bluuebunny/crossref_metadata_2025 huggingface dataset:
A significant role for maternal genetic nurture in the risk architecture of attention-deficit/hyperactivity disorder
Authors: Mahjani Behrang , Kępińska Adrianna P. , Smout Shelby , Cohen Lily , Caballero Madison , Buxbaum Joseph D. , Grice Dorothy E.
Published: December 2024

Objective

Previous studies have shown that parental factors are associated with an increased risk for attention-deficit/hyperactivity disorder (ADHD). However, the pathways by which parental factors are associated with risk of ADHD in offspring are not well understood. These associations can arise directly from parental genotypes inherited by offspring, and/or via environmental effects, some of which may themselves be influenced by the parental genotype (i.e., parental genetic nurture). This study specifically examines the impact of the maternal phenotype on offspring ADHD risk, above and beyond the direct genetic effect of maternally-inherited genes.

Methods

The study population consisted of 982,544 individuals from the Swedish Medical Birth Register. We partitioned the liability of ADHD into direct additive genetic effect, maternal genetic nurture effect, and maternal common environment effect.

Results

We identified 66,707 (7%) individuals in the birth cohort with an ADHD diagnosis. Maternal half-siblings were associated with a higher ADHD risk compared to paternal half-siblings, suggesting maternal effect. We estimated 66.1% direct additive genetic effect (95% credible interval, 0.647%-0.676%) and 14.3% maternal genetic nurture effect (95% credible interval, 0.136%-0.151%). Additionally, we also observed evidence for substantial assortative mating among individuals with ADHD.

Conclusions

Our findings indicate that maternal genotypes influence offspring’s risk of ADHD through environmental pathways beyond the effects of direct genetic transmission. Exploring the impact of the genetics of the mother beyond the maternally inherited genes can lead to new insights into ADHD risk. Future studies should also investigate paternal effects to provide a more comprehensive understanding of the ADHD risk architecture.
Artificial Intelligence Methods to Detect Heart Failure with Preserved Ejection Fraction (AIM-HFpEF) within Electronic Health Records: An equitable disease prediction model
Authors: Wu Jack , Biswas Dhruva , Brown Samuel , Ryan Matthew , Bernstein Brett , To Brian Tam , Searle Tom , Rizvi Maleeha , Fairhurst Natalie , Kaye George , Baral Ranu , Vijayakumar Dhanushan , Mehta Daksh , Melikian Narbeh , Sado Daniel , Carr-White Gerald , Chowienczyk Phil , Teo James , Dobson Richard JB , Bromage Daniel I , Lüscher Thomas F , Vazir Ali , McDonagh Theresa A , Webb Jessica , Shah Ajay M , O’Gallagher Kevin
Published: December 2024

Background and aims

Heart Failure with Preserved Ejection Fraction (HFpEF) accounts for approximately half of all heart failure cases, with high levels of morbidity and mortality. However, most cases of HFpEF are undiagnosed as conventional risk scores underestimate risk in non-White populations. Our aim was to develop and validate a diagnostic prediction model to detect undiagnosed HFpEF, AIM-HFpEF.

Methods

We applied natural language processing (NLP) and machine learning methods to routinely collected electronic health record (EHR) data from a tertiary centre hospital trust in London, UK, to derive the AIM-HFpEF model. We then externally validated the model and performed benchmarking against existing HFpEF prediction models (H2FPEF and HFpEF-ABA) for diagnostic power in patients of non-white ethnicity and patients from areas of increased socioeconomic deprivation.

Results

An XGBoost model combining demographic, clinical and echocardiogram data showed strong diagnostic performance in the derivation dataset (n=3170, AUC=0.88, [95% CI, 0.86-0.91]) and validation cohort (n=5383, AUC: 0.88 [95% CI, 0.87-0.89]). Diagnostic performance was maintained in patients of non-White ethnicity (AUC=0.88 [95% CI, 0.84-0.93]) and patients from areas of high socioeconomic deprivation (AUC=0.89 [95% CI, 0.84-0.94]). and AIM-HFpEF performed favourably in comparison to H2FPEF and HFpEF-ABA models. AIM-HFpEF model probabilities were associated with an increased risk of death, hospitalisation and stroke in the external validation cohort (P<0.001, P=0.01, P<0.001 respectively for highest versus middle tertile).

Conclusion

AIM-HFpEF represents a validated equitable diagnostic model for HFpEF, which can be embedded within an EHR to allow for fully automated HFpEF detection.
Association Between Oral Microbiota and Close-Range Proximity in a Primary School
Authors: Dall’Amico Lorenzo , Bai Xiangning , Weltzien Sandra Marie , Rayner Simon , Paolotti Daniela , Budin Ljøsne Isabelle Sylvie , Matussek Andreas , Furberg Anne-Sofie , Cattuto Ciro , Nielsen Christopher Sivert
Published: December 2024

The microbiota is the ensemble of microorganisms inhabiting the human body and it deeply influences human health and well-being. Recent studies showed its interplay with social behavior, suggesting that part of the microbiota might be socially transmissible. In this work, we investigate the association between closerange proximity and the oral microbiota composition in a group of children attending primary school. Unlike most related studies, our cohort comprises non-cohabiting individuals, and we use high-resolution proximity sensors to objectively measure social interactions. Our analysis shows that prolonged interactions between children pairs correlate with a higher similarity between their microbiota. These findings complement what is known for co-habiting individuals, suggesting that microbiota might be transmitted in social settings.
Interaction of the wireworm speciesAgriotes obscurus,A. sputatorandA. lineatuswith a new granule formulation ofMetarhizium brunneum
Authors: Paluch Maximilian , Seib Tanja , Stephan Dietrich , Jürgens Andreas , Lehmhus Jörn
Published: December 2024

The attract-and-kill strategy is a promising approach in integrated pest management to increase the efficiency of plant protection products by pushing the required contact between target pest and active ingredient. Within the project AgriMet, a new soil granule of the entomopathogenic fungusMetarhizium brunneumwas developed to control wireworms of the genusAgriotes(Coleoptera: Elateridae) in potato cultivation. The formulation is based on autoclaved millet as a substrate to lure the larvae to the infectious conidia on its surface. However, no data existed about the interactions of wireworms with the AgriMet-Granule. Here, I examined the behavioural response of the wireworm speciesA. obscurus,A. sputatorandA. lineatusto the AgriMet-Granule using an olfactometric bioassay in the laboratory. The foraging behaviour ofA. obscurusandA. sputator,with regard to the AgriMet-Granule, was tested with a feed-choice-experiment using a horizontal arena set-up. The tested wireworms significantly preferred autoclaved millet compared to the control. Fungal colonisation on the surface of the AgriMet-Granule did not influence their preference in general. However, differences were observed depending on the respective wireworm species and the twoMetarhiziumspp. isolates used. The feeding bioassay showed that the acceptance of wireworms for the AgriMet-Granule, with a low conidia concentration on its surface, was high. A high conidia concentration on the surface of the AgriMet-Granule led to a decreased acceptance that differed between the wireworm species. However, the survival analysis of wireworms isolated after the feed choice experiment indicated that the wireworms came in contact with the infectious conidia. Overall, the data suggests that autoclaved millet is a suitable substrate for the AgriMet-Granule. It attracts larvae of the genusAgriotesto the biocontrol agent using the formulatedM. brunneumisolate.
Calcium dynamics tune developmental tempo to generate evolutionarily divergent axon tract lengths
Authors: Lindhout Feline W. , Szafranska Hanna M. , Imaz-Rosshandler Ivan , Guglielmi Luca , Moarefian Maryam , Voitiuk Kateryna , Zernicka-Glover Natalia K. , Boulanger Jerome , Schulze Ulrike , Lloyd-Davies Sánchez Daniel J. , Minnick John , Teodorescu Mircea , Lancaster Madeline A.
Published: December 2024

The considerably slow pace of human brain development correlates with an evolutionary increase in brain size, cell numbers, and expansion of neuronal structures, with axon tracts undergoing an even greater evolutionary increase than other neuronal domains. However, whether tempo is responsible for these differences in magnitude, and how, remains to be determined. Here, we used brain organoids to investigate this and observed that human axon tracts spend more time growing and extend farther compared to those of mice, independent of their tissue environment. Single cell RNA sequencing analysis pointed to a subset of calcium-permeable ion channels expressed throughout neuron development, including during axon tract outgrowth. Calcium imaging during early neuron development consistently revealed a reduced calcium influx in human neurons compared to mouse neurons. Stimulating calcium influx and increasing cAMP levels resulted in premature halting of axon tract outgrowth and shorter axon tracts, mimicking the mouse phenotype, while abrogating calcium influx led to an even longer phase of axon tract outgrowth and longer axon tracts in humans. Thus, evolutionary differences in calcium regulation set the tempo of neuronal development, by extending the time window to foster the more elaborated human neuron morphology.
Single-cell transcriptome profiling of the myeloid cells repopulating after chemotherapy identifies a neutrophil-like monocyte subset with pro-tumor activities
Authors: Ding Zhi-chun , Zhou George I. , Okoko Ogacheko D. , Wang Xin , Bryan Locke J. , Zhou Gang , Shi Huidong
Published: December 2024

Patients with cancer often receive chemotherapy to control tumor progression and reduce disease symptoms. Cytotoxic chemotherapeutic agents not only kill rapidly growing cancer cells but also reduce normal cells including myeloid cells, the main innate immune population involved in fighting infections and repairing tissue damages. Rapid loss of myeloid cells caused by chemotherapy triggers myelopoiesis, a process in which the hematopoietic stem and progenitor cells in the bone marrow regenerate myeloid cells, including monocytes, neutrophils, dendritic cells and macrophages, to reconstitute the myeloid cell compartment. We previously reported that chemotherapy with an alkylating agent cyclophosphamide (CTX) in mice leads to repopulation of myeloid cells that acquire immunosuppressive activities within the monocyte subset. However, detailed information on the cellular composition and molecular identity of these chemotherapy- induced immunosuppressive monocytes is lacking. Here, we investigated how the various myeloid cell subsets in the bone marrow of mice respond to CTX chemotherapy through single-cell RNA sequencing analysis (scRNAseq). We found that myeloid progenitor cells and monocytes were reduced 2 days after chemotherapy but rebounded and surpassed their pretreatment levels by day 7. Further scRNAseq analysis of pre-enriched monocytes revealed that the monocyte population was heterogenous, and that chemotherapy tilted myelopoiesis towards the production of neutrophil-like monocytes (NeuMo). We identified Cxcr4 and Cx3cr1 as suitable markers for isolation of chemotherapy-induced NeuMo and demonstrated that these cells were suppressive to T cells. Together with the evidence that CTX-induced monocytes can promote breast cancer metastasis in mice, our data reveal the heterogeneity of the monocytes reemerging after chemotherapy and identify the NeuMo subset as a potential therapeutic target for enhancing the efficacy of chemotherapy in cancer.
Construction of a drug sensitisedCandida aurisstrain
Authors: Hassan Mahnoor , Furner-Pardoe Jessica , Chen Yiyuan , Mason A. James , Rahman Khondaker Miraz , Sutton J. Mark , Hind Charlotte , Panaretou Barry
Published: December 2024

Candida aurisis an emerging pathogenic fungus causing outbreaks of invasive disease in healthcare facilities worldwide with the majority of clinical isolates demonstrating intrinsic resistance to multiple drug classes. Therefore, there is a pressing need for new antifungals, but screening in wild-typeC. aurisstrains may miss scaffolds which would be good subjects for med-chem projects as antifungals. Work presented here indicates that deletion ofCDR1andMDR1inC. auris, respectively encoding an ATP-binding Cassette and a Major Facilitator Superfamily efflux pump, generates a strain that is hypersensitised to drugs and can act as a platform for antifungal drug screening. Thecdr1Δmdr1Δ mutant was 64- and 8- times more sensitive to fluconazole and voriconazole, respectively, compared with the wild-type strain. In a pilot study using a 2,000 compound library, use of thecdr1Δmdr1Δ mutant identified over twice as many compounds compared to wild-type. When assessing the capacity to form biofilms, there was a modest difference in biomass between the wild-type andcdr1Δmdr1Δ mutant, but there was little to no statistically significant difference observed when using a colorimetric dye that measured metabolic activity. Little to no statistically significant difference was observed between wild-type and the efflux pump mutant in virulence, as judged by the larvalGalleria mellonellainfectivity assay. Accordingly, thecdr1Δmdr1Δmutant will be useful when screening for drugs that limit formation of biofilms or limit fungal virulence, as these two properties are unaffected when drug efflux is compromised.
Gut bacterial sphingolipid production modulates dysregulated skin lipid homeostasis
Authors: Lee Min-Ting , Tan Xiaoqing , Le Henry H. , Besler Kevin , Thompson Sharon , Harris-Tryon Tamia , Johnson Elizabeth L.
Published: December 2024

Sphingolipids are an essential lipid component of the skin barrier with alterations in skin sphingolipid composition associated with multiple skin disorders including psoriasis, atopic dermatitis, and ichthyosis. Contributions to skin sphingolipid abundance are not well characterized, thus the main method of modulating skin lipid levels is the topical application of creams rich with sphingolipids at the skin surface. Evidence that diet and gut microbiome function can alter skin biology proposes an intriguing potential for the modulation of skin lipid homeostasis through gut microbial metabolism, but potential mechanisms of action are not well understood. Sphingolipid synthesis by prominent gut microbes has been shown to affect intestinal, hepatic and immune functions with the potential for sphingolipid-producing bacteria to affect skin biology through altering skin sphingolipid levels. To address this question, we used bioorthogonal chemistry to label lipids from the sphingolipid-producing bacteriaBacteroides thetaiotaomicronand trace these lipids to the skin epidermis. Exposing mice toB. thetaiotaomicronstrains mutant in the ability to produce sphingolipids resulted in significantly lower transfer of gut microbiome-derived lipids to the skin, while also altering skin biology and altering expression of skin barrier genes. Measurement of skin ceramide levels, a class of sphingolipids involved in skin barrier function, determined that skin sphingolipid levels were altered in the presence of gut sphingolipid-producing bacteria. Together this work demonstrates that gut bacterial lipids can transfer to the skin and provides a compelling avenue for modulating sphingolipid-dominant compartments of the skin using sphingolipid-producing bacteria of the gut microbiome.
Human Slip Control: Investigating the Role of Hand Acceleration Modulation in Preventing Slips
Authors: Nazari Kiyanoush , Mandil Willow , Santello Marco , Ghalamzan Amir
Published: December 2024

Ensuring a stable grasp during manipulative movements is crucial for robotic applications. While grip force has been the primary means of slip control, our human study revealed that trajectory modulation is also an effective slip control policy during pick-and-place tasks. Motivated by these findings, we developed and compared a slip control policy based on trajectory modulation to one based on grip force control for robotic pick-and-place tasks. Our results show that trajectory modulation significantly outperforms grip force control in certain scenarios, highlighting its potential for slip control in robotics. Moreover, we demonstrate the importance of incorporating forward models in developing effective trajectory modulation slip control systems. Overall, our study provides insight into an alternative method for slip control and suggests that humans use trajectory modulation as an alternative to grip force control for slippage prevention. This insight helps design algorithm for improving robotic manipulation tasks to prevent slippage.
Beta cell dysfunction occurs independently of insulitis in type 1 diabetes pathogenesis
Authors: Huber Mollie K. , Widener Adrienne E. , Cuaycal Alexandra E. , Smurlick Dylan , Butterworth Elizabeth A. , Lenchik Nataliya I. , Chen Jing , Beery Maria , Hiller Helmut , Verney Ellen , Kusmartseva Irina , Rupnik Marjan Slak , Campbell-Thompson Martha , Gerling Ivan C. , Atkinson Mark A. , Mathews Clayton E. , Phelps Edward A.
Published: December 2024

The loss of insulin secretory function associated with type 1 diabetes (T1D) is attributed to the immune-mediated destruction of beta cells. Yet, at onset of T1D, patients often have a significant beta cell mass remaining while T cell infiltration of pancreatic islets is sporadic. Thus, we investigated the hypothesis that the remaining beta cells in T1D are largely dysfunctional using live human pancreas tissue slices prepared from organ donors with recently diagnosed T1D. Beta cells in slices from donors with T1D had significantly diminished Ca2+mobilization and insulin secretion responses to glucose. Beta cell function was equally impaired in T cell-infiltrated and non-infiltrated islets. Fixed tissue staining and gene expression profiling of laser-capture microdissected islets revealed significant decreases of proteins and genes in the glucose stimulus secretion coupling pathway. From these data, we posit that functional defects occur in the remaining mass of beta cells during human T1D pathogenesis.
Organ injury accelerates stem cell differentiation by modulating a fate-transducing lateral inhibition circuit
Authors: Sanders Erin N. , Sun Hsuan-Te , Tabatabaee Saman , Lang Charles F. , van Dijk Sebastian G. , Su Yu-Han , Labott Andrew , Idris Javeria , He Li , Marchetti Marco , Xie Shicong , O’Brien Lucy Erin
Published: December 2024

Injured epithelial organs must rapidly replace damaged cells to restore barrier integrity and physiological function. In response, injury-born stem cell progeny differentiate faster compared to healthy-born counterparts, yet the mechanisms that expedite differentiation are unclear. Using the adultDrosophilaintestine, we find that injury accelerates differentiation by modulating the lateral inhibition circuit that transduces a fate-determining Notch signal. During routine intestinal turnover, balanced terminal (Notch-active) and stem (Notch-inactive) fates arise through lateral inhibition in which Notch-Delta signaling between two stem cell daughters resolves over time to activate Notch and extinguish Delta in one cell. When we feed flies a gut-damaging toxin, injury-induced cytokines cause Notch-activated cells to escape normal Delta suppression by inactivating the Notch co-repressor Groucho. Mathematical modeling predicts that this augmented Delta prompts faster Notch signaling; indeed,in vivolive imaging reveals that injury-born cells undergo markedly faster Notch signal transduction. Thus, Notch-Delta lateral inhibition—a switch that regulates fates during steady-state turnover—also serves as a throttle that tunes differentiation speed according to tissue need.
Exploring the microbiome of black soil from Central India and the impacts of agricultural practices on soil microbial communities
Authors: Kumar Sudhir , Saxena Rituja , Saxena Rajesh , Sharma Vineet K
Published: December 2024

Background: Healthy microbial communities in soil are indispensable for agricultural productivity. The diversity in physiochemical properties, their geological origins, and local climatic conditions lead to the evolution of diverse soil types with distinct bacterial communities. Despite a global distribution, the microbial composition of black soil remains largely unexplored. Here, we investigate the composition, diversity, and functional potential of bacterial communities in black soils from central India. We also examine how common agricultural disturbances like fertilizer application and the growth of crops impact soil communities in a three-year longitudinal field experiment involving three crops. Results: The black soil core microbiome was dominated by phyla Actinobacteriota and Proteobacteria members. Analysis of bacterial composition in vermicompost revealed the presence of plant growth-promoting taxa. Among the assessed cropping practices, crop growth significantly affected microbiome composition in soil. We also observed the impact of crops in selectively enhancing the microbiome in the soil, highlighting the role of plant species in shaping community structure. During this experiment, fertilizer treatment did not influence the microbiome significantly. Overall, the data showed the vulnerability and resilience of soil bacterial communities to agricultural disturbances. Conclusion: The microbial composition of black soil in central India was revealed, and the effects of agricultural management on black soil microbial composition were evaluated. The prominent impact of individual plants showed the role of plant-root microbiome interactions in shaping the composition of soil communities. Fertilizer application did not show significant effects during the field experiment, reflecting the resilience of soil communities to short-term disturbances. We also shed light on the functional metagenomic potential of black soil communities and the effect of common agricultural disturbances in a prominent soil type.
Electrophysiological correlates of cognitive reserve in healthy older adults at different cognitive states
Authors: Zhunussova Alina , Pellicciari Maria Concetta , Carreiras Manuel , Cespón Jesús
Published: December 2024

High cognitive reserve (CR) is associated with a set of lifestyle factors such as high education level and occupational attainment. Studies suggest that CR is linked to enhanced executive control functions. Nevertheless, it is unclear what are the functional neural activity patterns linked to high CR and to what extent they are steady across different cognitive states. The aim of the present study was to investigate electrophysiological differences between low CR (LCR) and high CR (HCR) at rest and during the performance of two cognitive control tasks with different difficulty level. Thus, 67 older adults performed an experimental session consisting of two spatial stimulus-response compatibility (SRC) tasks (i.e., the Simon task, and the more demanding spatial Stroop task), and a resting state during an electroencephalogram (EEG) recording. Cognitive control was better in HCR than LCR group, as revealed by higher accuracy in HCR compared to LCR group in incongruent conditions of the tasks. Moreover, event-related brain potentials (ERP) showed earlier latencies (P300) in HCR than LCR and time/frequency analysis showed higher alpha activity in HCR than LCR during the performance of the tasks, while no differences were observed at rest within any of the analyzed frequency bands. Higher P300 frontalization was observed in LCR than HCR in the more difficult task but it was not related to frontalization within a specific frequency band. Overall, results showed that electrophysiological differences between high and low CR depend on the cognitive state, with greater CR-related differences emerging at increased task demands.
scRNA+TCR-seq Reveals the Proportion and Characteristics of Dual TCR Treg Cells in Mouse Lymphoid and Non-lymphoid Tissues
Authors: Xu Yuanyuan ,   Qipeng, Lu Xiaoping , Ma Long , Li Jun , Yao Xinsheng
Published: December 2024

As an essential molecule for Treg cell function, TCR plays a critical role in various immune responses including cell development, immune tolerance, and self-antigen recognition. Current research has identified Treg cells in both lymphoid and non-lymphoid tissues as important for maintaining immune homeostasis and preventing autoimmune reactions. However, the TCR pairing types and CDR3 characteristics of these Treg cells are largely unknown. Through innovative analysis of scRNA+TCR-seq data, we discovered that 10.1% to 21.4% of dual TCR Treg cells exist in mouse lymphoid and non-lymphoid tissues. Dual TCR Treg cells in different tissues exhibit differential phenotypic and TCR repertoire characteristics. These findings provide key insights into the complex biological functions of Treg cell V(D)J recombination, tolerance selection, development, and migration.
Integration of head and body orientations in the macaque superior temporal sulcus is specific to upright bodies
Authors: Zafirova Yordanka , Vogels Rufin
Published: December 2024

The neural processing of faces and bodies is often studied separately, despite their natural integration in perception. Unlike prior research on the neural selectivity for either head or body orientation, we investigated their interaction in macaque superior temporal sulcus (STS) using a monkey avatar with diverse head-body orientation angles. STS neurons showed selectivity for specific combinations of head-body orientations. Anterior STS (aSTS) neurons enabled more reliable decoding of head-body configuration angles compared to middle STS neurons. Decoding accuracy in aSTS was lowest for head-body angle pairs differing only in sign (e.g. head-body orientation difference of ±90° relative to the anatomical midline), and highest for aligned (0°) head-body orientations versus those with maximum angular difference. Inverted bodies showed diminished decoding of head-body orientation angle compared to upright bodies. These findings show that aSTS integrates head and body orientation cues, revealing configuration-specific neural mechanisms, and advance our understanding of social perception.
Predicting non-coding RNA function using Artificial Intelligence
Authors: da Costa Correia David , Couto Francisco M. , Martiniano Hugo
Published: December 2024

Non-coding RNAs (ncRNAs) represent the majority of human gene products, and are involved in various important biological processes, being considered relevant disease biomarkers and therapeutic agents. However, information about these biomolecules remains sparsely distributed, mostly in the form of scientific research articles. It is then of pivotal importance to aggregate and summarize the existing information.

Natural Language Processing (NLP) methods applied to text mining enable automatic information extraction and summarization from textual data. These techniques can be used to generate collections of annotated sentences expressing relations between entities, called relational corpora.

In this work we developed a text mining pipeline to generate a ncRNA-phenotype relational corpus (ncoRP) using Distant Supervision Relation Extraction (DSRE), comprising 21,608 annotated articles, 2,835 unique ncRNAs, 1,118 unique phenotypes and 35,295 unique relations, with a precision of 0.761 and F1-score of 0.593, calculated through human validation. DSRE methods require a set of pre-documented relations to function, as such, a high-fidelity ncRNA-phenotype relation dataset, consisting of 214,300 unique relations, was created by the aggregation of five comprehensive ncRNA-disease functional annotation databases. Then, both ncoRP and the relation dataset represent important contributions towards solving the problem with the sparseness of information about ncRNAs.

Large Language Models (LLMs) are an emergent type of language model, showing great capabilities in general task-solving through text generation, without the requirement of fine-tuning with large datasets. This benefit shows promise for applications in Relation Extraction (RE), when compared to data-intensive state-of-the-art deep learning methods. In this work, a LLM RE methodology is proposed and evaluated, achieving an F1-score of 0.978 by combining the RE task with a preceding sentence filtering task and applying prompting principles such as in-context learning and Chain-of-Thought self-explanation.
Rational Design of Unsaturated, Thioether Ionizable Lipids for EnhancedIn vivomRNA Delivery
Authors: Samaridou Eleni , Simon Johanna , Beck-Broichsitter Moritz , Davidson Gary , Levkin Pavel A.
Published: December 2024

Therapies based on mRNA technology have offered hope to millions of patients worldwide by disrupting the way we treat diseases. The safe and functional delivery of the delicate mRNA molecules to the target tissue is a crucial step in the development of effective vaccines and therapeutic interventions. Lipid nanoparticles (LNP) are the most clinically advanced delivery vehicles for mRNA drugs. Key to the success of LNP is the inclusion of an ionizable cationic lipid. However, the structure-function relationships between ionizable lipids and efficientin-vivomRNA delivery are still poorly understood. In this work, we focused on the rational design and sequential structural optimization of previously identified ionizable lipids that performed wellin vitro, but notin vivo. Through two distinct iterative optimization cycles — one targeting the lipid tail and the other the headgroup — we aimed to understand how the fusogenicity and apparent pKa of the ionizable lipid contribute to LNP delivery performancein vivo. By engineering unsaturated lipids with more hydrophobic, less protonatable amino headgroups with longer alkyl group at the tertiary nitrogen, we achieved both significant improvement of protein expressionin vitro, reduced hemolysis risk, and more than 200-fold improvement ofin vivomRNA delivery. When compared head-to-head to a market-approved LNP benchmark, the newly developed ionizable lipids/LNP resulted in equally highly efficientin vivomRNA delivery, with strong liver and spleen tropism upon intravenous injection, while matching the safety of the approved platform. Our findings are pivotal for the development of next-generation mRNA-LNP therapies and vaccines.
Study of neutron production for 360 GeV cosmic muons
Authors: Zhang Xinshun , Li Jinjing , Chen Shaomin , Dou Wei , Fu Haoyang , Liang Ye , Liu Qian , Luo Wentai , Qi Ming , Shao Wenhui , Sun Haozhe , Tang Jian , Wang Yuyi , Wang Zhe , Wei Changxu , Weng Jun , Wu Yiyang , Xu Benda , Xu Chuang , Xu Tong , Yang Yuzi , Zhang Aiqiang , Zhang Bin ,   JNE Collaboration
Published: December 2024

The China Jinping underground Laboratory (CJPL) is an excellent location for studying solar, terrestrial, and supernova neutrinos due to its 2400-meter vertical rock overburden. Its unparalleled depth gives an opportunity to investigate the cosmic-ray muons with exceptionally high average energy at ∼360  GeV. This paper details a study of muon-related backgrounds based on 1178 days of data collected by the 1-ton prototype neutrino detector used for the Jinping Neutrino Experiment (JNE) since 2017. The apparent effects for the leakage of muons’ secondary particles due to detector’s finite size on the measured neutron yield are first discussed in detail. The analysis of 493 cosmic-ray muon candidates and 13.6±5.7 cosmogenic neutron candidates, along with a thorough evaluation of detection efficiency and uncertainties, gives a muon flux of (3.56±0.16stat±0.10syst)×10−10  cm−2 s−1 and a cosmogenic neutron yield of (3.37±1.41stat±0.31syst)×10−4  μ−1 g−1 cm2 in LAB-based liquid scintillator.

Published by the American Physical Society
2024
Construction of isoscalar
2−+
mesonic states inspired by the
X(2600)
discovery
Authors: Wang Li-Ming , Tian Wen-Xin , Li Ting-Yan , Liu Cheng-Xi , Liu Xiang
Published: December 2024

The BESIII observation of the X(2600) suggests that one possible assignment for its spin-parity quantum numbers is JPC=2−+. This finding motivates us to systematically revisit isoscalar pseudotensor mesonic states through a comprehensive spectroscopic study. In this work, we employ a potential model to calculate the mass spectrum of isoscalar pseudotensor meson states with varying radial quantum numbers. Additionally, we analyze their strong decay behaviors, as allowed by the Okubo-Zweig-Iizuka rule, using the quark pair creation model. Our findings yield valuable information about their resonant parameters and partial decay widths, which can aid in identifying the observed isoscalar pseudotensor states when combined with current experimental data. Importantly, we also predict several radial excitations of isoscalar pseudotensor mesons that remain unobserved experimentally. Furthermore, we exclude the X(2600) from being classified as an isoscalar pseudotensor meson, which is critical for elucidating the properties of the X(2600).

Published by the American Physical Society
2024
Electric field induction in quark-gluon plasma due to thermoelectric effects
Authors: Singh Kamaljeet , Dey Jayanta , Sahoo Raghunath
Published: December 2024

Relativistic heavy-ion collisions produce quark-gluon plasma (QGP), which is locally thermalized. Due to electrically charged particles (quarks), QGP exhibits interesting thermoelectric phenomena during its evolution, resulting in an electromagnetic (EM) field in the medium. In this study, for the first time, we estimate the induced electric field in QGP due to the thermoelectric effect. This phenomenon can induce an EM field even in QGP produced by the head-on heavy-ion collision. In peripheral heavy-ion collisions, the presence of a spectator current generates a transient magnetic field at the early stage, which disrupts the isotropy of the induced electric field. For the numerical estimation, we use a quasiparticle-based model that incorporates the lattice quantum chromodynamics equation of state for QGP. The induced electric field is estimated with cooling rates derived from Gubser hydrodynamic flow. Thermoelectric coefficients such as Seebeck, magneto-Seebeck, and Nernst coefficients play a crucial role in determining the induced field. Additionally, we account for the temperature evolution of QGP using different hydrodynamic cooling rates to calculate the transport coefficients. We also estimate the transport coefficients and the induced electric field in the presence of an external time-varying magnetic field, including the quantum effect of Landau quantization, and explore the effects of the intensity and decay parameter of the magnetic field on the induced electric field. Our findings reveal that the space-time profile of the induced electric field is zero at the center and increases as we go away from the center. During the early stages of evolution, the electric field can reach a maximum value of eE≈1mπ2, decreasing in strength over time.

Published by the American Physical Society
2024
Kaons and antikaons in isospin asymmetric dense resonance matter at finite temperature
Authors: Kaur Manpreet , Kumar Arvind
Published: December 2024

We study the in-medium properties of kaons and antikaons in isospin asymmetric hot and dense resonance matter within the chiral SU(3) hadronic mean field model. Along with nucleons and hyperons, the interactions of K and K¯ mesons with all decuplet baryons (Δ++,+,0,−,Σ*±,0,Ξ*0,−,Ω−) are explicitly considered in the dispersion relations. The properties of mesons in the chiral SU(3) model are modified at finite density and temperature of asymmetric resonance matter through the exchange of scalar fields σ, ζ, and δ and the vector fields ω, ρ, and ϕ. The presence of resonance baryons in the medium at finite temperature is observed to modify significantly the effective masses of K and K¯ mesons. We also calculated the optical potentials of kaons and antikaons as a function of momentum in resonance matter. The present study of in-medium masses and optical potentials of kaons and antikaons will be important for understanding the experimental observables from the heavy-ion collision experiments where hot and dense matter may be produced. Our results indicate that when resonance baryons are present within the medium at finite baryonic density, the mass reduction of kaons and antikaons becomes more pronounced as the temperature of the medium increases from zero to 100 and 150 MeV. The study of the optical potentials of kaons and antikaons reveals a stronger correlation with strangeness fraction compared to isospin asymmetry.

Published by the American Physical Society
2024
Searching for heavy millicharged particles from the atmosphere
Authors: Wu Han , Hardy Edward , Song Ningqiang
Published: December 2024

If millicharged particles (MCPs) exist they can be created in the atmosphere when high energy cosmic rays collide with nuclei and could subsequently be detected at neutrino experiments. We extend previous work, which considered MCPs from decays of light mesons and proton bremsstrahlung, by including production from ϒ meson decays and the Drell-Yan process. MCPs with masses below a GeV primarily arise from proton bremsstrahlung, while heavier MCPs predominantly originate from heavy meson decays and Drell-Yan. We analyze the resulting single scatter and multiple scatter signals at SuperK and JUNO. Searches for low energy coincident signals at JUNO will be sensitive to MCPs with millicharges up to an order of magnitude beyond current constraints for MCP masses between 2 and 10 GeV.

Published by the American Physical Society
2024
Back to the phase space: Thermal axion dark radiation via couplings to standard model fermions
Authors: D’Eramo Francesco , Lenoci Alessandro
Published: December 2024

We investigate the cosmological consequences of axion interactions with standard model fermions accurately and precisely. Our analysis is entirely based on a phase space framework that allows us to keep track of the axion distribution in momentum space across the entire expansion history. First, we consider flavor-diagonal couplings to charged leptons and quantify the expected amount of dark radiation as a function of the coupling strength. Leptophilic axions are immune from complications due to strong interactions and our predictions do not suffer from theoretical uncertainties. We then focus on flavor-diagonal interactions with the three heavier quarks whose masses are all above the scale where strong interactions become nonperturbative. The top quark case is rather safe because its mass is orders of magnitude above the confinement scale, and the consequent predictions are solid. The bottom and charm masses are in more dangerous territory because they are very close to the QCD crossover. We present a comprehensive discussion of theoretical uncertainties due to both the choice of the scale where we stop the Boltzmann evolution and the running of QCD parameters. Finally, we compute the predicted amount of dark radiation expressed as an effective number of additional neutrino species. We compare our predictions with the ones obtained via standard approximate procedures, and we find that adopting a rigorous phase space framework alters the prediction by an amount larger than the sensitivity of future cosmic microwave background observatories.

Published by the American Physical Society
2024
Casimir stresses of the dielectric ball: Inhomogeneity and divergences
Authors: Li Yang
Published: December 2024

Puzzles are still preventing people from further understanding and manipulating the Casimir interaction in spherical systems. Here we investigate the behaviors of Casimir stresses in the system consisting of a ball immersed in the background, emphasizing the roles of spherical geometry and inhomogeneity. Spherical modes are employed to evaluate Green’s dyadic and thus the Casimir stresses. The inhomogeneity of the media essentially modifies the wave form of the spherical mode, leading to significant impacts on the Casimir stresses, especially when far away from the surface of the ball. As the surface approached, the divergence (surface divergence) in Casimir stresses is seen. For both homogeneous and inhomogeneous cases, the leading behaviors (zero for the radial component, and inverse quantic order of distance for the transverse components) of Casimir stresses are exactly the same as those for the corresponding planar homogeneous wall, involving only properties of media at the surface and reflecting no information about the spherical geometry and the inhomogeneity, which implies the local nature. The other surface divergences are influenced by the spherical geometry and for the transverse component always weaker than the planar contribution. The general impacts from the inhomogeneity of media to the surface divergences are also shown. The inhomogeneity will further soften the surface divergence. For two touching media with permittivities and permeabilities equal up to a high enough order of their expansion over the distance to the surface, surface divergences may disappear together with the interaction Casimir stresses. Other factors, such as the refractivity and anisotropy, are also included, which may raise considerable complexities, but typically not related to divergences. Perspectives on the renormalization of the surface divergence are briefly outlined.

Published by the American Physical Society
2024
Unified study of nucleon and
Δ
baryon spectra and their strong decays with chiral dynamics
Authors: Zhong Hui-Hua , Liu Ming-Sheng , Ni Ru-Hui , Chen Mu-Yang , Zhong Xian-Hui , Zhao Qiang
Published: December 2024

In this work, we systematically study both the mass spectra and strong decays of the nucleon and Δ resonances up to the N=2 shell within a unified quark model framework with chiral dynamics. In this framework we achieve a good description of the strong decay properties of the well-established nucleon and Δ resonances. Meanwhile, the mass reversal between N(1440)1/2+ as the first radial excitation state and the 1P-wave nucleon resonances can be explained. We show that the three-body spin-orbit potential arising from the one-gluon exchange can cause a large configuration mixing between N(1520)3/2− and N(1700)3/2− and is also responsible for the large splitting between Δ(1600)1/2− and Δ(1700)3/2−. Some of these baryon resonances tend to weakly couple to the Nπ, Nη, KΛ, and KΣ channels, which may answer the question of why they have not been established in these channels via the πN and γN scatterings. It shows that these “missing resonances” may have large potentials to be established in the Nππ final state due to their large decay rates into either the Δ(1232) or 1P-wave nucleon resonances via the pionic decays. Further experimental search for their signals in charmonium decays at BESIII is thus strongly recommended.

Published by the American Physical Society
2024
Pair production in circularly polarized waves
Authors: Kohlfürst Christian
Published: December 2024

We study electron-positron pair production within two counterpropagating, circularly polarized electromagnetic fields through the Wigner formalism. We numerically generate high-resolution momentum maps to perform a detailed spectroscopic analysis. We identify signatures of polarization and kinematics of the incident fields in the final positron distribution and, on this basis, provide an intuitive picture of helicity transfer in multiphoton pair production.

Published by the American Physical Society
2024
Optimization of conveyance of quantum particles by moving potential well
Authors: Morita Satoshi , Teranishi Yoshiaki , Miyashita Seiji
Published: December 2024

Quantum mechanical control of the position of a particle by using a trapping potential well is an important problem for the manipulation of a quantum particle. We study the probability of successful conveyance of the particle trapped in a potential well for a given length within a given fixed time, i.e., survival probability after the motion. For the actual motion of conveyance, we need to accelerate the particle to move and then decelerate it to stop at the destination. Acceleration and deceleration cause a dropoff of a particle from the trapping potential well. The relaxation of the survival probability in a process with a constant acceleration rate is studied in detail. First, the process is studied as the relaxation of the survival probability of the trapped particle by direct numerical calculations. The survival probability obeys an exponential decay in a long time, which is analyzed from a viewpoint of eigenvalue problem. The value of survival probability is also estimated by the Wentzel-Kramers-Brillouin method with connection formulas using the Airy function and the Weber function. The value is further estimated by a method of the resonance states. We emphasize the fact that an important source of dropoff comes from a nonanalytic change of velocity at the starting point. When the rested particle begins to move, the ground state of the rest frame is redistributed to eigenstates of the moving frame, and then each eigenstate of the moving frame evolves in time. The dephasing of wave functions of the distributed populations reduces the probability of successful conveyance. In general, a smooth start gives a small initial disturbance but it requires a large acceleration during the process to reach the destination in the fixed time which causes a larger dropoff in the process. Considering these conflicting facts, we study the survival probability in concrete conveyance schemes, i.e., protocols with (1) a sudden change of velocity to a constant velocity, (2) a sudden change of acceleration rate to a constant acceleration, and (3) a smooth change of acceleration by studying the real-time change of populations of the adiabatic (instantaneous) eigenstates. We observe the time evolution of the trapped probability and the population distribution during the conveyance process. In cases that the potential well has several bound states, we propose a method to select the particle trapped at the ground state by making use of the difference of survival probabilities of bound states.

Published by the American Physical Society
2024
Equation of state of Bose gases beyond the universal regime
Authors: Planasdemunt-Hospital Martí , Pera Jordi , Boronat Jordi
Published: December 2024

The equation of state of dilute Bose gases, in which the energy only depends on the s-wave scattering length, is rather unknown beyond the universal limit. We have carried out a set of diffusion Monte Carlo calculations up to gas parameters of 10−2 to explore how the departure from the universality emerges. Using different model potentials, we calculate the energies of the gas in an exact way, within some statistical noise, and report the results as a function of the three relevant scattering parameters: the s-wave scattering length a0, the s-wave effective range r0, and the p-wave scattering length a1. If the effective range is not large, we observe universality in terms of a0 and r0 up to gas parameters of 10−2. If r0 grows, the regime of universality in these two parameters is reduced and effects of a1 start to be observed. In the (a0,r0) universal regime we propose an analytical law that reproduces fairly well the exact energies.

Published by the American Physical Society
2024