity of homologous schemes using the ChAdOx1-S, Sputnik V, or BNT162b2 vaccines and the effect of a booster dose with ChAdOx1-S in middle-aged adults who were seropositive or seronegative to the SARS-CoV-2 spike protein before vaccination. The study was conducted post-vaccination with a follow-up of 4 months for antibody titre using enzyme-linked immunosorbent assay (ELISA) and pseudovirus (PV) neutralization assays (PNAs). All three vaccines elicited a superior IgG anti-receptor-binding domain (RBD) and neutralization response against the Alpha and Delta variants when administered to individuals with a previous infection by SARS-CoV-2. The booster dose spiked the neutralization activity among individuals with and without a prior SARS-CoV-2 infection. The ChAdOx1-S vaccine induced weaker antibody responses in infection-naive subjects. A follow-up of 4 months post-vaccination showed a drop in antibody titre, with about 20% of the infection-naive and 100% of SARS-CoV-2 pre-exposed participants with detectable neutralization capacity against Alpha pseudovirus (Alpha-PV) and Delta PV (Delta-PV). Our observations support the use of different vaccines in a country with high seroprevalence at the vaccination time.
Food and nutrition information requirements of Australian primary school parents
Authors: Aydin Gozde , Margerison Claire , Worsley Anthony , Booth Alison
Published: February 2024

Objective:

To explore what Australian primary school parents want to learn about food and nutrition to improve their children’s eating behaviours, as well as the associations between parents’ personal and demographic characteristics and their views regarding their food and nutrition knowledge needs.

Design:

An online nationwide cross-sectional survey was conducted in 2021 using a mixed-methods approach. Logistic regression analysis was utilised to examine the relationship between parents’ demographics, personal values and their views. Content analysis was performed using Leximancer.

Setting:

Australia.

Participants:

Seven hundred and eighty-seven parents.

Results:

Fifty-one per cent wanted to learn more about food and nutrition to improve their children's healthy eating habits, and 77% of those preferred schools to provide that information. Online/printed newsletters and YouTube were the most preferred methods for receiving food and nutrition related information. Higher universalism-concern value (concern for the welfare of those in the larger society and world) scores were positively associated parents’ preference for schools to provide food and nutrition-related information. Parents with non-English-speaking backgrounds and younger parents were more likely to want to learn about food and nutrition. Parents wanted to learn more about encouraging healthy eating, ideas for the lunchbox, food labels and age-specific portion sizes and recommendations.

Conclusions:

Findings can inform public health educators and assist them in designing future food and nutrition education programmes and resources targeting primary school parents.
Epistemic Logic Programs: A Study of Some Properties
Authors: COSTANTINI STEFANIA , FORMISANO ANDREA
Published: February 2024

Epistemic logic programs (ELPs), extend answer set programming (ASP) with epistemic operators. The semantics of such programs is provided in terms of world views, which are sets of belief sets, that is, syntactically, sets of sets of atoms. Different semantic approaches propose different characterizations of world views. Recent work has introduced semantic properties that should be met by any semantics for ELPs, like the Epistemic Splitting Property, that, if satisfied, allows to modularly compute world views in a bottom-up fashion, analogously to “traditional” ASP. We analyze the possibility of changing the perspective, shifting from a bottom-up to a top-down approach to splitting. We propose a basic top-down approach, which we prove to be equivalent to the bottom-up one. We then propose an extended approach, where our new definition: (i) is provably applicable to many of the existing semantics; (ii) operates similarly to “traditional” ASP; (iii) provably coincides under any semantics with the bottom-up notion of splitting at least on the class of Epistemically Stratified Programs (which are, intuitively, those where the use of epistemic operators is stratified); (iv) better adheres to common ASP programming methodology.
Pricing of hospital services: evidence from a thematic review
Authors: Sirur Andria J. N. , Pillai K Rajasekharan
Published: February 2024

The management implications of pricing healthcare services, especially hospitals, have received insufficient scholarly attention. Additionally, disciplinary overlaps have led to scattered academic efforts in this domain. This study performs a thematic synthesis of the literature and applies retrospective analysis to hospital service pricing articles to address these issues. The study's inputs were sourced from well-known online repositories, using a structured search string and PRISMA flow chart to select the pertinent documents. Our thematic analysis of pricing literature encompasses: (a) comprehension of hospital service pricing nature; (b) pricing objectives, strategies and practices differentiation; (c) presentation of factors impacting hospital service pricing. We observe that hospital pricing is an intricate and unclear matter. The terms ‘pricing strategies’ and ‘pricing practices’ are often used interchangeably in academic literature. Hospital service pricing is influenced by costs, demand and supply factors, market structure, pricing regulation and third-party reimbursements. The study's findings provide policy implications for service pricing in hospitals, in addition to suggesting avenues for future research on hospital pricing.
Recentering evolution for sustainability science
Authors: Vázquez-Domínguez Ella , Kassen Rees , Schroer Sibylle , De Meester Luc , Johnson Marc T. J.
Published: February 2024

Non-technical summary

Evolutionary biology considers how organisms and populations change over multiple generations, and so is naturally focused on issues of sustainability through time. Yet, sustainability science rarely incorporates evolutionary thinking and most scientists and policy makers do not account for how evolutionary processes contribute to sustainability. Understanding the interplay between evolutionary processes and nature's contribution to people is key to sustaining life on Earth.

Technical summary

Evolution, the change in gene frequencies within populations, is a process of genetically based modification by descent, providing the raw material essential for adaptation to environmental change. Therefore, it is crucial that we understand evolutionary processes if we aim for a sustainable planet. We here contribute to this development by describing examples of contemporary, rapid evolutionary changes of concern for sustainability, specifically highlighting the global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and how the evolutionary toolbox allowed tracking the origins and evolution of SARS-CoV-2 in real time and predicting potential future outbreaks. We also consider how urban development accelerates evolutionary processes such as altered phenotypic and physiological changes and the spread of infectious and zoonotic diseases. We show the importance of evolutionary concepts and techniques for public-health decision making. Many examples of the potential of evolutionary insights contributing to crucial sustainability challenges exist, including infectious and zoonotic diseases, ecosystem and human health, and conservation of natural resources. We thus join recent calls advocating for a stronger collaboration between evolutionary biologists and the sustainability community, increasing interdisciplinarity and the awareness about the knowledge of evolutionary processes for decision making and policies.

Social media summary

Evolution is fundamental to sustaining life on Earth and should be incorporated in sustainability measures and policies.
Neural Network Parameterization of Subgrid‐Scale Physics From a Realistic Geography Global Storm‐Resolving Simulation
Authors: Watt‐Meyer Oliver , Brenowitz Noah D. , Clark Spencer K. , Henn Brian , Kwa Anna , McGibbon Jeremy , Perkins W. Andre , Harris Lucas , Bretherton Christopher S.
Published: February 2024

Parameterization of subgrid‐scale processes is a major source of uncertainty in global atmospheric model simulations. Global storm‐resolving simulations use a finer grid (less than 5 km) to reduce this uncertainty by explicitly resolving deep convection and details of orography. This study uses machine learning to replace the physical parameterizations of heating and moistening rates, but not wind tendencies, in a coarse‐grid (200 km) global atmosphere model, using training data obtained by spatially coarse‐graining a 40‐day realistic geography global storm‐resolving simulation. The training targets are the three‐dimensional fields of effective heating and moistening rates, including the effect of grid‐scale motions that are resolved but imperfectly simulated by the coarse model. A neural network is trained to predict the time‐dependent heating and moistening rates in each grid column using the coarse‐grained temperature, specific humidity, surface turbulent heat fluxes, cosine of solar zenith angle, land‐sea mask and surface geopotential of that grid column as inputs. The coefficient of determination R2 for offline prediction ranges from 0.4 to 0.8 at most vertical levels and latitudes. Online, we achieve stable 35‐day simulations, with metrics of skill such as the time‐mean pattern of near‐surface temperature and precipitation comparable or slightly better than a baseline simulation with conventional physical parameterizations. However, the structure of tropical circulation and relative humidity in the upper troposphere are unrealistic. Overall, this study shows potential for the replacement of human‐designed parameterizations with data‐driven ones in a realistic setting.
Cardiac manifestations of human ACTA2 variants recapitulated in a zebrafish model
Authors: Sebastian Wulan Apridita , Inoue Masanori , Shimizu Nobuyuki , Sato Ryosuke , Oguri Saori , Itonaga Tomoyo , Kishimoto Shintaro , Shiraishi Hiroshi , Hanada Toshikatsu , Ihara Kenji
Published: February 2024

The ACTA2 gene encodes actin α2, a major smooth muscle protein in vascular smooth muscle cells. Missense variants in the ACTA2 gene can cause inherited thoracic aortic diseases with characteristic symptoms, such as dysfunction of smooth muscle cells in the lungs, brain vessels, intestines, pupils, bladder, or heart. We identified a heterozygous missense variant of Gly148Arg (G148R) in a patient with a thoracic aortic aneurysm, dissection, and left ventricular non-compaction. We used zebrafish as an in vivo model to investigate whether or not the variants might cause functional or histopathological abnormalities in the heart. Following the fertilization of one-cell stage embryos, we injected in vitro synthesized ACTA2 mRNA of wild-type, novel variant G148R, or the previously known pathogenic variant Arg179His (R179H). The embryos were maintained and raised for 72 h post-fertilization for a heart analysis. Shortening fractions of heart were significantly reduced in both pathogenic variants. A histopathological evaluation showed that the myocardial wall of ACTA2 pathogenic variants was thinner than that of the wild type, and the total cell number within the myocardium was markedly decreased in all zebrafish with pathogenic variants mRNAs. Proliferating cell numbers were also significantly decreased in the endothelial and myocardial regions of zebrafish with ACTA2 variants compared to the wild type. These results demonstrate the effects of ACTA2 G148R and R179H on the development of left ventricle non-compaction and cardiac morphological abnormalities. Our study highlights the previously unknown significance of the ACTA2 gene in several aspects of cardiovascular development.
Optimizing multi-parameter distributed fiber sensors: a hybrid Rayleigh-Brillouin-Raman System approach
Authors: Song Kwang Yong
Published: February 2024

An optimized single-end hybrid Rayleigh, Brillouin, and Raman distributed fiber sensing system has been developed for simultaneous measurement of multiple parameters. This system integrates 3-bit pulse coding for the Raman signal and the Brillouin amplification of the Rayleigh-backscattered signal, discriminating strain, temperature, and vibration using a single sensing fiber.
Single-cell insights into immune dysregulation in rheumatoid arthritis flare versus drug-free remission
Authors: Baker Kenneth F. , McDonald David , Hulme Gillian , Hussain Rafiqul , Coxhead Jonathan , Swan David , Schulz Axel R. , Mei Henrik E. , MacDonald Lucy , Pratt Arthur G. , Filby Andrew , Anderson Amy E. , Isaacs John D.
Published: February 2024

Immune-mediated inflammatory diseases (IMIDs) are typically characterised by relapsing and remitting flares of inflammation. However, the unpredictability of disease flares impedes their study. Addressing this critical knowledge gap, we use the experimental medicine approach of immunomodulatory drug withdrawal in rheumatoid arthritis (RA) remission to synchronise flare processes allowing detailed characterisation. Exploratory mass cytometry analyses reveal three circulating cellular subsets heralding the onset of arthritis flare – CD45RO+PD1hi CD4+ and CD8+ T cells, and CD27+CD86+CD21- B cells – further characterised by single-cell sequencing. Distinct lymphocyte subsets including cytotoxic and exhausted CD4+ memory T cells, memory CD8+CXCR5+ T cells, and IGHA1+ plasma cells are primed for activation in flare patients. Regulatory memory CD4+ T cells (Treg cells) increase at flare onset, but with dysfunctional regulatory marker expression compared to drug-free remission. Significant clonal expansion is observed in T cells, but not B cells, after drug cessation; this is widespread throughout memory CD8+ T cell subsets but limited to the granzyme-expressing cytotoxic subset within CD4+ memory T cells. Based on our observations, we suggest a model of immune dysregulation for understanding RA flare, with potential for further translational research towards novel avenues for its treatment and prevention.
Transport mechanism of human bilirubin transporter ABCC2 tuned by the inter-module regulatory domain
Authors: Mao Yao-Xu , Chen Zhi-Peng , Wang Liang , Wang Jie , Zhou Cong-Zhao , Hou Wen-Tao , Chen Yuxing
Published: February 2024

Bilirubin is mainly generated from the breakdown of heme when red blood cells reach the end of their lifespan. Accumulation of bilirubin in human body usually leads to various disorders, including jaundice and liver disease. Bilirubin is conjugated in hepatocytes and excreted to bile duct via the ATP-binding cassette transporter ABCC2, dysfunction of which would lead to Dubin-Johnson syndrome. Here we determine the structures of ABCC2 in the apo, substrate-bound and ATP/ADP-bound forms using the cryo-electron microscopy, exhibiting a full transporter with a regulatory (R) domain inserted between the two half modules. Combined with substrate-stimulated ATPase and transport activity assays, structural analysis enables us to figure out transport cycle of ABCC2 with the R domain adopting various conformations. At the rest state, the R domain binding to the translocation cavity functions as an affinity filter that allows the substrates of high affinity to be transported in priority. Upon substrate binding, the R domain is expelled from the cavity and docks to the lateral of transmembrane domain following ATP hydrolysis. Our findings provide structural insights into a transport mechanism of ABC transporters finely tuned by the R domain.
Stringent sustainability regulations for global supply chains are supported across middle-income democracies
Authors: Smith E. Keith , Kolcava Dennis , Bernauer Thomas
Published: February 2024

Expanded international trade and globalised production networks are increasing the environmental and social impacts in middle-income countries (GNI per capita $1,136-$13,845). High-income countries (>$13,845) are seeking to mitigate the negative impacts of domestic consumption by imposing new sustainability regulations on global supply chains. Recent evidence suggests that these regulations are broadly supported across high-income countries. However, it remains unclear whether citizens of middle-income countries support aligning domestic sustainability regulations with the measures developed by high-income countries. Concerns about economic competitiveness and foreign imposition could increase public resistance toward such alignment. Alternatively, desires for continued market access in high-income countries and aspirations for strengthening local environmental and labour regulations could foster support for alignment. Based on survey-embedded experiments in the three largest democratic non-OECD economies (Brazil, India, Indonesia), we find surprisingly strong support for domestic-based measures that are aligned with emerging global supply chain sustainability regulations. Our findings suggest that support is largely driven by positive impact expectations, where the future benefits of alignment are perceived as outweighing concerns about increased costs. These results bode well for initiatives to install stricter sustainability regulations for global supply chains that are acceptable not only in high-income economies but also in non-OECD countries.
DynamicBind: predicting ligand-specific protein-ligand complex structure with a deep equivariant generative model
Authors: Lu Wei , Zhang Jixian , Huang Weifeng , Zhang Ziqiao , Jia Xiangyu , Wang Zhenyu , Shi Leilei , Li Chengtao , Wolynes Peter G. , Zheng Shuangjia
Published: February 2024

While significant advances have been made in predicting static protein structures, the inherent dynamics of proteins, modulated by ligands, are crucial for understanding protein function and facilitating drug discovery. Traditional docking methods, frequently used in studying protein-ligand interactions, typically treat proteins as rigid. While molecular dynamics simulations can propose appropriate protein conformations, they’re computationally demanding due to rare transitions between biologically relevant equilibrium states. In this study, we present DynamicBind, a deep learning method that employs equivariant geometric diffusion networks to construct a smooth energy landscape, promoting efficient transitions between different equilibrium states. DynamicBind accurately recovers ligand-specific conformations from unbound protein structures without the need for holo-structures or extensive sampling. Remarkably, it demonstrates state-of-the-art performance in docking and virtual screening benchmarks. Our experiments reveal that DynamicBind can accommodate a wide range of large protein conformational changes and identify cryptic pockets in unseen protein targets. As a result, DynamicBind shows potential in accelerating the development of small molecules for previously undruggable targets and expanding the horizons of computational drug discovery.
Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche
Authors: Dawson Amy , Zarou Martha M. , Prasad Bodhayan , Bittencourt-Silvestre Joana , Zerbst Désirée , Himonas Ekaterini , Hsieh Ya-Ching , van Loon Isabel , Blanco Giovanny Rodriguez , Ianniciello Angela , Kerekes Zsombor , Krishnan Vaidehi , Agarwal Puneet , Almasoudi Hassan , McCluskey Laura , Hopcroft Lisa E. M. , Scott Mary T. , Baquero Pablo , Dunn Karen , Vetrie David , Copland Mhairi , Bhatia Ravi , Coffelt Seth B. , Tiong Ong Sin , Wheadon Helen , Zanivan Sara , Kirschner Kristina , Helgason G. Vignir
Published: February 2024

Macrophages are fundamental cells of the innate immune system that support normal haematopoiesis and play roles in both anti-cancer immunity and tumour progression. Here we use a chimeric mouse model of chronic myeloid leukaemia (CML) and human bone marrow (BM) derived macrophages to study the impact of the dysregulated BM microenvironment on bystander macrophages. Utilising single-cell RNA sequencing (scRNA-seq) of Philadelphia chromosome (Ph) negative macrophages we reveal unique subpopulations of immature macrophages residing in the CML BM microenvironment. CML exposed macrophages separate from their normal counterparts by reduced expression of the surface marker CD36, which significantly reduces clearance of apoptotic cells. We uncover aberrant production of CML-secreted factors, including the immune modulatory protein lactotransferrin (LTF), that suppresses efferocytosis, phagocytosis, and CD36 surface expression in BM macrophages, indicating that the elevated secretion of LTF is, at least partially responsible for the supressed clearance function of Ph- macrophages.
Unacceptable use of substandard metrics in policy decisions which mandate large reductions in animal-source foods
Authors: Stanton Alice V.
Published: February 2024

Many recent very influential reports, including those from the Global Burden of Disease (GBD) Risk Factor Collaborators, the EAT-Lancet Commission on Food, Planet, Health, and the Lancet Countdown on Health and Climate Change, have recommended dramatic reductions or total exclusion of animal-source foods, particularly ruminant products (red meat and dairy), from the human diet. They strongly suggest that these dietary shifts will not only benefit planetary health but also human health. However, as detailed in this perspective, there are grounds for considerable concern in regard to the quality and transparency of the input data, the validity of the assumptions, and the appropriateness of the statistical modelling, used in the calculation of the global health estimates, which underpin the claimed human health benefits. The lessor bioavailability of protein and key micronutrients from plant-source foods versus animal-source foods was not adequately recognised nor addressed in any of these reports. Furthermore, assessments of bias and certainty were either limited or absent. Despite many of these errors and limitations being publically acknowledged by the GBD and the EAT-Lancet authors, no corrections have been applied to the published papers. As a consequence, these reports continue to erroneously influence food policy decisions and international dietary guidelines, such as the World Wildlife Fund’s Livewell Diet, and the Nordic Nutrition Recommendations 2023.
Whole-genome variants dataset of 209 local chickens from China
Authors: Tan Xiaodong , Zhang Jiawen , Dong Jie , Huang Minjie , Li Qinghai , Wang Huanhuan , Bai Lijuan , Cui Ming , Zhou Zhenzhen , Yang Shuyuan , Wang Deqian
Published: February 2024

Compared to commercial chickens, local breeds exhibit better in meat quality and flavour, but the productivity (e.g., growth rate, body weight) of local chicken breeds is rather low. Genetic analysis based on whole-genome sequencing contributes to elucidating the genetic markers or putative candidate genes related to some economic traits, facilitating the improvement of production performance, the acceleration of breeding progress, and the conservation of genetic resources. Here, a total of 209 local chickens from 13 breeds were investigated, and the observation of approximately 91.4% high-quality sequences (Q30 > 90%) and a mapping rate over 99% for each individual indicated good results of this study, as confirmed by a genome coverage of 97.6%. Over 19 million single nucleotide polymorphisms (SNPs) and 1.98 million insertion-deletions (InDels) were identified using the reference genome (GRCg7b), further contributing to the public database. This dataset provides valuable resources for studying genetic diversity and adaptation and for the cultivation of new chicken breeds/lines.
Digital economy development boosts urban resilience—evidence from China
Authors: Wang Haohui , Peng Gang , Du Hongmei
Published: February 2024

Focusing on the impact of the digital economy on urban resilience is beneficial to the sustainable development of cities. This paper empirically examines the impact of digital economic development on urban resilience and its mechanisms by measuring urban resilience and the level of urban digital economy with the entropy-weighted TOPSIS method using the data of 252 Chinese cities from 2011 to 2020. The findings show that digital economic development effectively promotes urban resilience at the 1% significance level, and this conclusion remains valid after a series of endogeneity and robustness tests. The channel mechanism suggests that the development of the digital economy can improve urban resilience by optimizing urban distributional effects and promoting the upgrading of urban industrial structures. This paper discusses the nonlinear relationship between the two using the MMQR model and the threshold model. The results show that urban resilience development level is in a higher quartile of cities, and digital economy development has a greater impact on urban resilience improvement. Meanwhile, there are two threshold values for the nonlinear impact of the digital economy on urban resilience, which are 0.026 and 0.082, respectively. Further, the spatial effect between the two is also verified. From the perspective of heterogeneity analysis, the digital economy development of high-class cities, key city clusters, and cities in eastern and western regions has a greater effect on urban resilience. This study can provide ideas and inspiration for countries to enhance urban resilience and promote sustainable urban development through the development of the digital economy.
Techno-economic optimization for isolated hybrid PV/wind/battery/diesel generator microgrid using improved salp swarm algorithm
Authors: Belboul Zakaria , Toual Belgacem , Bensalem Abderrahman , Ghenai Chaouki , Khan Baseem , Kamel Salah
Published: February 2024

The main objective of this study is to develop a new method for solving the techno-economic optimization problem of an isolated microgrid powered by renewable energy sources like solar panels, wind turbines, batteries, and diesel generators while minimizing greenhouse gas emissions. An Improved Salp Swarm Algorithm (ISSA) with a position adaptation mechanism for the salp leader that involves a leader salp that moves about depending on both food availability and its previous position has been proposed to overcome the convergence problem. In the original SSA, as the approach converges, it can no longer find optimal solutions and becomes trapped in a local minimum. Three Microgrid System (MS) configurations are discussed: PV/WT/BESU/DG, PV/BESU/DG, and WT/BESU/DG. The proposed method seeks to find a middle ground between technical criteria and environmental concerns when deciding on PV, WT, BESU, and DG sizes. The findings indicate that the proposed ISSA approach gives superior results compared to other well-known algorithms like the original SSA, the Ant Lion Optimizer (ALO), the Dragonfly Approach (DA), and the Moth-Flame Optimization Algorithm (MFO), which, after significant investigation, has been proven to help determine the appropriate microgrid size. With PV sizes of 10, 9 WT, 24 BESU, and 3 DG, the PV/WT/BESU/DG configuration offers the highest level of cost-effectiveness with Cost of Energy (COE) of 0.2109 $/kWh, Net Present Cost (NPC) of 376,063.8 $, Loss of Power Supply Probability (LPSP) of 4%, Renewable Energy Fraction (REF) of 96%, and CO2 emission of 12.4457 tons/year. ISSA is brought up as a possible solution to both the problem of rising energy prices and the difficulties inherent in microgrid design.
Characterising the behaviours in most severe and least severe emotional outbursts in young people
Authors: Shenton Benjamin Daniel Kitchen , Chung Justin Cheuk Yin , Woodcock Kate Anne
Published: February 2024

Emotional outbursts are displays of intense, challenging behaviour and are prevalent in individuals with neurodevelopmental disorders. Outbursts present a danger to individuals and their carers and are cited as reasons for referral to mental health services. However, it is currently unclear how the characteristics of outbursts may determine their severity. Carers (n = 214) of individuals aged between 6 and 25 and experiencing outbursts at least once per month completed the Emotional Outburst Questionnaire. Questionnaire items were used to compare behaviours observed in most severe and least severe outbursts through quantitative and content analyses of open ended data. Signs of physiological arousal and aggression were seen significantly more in most severe outbursts compared to least severe outbursts. Least severe outbursts were seen more frequently, but most severe outbursts were reported to have a longer duration, be at a higher intensity, and have a longer recovery time. Additionally, associations were found between reduced eye contact and most severe outbursts, as well as expression of suicidal ideation and most severe outbursts. Certain behaviours, notably forms of aggression and physiological arousal, are associated with most severe outbursts. Findings of this study may allow future work examining cross-disorder differences in outbursts to inform targeted interventions aiming to reduce outburst severity and impact. Additionally, identification of such outburst characteristics could aid in measurement of outburst severity, which would allow for more reliable and valid studies on outburst interventions.
Uncovering the clinicopathological features of early recurrence after surgical resection of pancreatic cancer
Authors: Chon Hye Yeon , Lee Hee Seung , Sung You-Na , Tae Yoo Keung , Park Chan Hee , Leem Galam , Kim So Jung , Jo Jung Hyun , Chung Moon Jae , Park Jeong Youp , Park Seung Woo , Hong Seung-Mo , Bang Seungmin
Published: February 2024

To identify risk factors and biomarker for early recurrence in patients diagnosed with pancreatic cancer who undergo curative resection. Early recurrence after curative resection of pancreatic cancer is an obstacle to long-term survival. We retrospectively reviewed 162 patients diagnosed with pancreatic cancer who underwent curative resection. Early recurrence was defined as recurrence within 12 months of surgery. We selected S100A2 as a biomarker and investigated its expression using immunohistochemistry. Of the total, 79.6% (n = 129) of patients received adjuvant chemotherapy after surgery and 117 (72.2%) experienced recurrence, of which 73 (45.1%) experience early recurrence. In multivariate analysis, age < 60 years, presence of lymph node metastasis, and no adjuvant chemotherapy were significantly associated with early recurrence (all P < 0.05). The proportion of patients with high S100A2 expression (H-score > 5) was significantly lower in the early recurrence group (41.5% vs. 63.3%, P = 0.020). The cumulative incidence rate of early recurrence was higher in patients with an S100A2 H-score < 5 (41.5% vs. 63.3%, P = 0.012). The median overall survival of patients with higher S100A2 expression was longer than those with lower S100A2 expression (median 30.1 months vs. 24.2 months, P = 0.003). High-risk factors for early recurrence after surgery for pancreatic cancer include young age, lymph node metastasis, and no adjuvant therapy. Neoadjuvant treatment or intensive adjuvant therapy after surgery may improve the prognosis of patients with high-risk signatures. In patients who receive adjuvant therapy, high S100A2 expression is a good predictor.