bluuebunny/crossref_metadata_2025 huggingface dataset:
How many animal‐pollinated angiosperms are nectar‐producing?
Authors: Ballarin Caio S. , Fontúrbel Francisco E. , Rech André R. , Oliveira Paulo E. , Goés Guilherme Alcarás , Polizello Diego S. , Oliveira Pablo H. , Hachuy‐Filho Leandro , Amorim Felipe W.
Published: July 2024

The diversity of plant–pollinator interactions is grounded in floral resources, with nectar considered one of the main floral rewards plants produce for pollinators. However, a global evaluation of the number of animal‐pollinated nectar‐producing angiosperms and their distribution world‐wide remains elusive.

We compiled a thorough database encompassing 7621 plant species from 322 families to estimate the number and proportion of nectar‐producing angiosperms reliant on animal pollination. Through extensive sampling of plant communities, we also explored the interplay between nectar production, floral resource diversity, latitudinal and elevational gradients, contemporary climate, and environmental characteristics.

Roughly 223 308 animal‐pollinated angiosperms are nectar‐producing, accounting for 74.4% of biotic‐pollinated species. Global distribution patterns of nectar‐producing plants reveal a distinct trend along latitudinal and altitudinal gradients, with increased proportions of plants producing nectar in high latitudes and altitudes. Conversely, tropical communities in warm and moist climates exhibit greater floral resource diversity and a lower proportion of nectar‐producing plants.

These findings suggest that ecological trends driven by climate have fostered the diversification of floral resources in warmer and less seasonal climates, reducing the proportion of solely nectar‐producing plants. Our study provides a baseline for understanding plant–pollinator relationships, plant diversification, and the distribution of plant traits.
Spousal Agreement on Sex Preferences for Children and Gender Gaps in Children's Education
Authors: Maralani Vida , Pinar Candas
Published: July 2024

Using data from 60 countries, we measure how much couples agree on sex preferences for children and whether differences in sex preferences are associated with gender gaps in children's education. Results show extensive disagreement in sex preferences for children, with husbands far more likely to want more sons but their wives more likely to prefer having equal numbers of boys and girls, wanting more daughters, or having no preference. India has the highest share of agreement on sex preferences (59 percent), and Niger has the lowest (32 percent). The association between couples’ sex preferences and gender gaps in education differs considerably by country. In some countries, girls have worse outcomes when their parents agree on son preference and better ones when parents agree on daughter/no preference. But there are numerous counter‐examples as well. Gender gaps in education appear more often when wives hold son preference but not their husbands than the reverse combination. Agreement on daughter/no preference is the only category that is systematically associated with better outcomes for girls relative to boys (although even here there are caveats). Balanced preference (wanting as many boys as girls) is an ambiguous category with heterogenous patterns in terms of educational gender gaps.
A community‐based participatory research approach to evaluating and improving hepatitis C risk, knowledge, and stigma associations among people who inject substances in Indiana
Authors: Woodward Brennan , Millar Krystina , Carter Gregory
Published: July 2024

Objectives

To explore hepatitis C risk, knowledge, and stigma among individuals who inject substances in South Central Indiana.

Design

A cross‐sectional study design was employed using a community‐based participatory research approach. The community partner was a grassroots harm reduction organization.

Sample

Participants in this study were at least 18 years of age, current residents of Indiana, and self‐identified as injection substance users (n = 179).

Measurements

The survey measured hepatitis C risk, knowledge, and stigma, as well as differences in hepatitis C risk scores among key demographic characteristics.

Results

Most participants identified as male (n = 106, 59%), White (n = 139, 78%), and straight (n = 143, 80%). People of color reported lower hepatitis C knowledge than White participants. Women had significantly lower hepatitis C knowledge compared with men. LGBTQ participants reported increased hepatitis C risk compared with straight participants. Increased frequency of substance use was associated with decreased stigma. Unhoused participants demonstrated significantly lower hepatitis C knowledge compared with housing‐secure participants.

Conclusions

Our findings increase understanding that knowledge and risk around hepatitis C are associated with demographic characteristics. Results underscore the need for tailored public health interventions to increase hepatitis C knowledge, reduce stigma, and improve testing and treatment among vulnerable populations.
Moderate cardiac vagal tone predicts more cooperation in highly sensitive individuals
Authors: Mastromatteo Libera Ylenia , Lionetti Francesca , Pluess Michael , Scrimin Sara
Published: July 2024

Cooperation, as a mutual collaboration, is a defining feature of human social life. Individual characteristics can influence cooperation. Recent studies have shown a quadratic relationship between cardiac vagal tone (CVT), an index of self‐regulation, and prosocial behaviors. Individual differences in cooperation might also vary as a function of people's environmental sensitivity (ES), i.e., may be influenced by individual differences in the perception and processing of inner and external stimuli. We tested the direct and interactive effect of CVT and ES on cooperative behaviors in two independent samples. We measured heart rate and engagement in cooperative acts in 80 young adults (M = 23.61; SD = 1.60) who were also asked to self‐report on ES. We found an inverted‐U relationship between CVT and cooperative behaviors. ES, on the other hand, did not predict differences in cooperative behaviors but moderated the relationships between CVT and cooperation, although the magnitude of this result was small. Specifically, only among individuals with higher ES cooperative behaviors change as a function of CVT. Highly sensitive individuals with lower or higher CVT, were less cooperative than low sensitive ones. Subsequently, we replicated the same study design in a second sample of 88 undergraduate students (M = 23.69; SD = 4.91). Once again, we found evidence supporting the presence of an inverted‐U relationship between CVT and cooperative behaviors, and we also found that ES moderated the relationships between the quadratic CVT term and cooperation.
Corporate governance and innovation: a predictive modeling approach using machine learning
Authors: de Pilla Leonardo Henrique Lima , Silveira Elaine Barbosa Couto , Caldieraro Fábio , Peci Alketa , Aggarwal Ishani
Published: July 2024

The examination of the associations between internal corporate governance (CG) mechanisms and innovation faces challenges due to nonlinear patterns and complex interactions. Consequently, existing literature rarely reaches a consensus on the directions or strengths of these relationships. Furthermore, to investigate the CG–innovation association, prior research has predominantly relied on explanatory modeling, which involves applying statistical models to data to test correlational or causal hypotheses about theoretical constructs. These are the reasons why it remains unclear whether internal CG mechanisms, when considered collectively as an extensive array of interconnected variables, offer valuable insights for accurately predicting innovation. To address this gap, we analyze a dataset of research and development (R&D) projects from the Brazilian electricity sector by employing predictive modeling, which entails using statistical models or data mining algorithms to predict new observations, particularly using supervised machine learning (ML) methods. Our study demonstrates that a comprehensive set of variables representing internal CG mechanisms significantly enhances the predictive capabilities of ML algorithms for innovation. Furthermore, we illustrate how ML can illuminate nonlinear and non‐monotonic patterns, and interactions among variables, in the CG–innovation relationship. Our contribution to the literature encompasses three key aspects: introducing a predictive modeling approach to the discourse on the role of CG in innovation attainment through R&D endeavors, which can complement and enrich existing explanatory research; investigating non‐linear and non‐monotonic relationships, as well as interactions, in innovation prediction; and affirming the emerging body of literature that recognizes supervised ML as a valuable tool accessible to management researchers.
The causal relationship between immune cells mediating FIT3L, CCL4, OSM, and skin‐derived deteriorated tumors
Authors: Gong Wanli , Zhou Jiayi , Hou Yaqi , Zhang juan , He Peifeng , Yu Qi
Published: July 2024

Objective

Observational studies have identified a dual effect of circulating inflammatory proteins and immune cells on cancer progression. However, the specific mechanisms of action have not been clarified in the exacerbation of cutaneous‐origin tumors. Therefore, this study aims to investigate whether the causal relationship between circulating inflammatory factors and basal cell carcinoma (BCC), cutaneous malignant melanoma (SKCM), and cutaneous squamous cell carcinoma (cSCC) is regulated by immune cells.

Methods

This study employed the Two‐Sample Mendelian Randomization (TSMR) approach to investigate the causal relationships between 91 circulating inflammatory factors and three prevalent types of skin cancer from a genetic perspective. Bayesian Weighted Mendelian Randomization (BWMR) was also used to validate correlation and reverse MR to assess inverse relationships. Subsequent sensitivity analyses were conducted to limit the impact of heterogeneity and pleiotropy. Finally, the two‐step Mendelian Randomization (two‐step MR) method was utilized to ascertain the mediating effects of specific immune cell traits in the causal pathways linking circulating inflammatory factors with BCC, SKCM, and cSCC.

Results

The Inverse Variance Weighted (IVW) method and the Bayesian Weighted Algorithm collectively identified nine inflammatory factors causally associated with BCC, SKCM, and cSCC. The results from Cochran's Q test, mendelian randomization pleiotropy residual sum and outlier (MR‐PRESSO), and MR‐Egger intercept were not statistically significant (p < 0.05). Additionally, the proportions mediated by CD4+ CD8dim T cell %leukocyte, CD4‐CD8‐Natural Killer T %T cell, and CD20 on IgD‐CD38‐B cell for FIt3L, CCL4, and OSM were 9.26%, 8.96%, and 10.16%, respectively.

Conclusion

Immune cell levels potentially play a role in the modulation process between circulating inflammatory proteins and cutaneous‐origin exacerbated tumors. This finding offers a new perspective for the in‐depth exploration of cutaneous malignancies.
HelioPoint – A Fast Airborne Calibration Method for Heliostat Fields
Authors: Krauth Julian J. , Happich Christoph , Algner Niels , Broda Rafal , Kämpgen Andreas , Schnerring Alexander , Ulmer Steffen , Röger Marc
Published: July 2024

The pointing calibration of a newly built heliostat field can take up to several years. The state-of-the-art method typically used is accurate but slow. A faster method could reduce the commissioning time and therefore increase the viability of a solar tower plant significantly. In this work, we present HelioPoint, a fast airborne heliostat calibration technique, and demonstrate its accuracy to be better than 0.3 mrad. The measurement is performed using a light-emitting diode (LED) and a camera fitted to a drone. The only infrastructure required is the roughly pre-aligned heliostats themselves. The method is independent of the sun position and can be performed at any time for arbitrary calibration points.
Momentum and angular momentum reciprocity theorems for acoustic fields
Authors: Zang Yuchen
Published: July 2024

As a universal theorem applicable to linear physical systems, reciprocity theorems describe the reciprocity between the input and output of linear systems. As for the electromagnetic field, there have been detailed studies on the reciprocity theorems of energy, momentum, and angular momentum, which reveal the correlation between two electromagnetic field sources from different aspects. Based on the fundamentals of linear acoustic theory, the momentum-based and angular momentum-based reciprocity theorems for acoustic fields are derived. They indicate the correlation between two acoustic systems from the perspective of momentum and angular momentum, respectively. On this basis, a systematic summary and analogical study is also performed on various reciprocity theorems for acoustic and electromagnetic fields, which deepens our understanding of the reciprocity theorem as a universal law for linear physical fields. The results obtained in this work can further improve the reciprocity theory of linear acoustic systems, as well as provide theoretical guidance for practical applications, such as audio signal processing and acoustic measurement.
YAP represses the TEAD–NF-κB complex and inhibits the growth of clear cell renal cell carcinoma
Authors: Li Zhongbo , Su Peng , Yu Miao , Zhang Xufeng , Xu Yaning , Jia Tianwei , Yang Penghe , Zhang Chenmiao , Sun Yanan , Li Xin , Yang Huijie , Ding Yinlu , Zhuang Ting , Guo Haiyang , Zhu Jian
Published: July 2024

The Hippo pathway is generally understood to inhibit tumor growth by phosphorylating the transcriptional cofactor YAP to sequester it to the cytoplasm and reduce the formation of YAP-TEAD transcriptional complexes. Aberrant activation of YAP occurs in various cancers. However, we found a tumor-suppressive function of YAP in clear cell renal cell carcinoma (ccRCC). Using cell cultures, xenografts, and patient-derived explant models, we found that the inhibition of upstream Hippo-pathway kinases MST1 and MST2 or expression of a constitutively active YAP mutant impeded ccRCC proliferation and decreased gene expression mediated by the transcription factor NF-κB. Mechanistically, the NF-κB subunit p65 bound to the transcriptional cofactor TEAD to facilitate NF-κB–target gene expression that promoted cell proliferation. However, by competing for TEAD, YAP disrupted its interaction with NF-κB and prompted the dissociation of p65 from target gene promoters, thereby inhibiting NF-κB transcriptional programs. This cross-talk between the Hippo and NF-κB pathways in ccRCC suggests that targeting the Hippo-YAP axis in an atypical manner—that is, by activating YAP—may be a strategy for slowing tumor growth in patients.
Thorough QT/QTc study to evaluate the effect of a single supratherapeutic dose of islatravir on QTc interval prolongation in healthy adults
Authors: Matthews Randolph P. , Liu Yang , Matthews Catherine , Butterfield Kristin L. , O'Reilly Terry , Stoch S. Aubrey , Iwamoto Marian
Published: July 2024

Islatravir is a deoxynucleoside analog being developed for the treatment of HIV-1 infection. Clinical studies are being conducted to evaluate islatravir, administered in combination with other antiretroviral therapies, at doses of 0.25 mg once daily and 2 mg once weekly. In multiple previous clinical studies, islatravir was generally well tolerated, with no clear trend in cardiac adverse events. A trial was conducted to evaluate the effect of islatravir on cardiac repolarization. A randomized, double-blind, active- and placebo-controlled phase 1 trial was conducted, in which a single dose of islatravir 0.75 mg, islatravir 240 mg (supratherapeutic dose), moxifloxacin 400 mg (active control), or placebo was administered. Continuous 12-lead electrocardiogram monitoring was performed before dosing through 24 hours after dosing. QT interval measurements were collected, and safety and pharmacokinetics were evaluated. Sixty-three participants were enrolled, and 59 completed the study. Fridericia’s QT correction for heart rate was inadequate; therefore, a population-specific correction was applied (QTcP). The placebo-corrected change from baseline in QTcP (ΔΔQTcP) interval at the observed geometric mean maximum plasma concentration associated with islatravir 0.75 mg and islatravir 240 mg was <10 ms at all time points. Assay sensitivity was confirmed because the use of moxifloxacin 400 mg led to a ΔΔQTcP >10 ms. The pharmacokinetic profile of islatravir was consistent with that of previous studies, and islatravir was generally well tolerated. Results from the current trial suggest that single doses of islatravir as high as 240 mg do not lead to QTc interval prolongation.
Characterization of human tibrovirus envelope glycoproteins
Authors: Munyeku-Bazitama Yannick , Saito Takeshi , Hattori Takanari , Miyamoto Hiroko , Lombe Boniface Pongombo , Mori-Kajihara Akina , Kajihara Masahiro , Muyembe-Tamfum Jean-Jacques , Igarashi Manabu , Park Eun-sil , Morikawa Shigeru , Makiala-Mandanda Sheila , Takada Ayato
Published: July 2024

Tibroviruses are novel rhabdoviruses detected in humans, cattle, and arthropods. Four tibroviruses are known to infect humans: Bas-Congo virus (BASV), Ekpoma virus 1 (EKV-1), Ekpoma virus 2, and Mundri virus. However, since none of them has been isolated, their biological properties are largely unknown. We aimed to characterize the human tibrovirus glycoprotein (G), which likely plays a pivotal role in viral tropism and pathogenicity. Human tibrovirus Gs were found to share some primary structures and display 14 conserved cysteine residues, although their overall amino acid homology was low (29%–48%). Multiple potential glycosylation sites were found on the G molecules, and endoglycosidase H- and peptide-N-glycosidase F-sensitive glycosylation was confirmed. AlphaFold-predicted three-dimensional (3D) structures of human tibrovirus Gs were overall similar. Membrane fusion mediated by these tibrovirus Gs was induced by acidic pH. The low pH-induced conformational change that triggers fusion was reversible. Virus-like particles (VLPs) were produced by transient expression of Gs in cultured cells and used to produce mouse antisera. Using vesicular stomatitis Indiana virus pseudotyped with Gs, we found that the antisera to the respective tibrovirus VLPs showed limited cross-neutralizing activity. It was also found that human C-type lectins and T-cell immunoglobulin mucin 1 acted as attachment factors for G-mediated entry into cells. Interestingly, BASV-G showed the highest ability to utilize these molecules. The viruses infected a wide range of cell lines with preferential tropism for human-derived cells whereas the preference of EKV-1 was unique compared with the other human tibroviruses. These findings provide fundamental information to understand the biological properties of the human tibroviruses.

IMPORTANCE

Human tibroviruses are poorly characterized emerging rhabdoviruses associated with either asymptomatic infection or severe disease with a case fatality rate as high as 60% in humans. However, the extent and burden of human infection as well as factors behind differences in infection outcomes are largely unknown. In this study, we characterized human tibrovirus glycoproteins, which play a key role in virus-host interactions, mainly focusing on their structural and antigenic differences and cellular tropism. Our results provide critical information for understanding the biological properties of these novel viruses and for developing appropriate preparedness interventions such as diagnostic tools, vaccines, and effective therapies.
Simultaneous quantitation of neutralizing antibodies against all four dengue virus serotypes using optimized reporter virus particles
Authors: Lingemann Matthias , Amaro-Carambot Emérito , Lamirande Elaine W. , Pierson Theodore C. , Whitehead Stephen S.
Published: July 2024

Serum-neutralizing antibody titers are a critical measure of vaccine immunogenicity and are used to determine flavivirus seroprevalence in study populations. An effective dengue virus (DENV) vaccine must confer simultaneous protection against viruses grouped within four antigenic serotypes. Existing flavivirus neutralization assays, including the commonly used plaque/focus reduction neutralization titer (PRNT/FRNT) assay, require an individual assay for each virus, serotype, and strain and easily become a labor-intensive and time-consuming effort for large epidemiological studies or vaccine trials. Here, we describe a multiplex reporter virus particle neutralization titer (TetraPlex RVPNT) assay for DENV that allows simultaneous quantitative measures of antibody-mediated neutralization of infection against all four DENV serotypes in a single low-volume clinical sample and analyzed by flow cytometry. Comparative studies confirm that the neutralization titers of antibodies measured by the TetraPlex RVPNT assay are similar to FRNT/PRNT assay approaches performed separately for each viral strain. The use of this high-throughput approach enables the careful serological study in DENV endemic populations and vaccine recipients required to support the development of a safe and effective tetravalent DENV vaccine.

IMPORTANCE

As a mediator of protection against dengue disease and a serological indicator of prior infection, the detection and quantification of neutralizing antibodies against DENV is an important “gold standard” tool. However, execution of traditional neutralizing antibody assays is often cumbersome and requires repeated application for each virus or serotype. The optimized RVPNT assay described here is high-throughput, easily multiplexed across multiple serotypes, and targets reporter viral particles that can be robustly produced for all four DENV serotypes. The use of this transformative RVPNT assay will support the expansion of neutralizing antibody datasets to answer research and public health questions often limited by the more cumbersome neutralizing antibody assays and the need for greater quantities of test serum.
Whole-genome sequencing and characterization of human fecal isolate
Lacticaseibacillus casei
LC130 from NORDBIOTIC collection
Authors: Szczepankowska Agnieszka K. , Cukrowska Bożena , Aleksandrzak-Piekarczyk Tamara
Published: July 2024

We report the complete genome sequence of
Lacticaseibacillus casei
LC130, isolated from a healthy human fecal sample and part of the NORDBIOTIC collection. The 2.969 Mb genome of LC130 includes genes potentially involved in lactose metabolism and the production of bacteriocins, peptidases, and polyamines, suggesting potential health benefits.
The impact of DNA extraction on the quantification of
Legionella
, with implications for ecological studies
Authors: Cavallaro Alessio , Gabrielli Marco , Hammes Frederik , Rhoads William J.
Published: July 2024

Monitoring the levels of opportunistic pathogens in drinking water is important to plan interventions and understand the ecological niches that allow them to proliferate. Quantitative PCR is an established alternative to culture methods that can provide a faster, higher-throughput, and more precise enumeration of the bacteria in water samples. However, PCR-based methods are still not routinely applied for
Legionella
monitoring, and techniques, such as DNA extraction, differ notably between laboratories. Here, we quantify the impact that DNA extraction methods had on downstream PCR quantification and community sequencing. Through a community science campaign, we collected 50 water samples and corresponding shower hoses, and compared two commonly used DNA extraction methodologies to the same biofilm and water phase samples. The two methods showed clearly different extraction efficacies, which were reflected in both the quantity of DNA extracted and the concentrations of
Legionella
enumerated in both the matrices. Notably, one method resulted in higher enumeration in nearly all samples by about one order of magnitude and detected
Legionella
in 21 samples that remained undetected by the other method. 16S rRNA amplicon sequencing revealed that the relative abundance of individual taxa, including sequence variants of
Legionella
, significantly varied depending on the extraction method employed. Given the implications of these findings, we advocate for improvement in documentation of the performance of DNA extraction methods used in drinking water to detect and quantify
Legionella
, and characterize the associated microbial community.

IMPORTANCE

Monitoring for the presence of the waterborne opportunistic pathogen
Legionella
is important to assess the risk of infection and plan remediation actions. While monitoring is traditionally carried on through cultivation, there is an ever-increasing demand for rapid and high-throughput molecular-based approaches for
Legionella
detection. This paper provides valuable insights on how DNA extraction affects downstream molecular analysis such as the quantification of
Legionella
through droplet digital PCR and the characterization of natural microbial communities through sequencing analysis. We analyze the results from a risk-assessment, legislative, and ecological perspective, showing how initial DNA processing is an important step to take into account when shifting to molecular-based routine monitoring and discuss the central role of consistent and detailed reporting of the methods used.
Migration of sclerosant material to the left renal vein following coil embolisation of a varicocele
Authors: Youssef Marina , Scott Steel , Grills Richard
Published: July 2024

Percutaneous testicular varicocele embolisation for symptomatic and subfertile males is often preferred over surgical ligation of the gonadal vein due to its minimally invasive approach and reduced complication rate. Glues, coils, vascular plugs, balloons and sclerosants are used in various combinations to achieve sufficient venous occlusion. Here, we report on the first known case of sclerosant material migration beyond the placement of an embolisation coil for treatment of a varicocele, resulting in a left renal vein thrombus. A man in his 20s presented to the emergency department 2 days following uncomplicated left varicocele embolisation with acute left-sided abdominal pain, found to have sclerosant material causing an ipsilateral non-occlusive left renal vein thrombus with extension towards his inferior vena cava on CT. He was treated with 3 months of anticoagulation and follow-up imaging at 3 months showed resolution of this thrombus without renal impairment.
Adaptability of prognostic prediction models for patients with acute coronary syndrome during the COVID-19 pandemic
Authors: Nishi Masahiro , Nakamura Takeshi , Yanishi Kenji , Matoba Satoaki
Published: July 2024

Background

The detrimental repercussions of the COVID-19 pandemic on the quality of care and clinical outcomes for patients with acute coronary syndrome (ACS) necessitate a rigorous re-evaluation of prognostic prediction models in the context of the pandemic environment. This study aimed to elucidate the adaptability of prediction models for 30-day mortality in patients with ACS during the pandemic periods.

Methods

A total of 2041 consecutive patients with ACS were included from 32 institutions between December 2020 and April 2023. The dataset comprised patients who were admitted for ACS and underwent coronary angiography for the diagnosis during hospitalisation. The prediction accuracy of the Global Registry of Acute Coronary Events (GRACE) and a machine learning model, KOTOMI, was evaluated for 30-day mortality in patients with ST-elevation acute myocardial infarction (STEMI) and non-ST-elevation acute coronary syndrome (NSTE-ACS).

Results

The area under the receiver operating characteristics curve (AUROC) was 0.85 (95% CI 0.81 to 0.89) in the GRACE and 0.87 (95% CI 0.82 to 0.91) in the KOTOMI for STEMI. The difference of 0.020 (95% CI −0.098–0.13) was not significant. For NSTE-ACS, the respective AUROCs were 0.82 (95% CI 0.73 to 0.91) in the GRACE and 0.83 (95% CI 0.74 to 0.91) in the KOTOMI, also demonstrating insignificant difference of 0.010 (95% CI −0.023 to 0.25). The prediction accuracy of both models had consistency in patients with STEMI and insignificant variation in patients with NSTE-ACS between the pandemic periods.

Conclusions

The prediction models maintained high accuracy for 30-day mortality of patients with ACS even in the pandemic periods, despite marginal variation observed.
Tethered IL15-IL15Rα augments antitumor activity of CD19 CAR-T cells but displays long-term toxicity in an immunocompetent lymphoma mouse model
Authors: Sánchez-Moreno Inés , Lasarte-Cia Aritz , Martín-Otal Celia , Casares Noelia , Navarro Flor , Gorraiz Marta , Sarrión Patricia , Hervas-Stubbs Sandra , Jordana Lorea , Rodriguez-Madoz Juan Roberto , San Miguel Jesús , Prosper Felipe , Lasarte Juan Jose , Lozano Teresa
Published: July 2024

Background

Adoptive cell therapy using genetically modified T cells to express chimeric antigen receptors (CAR-T) has shown encouraging results, particularly in certain blood cancers. Nevertheless, over 40% of B cell malignancy patients experience a relapse after CAR-T therapy, likely due to inadequate persistence of the modified T cells in the body. IL15, known for its pro-survival and proliferative properties, has been suggested for incorporation into the fourth generation of CAR-T cells to enhance their persistence. However, the potential systemic toxicity associated with this cytokine warrants further evaluation.

Methods

We analyzed the persistence, antitumor efficacy and potential toxicity of anti-mouse CD19 CAR-T cells which express a membrane-bound IL15-IL15Rα chimeric protein (CD19/mbIL15q CAR-T), in BALB/c mice challenged with A20 tumor cells as well as in NSG mice.

Results

Conventional CD19 CAR-T cells showed low persistence and poor efficacy in BALB/c mice treated with mild lymphodepletion regimens (total body irradiation (TBI) of 1 Gy). CD19/mbIL15q CAR-T exhibits prolonged persistence and enhanced in vivo efficacy, effectively eliminating established A20 B cell lymphoma. However, this CD19/mbIL15q CAR-T displays important long-term toxicities, with marked splenomegaly, weight loss, transaminase elevations, and significant inflammatory findings in some tissues. Mice survival is highly compromised after CD19/mbIL15q CAR-T cell transfer, particularly if a high TBI regimen is applied before CAR-T cell transfer.

Conclusion

Tethered IL15-IL15Rα augments the antitumor activity of CD19 CAR-T cells but displays long-term toxicity in immunocompetent mice. Inducible systems to regulate IL15-IL15Rα expression could be considered to control this toxicity.
Impact of patient selection in clinical trials: application of ROCKET AF and ARISTOTLE criteria in GARFIELD-AF
Authors: Himmelreich Jelle C L , Virdone Saverio , Camm John , Pieper Karen , Harskamp Ralf E , Oto Ali , Jacobson Barry F , Sawhney J P S , Lim Toon Wei , Gibbs Harry , Goto Shinya , Haas Sylvia , Fox Keith A A , Jansky Petr , Verheugt Freek , Kakkar Ajay K
Published: July 2024

Background

The extent to which differences in results from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial (ROCKET) atrial fibrillation (AF)—the landmark trials for the approval of apixaban and rivaroxaban, respectively, for non-valvular AF—were influenced by differences in their protocols is debated. The potential influence of selection criteria on trial results was assessed by emulating these trials in data from the Global Anticoagulant Registry in the Field (GARFIELD)-AF registry.

Methods

Vitamin K antagonist (VKA) and non-vitamin K oral antagonist (NOAC) users from GARFIELD-AF were selected according to eligibility for the original ARISTOTLE or ROCKET AF trials. A propensity score overlap weighted Cox model was used to emulate trial randomisation between treatment groups. Adjusted HRs for stroke or systemic embolism (SE) within 2 years of enrolment were calculated for each NOAC versus VKA.

Results

Among patients on apixaban, rivaroxaban and VKA, 2570, 3560 and 8005 were eligible for ARISTOTLE, respectively, and 1612, 2005 and 4368, respectively, for ROCKET AF. When selecting for ARISTOTLE criteria, apixaban users had significantly lower stroke/SE risk versus VKA (HR 0.57; 95% CI 0.34 to 0.94) while no reduction was observed with rivaroxaban (HR 0.98; 95% CI 0.68 to 1.40). When selecting for ROCKET AF criteria, safety and efficacy versus VKA were similar across the NOACs.

Conclusion

Apixaban and rivaroxaban showed similar results versus VKA in high-risk patients selected according to ROCKET AF criteria, whereas differences emerged when selecting for the more inclusive ARISTOTLE criteria. Our results highlight the importance of trial selection criteria in interpreting trial results and underline the problems faced in comparing treatments across rather than within clinical trials.
Effects of shape/phase transition regions on neutron capture cross sections
Authors: Couture A. , Cakirli R. B. , Casten R. F.
Published: July 2024

A recent study found a new, purely empirical correlation between two-neutron separation energies and neutron capture cross sections in keV neutron energy regimes. In shape/phase transition regimes, such as that near A= 150, S$$_{2n}$$

2
n

values show an anomaly—a flattening of the normal near linear decrease with neutron number. This paper addresses two questions: (1) Using this new correlation, is this anomaly in S$$_{2n}$$

2
n

values sizeable enough to produce an observable effect in capture cross sections? and (2) Can the correlation be used to quantitatively reproduce the cross sections in the transition region? It is found that the answer to both questions is in the affirmative. Possible relations to the r-process are briefly discussed.
Framed DDF operators and the general solution to Virasoro constraints
Authors: Biswas Dripto , Pesando Igor
Published: July 2024

We define the framed DDF operators by introducing the concept of local frames in the usual formulation of DDF operators. In doing so it is possible to completely decouple the DDF operators from the associated tachyon and show that they are good zero-dimensional conformal operators. These framed DDFs allow for an explicit covariant formulation of the general solution of the Virasoro constraints both on-shell and off-shell which depends on a unique set of tangent space lightcone polarizations. This is possible since the frame allows us to embed the $$SO(D-2)$$

S
O
(
D
-
2
)

lightcone physical polarizations into the $$SO(1,D-1)$$

S
O
(
1
,
D
-
1
)

covariant ones in the most general way. The solution to the Virasoro constraints is not in the gauge that is usually used since the states obtained from DDF operators are generically the sum of terms which are partially transverse due to the presence of a projector but not traceless and terms which are partially traceless but not transverse. We then show that different embeddings are connected by states generated by improved Brower operators both on shell and off shell. Brower states are null on-shell and equivalent to BRST exact states. Therefore on shell one embedding is sufficient to compute all amplitudes except the ones with vanishing momentum. Off-shell a change of frame cannot be obtained by null states but only by Brower states. Improved Brower operators generate a gauge invariance associated with local frame rotations, which replaces the usual gauge invariance generated by Virasoro operators or BRST. To check the identification, we verify the matching of the expectation value of the second Casimir of the Poincaré group for some lightcone states with the corresponding covariant states built using the framed DDFs.
Nonlocal QED and lepton g-2 anomalies
Authors: Li Hang , Wang P.
Published: July 2024

Quantum electrodynamics is generally extended to a nonlocal QED by introducing the correlation functions. The gauge link is introduced to guarantee that the nonlocal QED is locally U(1) gauge invariant. The corresponding Feynman rules as well as the proof of Ward–Takahashi identity are presented. As an example, the anomalous magnetic moments of leptons are studied in nonlocal QED. At one-loop level, besides the ordinary diagrams, there are many additional Feynman diagrams which are generated from the gauge link. It shows the nonlocal QED can provide a reasonable explanation for lepton $$g-2$$

g
-
2

anomalies.
Time-periodic electrokinetic analysis of a micropolar fluid flow through hydrophobic microannulus
Authors: Faltas M. S. , El-Sapa Shreen
Published: July 2024

The oscillating aspects of pressure-driven micropolar fluid flow through a hydrophobic cylindrical microannulus under the influence of electroosmotic flow are analytically studied. The study is based on a linearized Poisson–Boltzmann equation and the micropolar model of Eringen for microstructure fluids. An analytical solution is obtained for the distributions of electroosmotic flow velocity and microrotation as functions of radial distance, periodic time, and relevant parameters. The findings of the present study demonstrate that, unlike the decrease in flow rate resulting from the micropolarity of fluid particles, velocity slip and spin velocity slip, when contrasted with Newtonian fluids, act as a counteractive mechanism that tends to enhance the flow rate. Additionally, the findings indicate that a square plug-like profile in electroosmotic velocity amplitude is observed when the electric oscillating parameter is low and the electrokinetic width is large, for both Newtonian and micropolar fluids. Moreover, in cases where there is a wide gap between the cylindrical walls and a high-frequency parameter, the electroosmotic velocity and microrotation amplitudes tend to approach zero at the center of the microannulus across all ranges of micropolarity and zeta potential parameters. Furthermore, it has been observed that the amplitude of microrotation strength rises as slip and spin slip parameters increase. Across the entire spectrum of micropolarity, the zeta potential ratio influences both the dimension and direction of the electroosmotic velocity profiles within the electric double layer near the two cylindrical walls of the microannulus. The study emphasizes the physical quantities by presenting graphs for various values of the pertinent parameters juxtaposing them with existing data in the literature and comparing them with the Newtonian fluids.

Graphic abstract
Toward biodefence: a framework for the mitigation of malicious threats to livestock production enterprises in Australia
Authors: Evans Deborah , Coole Michael , Brooks David J.
Published: July 2024

Biosecurity underpins the Australian agricultural sector, estimated to be worth $51 billion in exports and trade, $50 billion in tourism, $5.7 trillion in environmental assets, and more than 1.6 million jobs. Given the value to the Australian economy and the potential consequences of a deliberately introduced biological agent, measures to prevent malicious biosecurity threats are critical for national security. Using the framework of Situational Crime Prevention (SCP), the study examined recommended biosecurity practices for cattle production enterprises in Australia and explored the extent to which the Australian biosecurity framework is underpinned by preventative security. The study found the existing biosecurity framework has limited theoretical security underpinning and is constituted by practices primarily aimed at preventing naturally occurring and accidental threats, rather than an active preventative security approach at the farming level to mitigate threats of a malicious or deliberate nature. These findings identify a deficit in Australia’s national security approach to biosecurity in cattle production enterprises, establishing a need for biosecurity recommendations at an industry and primary production level to embed security theory and principles to account for malicious actors in alignment with international biodefence strategy. Subsequently, the study demonstrated how security theory can be applied to biosecurity and the agricultural sector more broadly and developed an SCP framework toward biodefence of agriculture, converging biosecurity and security as a bilateral approach to mitigating naturally occurring, accidental, and deliberate biosecurity threats.
Quantized heat flow in graphene quantum Hall phases: Probing the topological order
Authors: Srivastav Saurabh Kumar , Das Anindya
Published: July 2024

Topological quantum numbers are often used to characterize the topological order of phase having protected gapless edge modes when the system is kept in a space with the boundary. The famous examples in this category are the quantized electrical Hall conductance and thermal Hall conductance, which encodes the topological order of integer and fractional quantum Hall states. Here, we review the recent thermal transport study of integer and fractional quantum Hall states realized in graphene-based van der Waals heterostructures.
The Cretaceous post-rift series from the Portuguese onshore ranges of the West Iberian Margin and their history of research
Authors: Callapez Pedro M. , Barroso-Barcenilla Fernando , Berrocal-Casero Melani , Cunha Pedro P. , Dinis Pedro A. , Lopes Fernando C. , Ozkaya de Juanas Senay , Mendes Mário M. , Pimentel Ricardo J. , dos Santos Vanda F. , Segura Manuel
Published: July 2024

The thick post-rift series that covers the Triassic to Lower Cretaceous sedimentary succession of the Lusitanian Basin, in west central Portugal, is crucial to understanding the Mesozoic evolution of the West Iberian Margin, motivating a long history of studies, including those by Daniel Sharpe (1806–56). They record platform carbonates interbedded with marginal marine and alluvial facies. The post-rift infill was deposited above a late Aptian breakup unconformity and is organized into three unconformity bounded sequences: ‘UBS-4A’ (upper Aptian–upper Cenomanian), ‘UBS-4B’ (lower Turonian–lower Campanian) and ‘UBS-5B’ (lower Campanian–Maastrichtian). The first comprises alluvial siliciclastics and shallow-marine, carbonate sequences rich in Tethyan faunas with ammonites and rudists. During the late Cenomanian, the carbonate platform entirely covered the onshore sectors of the Lusitanian Basin. Several diapiric axes controlled the differentiation of inner platform areas with corals and rudists. The infill of ‘UBS-4B’ occurred after the tectonic uplift and emersion of the sectors located to the south of first-order Nazaré Fault Zone. The platform carbonate facies were overlain by regressive micaceous and alluvial coarse siliciclastics. The sequence ‘UBS-5’ overlies a lower Campanian unconformity and has a Campanian–Maastrichtian thick record of alluvial to lagoonal, reddish pelites, rich in vertebrate assemblages.
Click Fulfillment
Authors: Shasha Dennis
Published: July 2024

Off-the-shelf simulations.
In Memoriam: Gordon Bell
Authors: Garfinkel Simson , Spafford Eugene H.
Published: July 2024

Chester Gordon Bell, a pioneer of modern computing, died May 17, 2024. His work helped shape the field as we know it.
A Scalable Accelerator for Local Score Computation of Structure Learning in Bayesian Networks
Authors: Miyagi Ryota , Yasudo Ryota , Sano Kentaro , Takase Hideki
Published: July 2024

A Bayesian network is a powerful tool for representing uncertainty in data, offering transparent and interpretable inference, unlike neural networks’ black-box mechanisms. To fully harness the potential of Bayesian networks, it is essential to learn the graph structure that appropriately represents variable interrelations within data. Score-based structure learning, which involves constructing collections of potentially optimal parent sets for each variable, is computationally intensive, especially when dealing with high-dimensional data in discrete random variables. Our proposed novel acceleration algorithm extracts high levels of parallelism, offering significant advantages even with reduced reusability of computational results. In addition, it employs an elastic data representation tailored for parallel computation, making it FPGA-friendly and optimizing module occupancy while ensuring uniform handling of diverse problem scenarios. Demonstrated on a Xilinx Alveo U50 FPGA, our implementation significantly outperforms optimal CPU algorithms and is several times faster than GPU implementations on an NVIDIA TITAN RTX. Furthermore, the results of performance modeling for the accelerator indicate that, for sufficiently large problem instances, it is weakly scalable, meaning that it effectively utilizes increased computational resources for parallelization. To our knowledge, this is the first study to propose a comprehensive methodology for accelerating score-based structure learning, blending algorithmic and architectural considerations.
Unsupervised Adversarial Example Detection of Vision Transformers for Trustworthy Edge Computing
Authors: Li Jiaxing , Tan Yu’an , Yang Jie , Li Zhengdao , Ye Heng , Xia Chenxiao , Li Yuanzhang
Published: July 2024

Many edge computing applications based on computer vision have harnessed the power of deep learning. As an emerging deep learning model for vision, Vision Transformer models have recently achieved record-breaking performance in various vision tasks. But many recent studies on the robustness of the Vision Transformer have shown that the Vision Transformer is still vulnerable to adversarial attacks and is easily affected by adversarial attacks, causing the model to misclassify the input. In this work, we ask an intriguing question: “Can Adversarial Perturbations against Vision Transformers be detected with model explanations?” Driven by this question, we observe that benign samples and adversarial examples have different attribution maps after applying the Grad-CAM interpretability method on the Vision Transformer model. We demonstrate that an adversarial example is a
Feature Shift
of the input data, which leads to an
Attention Deviation
of the visual model. We propose a framework for capturing the
Attention Deviation
of vision models to defend against adversarial attacks. Furthermore, experiments show that our model achieves expectative results.
Neural Solving Uninterpreted Predicates with Abstract Gradient Descent
Authors: Yu Shiwen , Liu Zengyu , Wang Ting , Wang Ji
Published: July 2024

Uninterpreted predicate solving is a fundamental problem in formal verification, including loop invariant and constrained horn clauses predicate solving. Existing approaches have been mostly in symbolic ways. While achieving sustainable progress, they still suffer from inefficiency and seem unable to leverage the ever-increasing computility, such as GPU. Recently, neural relaxation has been proposed to tackle this problem. They treat the uninterpreted predicate-solving task as an optimization problem by relaxing the discrete search process into a learning process of neural networks. However, two bottlenecks keep them from being valid. First, relaxed neural networks cannot match the original semantics of predicates rigorously; second, the neural networks are difficult to train to reach global optimization. Therefore, this article presents a novel discrete neural architecture with the Abstract Gradient Decent (AGD) algorithm to directly solve uninterpreted predicates in the discrete hypothesis space. The abstract gradient is for discrete neurons whose calculation rules are designed in an abstract domain. Our approach conforms to the original semantics of predicates, and the proposed AGD algorithm can achieve global optimization satisfactorily. We implement the tool Dasp in the Boxes abstract domain to solve uninterpreted predicates in the QF-NIA SMT theory. In the experiments, Dasp has outperformed seven state-of-the-art tools across three predicate synthesis tasks.