bluuebunny/crossref_metadata_2025 huggingface dataset:
How does broadband supply affect participation in panel surveys?: Using geospatial broadband data at the district level to analyze mode choice and panel attrition
Authors: Schwerdtfeger Maikel , Bach Ruben L.
Published: June 2024

Good broadband supply is crucial for different aspects of participation behavior in web surveys. In this study, we combined geospatial broadband data and the survey data of 16 waves of the mixed-mode GESIS Panel to investigate mode choice and panel attrition. Since small-scale geospatial data is often unavailable or difficult to access for research purposes, we report here results of a feasibility study investigating whether publicly available broadband data at the district level are sufficient to draw meaningful conclusions about participation behavior. In the first part of the analysis, we investigated the effects of broadband supply on mode choice. The results showed a positive effect of the broadband category with the highest coverage rate on choosing the online mode. We also found effects for internet familiarity, age, and education. In the second part, we investigated the effects of broadband supply on panel attrition within the 16 survey waves. We did not find significant effects of broadband supply on panel attrition. However, we found effects for evaluation of duration, measured duration, and age. Overall, we conclude that the granularity of the geospatial data on broadband supply is not ideal. A detailed discussion on the granularity of the broadband data in the context of the general availability of fine-grained geospatial data is provided at the end of this study.
Accessing the efficacy of green growth, energy efficiency, and green innovation for environmental performance in top manufacturing nations in the framework of sustainable development
Authors: Javed Aamir , Subhani Bilal Haider , Javed Asif , Rapposelli Agnese
Published: June 2024

In recent years, the quality of the environment has declined dramatically as a result of human activities, which threaten the sustainability of our ecosystem. In this context, a number of earlier studies have investigated the environmental problems through the lens of different environmental indicators such as ecological footprint and carbon dioxide emissions. However, it is possible that by taking these factors into account, the supply side of environmental quality will be neglected. This research seeks to address this deficiency by investigating the impact of green growth, energy efficiency, green technology innovation, economic growth, trade openness, and human capital on the level of load capacity factor. This indicator places equal emphasis on the supply and demand sides of the ecosystem by taking into account both ecological footprint and bio capacity. In this setting, the present study makes use of CS-ARDL model for the top 10 manufacturing countries from the years 1990 to 2019. The short- and long-run findings of the CS-ARDL model unveil that green growth, energy efficiency, green technology innovation, and human capital all positively influence the load capacity factor, suggesting that these factors help the top 10 manufacturing countries to improve their sustainability limits. In contrast, trade openness and economic expansion in underlying countries increase environmental degradation by lowering the level of LCF. These outcomes are also validated by the AMG and CCEMG approaches and the granger causality test. On the basis of the findings, important policy recommendations are presented with the aim of assisting the top 10 manufacturing economies in enhancing the quality of their environment and fulfilling the United Nations Sustainable Development Goals.
Perceived health-related quality of life in people living with HIV co-infected with SARS-CoV-2 in France
Authors: Amboise Yvenie , Yaya Issifou , Yombo-Kokule Lisa. , Roucoux Guillaume , Ossima Arnaud Nze , Preau Marie , Griffith James W. , Marcellin Fabienne , Chassany Olivier , Cheret Antoine , Duracinsky Martin
Published: June 2024

Purpose

We aimed to assess health-related quality of life (HRQL) and its correlates among people living with HIV/AIDS (PLWHA) co-infected with SARS-CoV-2 in France.

Methods

This cross-sectional was study conducted among PLWHA co-infected with SARS-CoV-2. HRQL was measured using the four dimensions of the PROQOL-HIV scale. Factors associated with each dimension were identified using linear regression.

Results

mean (SD) scores for HRQL dimensions: 76.7 (± 21.1) for Physical Health and Symptoms (PHS), 79.2 (± 23.6) for Social Relationships (SR), 67.3 (± 27.4) for Mental and Cognitive (MC), and 83.9 (± 16.5) for Treatment Impact (TI). Employment status and COVID-19 knowledge were associated with higher PHS score, while blood transfusion-acquired HIV, CDC HIV, hospital discharge instructions, and self-reported symptoms were associated with lower PHS score. Couple status was associated with higher SR score, whereas, hospital discharge instructions, CDC HIV stage C, drug injection-acquired HIV, self-reported symptoms, and COVID-19 vulnerability perception were associated with lower SR score. Employment status and French birth were associated with higher MC score, while female sex, detectable HIV viral load, hospital discharge instructions, COVID-19 vulnerability perception, smoking, and self-reported symptoms were associated with lower MC score. French birth and homosexual/bisexual relationships-acquired HIV were associated with higher TI score, while detectable HIV viral load, psychiatric disorders, and self-reported symptoms were associated with lower TI score

Conclusion

Among PLWHA co-infected with SARS-CoV-2, the scores of HRQL were impaired, particularly in the MC dimension. Findings underscore the multidimensional nature of HRQL, with notable variations across different dimensions. Understanding these correlates is crucial for tailored interventions aimed at improving the well-being of this population.
Teachers’ intervention strategies for handling hate-speech incidents in schools
Authors: Bilz Ludwig , Fischer Saskia M. , Kansok-Dusche Julia , Wachs Sebastian , Wettstein Alexander
Published: June 2024

Despite ongoing global efforts to combat discrimination, hate speech is a growing problem in many countries. Hate speech is also widespread among young people and thus also affects schools. Because of the negative consequences of hate speech for the targeted individuals and for society in general, schools and teachers are generally encouraged to moderate hate speech. This binational study examines intervention strategies for hate speech in schools using the newly developed Hate-Speech Interventions Scale for Teachers. Data from German and Swiss teachers (N = 486) were analyzed. Self-reported strategies were best described using a three-factor structure. Teachers primarily direct their interventions at those directly involved in hate speech and frequently employ teaching-oriented strategies. In comparison, external partners and colleagues are relatively rarely involved. Measurement invariance testing supported the scales’ construct validity. A link was found between the use of these strategies, teachers’ task-specific self-efficacy, gender, and professional experience. These results indicate that schools should play an important role in moderating hate speech and that increasing teachers’ confidence in their own ability to address this phenomenon could be an important element of teacher training.
Efficient estimation and correction of selection-induced bias with order statistics
Authors: McLatchie Yann , Vehtari Aki
Published: June 2024

Model selection aims to identify a sufficiently well performing model that is possibly simpler than the most complex model among a pool of candidates. However, the decision-making process itself can inadvertently introduce non-negligible bias when the cross-validation estimates of predictive performance are marred by excessive noise. In finite data regimes, cross-validated estimates can encourage the statistician to select one model over another when it is not actually better for future data. While this bias remains negligible in the case of few models, when the pool of candidates grows, and model selection decisions are compounded (as in step-wise selection), the expected magnitude of selection-induced bias is likely to grow too. This paper introduces an efficient approach to estimate and correct selection-induced bias based on order statistics. Numerical experiments demonstrate the reliability of our approach in estimating both selection-induced bias and over-fitting along compounded model selection decisions, with specific application to forward search. This work represents a light-weight alternative to more computationally expensive approaches to correcting selection-induced bias, such as nested cross-validation and the bootstrap. Our approach rests on several theoretic assumptions, and we provide a diagnostic to help understand when these may not be valid and when to fall back on safer, albeit more computationally expensive approaches. The accompanying code facilitates its practical implementation and fosters further exploration in this area.
Cyanotoxin Monitoring and Detection Using Passive Sampling Application
Authors: Loaiza-González Jinna M. , Rubio-Clemente Ainhoa , Peñuela Gustavo A.
Published: June 2024

Cyanobacterial blooms in water have been extensively studied as they produce bioactive and toxic metabolites, commonly known as cyanotoxins. Additionally, the presence of cyanobacteria and, consequently, the production of cyanotoxins, have increased in extent and frequency worldwide. Therefore, the risk associated with the presence of these microorganisms and their toxins has become a matter of great concern. On the other hand, conventional processes for water treatment are inefficient for their elimination and/or degradation, so their presence in water persists at trace and ultra-trace concentrations. In this regard, it is important to develop alternatives to monitor cyanotoxins and allow their detection at low levels in water supply and purification systems, in order to ensure water of good quality for human consumption. In this work, different methodologies, implemented both at laboratory scale and in situ in aqueous bodies, are described. Among these methodologies, traditional and passive techniques are highlighted. Appropriate analytical and sample preparation methods used in the detection and quantification of cyanotoxins are also addressed. It was found that the use of passive samplers is a convenient and a cost-effective method of identifying the presence of these toxins in water at concentrations in the order of µg/L and ng/L. Moreover, studying the by-products generated from the degradation of natural toxins in aquatic environments and evaluating their possible adverse effects is crucial in terms of the management and control of cyanobacteria and cyanotoxin pollution in water.
Long-term durability of discarded cork-based composites obtained by geopolymerization
Authors: Poggetto Giovanni Dal , Barbieri Luisa , D’Angelo Antonio , Zambon Alfonso , Zardi Paolo , Leonelli Cristina
Published: June 2024

Geopolymers are amorphous aluminosilicate inorganic polymers synthesized by alkaline activation characterized by a lower carbon footprint, greater durability, and excellent mechanical properties compared to traditional concrete, making them promising building materials for sustainable construction. To develop sustainable lightweight geopolymer-based building materials useful as fire resistant thermal insulation materials, we added 5 and 10 wt% of discarded cork dust, a readily available industrial by-product, to metakaolin before and after the alkaline activation with sodium hydroxide 8 M and sodium silicate solutions. We followed the chemical, microstructural, antibacterial, and physical properties of the resulting composites for up to 90 days in order to monitor their long-term durability. The presence of cork does not interfere with the geopolymerization process and in fact reduces the density of the composites to values around 2.5 g/cm3, especially when added after alkaline activation. The composites resulted in chemically stable matrices (less than 10 ppm of cations release) and filler (no hazardous compounds released) with a bacterial viability of around 80%. This study provides valuable insights into the tailoring of discarded cork-based composites obtained by geopolymerization with a porosity between 32 and 48% and a mechanical resistance to compression from 15 to 5 MPa, respectively, suggesting their potential as durable interior panels with low environmental impact and desirable performance.
Prevalence of the Risk of Exercise Addiction Based on a New Classification: A Cross-Sectional Study in 15 Countries
Authors: Chhabra Bhavya , Granziol Umberto , Griffiths Mark D. , Zandonai Thomas , Landolfi Emilio , Solmi Marco , Zou Liye , Yang Peiying , Lichtenstein Mia Beck , Stoll Oliver , Akimoto Takayuki , Cantù-Berrueto Abril , Larios Angelica , Egorov Aleksei Y. , de la Vega Marcos Ricardo , Alpay Merve , Nazlıgül Merve Denizci , Yildirim Mustafa , Trott Mike , Portman Robert M. , Szabo Attila
Published: June 2024

Exercise addiction is widely studied, but an official clinical diagnosis does not exist for this behavioral addiction. Earlier research using various screening instruments examined the absolute scale values while investigating the disorder. The Exercise Addiction Inventory-3 (EAI-3) was recently developed with two subscales, one denoting health-relevant exercise and the other addictive tendencies. The latter has different cutoff values for leisure exercisers and elite athletes. Therefore, the present 15-country study (n = 3,760) used the EAI-3 to classify the risk of exercise addiction (REA), but only if the participant reported having had a negative exercise-related experience. Based on this classification, the prevalence of REA was 9.5% in the sample. No sex differences, and few cross-national differences were found. However, collectivist countries reported greater REA in various exercise contexts than individualist countries. Moreover, the REA among athletes was (i) twice as high as leisure exercisers, (ii) higher in organized than self-planned exercises, irrespective of athletic status, and (iii) higher among those who exercised for skill/mastery reasons than for health and social reasons, again irrespective of athletic status. Eating disorders were more frequent among REA-affected individuals than in the rest of the sample. These results do not align with recent theoretical arguments claiming that exercise addiction is unlikely to be fostered in organized sports. The present study questions the current research framework for understanding exercise addiction and offers a new alternative to segregate self-harming exercise from passionate overindulgence in athletic life.
The Development of Sharing Experiences: From Dyadic Engagement to Taking Others’ Perspectives
Authors: Moll Henrike , Ni Qianhui
Published: June 2024

We argue that the main difference between humans and other animals lies in humans’ unique form of sociality: their shared intentionality. Instead of conceiving of shared intentionality as a special skill humans have in addition to the skills they share with nonhuman animals (the additive account), we propose to think of shared intentionality as transforming human cognition in its entirety (the transformative account, as in the thesis of Kern and Moll). We discuss the relevance of the evolution of the human face for shared intentionality, and we argue that the development of shared intentionality proceeds in the following three steps: 1) newborns’ tendency to engage in preverbal, face-to-face dialogue, 2) 1-year-olds’ drive to jointly attend to the world with others as plural subjects, and 3) preschoolers’ appreciation of individuals’ different perspectives. The shared intentionality thesis defended here can be viewed as an extension of Lev Vygotsky’s sociocultural account of human development.
From recipe to reality: the Polish way of collective redress
Authors: Mucha Jagna
Published: June 2024

In comparison to other Member States, Poland has had experience in dealing with mass claims for quite some time, having introduced the Act of Pursuing Claims in Group Proceedings way back in 2009. This paper includes a brief overview of the legislative framework for collective redress in Poland with special consideration of consumer claims. Further, it examines the evidence-based reality of group proceedings with the purpose of identifying and addressing the problems in functioning of this mechanism in practice. To achieve this aim, it delves into a case study of one of the most significant group proceedings so far – that related to the so-called ‘Swiss loan crisis’ in Poland.
Sexual and Reproductive Service Interventions for Menstrual Regulation, Safe Abortion, and Post-abortion Care and Their Effectiveness During Disaster Response: A Global Systematic Review
Authors: Ray-Bennett Nibedita S. , Ekezie Winifred , Biswas Isha , Choudhary Nimra Iqbal , Cowie David , Dissanayake Lasith , Macleod Lauren , Nnaji Azukaeogo , Sahoo Madhulika
Published: June 2024

Sexual and reproductive health (SRH) services are crucial for women especially during disasters, to reduce maternal mortality and morbidity from miscarriages, unsafe abortions, and post-abortion complications. This study explored the SRH interventions provided during disaster response. A systematic review was conducted to identify what menstrual regulation (MR), safe abortion (SA), and post-abortion care (PAC) approaches/interventions exist to promote resilience in the health system in disaster settings; what intervention components were most effective; and challenges and opportunities to meeting SRH rights. Five electronic databases were searched, resulting in 4194 records. Following the screening process, seven publications were included. The intervention-related information in each publication was assessed based on availability, accessibility, acceptability, and quality. Two SRH approaches/interventions were found. The effectiveness of intervention components could not be conducted due to the limited number of relevant studies. Challenges were found at facility and community levels, and opportunities included overcoming them, making MR, SA, and PAC integral to the mitigation phase, and policy change to overcome barriers related to unaffordability and inaccessibility. Recommendations are provided to encourage research and policy towards improving neglected SRH in disaster settings to realize Sustainable Development Goal 3 and the Global Strategy and Sendai Framework’s priority to promote disaster-resilient health systems.
Quantitative liver MRI biomarkers: what the radiologist should know
Authors: Mazzola Mariasole , Cannella Roberto , Pilato Giulia , Blandino Antonino Andrea , Milazzo Monica , Matteini Francesco , Vernuccio Federica , Brancatelli Giuseppe
Published: June 2024

Quantitative MRI biomarkers are increasingly requested in clinical practice in the management of patients with chronic liver diseases, to evaluate fibrosis, steatosis, iron overloard and liver function. The proton density fat fraction (PDFF) is a quantitative biomarker for the quantification of steatosis, being the current noninvasive reference standard for steatosis grading. R2* is a biomarker of iron concentration and is bundled with PDFF. MR elastography measures liver stiffness through the quantification of mechanical waves generated by an external drive and it can be used to detect significant and advanced fibrosis. Hepatobiliary phase can provide information on residual liver function by quantitative or semiquantitative parameters. The functional liver imaging score is an emerging semiquantitative tool based on the three hepatobiliary phase features: liver parenchymal enhancement, biliary contrast excretion, and portal vein sign. This work discusses the role of quantitative MRI biomarkers, offering practical tips for the diagnosis of steatosis, iron, fibrosis and liver function.
Aerosol‐Cloud Interactions From Aviation Soot Emissions
Authors: Alsante Alyssa N. , Cheng Meng‐Dawn
Published: June 2024

Current models estimate global aviation contributes approximately 5% to the total anthropogenic climate forcing, with aerosol‐cloud interactions having the greatest effect. However, radiative forcing estimates from aviation aerosol‐cloud interactions remain undetermined. There is an expected significant increase in aircraft emissions with aviation demand expected to rise by over 4% per year. Soot may play an important role in the ice nucleation of aircraft‐induced cirrus formation due to a high emission rate, but the ice nucleating properties are poorly constrained. Understanding the microphysical processes leading to atmospheric ice crystal formation is crucial for the reliable parameterization of aerosol‐cloud interactions in climate models due to their impact on precipitation and cloud radiative properties. Ice nucleation of aircraft‐emitted soot is potentially affected by particle morphology with condensation of supercooled water occurring in pores followed by ice nucleation. However, soot has heterogeneous properties and undergoes atmospheric aging and oxidation that could change surface properties and contribute to complex ice nucleation processes. This review synthesizes current knowledge of ice nucleation catalyzed by aviation in the cirrus regime and its effects on global radiative forcing. Further research is required to determine the ice nucleation and microphysical processes of cirrus cloud formation from aviation emissions in both controlled laboratory and field investigations to inform models for more accurate climate predictions and to provide efficient mitigation strategies.
Improving All‐Sky Simulations of Typhoon Cloud/Rain Band Structures of NOAA‐20 CrIS Window Channel Observations
Authors: Niu Zeyi , Zou Xiaolei
Published: June 2024

The Cross‐track Infrared Sounder (CrIS) observations (O) contributed greatly to numerical weather prediction. Further contribution depends on the success of all‐sky data assimilation, which requires a method to produce realistic cloud/rain band structures from background fields (i.e., 6‐hr forecasts), and to remove large biases of all‐sky simulation of brightness temperature (TB) in the presence of clouds. In this study, CrIS all‐sky simulations of brightness temperatures at an arbitrarily selected window channel within Typhoon Hinnamnor (2022) are investigated. The 3‐km Weather Research and Forecasting model with three microphysics schemes were used to produce 6‐hr background forecasts (B). The O − B statistic deviate greatly from Gaussian distribution with large biases in either water clouds, or thin ice clouds, or thick ice clouds within Typhoon Hinnamnor. By developing a linear regression function of three all‐sky simulations of TB from 6‐hr forecasts with three microphysics schemes, the O − B statistics approximate a Gaussian normal distribution in water clouds, thin ice clouds and thick ice clouds. Taking the regression function that is established by a training data set to combine 6‐hr background forecasts at later times, the cloud/rain band structures compared much more favorably with CrIS observations than those from an individual microphysic. Furthermore, the regression coefficients derived from Typhoon Hinnamnor (2022) also work for Typhoon Khanun (2023). The work aims to quantify and remove biases in background fields of TB and generating realistic typhoon cloud/rain band structures in background fields will allow a better description of center position, intensity and size to improve typhoon forecasts.
Excursions, Reversals, and Secular Variation: Different Expressions of a Common Mechanism?
Authors: Buffett B. A.
Published: June 2024

Fluctuations in the geomagnetic field occur over a broad range of timescales. Short‐period fluctuations are called secular variation, whereas excursions and reversals are viewed as anomalous transient events. An open question is whether distinct mechanisms are required to account for these different forms of variability. Clues are sought in trends b of the axial dipole moment from six time‐dependent geomagnetic field models. Variability in b has a well‐defined dependence on the time interval (or window) for the trend. The variance of b reveals a simple relationship to trends during excursions and reversals. This connection hints at a link between reversals, excursions and secular variation. Stochastic models exhibit a similar behavior in response to random fluctuations in dipole generation. We find that excursions, reversals and secular variation can be distinguished on the basis of trend durations rather than differences in the underlying physical process. While this analysis does not rule out distinct physical mechanisms, the paleomagnetic observations suggest that such distinctions are not required.
KRAS and TP53 co-mutation predicts benefit of immune checkpoint blockade in lung adenocarcinoma
Authors: Budczies Jan , Romanovsky Eva , Kirchner Martina , Neumann Olaf , Blasi Miriam , Schnorbach Johannes , Shah Rajiv , Bozorgmehr Farastuk , Savai Rajkumar , Stiewe Thorsten , Peters Solange , Schirmacher Peter , Thomas Michael , Kazdal Daniel , Christopoulos Petros , Stenzinger Albrecht
Published: June 2024

Background

Predictive biomarkers in use for immunotherapy in advanced non-small cell lung cancer are of limited sensitivity and specificity. We analysed the potential of activating KRAS and pathogenic TP53 mutations to provide additional predictive information.

Methods

The study cohort included 713 consecutive immunotherapy patients with advanced lung adenocarcinomas, negative for actionable genetic alterations. Additionally, two previously published immunotherapy and two surgical patient cohorts were analyzed. Therapy benefit was stratified by KRAS and TP53 mutations. Molecular characteristics underlying KRASmut/TP53mut tumours were revealed by the analysis of TCGA data.

Results

An interaction between KRAS and TP53 mutations was observed in univariate and multivariate analyses of overall survival (Hazard ratio [HR] = 0.56, p = 0.0044 and HR = 0.53, p = 0.0021) resulting in a stronger benefit for KRASmut/TP53mut tumours (HR = 0.71, CI 0.55–0.92). This observation was confirmed in immunotherapy cohorts but not observed in surgical cohorts. Tumour mutational burden, proliferation, and PD-L1 mRNA were significantly higher in TP53-mutated tumours, regardless of KRAS status. Genome-wide expression analysis revealed 64 genes, including CX3CL1 (fractalkine), as specific transcriptomic characteristic of KRASmut/TP53mut tumours.

Conclusions

KRAS/TP53 co-mutation predicts ICI benefit in univariate and multivariate survival analyses and is associated with unique molecular tumour features. Mutation testing of the two genes can be easily implemented using small NGS panels.
Strand-resolved mutagenicity of DNA damage and repair
Authors: Anderson Craig J. , Talmane Lana , Luft Juliet , Connelly John , Nicholson Michael D. , Verburg Jan C. , Pich Oriol , Campbell Susan , Giaisi Marco , Wei Pei-Chi , Sundaram Vasavi , Connor Frances , Ginno Paul A. , Sasaki Takayo , Gilbert David M. ,   Liver Cancer Evolution Consortium, Aitken Stuart , Arnedo-Pac Claudia , Daunesse Maëlle , Drews Ruben M. , Ewing Ailith , Feig Christine , Flicek Paul , Kaiser Vera B. , Kentepozidou Elissavet , López-Arribillaga Erika , Lukk Margus , Rayner Tim F. , Sentís Inés , López-Bigas Núria , Semple Colin A. , Odom Duncan T. , Aitken Sarah J. , Taylor Martin S.
Published: June 2024

DNA base damage is a major source of oncogenic mutations1. Such damage can produce strand-phased mutation patterns and multiallelic variation through the process of lesion segregation2. Here we exploited these properties to reveal how strand-asymmetric processes, such as replication and transcription, shape DNA damage and repair. Despite distinct mechanisms of leading and lagging strand replication3,4, we observe identical fidelity and damage tolerance for both strands. For small alkylation adducts of DNA, our results support a model in which the same translesion polymerase is recruited on-the-fly to both replication strands, starkly contrasting the strand asymmetric tolerance of bulky UV-induced adducts5. The accumulation of multiple distinct mutations at the site of persistent lesions provides the means to quantify the relative efficiency of repair processes genome wide and at single-base resolution. At multiple scales, we show DNA damage-induced mutations are largely shaped by the influence of DNA accessibility on repair efficiency, rather than gradients of DNA damage. Finally, we reveal specific genomic conditions that can actively drive oncogenic mutagenesis by corrupting the fidelity of nucleotide excision repair. These results provide insight into how strand-asymmetric mechanisms underlie the formation, tolerance and repair of DNA damage, thereby shaping cancer genome evolution.
Endoplasmic reticulum–plasma membrane contact gradients direct cell migration
Authors: Gong Bo , Johnston Jake D. , Thiemicke Alexander , de Marco Alex , Meyer Tobias
Published: June 2024

Directed cell migration is driven by the front–back polarization of intracellular signalling1–3. Receptor tyrosine kinases and other inputs activate local signals that trigger membrane protrusions at the front2,4–6. Equally important is a long-range inhibitory mechanism that suppresses signalling at the back to prevent the formation of multiple fronts7–9. However, the identity of this mechanism is unknown. Here we report that endoplasmic reticulum–plasma membrane (ER–PM) contact sites are polarized in single and collectively migrating cells. The increased density of these ER–PM contacts at the back provides the ER-resident PTP1B phosphatase more access to PM substrates, which confines receptor signalling to the front and directs cell migration. Polarization of the ER–PM contacts is due to microtubule-regulated polarization of the ER, with more RTN4-rich curved ER at the front and more CLIMP63-rich flattened ER at the back. The resulting ER curvature gradient leads to small and unstable ER–PM contacts only at the front. These contacts flow backwards and grow to large and stable contacts at the back to form the front–back ER–PM contact gradient. Together, our study suggests that the structural polarity mediated by ER–PM contact gradients polarizes cell signalling, directs cell migration and prolongs cell migration.
Interactions between immune cell types facilitate the evolution of immune traits
Authors: Dubovik Tania , Lukačišin Martin , Starosvetsky Elina , LeRoy Benjamin , Normand Rachelly , Admon Yasmin , Alpert Ayelet , Ofran Yishai , G’Sell Max , Shen-Orr Shai S.
Published: June 2024

An essential prerequisite for evolution by natural selection is variation among individuals in traits that affect fitness1. The ability of a system to produce selectable variation, known as evolvability2, thus markedly affects the rate of evolution. Although the immune system is among the fastest-evolving components in mammals3, the sources of variation in immune traits remain largely unknown4,5. Here we show that an important determinant of the immune system’s evolvability is its organization into interacting modules represented by different immune cell types. By profiling immune cell variation in bone marrow of 54 genetically diverse mouse strains from the Collaborative Cross6, we found that variation in immune cell frequencies is polygenic and that many associated genes are involved in homeostatic balance through cell-intrinsic functions of proliferation, migration and cell death. However, we also found genes associated with the frequency of a particular cell type that are expressed in a different cell type, exerting their effect in what we term cyto-trans. The vertebrate evolutionary record shows that genes associated in cyto-trans have faced weaker negative selection, thus increasing the robustness and hence evolvability2,7,8 of the immune system. This phenomenon is similarly observable in human blood. Our findings suggest that interactions between different components of the immune system provide a phenotypic space in which mutations can produce variation with little detriment, underscoring the role of modularity in the evolution of complex systems9.
PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial
Authors: Dorff Tanya B. , Blanchard M. Suzette , Adkins Lauren N. , Luebbert Laura , Leggett Neena , Shishido Stephanie N. , Macias Alan , Del Real Marissa M. , Dhapola Gaurav , Egelston Colt , Murad John P. , Rosa Reginaldo , Paul Jinny , Chaudhry Ammar , Martirosyan Hripsime , Gerdts Ethan , Wagner Jamie R. , Stiller Tracey , Tilakawardane Dileshni , Pal Sumanta , Martinez Catalina , Reiter Robert E. , Budde Lihua E. , D’Apuzzo Massimo , Kuhn Peter , Pachter Lior , Forman Stephen J. , Priceman Saul J.
Published: June 2024

Despite recent therapeutic advances, metastatic castration-resistant prostate cancer (mCRPC) remains lethal. Chimeric antigen receptor (CAR) T cell therapies have demonstrated durable remissions in hematological malignancies. We report results from a phase 1, first-in-human study of prostate stem cell antigen (PSCA)-directed CAR T cells in men with mCRPC. The starting dose level (DL) was 100 million (M) CAR T cells without lymphodepletion (LD), followed by incorporation of LD. The primary end points were safety and dose-limiting toxicities (DLTs). No DLTs were observed at DL1, with a DLT of grade 3 cystitis encountered at DL2, resulting in addition of a new cohort using a reduced LD regimen + 100 M CAR T cells (DL3). No DLTs were observed in DL3. Cytokine release syndrome of grade 1 or 2 occurred in 5 of 14 treated patients. Prostate-specific antigen declines (>30%) occurred in 4 of 14 patients, as well as radiographic improvements. Dynamic changes indicating activation of peripheral blood endogenous and CAR T cell subsets, TCR repertoire diversity and changes in the tumor immune microenvironment were observed in a subset of patients. Limited persistence of CAR T cells was observed beyond 28 days post-infusion. These results support future clinical studies to optimize dosing and combination strategies to improve durable therapeutic outcomes. ClinicalTrials.gov identifier NCT03873805.
Chromosome-level genome assembly and annotation of a potential model organism Gossypium arboreum ZB-1
Authors: Sun Rongnan , Wu Yuqing , Zhang Xinyu , Lv Minghua , Yu Dongliang , Sun Yuqiang
Published: June 2024

Recent advancements in plant regeneration and synthetic polyploid creation have been documented in Gossypium arboreum ZB-1. These developments make ZB-1 a potential model within the Gossypium genus for investigating gene function and polyploidy. This work generated the sequence and annotation of the ZB-1 genome. The contig-level genome was constructed using the PacBio high-fidelity reads, encompassing 81 contigs with an N50 length of 112.12 Mb. The Hi-C data assisted the construction of the chromosome-level genome, which consists of 13 pseudo-chromosomes and 39 un-anchored contigs, with a total length of about 1.67 Gb. Repetitive sequences accounted for about 69.7% of the genome in length. Based on ab initio and evidence-based prediction, we have identified 48,021 protein-coding genes in the ZB-1 genome. Comparative genomics analysis revealed conserved gene content and arrangement between ZB-1 and G. arboreum SXY1. The single nucleotide polymorphism occurrence rate between ZB-1 and SXY1 was about 0.54 per 1,000 nucleotides. This study enriched the genomic resources for further exploration into cotton regeneration and polyploidy mechanisms.
Point-of-care AI-enhanced novice echocardiography for screening heart failure (PANES-HF)
Authors: Huang Weiting , Koh Tracy , Tromp Jasper , Chandramouli Chanchal , Ewe See Hooi , Ng Choon Ta , Lee Audry Shan Yin , Teo Louis Loon Yee , Hummel Yoran , Huang Feiqiong , Lam Carolyn Su Ping
Published: June 2024

The increasing prevalence of heart failure (HF) in ageing populations drives demand for echocardiography (echo). There is a worldwide shortage of trained sonographers and long waiting times for expert echo. We hypothesised that artificial intelligence (AI)-enhanced point-of-care echo can enable HF screening by novices. The primary endpoint was the accuracy of AI-enhanced novice pathway in detecting reduced LV ejection fraction (LVEF) < 50%. Symptomatic patients with suspected HF (N = 100, mean age 61 ± 15 years, 56% men) were prospectively recruited. Novices with no prior echo experience underwent 2-weeks’ training to acquire echo images with AI guidance using the EchoNous Kosmos handheld echo, with AI-automated reporting by Us2.ai (AI-enhanced novice pathway). All patients also had standard echo by trained sonographers interpreted by cardiologists (reference standard). LVEF < 50% by reference standard was present in 27 patients. AI-enhanced novice pathway yielded interpretable results in 96 patients and took a mean of 12 min 51 s per study. The area under the curve (AUC) of the AI novice pathway was 0.880 (95% CI 0.802, 0.958). The sensitivity, specificity, positive predictive and negative predictive values of the AI-enhanced novice pathway in detecting LVEF < 50% were 84.6%, 91.4%, 78.5% and 94.1% respectively. The median absolute deviation of the AI-novice pathway LVEF from the reference standard LVEF was 6.03%. AI-enhanced novice pathway holds potential to task shift echo beyond tertiary centres and improve the HF diagnostic workflow.
Bio-oil modified binder derived from cotton stalks as an eco-friendly alternative binder for flexible pavements
Authors: Ullah Sahib , Zaidi Syed Bilal Ahmed , Khan Diyar , Fareed Ayyaz , Mohd Hasan Mohd Rosli , Milad Abdalrhman , Ali Basit
Published: June 2024

Scientists and engineers encounter considerable environmental and economic obstacles stemming from the depletion of crude oil or petroleum fossil fuel reservoirs. To mitigate this challenge, alternative solutions like bio-oil-modified binder derived from biomass have been innovated. This research aims to examine the feasibility of using bio-oil-modified binder obtained from cotton stalk waste as a modifier. Various mechanical and physical tests, including penetration, softening point, ductility, and dynamic shear rheometer tests, were conducted on asphalt binder incorporating 5% and 10% bio-oil-modified binder. Wheel tracker, four-point beam fatigue, and dynamic modulus tests were used to evaluate asphalt mixture performance, including rutting, fatigue, and dynamic stiffness. A rolling bottle test (RBT) and asphalt binder bond strength (BBS) were used to assess moisture susceptibility. A bio-oil-modified binder enhanced ductility and penetration characteristics while reducing the softening point. With the addition of a bio-oil-modified binder, stiffness was reduced in parameters such as complex shear modulus and phase angle. In fact, for both specimens containing 5% and 10% bio-oil-modified binder, statistically significant differences were observed among the measured samples. As a result of this reduced stiffness, the modified asphalt binder is more suitable for low-temperature applications. Additionally, 5.8% increased at 10% and 3.1% at 5% CS. Bio-oil-modified binder, compared to virgin mixtures, supports equal rut resistance. However, the RBT and BBS tests revealed that the addition of bio-oil-modified binder increased the susceptibility of conventional asphalt binder to moisture. The findings suggest that bio-oil-modified binder can enhance asphalt binder properties in low-temperature regions, but further research is needed to improve moisture resistance.
Effect of binder and activator composition on the characteristics of alkali-activated slag-based concrete
Authors: Heshmat Mohamed , Amer Ismail , Elgabbas Fareed , Khalaf Mohamed A.
Published: June 2024

Alkali Activated Slag Concrete (AASC) has been a sustained research activity over the past two decades. Its promising characteristics and being environmentally friendly compared to Ordinary Portland Cement made AASC of exceptional interest. However, there is still no firm mix design, for the AASC, that can provide desirable fresh and hardened properties based on the composition of the binder and activator. This research specifically aims to investigate the affecting parameters on the slump and compressive strength of alkali-activated slag/lime-based concrete and provide a better understanding of the potential reasons for these characteristics. The experimental program consisted of two stages; the first stage studied the effect of different binder and activator compositions, and the second stage studied the water-to-binder ratio and binder content effects on the slump and compressive strength of alkali-activated slag/lime-based concrete. The binder and activator compositions were defined through two main parameters, the hybrid factor (HF = CaO/Si2O + Al2O3) and the solution modulus (Ms = SiO2/Na2O). The compressive strength, initial slump, and slump loss were measured to evaluate the different mixes and specify the optimum range of compositions. Based on the studied parameters, the effective range to achieve desirable slump and concrete compressive strength is from HF 0.6 up to 0.8 at Ms 1.5, this would achieve a compressive strength of more than 30 MPa and a slump of 100 mm after 90 min.
An improved Differential evolution with Sailfish optimizer (DESFO) for handling feature selection problem
Authors: Azzam Safaa. M. , Emam O. E. , Abolaban Ahmed Sabry
Published: June 2024

As a preprocessing for machine learning and data mining, Feature Selection plays an important role. Feature selection aims to streamline high-dimensional data by eliminating irrelevant and redundant features, which reduces the potential curse of dimensionality of a given large dataset. When working with datasets containing many features, algorithms that aim to identify the most valuable features to improve dataset accuracy may encounter difficulties because of local optima. Many studies have been conducted to solve this problem. One of the solutions is to use meta-heuristic techniques. This paper presents a combination of the Differential evolution and the sailfish optimizer algorithms (DESFO) to tackle the feature selection problem. To assess the effectiveness of the proposed algorithm, a comparison between Differential Evolution, sailfish optimizer, and nine other modern algorithms, including different optimization algorithms, is presented. The evaluation used Random forest and key nearest neighbors as quality measures. The experimental results show that the proposed algorithm is a superior algorithm compared to others. It significantly impacts high classification accuracy, achieving 85.7% with the Random Forest classifier and 100% with the Key Nearest Neighbors classifier across 14 multi-scale benchmarks. According to fitness values, it gained 71% with the Random forest and 85.7% with the Key Nearest Neighbors classifiers.
Antagonistic potential and biological control mechanisms of Pseudomonas strains against banded leaf and sheath blight disease of maize
Authors: Sahgal Manvika , Saini Neha , Jaggi Vandana , Brindhaa N. T. , Kabdwal Manisha , Singh Rajesh Pratap , Prakash Anil
Published: June 2024

Rhizoctonia solani, the causal agent of banded leaf and sheath blight (BL&SB), poses a significant threat to maize and various crops globally. The increasing concerns surrounding the environmental and health impacts of chemical fungicides have encouraged intensified concern in the development of biological control agents (BCAs) as eco-friendly alternatives. In this study, we explored the potential of 22 rhizobacteria strains (AS1–AS22) isolates, recovered from the grasslands of the Pithoragarh region in the Central Himalayas, as effective BCAs against BL&SB disease. Among these strains, two Pseudomonas isolates, AS19 and AS21, exhibited pronounced inhibition of fungal mycelium growth in vitro, with respective inhibition rates of 57.04% and 54.15% in cell cultures and 66.56% and 65.60% in cell-free culture filtrates. Additionally, both strains demonstrated effective suppression of sclerotium growth. The strains AS19 and AS21 were identified as Pseudomonas sp. by 16S rDNA phylogeny and deposited under accession numbers NAIMCC-B-02303 and NAIMCC-B-02304, respectively. Further investigations revealed the mechanisms of action of AS19 and AS21, demonstrating their ability to induce systemic resistance (ISR) and exhibit broad-spectrum antifungal activity against Alternaria triticina, Bipolaris sorokiniana, Rhizoctonia maydis, and Fusarium oxysporum f. sp. lentis. Pot trials demonstrated significant reductions in BL&SB disease incidence (DI) following foliar applications of AS19 and AS21, with reductions ranging from 25 to 38.33% compared to control treatments. Scanning electron microscopy revealed substantial degradation of fungal mycelium by the strains, accompanied by the production of hydrolytic enzymes. These findings suggest the potential of Pseudomonas strains AS19 and AS21 as promising BCAs against BL&SB and other fungal pathogens. However, further field trials are warranted to validate their efficacy under natural conditions and elucidate the specific bacterial metabolites responsible for inducing systemic resistance. This study contributes to the advancement of sustainable disease management strategies and emphasizes the potential of Pseudomonas strains AS19 and AS21 in combating BL&SB and other fungal diseases affecting agricultural crops.
Constraint optimization of an integrated production model utilizing history matching and production forecast uncertainty through the ensemble Kalman filter
Authors: Fadaei Mehdi , Ameri Mohammad Javad , Rafiei Yousef
Published: June 2024

The calibration of reservoir models using production data can enhance the reliability of predictions. However, history matching often leads to only a few matched models, and the original geological interpretation is not always preserved. Therefore, there is a need for stochastic methodologies for history matching. The Ensemble Kalman Filter (EnKF) is a well-known Monte Carlo method that updates reservoir models in real time. When new production data becomes available, the ensemble of models is updated accordingly. The initial ensemble is created using the prior model, and the posterior probability function is sampled through a series of updates. In this study, EnKF was employed to evaluate the uncertainty of production forecasts for a specific development plan and to match historical data to a real field reservoir model. This study represents the first attempt to combine EnKF with an integrated model that includes a genuine oil reservoir, actual production wells, a surface choke, a surface pipeline, a separator, and a PID pressure controller. The research optimized a real integrated production system, considering the constraint that there should be no slug flow at the inlet of the separator. The objective function was to maximize the net present value (NPV). Geological data was used to model uncertainty using Sequential Gaussian Simulation. Porosity scenarios were generated, and conditioning the porosity to well data yielded improved results. Ensembles were employed to balance accuracy and efficiency, demonstrating a reduction in porosity uncertainty due to production data. This study revealed that utilizing a PID pressure controller for the production separator can enhance oil production by 59% over 20 years, resulting in the generation of 2.97 million barrels of surplus oil in the field and significant economic gains.