bluuebunny/crossref_metadata_2025 huggingface dataset:
Trajectories of Parental Warmth and the Role They Play in Explaining Adolescent Prosocial Behavior
Authors: Buckley Lisa , Atkins Tiffany , Perera Withanage , Waller Michael
Published: October 2023

Adolescent prosocial behavior suggests social competence and it is associated with greater parental warmth yet the experience of warmth through child and adolescent development is not well understood as it relates to such prosocial behavior. A nationally representative dataset from the Longitudinal Study of Australian Children cohort was used. The analyses involved multiple waves beginning when children were aged 4–5. The main analyses used a sample of 2723 adolescents aged 16–17 years (Mean, S.D. = 16.45, 0.50; 49.2% female, 50.8% male). Parental warmth trajectories (from ages 4–5 through 16–17 years) were created and used to explore the accumulated effect of a lifecourse of parental warmth on adolescent prosocial behavior as measured when adolescents were aged 16–17 years. There were three trajectories described as, consistent (28.7%), slight decline (51.4%), and declining warmth (19.8%). These were associated with prosocial behavior; adolescents with a slight decline in warmth were 2.2 times less likely than those with consistent warmth to have the highest prosocial behavior. Consistent parental warmth likely provides greatest benefit for increased prosocial behavior in mid-adolescence.
Human Rights in Sports Arbitration: What Should the Court of Arbitration for Sport do for Protecting Human Rights in Sports?
Authors: Shinohara Tsubasa
Published: October 2023

Sports governing bodies establish their sporting rules and regulations. Nevertheless, they confront a complex question concerning whether a female athlete who inherently possesses an advantageous quantity of testosterone may participate in female athletic competitions. InCaster Semenya and Athletics South Africa (ASA) v. IAAF, the Court of Arbitration for Sport (CAS) held that she could not participate in female sports events because “the elevated testosterone levels that such athletes possess can create an insuperable advantage over other female athletes who do not have a 46 XY DSD condition”. Consequently, the CAS ruled that she would no longer be eligible to compete in professional female competitions. In this scenario, the primary focus of this article is to examine how the CAS should address human rights-related issues, even though it is not a human rights court like the European Court of Human Rights (ECtHR) but rather an arbitral tribunal. To achieve this purpose, this article will address the following questions: (1) How can athletes claim a violation of their human rights before the CAS?; and (2) What steps should the CAS take to safeguard human rights in sports? Through this research, it may serve to identify the CAS’s role in human rights protection in sports.
A Visit to the Pediatrician as a Part of Comprehensive Prenatal Care?
Authors: Mei Tiffany L. , Aligne C. Andrew , VanScott Jessica L.
Published: October 2023

Introduction

The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists recommend that expectant parents receive a preventive visit with a pediatrician in the prenatal period (a pediatric prenatal visit, or PPV). Discussing newborn health topics in the prenatal period tends to be more effective than immediately postpartum, and research suggests, for example, that the PPV increases timely childhood immunizations. However, only 22% of expectant parents have these visits, and there are significant disparities by race and income.

Methods

A 2-min online survey with open-ended questions was emailed to 304 eligible obstetrics providers in Rochester, NY. Simple descriptive statistics and chisquare analysis were applied to survey responses. Responses were organized within the framework of knowledge, attitudes, and practices to identify barriers to guideline adherence resulting in chronic under-utilization of the PPV.

Results

Ninety obstetric providers completed the survey. 66 reported awareness of the PPV, and 45 reported referring patients for a PPV. However, in open-ended questions, respondents expressed confusion between the PPV and a “meet and greet” visit with a pediatrician. Some respondents believed that the PPV is not covered by insurance, even though these visits are covered by Medicaid and marketplace insurance. Providers who had personally received one as a parent expressed positive attitudes.

Discussion

These findings indicate that unfamiliarity with the PPV is one barrier to referral. Educating providers about the guideline recommendations, evidence base, and insurance coverage could overcome this barrier. Doing so could reduce disparities in utilization of the pediatric prenatal visit.
Agenda-setting in nascent policy subsystems: issue and instrument priorities across venues
Authors: Lemke Nicole , Trein Philipp , Varone Frédéric
Published: October 2023

The “policy subsystem” has long been a key concept in our understanding of how policies on a given topic are produced. However, we know much less about policymaking in nascent policy subsystems. This article draws on the theories of agenda-setting and venue shopping to argue that the similarity and convergence of policy subsystems’ agendas across different institutional venues and over time are features that distinguish more nascent policy subsystems from their more established, mature counterparts. In simple terms, policy venues’ agendas converge when policy actors begin to discuss the same issues and instruments instead of talking past one another. The article illustrates this argument using textual data on Germany’s emerging Artificial Intelligence (AI) policy: print media debates, parliamentary debates, and a government consultation from the period between November 2017 and November 2019. The insights from our analysis show that actors emphasize somewhat different policy issues and instruments related to AI in different venues. Nevertheless, the longitudinal analysis suggests that the debate does seem to converge across different venues, which indicates the formation of a subsystem-specific policy agenda regarding AI.
Optimal mitigation and control over power system dynamics for stochastic grid resilience
Authors: Stewart Nathan , Arguello Bryan , Hoffman Matthew , Nicholson Bethany , Garrett Richard
Published: October 2023

Optimal mitigation planning for highly disruptive contingencies to a transmission-level power system requires optimization with dynamic power system constraints, due to the key role of dynamics in system stability to major perturbations. We formulate a generalized disjunctive program to determine optimal grid component hardening choices for protecting against major failures, with differential algebraic constraints representing system dynamics (specifically, differential equations representing generator and load behavior and algebraic equations representing instantaneous power balance over the transmission system). We optionally allow stochastic optimal pre-positioning across all considered failure scenarios, and optimal emergency control within each scenario. This novel formulation allows, for the first time, analyzing the resilience interdependencies of mitigation planning, preventive control, and emergency control. Using all three strategies in concert is particularly effective at maintaining robust power system operation under severe contingencies, as we demonstrate on the western system coordinating council 9-bus test system using synthetic multi-device outage scenarios.
Learning to Collaborate in a Project-based Graduate Course: A Multilevel Study of Student Outcomes
Authors: Johnsen Mette Mari Wold , Sjølie Ela , Johansen Vegard
Published: October 2023

The context of this study is an interdisciplinary project-based course at a large public university in Scandinavia. The course is taught annually to 3,300 graduate students from all fields of study, and learning to collaborate is a specified learning objective. Similar courses are widespread in higher education institutions worldwide, and empirical evidence of their impacts on students’ skill development is needed. This study examined students’ collaboration skill outcomes; whether outcomes vary by gender, academic achievement, field of study, course format (accelerated and semester based); and variations in outcomes across student groups and course classes. We used a pretest-posttest design in which 89% of students answered a self-report questionnaire about collaboration skills. The results indicate that the participating students’ interdisciplinary, interpersonal, and conflict management skills improved significantly from the beginning to the end of the course (p < .001, d > 0.4). We also found that the accelerated course format positively influenced the students’ conflict management skill outcomes and that the variability in the students’ overall collaboration outcomes was related to their student group (not their course classes). Another important takeaway from our study is that the students’ gender, academic achievement, and field of study showed little impact on their collaboration skills. The non-significance of the measured individual characteristics and the significance of the student group for students’ collaboration outcomes are important reminders for teachers in higher education to guide and support both their students’ learning and group processes in project-based courses.
Analysis of the bacterial and fungal populations in South African sorghum beer (umqombothi) using full-length 16S rRNA amplicon sequencing
Authors: Hlangwani Edwin , Abrahams Adrian , Masenya Kedibone , Adebo Oluwafemi Ayodeji
Published: October 2023

There is a need to profile microorganisms which exist pre-and-post-production ofumqombothi, to understand its microbial diversity and the interactions which subsequently influence the final product. Thus, this study sought to determine the relative microbial abundance inumqombothiand predict the functional pathways of bacterial and fungal microbiota present. Full-length bacterial 16S rRNA and internal transcribed spacer (ITS) gene sequencing using PacBio single-molecule, real-time (SMRT) technology was used to assess the microbial compositions. PICRUSt2 was adopted to infer microbial functional differences. A mixture of harmful and beneficial microorganisms was observed in all samples. The microbial diversity differed significantly between the mixed raw ingredients (MRI), customary beer brew (CB), and optimised beer brew (OPB). The highest bacterial species diversity was observed in the MRI, while the highest fungal species diversity was observed in the OPB. The dominant bacterial species in the MRI, CB, and OPB wereKosakonia cowanii,Apilactobacillus pseudoficulneus, andVibrio alginolyticus, respectively, while the dominant fungal species wasApiotrichum laibachii.The predicted functional annotations revealed significant (p < 0.05) differences in the microbial pathways of the fermented and unfermented samples. The most abundant pathways in the MRI were the branched-chain amino acid biosynthesis super pathway and the pentose phosphate pathway. The CB sample was characterised by folate (vitamin B9) transformations III, and mixed acid fermentation. Biotin (vitamin B7) biosynthesis I andl-valine biosynthesis characterised the OPB sample. These findings can assist in identifying potential starter cultures for the commercial production ofumqombothi. Specifically,A. pseudoficulneuscan be used for controlled fermentation during the production ofumqombothi. Likewise, the use ofA. laibachiican allow for better control over the fermentation kinetics such as carbohydrate conversion and end-product characteristics, especially esters and aroma compounds.
Poultices as biofilms of titanium dioxide nanoparticles/carboxymethyl cellulose/Phytagel for cleaning of infected cotton paper by Aspergillus sydowii and Nevskia terrae
Authors: Mansour Maisa M. A. , Salem Mohamed Z. M.
Published: October 2023

In this study, TiO2 nanoparticle (TiO2NP)-coated film was produced to protect manuscripts against microorganisms using ecofriendly benign materials. As a result, a simple method was created that uses poultice biofilm made of carboxymethyl cellulose (CMC) and Phytagel plant cell (PGP) loaded with TiO2NPs to preserve manuscripts against microbes in an environmentally responsible way. Three volumes (1, 2, 4 mL) of TiO2NPs were put into a biofilm combination to produce the poultices known as CMC/PGP/TiO2-1, CMC/PGP/TiO2-2, and CMC/PGP/TiO2-3. The synthesized TiO2NPs were nearly spherical in shape, small in size (98 nm), and stable (zeta potential value − 33 mV). The results showed that the unique deposition of TiO2NPs on the biofilm surface gave the produced films loaded with TiO2NPs a rough structure. The highest values of mechanical characteristics were determined to be in CMC/PGP/TiO2-1 with values of 25.4 g, 6.6 MPa, and 11.4%, for tensile strength, elongation at break, and tear strength, respectively. Based on molecular identification, the fungus Aspergillus sydowii and the bacterium Nevskia terrae, with accession numbers MG991624 and AB806800, respectively, were isolated and identified from an antiquated manuscript formed from cellulosic fibers. Before the experiments, the produced cotton paper samples were aged, and then, one group was infected for 6 months by A. sydowii and the second group with N. terrae. Following the preparation of a CMC/PGP biofilm loaded with various volumes of TiO2NPs, poultices were applied to infected cotton paper in order to clean it. The infected cotton paper was placed inside the sandwich-like poultices that were created. The poultice CMC/PGP/TiO2-2 demonstrated potential for preventing the growth of A. sydowii and N. terrae-infected cotton paper, when the fibers were saved, cleaned, and coated with CMC/PGP/TiO2-2 after absorbing the fungus and the bacterium and exhibiting exceptional antimicrobial activities. Finally, the novel biofilms have demonstrated their capacity to lessen microbial contamination of cotton paper. In order to generalize the usage of these poultices, it is also advised that they be produced on a large scale and tested on a variety of organic materials in the future.

Graphical Abstract
Evidence-Based Recommendations for the Pharmacological Treatment of Women with Schizophrenia Spectrum Disorders
Authors: Brand Bodyl A. , Willemse Elske J. M. , Hamers Iris M. H. , Sommer Iris E.
Published: October 2023

Purpose of Review

Despite clear evidence that sex differences largely impact the efficacy and tolerability of antipsychotic medication, current treatment guidelines for schizophrenia spectrum disorders (SSD) do not differentiate between men and women. This review summarizes the available evidence on strategies that may improve pharmacotherapy for women and provides evidence-based recommendations to optimize treatment for women with schizophrenia.

Recent Findings

We systematically searched PubMed and Embase for peer-reviewed studies on three topics: (1) sex differences in dose-adjusted antipsychotic serum concentrations, (2) hormonal augmentation therapy with estrogen and estrogen-like compounds to improve symptom severity, and (3) strategies to reduce antipsychotic-induced hyperprolactinemia. Based on three database studies and one RCT, we found higher dose-adjusted concentrations in women compared to men for most antipsychotics. For quetiapine, higher concentrations were specifically found in older women. Based on two recent meta-analyses, both estrogen and raloxifene improved overall symptomatology. Most consistent findings were found for raloxifene augmentation in postmenopausal women. No studies evaluated the effects of estrogenic contraceptives on symptoms. Based on two meta-analyses and one RCT, adjunctive aripiprazole was the best-studied and safest strategy for lowering antipsychotic-induced hyperprolactinemia.

Evidence-based recommendations for female-specific pharmacotherapy for SSD consist of (1) female-specific dosing for antipsychotics (guided by therapeutic drug monitoring), (2) hormonal replacement with raloxifene in postmenopausal women, and (3) aripiprazole addition as best evidenced option in case of antipsychotic-induced hyperprolactinemia. Combining these strategies could reduce side effects and improve outcome of women with SSD, which should be confirmed in future longitudinal RCTs.
Decision support in engineering design: the ELIGERE open source software platform
Authors: Grazioso Stanislao , Caporaso Teodorico , Di Gironimo Giuseppe
Published: October 2023

In engineering design, the selection of the optimal design solution represents a critical phase for the development of successful products. In this paper, we present ELIGERE, an open source decision support system targeted at engineering design applications. It allows to rank multiple design solutions with respect to different evaluation criteria according to the evaluations provided by a group of experts. ELIGERE is composed by three main modules: (1) a distributed web application, for generation and participation to the decision making session; (2) a mathematical engine, based on the fuzzy analytical hierarchy process, to quantify the results of the decision making session according to the evaluation of the experts; (3) a relational database, to collect and store data. The most important contribution of this paper is introducing a practical and effective software tool that facilitates decision-making analysis based on the fuzzy analytical hierarchy process, thereby allowing better-informed choices on concept selection, as it has been designed with a specific focus on the engineering field. In this paper we describe the key concepts of ELIGERE and its modalities of use in several real use cases. Finally, we compare ELIGERE with the widely used general purpose decision support software based on the fuzzy analytical hierarchy process.
Fibroblast growth factor inhibition by molecular-targeted agents mitigates immunosuppressive tissue microenvironment in hepatocellular carcinoma
Authors: Suzuki Hiroyuki , Iwamoto Hideki , Tanaka Toshimitsu , Sakaue Takahiko , Imamura Yasuko , Masuda Atsutaka , Nakamura Toru , Koga Hironori , Hoshida Yujin , Kawaguchi Takumi
Published: October 2023

Background & aims

Combination immunotherapy refers to the use of immune checkpoint inhibitors (ICI) and molecular-targeted agents (MTA), which have recently been approved for the treatment of advanced hepatocellular carcinoma (HCC). Owing to its relatively low antitumor effect (up to 30%), sequential therapy following ICIs treatment is required in patients with HCC. This study aimed to determine the impact of MTAs on the tumor immune microenvironment (TIME).

Methods

We established immune syngeneic orthotopic HCC mouse models using Hep-55.1C and Hep-53.4, and treated them with MTAs (lenvatinib, sorafenib, regorafenib, cabozantinib, and DC101 as anti-vascular endothelial growth factor receptor-2 antibodies, and AZD4547 as a fibroblast growth factor receptor (FGFR)-1/2/3/4 inhibitor) for 2 weeks. Subsequently, alterations in the TIME caused by MTAs were evaluated using immunohistochemistry (antibodies for CD3, CD8, Foxp3, Granzyme B, Arginase-1, NK1.1, F4/80, CD11c, PD-1, and PD-L1). We conducted RNA-seq analysis using lenvatinib- and AZD4547-treated tumors. To confirm the clinical relevance of these findings, we analyzed the transcriptome data of human HCC cells (MHCC-97H) treated with various concentrations of lenvatinib for 24 h using RNA-seq data from the Gene Expression Omnibus database.

Results

The number of Foxp3- and F4/80-positive cells in the TIME was decreased in many MTAs. Cabozantinib increased the numbers in NK1.1-, Granzyme B, and CD11c-positive cells. Lenvatinib and AZD4547 increased the number of CD8, Granzyme B, and PD-L1-positive cells. Gene ontology enrichment analysis revealed that lipid metabolism-related genes were downregulated by lenvatinib and AZD4547. In total, 161 genes downregulated by FGFR inhibition in rodent models overlapped with those downregulated by lenvatinib in human HCC cells.

Conclusions

In this study, we showed that cabozantinib activated the innate immune system, and lenvatinib and AZD4547, which commonly inhibit FGFR signaling, altered TIME to a hot immune state by downregulating lipid metabolism-related genes. These findings support the therapeutic use of combination immunotherapies.
Are Schools in Prison Worth It? The Effects and Economic Returns of Prison Education
Authors: Stickle Ben , Schuster Steven Sprick
Published: October 2023

Recent expansions in prison school offerings and the re-introduction of the Second Chance Pell Grant have heightened the need for a better understanding of the effectiveness of prison education programs on policy-relevant outcomes. We estimate the effects of various forms of prison education on recidivism, post-release employment, and post-release wages. Using a sample of 152 estimates drawn from 79 papers, we conducted a meta-analysis to estimate the effect of four forms of prison education (adult basic education, secondary, vocational, and college). We find that prison education decreases recidivism and increases post-release employment and wages. The largest effects are experienced by prisoners participating in vocational or college education programs. We also calculate the economic returns on educational investment for prisons and prisoners. We find that each form of education yields large, positive returns due primarily to the high costs of incarceration and, therefore, high benefits to crime avoidance. The returns vary across education types, with vocational education having the highest return per dollar spent ($3.05) and college having the highest positive impact per student participating ($16,908).
A Comparative Study of Effects of Biodegradable and Non-biodegradable Microplastics on the Growth and Development of Black Soldier Fly Larvae (Hermetia illucens)
Authors: Heussler Carina D. , Dittmann Isabel L. , Egger Bernhard , Robra Sabine , Klammsteiner Thomas
Published: October 2023

Purpose

This study aimed to investigate the digestion process of biodegradable and non-biodegradable microplastics (MPs) within black soldier fly larvae (BSFL) and assess their impact on larval growth and development. The goal was to understand the fate of MPs within BSFL, considering their potential for waste conversion polluted with MPs.

Methods

BSFL were exposed to two types of MPs, and their growth, development, potential accumulation and excretion of MPs were monitored.

Results

The findings revealed that the MPs accumulated solely in the larval gut and had no adverse effects on the growth and development of BSFL. Larvae efficiently excreted MPs before reaching the pupation stage.

Conclusion

This research emphasizes the potential of BSFL as a bioconversion agent for organic waste, even in the presence of MPs. The effective excretion of MPs by BSFL before pupation suggests their ability to mitigate potential harm caused by MP accumulation. The fact that BSFL may excrete MPs before pupation would contribute to their safe use as animal feedstock. A careful evaluation of the effects of using BSFL reared on contaminated substrates especially containing visually non-detectable residuals like nanoplastics, chemicals or toxic metals and further examination of the broader implications for waste management and sustainable livestock farming remains important.

Graphical Abstract

Experimental design outlining the workflow for the analyses used to investigate the effect of two types of microplastics, polyamide (PA), and polylactic acid (PLA), on growth and development of black soldier fly larvae.
Learning to Mitigate Epidemic Risks: A Dynamic Population Game Approach
Authors: Hota Ashish R. , Maitra Urmee , Elokda Ezzat , Bolognani Saverio
Published: October 2023

We present a dynamic population game model to capture the behavior of a large population of individuals in presence of an infectious disease or epidemic. Individuals can be in one of five possible infection states at any given time: susceptible, asymptomatic, symptomatic, recovered and unknowingly recovered, and choose whether to opt for vaccination, testing or social activity with a certain degree. We define the evolution of the proportion of agents in each epidemic state, and the notion of best response for agents that maximize long-run discounted expected reward as a function of the current state and policy. We further show the existence of a stationary Nash equilibrium and explore the transient evolution of the disease states and individual behavior under a class of evolutionary learning dynamics. Our results provide compelling insights into how individuals evaluate the trade-off among vaccination, testing and social activity under different parameter regimes, and the impact of different intervention strategies (such as restrictions on social activity) on vaccination and infection prevalence.
Mindful eating and eating behaviours in Greece: exploring the validity and reliability of two mindful eating scales and other eating behaviours for Greek-speaking populations
Authors: Mantzios Michail , Zervos Konstantinos , Koletsi Marsha , Giannou Kyriaki
Published: October 2023

Background

Mindful eating has seen an increase in clinical and non-clinical practices of changing health outcomes. Meanwhile, the restriction of not having validated scales in other languages proposes a barrier to exploring the impact of mindful eating cross-culturally, and specific to the present project, across Greek-speaking populations, limiting the potential of exploring the association with Mediterranean dieting.

Methods

In the present research, volunteers (n = 706) completed online the Mindful Eating Behaviour Scale and the Mindful Eating Scale. A forward–backwards translation, leading to face validity, and was assessed for internal consistency (Cronbach’s Alpha) and followed up by an assessment of the factorial structure of the scales. Divergent and convergent validity was explored using motivations to eat palatable foods, grazing, craving, Dusseldorf orthorexia, Salzburg emotional eating, and the Salzburg stress eating scales.

Results

Results indicated that both scales displayed good internal consistency, and the assessment of the factorial structure of the scales was equally good and semi-consistent with the English versions, with parallel analyses and item loadings proposing problems that have been shown in critical review literature. Associations of mindful eating scales to other eating behaviours were replicated to previously established findings with English-speaking populations.

Conclusions

Findings that deviated from the expected outcomes are central to the discussion on the measurement of mindful eating, and further direction highlights the way forward for researchers and clinicians.

Level V

Descriptive studies.
Effects of surface morphology on tribological properties of Arapaima gigas scales
Authors: Zhang Shuaijun , Bai Pengpeng , Wen Xiangli , Wen Chengwei , Cao Hui , Yang Wanyou , Tian Yu
Published: October 2023

The remarkable mechanical adaptability of arapaima (Arapaima gigas) scales has made them an important subject of study. However, no research has been conducted into their tribological properties, which are crucial for the protectability and flexibility of arapaimas. In this study, by combining morphological characterizations, friction experiments, and theoretical analyses, the relationship between the surface morphology and tribological properties of arapaima scales is determined. These results indicate that arapaima scales exhibit varying surface morphologies in different regions. More specifically, the exposed regions of scales feature grooves and a circulus, whereas the covered regions exhibit bumps. The specific surface morphology of arapaima scales produces varying tribological properties across different regions and sliding directions. The unique tribological properties of arapaima scales influence the forces received from predator attacks and neighboring scales, directly influencing the arapaima’s protective capabilities. This study provides new insights into the mechanisms of natural flexible dermal armors, and it has potential applications in personal protective systems.
Spatial Pattern of Plant Transpiration Over China Constrained by Observations
Authors: Cui Jiangpeng , He Mingzhu , Lian Xu , Wei Zhongwang , Wang Tao
Published: October 2023

Plant transpiration is a key flux of surface water loss to the atmosphere, determining the available surface water for ecosystem and human use. However, over China, the magnitude of transpiration and its spatial pattern remain poorly understood due to a lack of constraints from in situ observations. Here we compile 34 plot‐scale annual transpiration measurements across China to evaluate the performance of four transpiration products, and then produce a new constrained transpiration map for China. The transpiration map reveals an annual value of 209.0 mm yr−1, while the four transpiration products have a large spread of values (173.4–307.9 mm yr−1), especially in the wet southeastern regions. Land surface models exhibit large biases in modeled transpiration (−62.8% to 49.1%) compared to our constrained transpiration, and tend to underestimate transpiration in wet regions while overestimating it in dry regions. This behavior introduces bias in runoff projections which has ramifications for regional water resource management policies.
Solar Wind Parameters Influencing Magnetosheath Jet Formation: Low and High IMF Cone Angle Regimes
Authors: Vuorinen Laura , Hietala Heli , LaMoury Adrian T. , Plaschke Ferdinand
Published: October 2023

Magnetosheath jets are localized flows of enhanced dynamic pressure that are frequently observed downstream of the Earth's bow shock. They are significantly more likely to occur downstream of the quasi‐parallel shock than the quasi‐perpendicular shock. However, as the quasi‐perpendicular geometry is a more common configuration at the Earth's subsolar bow shock, quasi‐perpendicular jets comprise a significant fraction of the observed jets. We study the influence of solar wind conditions on jet formation by looking separately at jets during low and high interplanetary magnetic field (IMF) cone angles. According to our results, jet formation commences when Alfvén Mach number MA ≳ 5. We find that during low IMF cone angles (downstream of the quasi‐parallel shock) other solar wind parameters do not influence jet occurrence. However, during high IMF cone angles (downstream of the quasi‐perpendicular shock) jet occurrence is higher during low IMF magnitude, low density, high plasma beta (β), and high MA conditions. The distribution of quasi‐parallel (quasi‐perpendicular) jet sizes parallel to flow peaks at ∼0.3 RE (∼0.1 RE). Some quasi‐perpendicular jets formed during high β and MA are particularly small. We show two examples of high β and MA quasi‐perpendicular shock crossings. Jets were observed in the transition region, but not deeper in the magnetosheath. A more detailed look into one jet revealed signatures of gyrating ions, indicating that gyrobunched ions near the shock may produce jet‐like enhancements. Our results suggest that jets form as part of the quasi‐perpendicular shock dynamics amplified by high solar wind MA and β.
Different Behaviors of Outer Radiation Belt keV and MeV Electrons During Two Sequential Geomagnetic Storms
Authors: Wu H. , Chen T. , Kalegaev V. , Ye S.
Published: October 2023

Electron flux dropout is an extraordinary phenomenon in the outer radiation belt, which is characterized by a drastic depletion in trapped electron populations over a broad range of energies, pitch angles, and L‐shells. Using data from multiple satellites, we study a 5‐day dropout of MeV electrons and a several‐hour dropout of keV electrons in geostationary Earth orbit (GEO) during two sequential geomagnetic storms. Outward radial diffusion caused real loss of MeV electrons, while asymmetric and depressed magnetic fields led to adiabatic variations in keV electron fluxes. In addition to time scale differences, low‐energy keV, medium‐energy keV and high‐energy MeV electron fluxes behaved differently, involving an increasing trend, an initial decreasing trend followed by an increasing trend, and a decreasing trend, respectively, as observed by Radiation Belt Storm Probes (RBSPs) and low‐altitude satellites during the first storm. Substorm injections accompanied by inward radial diffusion initially produced an enhanced flux of electrons with energies up to ∼100 keV. Chorus waves generated in morning side of magnetosphere were responsible for scattering part of this seed population into the atmosphere. In turn, these enhanced but short‐lived chorus waves accelerated lower‐energy keV electrons to achieve a moderate energy level of hundreds of keV within one day. Additionally, the initial slow outward radial diffusion was associated with MeV electron loss, and there was insufficient time for acceleration by chorus waves, so only MeV electrons could maintain long‐term dropout. Competition between energy‐ and L‐shell‐dependent acceleration and loss mechanisms caused different keV and MeV electron behaviors.
Image‐Based Classification of Intense Radio Bursts From Spectrograms: An Application to Saturn Kilometric Radiation
Authors: O’Dwyer E. P. , Jackman C. M. , Domijan K. , Lamy L.
Published: October 2023

Saturn Kilometric Radiation (SKR) is a non‐thermal auroral emission with peak emission occurring at 100–400 kHz. Its properties have been extensively studied since Cassini's arrival at Saturn until mission end with its Radio and Plasma Wave Science (RPWS) experiment. Low Frequency Extensions (LFEs) of SKR which consist of global intensifications of SKR accompanied by extensions of the main SKR band down to lower frequencies have been studied in particular. Low Frequency Extensions result from internally driven tail reconnection and from solar wind compressions of the magnetosphere, which also trigger tail reconnection. They have been cataloged through visual inspection with two approaches, using an intensity threshold for LFEs in 2006 (Reed et al., 2018, https://doi.org/10.1002/2017ja024499) and more recently O’Dwyer et al. (2023a, https://doi.org/10.25546/103103) produced a sample of LFEs detected by Cassini/RPWS by fitting their exact frequency‐time coordinates with polygons. In this study we use the latter catalog of LFEs as a training set for an image based machine learning algorithm to classify all LFEs detected by Cassini/RPWS. The inputs to the model are multi‐channel images consisting of spectrogram images in flux density and degree of circular polarization. The outputs of the model are binary masks showing the exact location of the LFE in frequency‐time space. The median Intersection Over Union across the testing and training set were calculated to be 0.97 and 0.98, respectively. The output of this study is a list of all 4,874 LFEs detected using this method. The list of LFE frequency‐time coordinates is available for use amongst the scientific community.
Mutualism reduces the severity of gene disruptions in predictable ways across microbial communities
Authors: Martinson Jonathan N V , Chacón Jeremy M , Smith Brian A , Villarreal Alex R , Hunter Ryan C , Harcombe William R
Published: October 2023

Predicting evolution in microbial communities is critical for problems from human health to global nutrient cycling. Understanding how species interactions impact the distribution of fitness effects for a focal population would enhance our ability to predict evolution. Specifically, does the type of ecological interaction, such as mutualism or competition, change the average effect of a mutation (i.e., the mean of the distribution of fitness effects)? Furthermore, how often does increasing community complexity alter the impact of species interactions on mutant fitness? To address these questions, we created a transposon mutant library in Salmonella enterica and measured the fitness of loss of function mutations in 3,550 genes when grown alone versus competitive co-culture or mutualistic co-culture with Escherichia coli and Methylorubrum extorquens. We found that mutualism reduces the average impact of mutations, while competition had no effect. Additionally, mutant fitness in the 3-species communities can be predicted by averaging the fitness in each 2-species community. Finally, we discovered that in the mutualism S. enterica obtained vitamins and more amino acids than previously known. Our results suggest that species interactions can predictably impact fitness effect distributions, in turn suggesting that evolution may ultimately be predictable in multi-species communities.
Outcomes for patients with EBV-positive PTLD post-allogeneic HCT after failure of rituximab-containing therapy
Authors: Socié Gérard , Barba Pere , Barlev Arie , Sanz Jaime , García-Cadenas Irene , Chevallier Patrice , Fagioli Franca , Guzman-Becerra Norma , Kumar Deepali , Ljungman Per , Pigneux Arnaud , Sadetsky Natalia , Yáñez San Segundo Lucrecia , Shadman Mazyar , Storek Jan , Thirumalai Dhanalakshmi , Xing Baodong , Mohty Mohamad
Published: October 2023

Epstein–Barr virus-positive (EBV+) post-transplant lymphoproliferative disease (PTLD) is an ultra-rare and aggressive condition that may occur following allogeneic hematopoietic cell transplant (HCT) due to immunosuppression. Approximately half of EBV+ PTLD cases are relapsed or refractory (R/R) to initial rituximab-containing therapy. There are limited treatment options and no standard of care for patients with R/R EBV+ PTLD, and little is known about their treatment history and outcomes. We performed a multinational, multicenter, retrospective chart review of patients with R/R EBV+ PTLD following HCT to describe patients’ demographic and disease characteristics, treatment history, and overall survival (OS) from rituximab failure. Among 81 patients who received initial treatment with rituximab as monotherapy (84.0%) or in combination with chemotherapy (16.0%), median time from HCT to PTLD diagnosis was 3.0 months and median OS was 0.7 months. Thirty-six patients received a subsequent line of treatment. The most frequent causes of death were PTLD (56.8%), graft-versus-host disease (13.5%) and treatment-related mortality (10.8%). In multivariate analysis, early PTLD onset and lack of response to initial treatment were associated with mortality. This real-world study demonstrates that the prognosis of patients with R/R EBV+ PTLD following HCT remains poor, highlighting the urgent unmet medical need in this population.
IGF2BP2-meidated m6A modification of CSF2 reprograms MSC to promote gastric cancer progression
Authors: Ji Runbi , Wu Chenxi , Yao Jun , Xu Jiajin , Lin Jiang , Gu Hongbing , Fu Min , Zhang Xiaoxin , Li Yongkang , Zhang Xu
Published: October 2023

The interaction between tumor cells and stromal cells within the tumor microenvironment plays a critical role in cancer progression. Mesenchymal stem cells (MSCs) are important tumor stromal cells that exhibit pro-oncogenic activities when reprogrammed by the tumor. However, the precise mechanisms underlying MSC reprogramming in gastric cancer remain not well understood. QRT-PCR, western blot, and immunohistochemistry were used to examine gene and protein expression levels. In vitro and in vivo experiments were conducted to assess the biological functions of gastric cancer cells. RNA-sequencing, RNA immunoprecipitation (RIP), and meRIP assays were performed to investigate underlying molecular mechanisms. We found a significant increase in the expression and N6-methyladenosine (m6A) modification levels of colony-stimulating factor 2 (CSF2) in gastric cancer MSCs. CSF2 gene overexpression induced the reprogramming of normal MSCs into cancer-promoting MSCs, thereby enhancing the proliferation, migration, and drug resistance of gastric cancer cells through the secretion of various pro-inflammatory factors. Additionally, we demonstrated that the m6A reader IGF2BP2 bound to and stabilized CSF2 mRNA in gastric cancer MSCs. Notably, overexpression of IGF2BP2 mimicked the effect of CSF2 on MSCs, promoting gastric cancer progression. Finally, we unveiled that CSF2 induced the ubiquitination of Notch1 to reprogram MSCs. Our study highlights a critical role of IGF2BP2-mediated m6A modification of CSF2 in reprogramming MSCs, which presents a promising therapeutic target for gastric cancer.
The squeezed dark nuclear spin state in lead halide perovskites
Authors: Kirstein E. , Smirnov D. S. , Zhukov E. A. , Yakovlev D. R. , Kopteva N. E. , Dirin D. N. , Hordiichuk O. , Kovalenko M. V. , Bayer M.
Published: October 2023

Coherent many-body states are highly promising for robust quantum information processing. While far-reaching theoretical predictions have been made for various implementations, direct experimental evidence of their appealing properties can be challenging. Here, we demonstrate optical manipulation of the nuclear spin ensemble in the lead halide perovskite semiconductor FAPbBr3 (FA = formamidinium), targeting a long-postulated collective dark state that is insensitive to optical pumping after its build-up. Via optical orientation of localized hole spins we drive the nuclear many-body system into this entangled state, requiring a weak magnetic field of only a few milli-Tesla strength at cryogenic temperatures. During its fast establishment, the nuclear polarization along the optical axis remains small, while the transverse nuclear spin fluctuations are strongly reduced, corresponding to spin squeezing as evidenced by a strong violation of the generalized nuclear squeezing-inequality with ξs < 0.5. The dark state corresponds to an ~35-body entanglement between the nuclei. Dark nuclear spin states can be exploited to store quantum information benefiting from their long-lived many-body coherence and to perform quantum measurements with a precision beyond the standard limit.
Ultra-high-throughput mapping of the chemical space of asymmetric catalysis enables accelerated reaction discovery
Authors: Nie Wenjing , Wan Qiongqiong , Sun Jian , Chen Moran , Gao Ming , Chen Suming
Published: October 2023

The discovery of highly enantioselective catalysts and elucidating their generality face great challenges due to the complex multidimensional chemical space of asymmetric catalysis and inefficient screening methods. Here, we develop a general strategy for ultra-high-throughput mapping of the chemical space of asymmetric catalysis by escaping the time-consuming chiral chromatography separation. The ultrafast ( ~ 1000 reactions/day) and accurate (median error < ±1%) analysis of enantiomeric excess are achieved through the ion mobility-mass spectrometry combines with the diastereoisomerization strategy. A workflow for accelerated asymmetric reaction screening is established and verified by mapping the large-scale chemical space of more than 1600 reactions of α-asymmetric alkylation of aldehyde with organocatalysis and photocatalysis. Importantly, a class of high-enantioselectivity primary amine organocatalysts of 1,2-diphenylethane-1,2-diamine-based sulfonamides is discovered by the accelerated screening, and the mechanism for high-selectivity is demonstrated by computational chemistry. This study provides a practical and robust solution for large-scale screening and discovery of asymmetric reactions.
Palmitoyltransferase DHHC9 and acyl protein thioesterase APT1 modulate renal fibrosis through regulating β-catenin palmitoylation
Authors: Gu Mengru , Jiang Hanlu , Tan Mengzhu , Yu Long , Xu Ning , Li Ying , Wu Han , Hou Qing , Dai Chunsun
Published: October 2023

palmitoylation, a reversible post-translational modification, is initiated by the DHHC family of palmitoyltransferases and reversed by several acyl protein thioesterases. However, the role and mechanisms for protein palmitoylation in renal fibrosis have not been elucidated. Here we show protein palmitoylation and DHHC9 were downregulated in the fibrotic kidneys of mouse models and chronic kidney disease (CKD) patients. Ablating DHHC9 in tubular cells aggravated, while inducing DHHC9 overexpression with adeno-DHHC9 transfection or iproniazid treatment protected against kidney fibrosis in male mouse models. Mechanistically, DHHC9 palmitoylated β-catenin, thereby promoted its ubiquitination and degradation. Additionally, acyl protein thioesterase 1 (APT1) was induced in the fibrotic kidneys, which depalmitoylated β-catenin, increased its abundance and nuclear translocation. Ablating tubular APT1 or inhibiting APT1 with ML348 markedly protected against unilateral ureter obstruction (UUO) or ischemia/reperfusion injury (IRI)-induced kidney fibrosis in male mice. This study reveals the regulatory mechanism of protein palmitoylation in kidney fibrosis.
Liquid biopsy epigenomic profiling for cancer subtyping
Authors: Baca Sylvan C. , Seo Ji-Heui , Davidsohn Matthew P. , Fortunato Brad , Semaan Karl , Sotudian Shahabbedin , Lakshminarayanan Gitanjali , Diossy Miklos , Qiu Xintao , El Zarif Talal , Savignano Hunter , Canniff John , Madueke Ikenna , Saliby Renee Maria , Zhang Ziwei , Li Rong , Jiang Yijia , Taing Len , Awad Mark , Chau Cindy H. , DeCaprio James A. , Figg William D. , Greten Tim F. , Hata Aaron N. , Hodi F. Stephen , Hughes Melissa E. , Ligon Keith L. , Lin Nancy , Ng Kimmie , Oser Matthew G. , Meador Catherine , Parsons Heather A. , Pomerantz Mark M. , Rajan Arun , Ritz Jerome , Thakuria Manisha , Tolaney Sara M. , Wen Patrick Y. , Long Henry , Berchuck Jacob E. , Szallasi Zoltan , Choueiri Toni K. , Freedman Matthew L.
Published: October 2023

Although circulating tumor DNA (ctDNA) assays are increasingly used to inform clinical decisions in cancer care, they have limited ability to identify the transcriptional programs that govern cancer phenotypes and their dynamic changes during the course of disease. To address these limitations, we developed a method for comprehensive epigenomic profiling of cancer from 1 ml of patient plasma. Using an immunoprecipitation-based approach targeting histone modifications and DNA methylation, we measured 1,268 epigenomic profiles in plasma from 433 individuals with one of 15 cancers. Our assay provided a robust proxy for transcriptional activity, allowing us to infer the expression levels of diagnostic markers and drug targets, measure the activity of therapeutically targetable transcription factors and detect epigenetic mechanisms of resistance. This proof-of-concept study in advanced cancers shows how plasma epigenomic profiling has the potential to unlock clinically actionable information that is currently accessible only via direct tissue sampling.
The herbicide glyphosate inhibits hippocampal long-term potentiation and learning through activation of pro-inflammatory signaling
Authors: Izumi Yukitoshi , O’Dell Kazuko A. , Zorumski Charles F.
Published: October 2023

Glyphosate, a herbicide marketed as Roundup, is widely used but there are concerns this exposure could impair cognitive function. In the CA1 region of rat hippocampal slices, we investigated whether glyphosate alters synaptic transmission and long-term potentiation (LTP), a cellular model of learning and memory. Our hypothesis is that glyphosate alters neuronal function and impairs LTP induction via activation of pro-inflammatory processes. Roundup depressed excitatory synaptic potentials(EPSPs) in a dose-dependent manner with complete suppression at 2000 mg/L. At concentrations ≤ 20 mg/L Roundup did not affect basal transmission, but 4 mg/L Roundup administered for 30 min inhibited LTP induction. Acute administration of 10–100 μM glyphosate also inhibited LTP induction. Minocycline, an inhibitor of microglial activation, and TAK-242, an inhibitor of toll-like receptor 4 (TLR4), both overcame the inhibitory effects of 100 µM glyphosate. Similarly, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), a different TLR4 antagonist, overcame the inhibitory effects. In addition, ISRIB (integrated stress response inhibitor) and quercetin, an inhibitor of endoplasmic reticulum stress, overcame the inhibitory effects. We also observed that in vivo glyphosate injection (16.9 mg/kg i.p.) impaired one-trial inhibitory avoidance learning. This learning deficit was overcome by TAK-242. These observations indicate that glyphosate can impair cognitive function through pro-inflammatory signaling in microglia.