bluuebunny/crossref_metadata_2025 huggingface dataset:
Substance P and neurokinin 1 receptor boost the pathogenicity of granulocyte‐macrophage colony‐stimulating factor‐producing T helper cells in dry eye disease
Authors: Rong Hua , Yang Hai , Liu Qingqing , Zhang Hui , Wang Shaolin
Published: January 2025

Dry eye disease (DED) is an inflammatory disorder in which CD4+ T cells play a significant role in its pathogenesis. A CD4+ T cell subset termed granulocyte‐macrophage colony‐stimulating factor‐producing T helper (ThGM) cells would contribute to DED pathogenesis. However, the mechanisms by which the activity of ThGM cells is modulated are not thoroughly understood. In this research, we characterized the effects of neurokinin 1 receptor (NK1R) and neurokinin 2 receptor (NK2R) on ThGM cells and T helper 1 (Th1) cells in a murine DED model. We found that ThGM cells expressed NK1R and NK2R, whereas Th1 cells predominantly expressed NK1R. Furthermore, substance P and neurokinin A (NKA), the ligands of NK1R and NK2R, were upregulated in post‐DED LNs and conjunctivae. Substance P significantly promoted granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) expression while mildly upregulating the expression of interferon‐gamma (IFN‐γ) and interleukin 2 (IL‐2) in ThGM cells. By contrast, NKA did not change GM‐CSF expression but significantly increased IFN‐γ expression in ThGM cells. Importantly, the adoptive transfer of NK1R‐expressing ThGM cells significantly exacerbated DED, whereas the transfer of NK1R‐knockdown ThGM cells weakly aggravated DED. NK2R knockdown in ThGM cells did not affect DED progression. In conclusion, this study identifies the substance P‐NK1R axis as a novel mechanism that reinforces the pathogenicity of ThGM cells in DED.
Classifying Impact Loading Using Axial Peak Tibial Acceleration and Impact‐Related Biomechanical Differences During Treadmill Running
Authors: Doyle Eoin W. , Doyle Tim L. A. , Bonacci Jason , Wills Jodie , Campbell Rhiannon , Fuller Joel T.
Published: January 2025

Measuring lower extremity impact acceleration is a common strategy to identify runners with increased injury risk. However, existing axial peak tibial acceleration (PTA) thresholds for determining high‐impact runners typically rely on small samples or fixed running speeds. This study aimed to describe the distribution of axial PTA among runners at their preferred running speed, determine an appropriate adjustment for investigating impact magnitude at different speeds, and compare biomechanics between runners classified by impact magnitude. A total of 171 runners ran on an instrumented treadmill at their preferred running speed during 3D motion capture. Axial PTA was collected at the distal tibia. The relationship between axial PTA and running speed was investigated using linear regression. Runners were categorized into impact sub‐groups, with high‐ and low‐impact runners identified if their axial PTA was ±1 standard deviation of the model predicted value. Differences in demographics, training, and running biomechanics between impact sub‐groups were compared. Mean axial PTA was 7.8 g across all running speeds. Axial PTA increased with running speed, with a 1.7 g increase for every 1.0 m/s increase. There were no differences in axial PTA between males and females (p = 0.214) and lower limbs (p = 0.312). High‐impact runners had higher vertical loading rates (p < 0.001) and greater ankle dorsiflexion at initial contact (p < 0.001) compared to low‐impact runners. No differences in age, body mass, height, or weekly running distances were observed across impact sub‐groups. This study proposes a method to identify the impact classification of runners based on their axial PTA for screening, monitoring, or gait retraining.
Novel Synonymous HLA‐B*35:01:80 Allele Identified by Next‐Generation Sequencing
Authors: Cheranev Valery , Jankevich Tatiana , Makhova Olga , Loginova Maria , Goltsov Andrey
Published: January 2025

The new HLA‐B*35:01:80 allele showed one synonymous nucleotide difference compared to the HLA‐B*35:01:01:01 allele in codon 137.
Comparative Effectiveness of Outpatient COVID‐19 Therapies in Solid Organ Transplant Recipients
Authors: Yetmar Zachary A. , Thao Viengneesee , Helfinstine David A. , Pennington Kelly M. , Razonable Raymund R.
Published: January 2025

Background

Multiple outpatient therapies have been developed for COVID‐19 in high‐risk individuals, but solid organ transplant (SOT) recipients were not well represented in controlled clinical trials. To date, few comparative studies have evaluated outcomes between outpatient therapies in this population.

Methods

We performed a retrospective cohort study using de‐identified administrative claims data from OptumLabs Data Warehouse. Patients were included if they were age ≥ 18 years, diagnosed with COVID‐19 between January 2022 and December 2023, and underwent SOT prior to COVID‐19. The primary outcome was 30‐day hospitalization. Stabilized inverse probability of treatment weighting was used to account for potential confounding variables.

Results

4192 SOT recipients with COVID‐19 were identified. 1403 received an outpatient COVID‐19 therapy, including anti‐spike monoclonal antibodies (N = 748, 53.3%), molnupiravir (N = 327, 23.3%), ritonavir‐boosted nirmatrelvir (N = 217, 15.5%), or remdesivir (N = 141, 10.0%). In weighted analysis compared to no treatment, anti‐spike monoclonal antibodies (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.28–0.55; p < 0.001), molnupiravir (HR 0.56, 95% CI 0.36–0.89; p = 0.013), and nirmatrelvir (HR 0.47, 95% CI 0.25–0.89; p = 0.020) were associated with reduced hospitalization risk, while remdesivir (HR 1.00, 95% CI 0.50–1.98; p = 0.992) was not. Hospitalization rates were similar between the treatment agents, apart from remdesivir showing a higher risk compared to anti‐spike monoclonal antibodies.

Conclusions

Outpatient COVID‐19 therapies were largely associated with improved outcomes among SOT recipients. These treatment agents showed similar rates of 30‐day hospitalization, except for remdesivir. The choice of outpatient COVID‐19 therapy in SOT recipients should primarily account for patients’ individual circumstances and drug‐drug interactions rather than differential therapeutic efficacy.

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Dissociation of IgM antibodies from red blood cells using ethylenediamine tetraacetate/glycine acid or chloroquine diphosphate
Authors: Abe Yuko , Matsuura Hideaki , Yamada Ayuna , Nakagawa Rie , Kojima Hayato , Ishihara Yuya , Doi Hiroki , Fujii Sumie , Miura Yasuo
Published: January 2025

Background

Ethylenediamine tetraacetate/glycine acid (EGA) and chloroquine diphosphate (CDP) are used in transfusion testing to dissociate IgG antibodies from red blood cells (RBCs). However, the ability of these reagents to dissociate IgM antibodies sensitized to RBCs has not been comprehensively elucidated. We investigated whether EGA and CDP could dissociate cold‐reactive antibodies from RBCs and their effect on RBCs after dissociation treatment.

Study Design and Methods

Cold‐reactive antibody‐sensitized RBC samples were prepared by mixing group A RBCs and group B plasma and treated with EGA, CDP, and dithiothreitol (DTT). Before and after the dissociation treatment, changes in the agglutination of these RBCs were assessed using the test tube method. Flow cytometric analysis was used to confirm the nature of antibodies bound to RBCs. Additionally, RBC morphology was evaluated using scanning electron microscopy. This study utilized off‐label use of EGA and CDP.

Results

Flow cytometric analysis showed that antibodies sensitized to RBCs were mainly IgM antibodies. After antibody dissociation, agglutination disappeared in the EGA‐treated samples to the same degree as in the DTT‐treated samples. However, IgM antibodies remained in the CDP‐treated samples. Regarding RBC morphology, RBC surface appeared coarser in both EGA‐ and CDP‐treated samples, and RBC area was significantly smaller in the CDP‐treated samples than in the EGA‐treated samples.

Discussion

EGA could dissociate cold‐reactive antibodies, whereas CDP had a higher residual antibody content. This difference in dissociation ability appears to correlate with the antibody pH of the dissociation reagent. EGA treatment may be useful in cases of sensitization by high‐titer cold‐reactive antibodies.
Universality for transversal Hamilton cycles
Authors: Bowtell Candida , Morris Patrick , Pehova Yanitsa , Staden Katherine
Published: January 2025

Let be a graph collection on a common vertex set of size such that for every . We show that contains every Hamilton cycle pattern. That is, for every map there is a Hamilton cycle whose th edge lies in .
Rational approximation of holomorphic semigroups revisited
Authors: Batty Charles , Gomilko Alexander , Tomilov Yuri
Published: January 2025

Using a recently developed ‐calculus we propose a unified approach to the study of rational approximations of holomorphic semigroups on Banach spaces. We provide unified and simple proofs to a number of basic results on semigroup approximations and substantially improve some of them. We show that many of our estimates are essentially optimal, thus complementing the existing literature.
Fracture Analysis of Sharp Notches Under Mode III Loading: A Local Approach
Authors: Yan Xiangqiao
Published: January 2025

In this study, an attempt is made to propose a local approach for fracture analysis of sharp notches under Mode III loading. Under the assumption that the stress concentration factor eigenvalue k* for V-notches under Mode I loading proposed by Yan is valid for V-notches under Mode III loading, in fact, the local approach for fracture analysis of sharp notches under Mode III loading is similar to that under Mode I loading. The experimental verifications by experimental data from the literature show that the attempt is successful. In addition, the experimental verifications show that the empirical equation of determining the fracture toughness proposed by Yan is also suited for Mode III loading. By using the empirical equation, thus, the local approach proposed by Yan and the local approach proposed in this study have a wide of applications for fracture assessment of sharp notches.
Integrated Energy Optimization in Manufacturing Through Multiagent Deep Reinforcement Learning: Holistic Control of Manufacturing, Microgrid Systems, and Battery Storage
Authors: Waseem Muhammad , Maithripala Mihitha Sarinda , Chang Qing , Lin Zongli
Published: January 2025

Microgrid technology integrates storage devices, renewable energy sources, and controllable loads and has been widely explored in residential, commercial, and critical facilities. However, its potential in manufacturing remains largely underexplored, where optimal control of microgrids containing energy storage systems (ESS) is crucial. Two primary challenges arise in integrated microgrid-manufacturing systems: fluctuating renewable energy output and nondeterministic polynomial (NP)-hard demand-side control. Addressing both challenges simultaneously increases complexity. This article proposes an integrated control considering ESS degradation, optimizing control on both the manufacturing demand and microgrid energy supply sides within the production constraints. It formulates the problem in a decentralized partially observable Markov decision process (Dec-POMDP) framework, treating the system as a multiagent environment. The multiagent deep deterministic policy gradient (MADDPG) algorithm is adapted to optimize control policies. Investigating the trained policies provides insights into their logic, and a rule-based policy is introduced for practical implementation. Experimental validation on a manufacturing system validates the effectiveness of the proposed method and the rule-based policy.
Determining the Parameters of Gurson–Tvergaard–Needleman Model for Predicting the Failure of Wrought and Fused Filament Fabricated 17-4 PH Stainless Steel
Authors: Porrang Bita , Ghaffar Muhammad Asim , Hosseini Ali
Published: January 2025

Metal additive manufacturing is an emerging technology for creating metallic parts, with metal fused filament fabrication (FFF) rapidly gaining popularity due to its cost-effectiveness. Despite the acceptable mechanical properties of additively manufactured metals using FFF, a significant technical challenge is the presence of undesirable porosity, which affects material performance. This study aims to model the material behavior of FFF 17-4 PH stainless steel, considering its porosity, using the Gurson–Tvergaard–Needleman (GTN) damage model. The GTN model, which incorporates the micromechanical behavior of ductile metals, shows great potential for failure prediction. The GTN model parameters were identified for both wrought and FFF 17-4 PH stainless steel through a series of proposed methods. Initial void volume fractions were determined using density measurements. The evolution of void volume fractions was experimentally assessed through interrupted uniaxial tensile tests, leading to the analytical derivation of three void nucleation parameters based on continuum damage mechanics. Additional GTN model parameters related to material failure were determined through microscopic analysis of rupture surfaces and finite element (FE) trial-and-error methods. FE simulations using the GTN damage model, represented as porous metal plasticity in abaqus, were conducted to verify the identified parameters. The results demonstrated that the numerical calculations of the FE model are in good agreement with the experimental data. The use of experimentally derived GTN model parameters from the proposed methods effectively predicts material behavior, particularly in the post-necking region where traditional FE modeling fails to simulate the realistic material response.
Adaptive Robot Motion Planning for Smart Manufacturing Based on Digital Twin and Bayesian Optimization-Enhanced Reinforcement Learning
Authors: Zhou Qi , Wu Jin , Li Boyan , Li Sikai , Feng Bohan , Liu Jiangshan , Bi Youyi
Published: January 2025

Advanced motion planning is crucial for safe and efficient robotic operations in various scenarios of smart manufacturing, such as assembling, packaging, and palletizing. Compared to traditional motion planning methods, Reinforcement Learning (RL) shows better adaptability to complex and dynamic working environments. However, the training of RL models is often time-consuming, and the determination of well-behaved reward function parameters is challenging. To tackle these issues, an adaptive robot motion planning approach is proposed based on digital twin and reinforcement learning. The core idea is to adaptively select geometry-based or RL-based methods for robot motion planning through a real-time distance detection mechanism, which can reduce the complexity of RL model training and accelerate the training process. In addition, Bayesian Optimization is integrated within RL training to refine the reward function parameters. The approach is validated with a Digital Twin-enabled robot system through five kinds of tasks (Pick and Place, Drawer Open, Light Switch, Button Press, and Cube Push) in dynamic environments. Experiment results show that our approach outperforms the traditional RL-based method with improved training speed and guaranteed task performance. This work contributes to the practical deployment of adaptive robot motion planning in smart manufacturing.
Surface Wettability Effects on Droplet Dynamics and Heat Transfer on Heated Stainless-Steel Foils
Authors: Shahdhaar Mohammad Autif , Shukla Sagar , Srivastava Atul
Published: January 2025

We report the dynamics and heat transfer characteristics of water droplets impacting a thin stainless-steel foil maintained at different temperatures. The hydrophobic characteristics are imparted to the surface through polysiloxane coating, and water droplets impact the uncoated and coated heated surfaces at different velocities. High-speed videography is utilized to capture the dynamics of the droplet upon impact, while the temperature field of the substrate, during the phenomenon, is simultaneously recorded using high-speed infrared thermography. Heat transfer to the droplet over different surfaces is determined through energy balance on the foil using the captured thermographs. The results reveal that the spreading phase duration is independent of droplet impact velocity, irrespective of surface wettability, whereas surface wettability primarily affects the receding phase. The coated hydrophobic surfaces exhibited lower resistance to motion at the three-phase contact line, resulting in reduced spread ratios during the receding phase. It is noted that the majority of heat transfer occurred during the initial spreading and receding phases, driven primarily by forced convection. The maximum heat fluxes were observed along the three-phase contact line, particularly at the onset of the receding phase. The coated surface demonstrated lower overall heat transfer rates compared to non-coated surfaces, with the difference increasing at higher surface temperatures. Additionally, an increase in surface temperature to 75 °C enhanced the hydrophobicity of the coated surface, leading to prolonged receding phases and extended time to reach the sessile state.
Influence of Propagation Velocity and Peak Pressure of the Rotating Pressure Wave on the Flow Characteristics of a Centrifugal Compressor
Authors: Xia Yiqing , Wu Yuwen , Weng Chunsheng , Li Qun , Nie Jiayi
Published: January 2025

Rotating detonation turbine engine represents an innovative advancement in the state-of-art gas turbines. When a rotating detonation combustor is coupled with turbomachinery, the rotating detonation wave propagates upstream toward the compressor, affecting its aerodynamic and overall performance. In the present study, a three-dimensional numerical simulation is carried out to study the flow characteristics of a centrifugal compressor with the presence of a rotating pressure wave (RPW) at the outlet based on the unsteady Reynolds-Averaged Navier−Stokes method. Effects of RPW propagation velocity and peak pressure are investigated. The results showed that the rotating pressure wave forms a forward propagating wave (FPW) in the compressor, interacting with the diffuser and impeller blades. In the diffuser, the peak pressure of the FPW initially decreases with a slight recovery. It then decreases rapidly in the impeller. Effects of FPW are distinct from those of the unsteady rotor−stator interaction. A decrease in the propagation velocity enhances the strength of FPW passing through the diffuser channel while lowering the peak pressure mitigates the influence of FPW on the compressor flow field. The FPW leads to the decline of the mass flowrate and the rise of the total pressure ratio. While the mass flowrate and efficiency rise with the increase of propagation velocity, the peak pressure decreases. The isentropic efficiency can increase by up to 2.8% under high propagation velocity and low peak pressure conditions.
Influences of Particulate Deposition on Vane Trailing-Edge Film Cooling: Adiabatic and Overall Cooling Effectiveness
Authors: Yang Xing , Hao Zihan , Feng Zhenping
Published: January 2025

Thermal design for the trailing edge of a turbine vane is critically challenging because the thinnest trailing-edge region has a low-thermal capacity, resulting in a much quicker thermal response to the hot gas. Cooling air for this region is usually extracted from the internal cooling passages inside the vane main body and thus the post-cooling air has a relatively weaker cooling potential. The thermal mismatch in the metal can be further exacerbated by the deposition of fine contaminant particulates resulting from the intake air as well as the unburned hydrocarbon fuel. Changes of the surface conditions caused by deposition are able to affect film cooling and to enhance heat transfer substantially. However, the deposition layer has low-thermal conductivity (approximately 0.1 W · m−1 · K−1), which thermally insulates the wall from the hot gas. The presence of deposition thereby further complicates the heat convection and conduction issues in this area. The current study had the uniqueness of evaluating deposition effects on vane trailing-edge film cooling by conducting deposition simulation experiments, where a scaled-up vane model featured cutback slots with a thick lip on the pressure surface. The coupling effects of deposition and the slot discharge coolant were investigated by examining the dynamic evolution of deposition and flow mixing of the coolant with the mainstream flows for various slot discharge ratios. The resulting film cooling performance was further assessed in adiabatic and conjugate heat transfer conditions to document the deposition-induced changes of heat/mass transfer and conduction. The thick slot lip and higher discharge ratios were found to reduce deposition, but simultaneously, to generate stronger flow mixing. Deposition on the pressure-surface degraded adiabatic cooling effectiveness regardless of deposition thickness, with a maximum reduction of 35%, whereas thicker deposition on the cutback surface was favorable to film cooling at the highest discharge ratio. The insulation effects of the deposition layer were not able to erase out the reduction in adiabatic effectiveness and potentially increased heat transfer levels over the rough deposition surface, resulting in lower overall cooling effectiveness. The reduction in overall effectiveness, however, was alleviated by increasing the discharge ratio.
Research on Qualification Requirements for Electrical and Instrumentation Equipment Based on Safety Classification
Authors: Sun Qian , Liu Jiahao
Published: January 2025

In 2014, the IAEA issued new safety classification guidelines for nuclear power plants called Safety Classification of Structures, Systems and Components in Nuclear Power Plants. It is stipulated that items are classified based on their function importance, and after determining the safety class, equipment qualification requirements need to be determined to ensure that items have suitable quality under all expected operating conditions and to ensure the realization of safety functions. Therefore, it is necessary to identify safety important items that can perform their necessary expected functions throughout their entire design operating life and under dominant environmental conditions, including maintenance and testing of nuclear power plants. The qualification procedure for important safety items must take into account the aging effects caused by various environmental factors (such as vibration, radiation, humidity, temperature) during the expected lifespan of safety important items. Therefore, it is necessary to clarify the qualification requirements for equipment and carry out equipment qualification activities from the perspective of equipment selection. This article investigates the relevant codes and standards such as RCC-E and IEEE as well as different reactor experiences, and analyzes the actual environmental conditions under which electrical and instrumentation equipment performs its functions. This includes determining the environmental and load conditions for device execution, the timing and duration of device execution, and the type of function performed by the device.
Exploring offshore particle motion soundscapes
Authors: Jones Ian T. , Martin S. B. , Miksis-Olds J. L.
Published: January 2025

Fishes and aquatic invertebrates utilize acoustic particle motion for hearing, and some additionally detect sound pressure. Yet, few underwater soundscapes studies report particle motion, which is often assumed to scale predictably with pressure in offshore habitats. This relationship does not always exist for low frequencies or near reflective boundaries. This study compared particle motion and sound pressure from hydrophone arrays near the seafloor at six sites on the U.S. Mid and South Atlantic Outer Continental Shelf and assessed predictability of sound pressure and particle motion levels by environmental indicators (wind, vessels, temperature, currents). Unidentified fish sounds (100–750 Hz) had particle motion magnitudes 4.8–12.6 dB greater than those predicted from single hydrophone (pressure) measurements, indicating that these sounds were received in the near field. Excess particle motion attributed to hydrodynamic flow noise (<100 Hz) was also present at all sites. Most sounds (25th–75th percentile) from other sources received in the far field (vessels, mammals), had measured particle motion within ±3 dB of that predicted from single hydrophone measurements. The results emphasize for offshore soundscapes the importance of particle motion measurement for short-time (1 min) and near field signals, and that pressure measurement is sufficient for long-term (1 year) predictive modeling.
Preservation and early evolution of scalidophoran ventral nerve cord
Authors: Wang Deng , Vannier Jean , Martín-Durán José M. , Herranz María , Yu Chiyang
Published: January 2025

Ecdysozoan worms (Nematoida + Scalidophora) are typified by disparate grades of neural organization reflecting a complex evolutionary history. The fossil record offers a unique opportunity to reconstruct the early character evolution of the nervous system via the exceptional preservation of extinct representatives. We focus on their nervous system as it appears in early and mid-Cambrian fossils. We show that some of the oldest known representatives of the group either preserved in carbonaceous compression (early and mid-Cambrian Burgess-type preservation) or secondarily phosphatized in three dimensions (e.g., basal Cambrian Kuanchuanpu Formation, ca. 535 million years) had an unpaired ventral nerve cord (VNC) that ran along the trunk in an eccentric position as in modern priapulids and nematodes. A phylogenetic analysis integrating these fossil data suggests that ancestral scalidophorans had an unpaired VNC and that paired nervous systems probably evolved independently in Kinorhyncha and Loricifera, and, more importantly, in panarthropods in possible relation with the rise of paired appendages and bilaterally coordinated motricity.
Molecular basis for the stepwise and faithful maturation of the 20
S
proteasome
Authors: Han Yaoyao , Han Qian , Tang Qianqian , Zhang Yixiao , Liu Kai
Published: January 2025

The proteasome degrades most superfluous and damaged proteins, and its decline is associated with many diseases. As the proteolytic unit, the 20
S
proteasome is assembled from 28 subunits assisted by chaperones PAC1/2/3/4 and POMP; then, it undergoes the maturation process, in which the proteolytic sites are activated and the assembly chaperones are cleared. However, mechanisms governing the maturation remain elusive. Here, we captured endogenous maturation intermediates of human 20
S
proteasome, which are low abundance and highly dynamic, and determined their structures by cryo–electron microscopy. Through structure-based functional studies, we identified the key switches that remodel and activate the proteolytic sites. Our results also revealed that the POMP degradation is tightly controlled by a dual-checking mechanism, while the α5 subunit senses POMP degradation to induce PAC1/2 release, achieving the full maturation. These findings elucidate mechanisms directing and safeguarding the proteasome maturation and set basis for building proteasomes to counteract the decline of protein degradation in aging and disease.
Cpeb1 remodels cell type–specific translational program to promote fear extinction
Authors: Zhang Juan , Yang Chun-Qing , Liu Zhi-Qiang , Wu Shi-Ping , Li Zu-Guang , Zhang Luo-Man , Fan Hong-Wei , Guo Zi-Yuan , Man Heng-Ye , Li Xiang , Lu You-Ming , Zhu Ling-Qiang , Liu Dan
Published: January 2025

Protein translation is crucial for fear extinction, a process vital for adaptive behavior and mental health, yet the underlying cell-specific mechanisms remain elusive. Using a Tet-On 3G genetic approach, we achieved precise temporal control over protein translation in the infralimbic medial prefrontal cortex (
IL
) during fear extinction. In addition, our results reveal that the disruption of cytoplasmic polyadenylation element binding protein 1 (Cpeb1) leads to notable alterations in cell type–specific translational programs, thereby affecting fear extinction. Specifically, Cpeb1 deficiency in neurons activates the translation of heterochromatin protein 1 binding protein 3, which enhances microRNA networks, whereas in microglia, it suppresses the translation of chemokine receptor 1 (
Cx3cr1
), resulting in an aged-like microglial phenotype. These coordinated alterations impair spine formation and plasticity. Our study highlights the critical role of cell type–specific protein translation in fear extinction and provides an insight into therapeutic targets for disorders with extinction deficits.
Laws about bodily damage originate from shared intuitions about the value of body parts
Authors: Wee Yunsuh Nike , Sznycer Daniel , Krems Jaimie Arona
Published: January 2025

From the biblical
lex talionis
to the medieval wergild system and modern workers’ compensation laws, laws about bodily damage may originate from cognitive mechanisms that capitalize on an enduring regularity: Different body parts vary in their incremental contributions to human functionality. To evaluate this hypothesis, we conducted a preregistered study with materials based on five legal codes from highly diverse cultures and historical eras: the Law of Æthelberht (Kent, approximately 600 CE), the Guta lag (Gotland, approximately 1220 CE), and workers’ compensation laws from the United States, the Republic of Korea, and the United Arab Emirates; and 614 laypeople from the United States and India. The data indicate ordinal agreement in the values attached to body parts by ancient and modern lawmakers, as well as by laypeople in the United States and India. The observed agreement across time, space, and levels of legal expertise suggests that laws about bodily damage originate from shared intuitions about the value of body parts.
Noncanonical UPR factor CREB3L2 drives immune evasion of triple-negative breast cancer through Hedgehog pathway modulation in T cells
Authors: Cao Zi-Jian , You Jia , Fan Yu-Meng , Yang Jia-Ying , Sun Jirui , Ma Xiuli , Zhang Jinku , Li Zhongwu , Wang Xiang , Feng Yu-Xiong
Published: January 2025

The unfolded protein response (UPR) pathway is crucial for tumorigenesis, mainly by regulating cancer cell stress responses and survival. However, whether UPR factors facilitate cell-cell communication between cancer cells and immune cells to drive cancer progression remains unclear. We found that adenosine 3′,5′-monophosphate response element–binding protein 3–like protein 2 (CREB3L2), a noncanonical UPR factor, is overexpressed and activated in triple-negative breast cancer, where its cleavage releases a C-terminal fragment that activates the Hedgehog pathway in neighboring CD8+ T cells. The enhanced Hedgehog pathway represses CD8+ T cell activation and inhibits its cytotoxic effects. Consequently, overexpression of CREB3L2 not only promotes tumor growth but also causes resistance to immune checkpoint blockade (ICB). Inhibition of the Hedgehog pathway impedes the growth of CREB3L2-overexpressed tumors and sensitizes them to ICB therapy. In summary, we identified a previously unidentified mechanism by which the UPR pathway dictates cross-talk between cancer cells and immune cells, providing important anticancer therapeutic opportunities.
Closed genomes of commercial inoculant rhizobia provide a blueprint for management of legume inoculation
Authors: Kohlmeier MacLean G. , O'Hara Graham W. , Ramsay Joshua P. , Terpolilli Jason J.
Published: January 2025

Rhizobia are soil bacteria capable of establishing symbiosis within legume root nodules, where they reduce atmospheric N
2
into ammonia and supply it to the plant for growth. Australian soils often lack rhizobia compatible with introduced agricultural legumes, so inoculation with exotic strains has become a common practice for over 50 years. While extensive research has assessed the N
2
-fixing capabilities of these inoculants, their genomics, taxonomy, and core and accessory gene phylogeny are poorly characterized. Furthermore, in some cases, inoculant strains have been developed from isolations made in Australia. It is unknown whether these strains represent naturalized exotic organisms, native rhizobia with a capacity to nodulate introduced legumes, or recombinant strains arising from horizontal transfer between introduced and native bacteria. Here, we describe the complete, closed genome sequences of 42 Australian commercial rhizobia. These strains span the genera,
Bradyrhizobium
,
Mesorhizobium
,
Methylobacterium
,
Rhizobium
, and
Sinorhizobium
, and only 23 strains were identified to species level. Within inoculant strain genomes, replicon structure and location of symbiosis genes were consistent with those of model strains for each genus, except for
Rhizobium
sp. SRDI969, where the symbiosis genes are chromosomally encoded. Genomic analysis of the strains isolated from Australia showed they were related to exotic strains, suggesting that they may have colonized Australian soils following undocumented introductions. These genome sequences provide the basis for accurate strain identification to manage inoculation and identify the prevalence and impact of horizontal gene transfer (HGT) on legume productivity.

IMPORTANCE

Inoculation of cultivated legumes with exotic rhizobia is integral to Australian agriculture in soils lacking compatible rhizobia. The Australian inoculant program supplies phenotypically characterized high-performing strains for farmers but in most cases, little is known about the genomes of these rhizobia. Horizontal gene transfer (HGT) of symbiosis genes from inoculant strains to native non-symbiotic rhizobia frequently occurs in Australian soils and can impact the long-term stability and efficacy of legume inoculation. Here, we present the analysis of reference-quality genomes for 42 Australian commercial rhizobial inoculants. We verify and classify the genetics, genome architecture, and taxonomy of these organisms. Importantly, these genome sequences will facilitate the accurate strain identification and monitoring of inoculants in soils and plant nodules, as well as enable detection of horizontal gene transfer to native rhizobia, thus ensuring the efficacy and integrity of Australia’s legume inoculation program.
Draft genome sequence of
Mycobacterium
sp. SA01 isolated from
Sporobolus alterniflorus
seedlings collected in Cape Cod (USA)
Authors: Peredo Elena L. , Thomas Suzanne , Cardon Zoe G.
Published: January 2025

A draft genome was generated for a strain of
Mycobacterium
closely related to
Mycobacterium
sp. ENV421 isolated
in vitro
from plants of smooth cordgrass germinated
in vitro
from seeds collected in a salt marsh in Cape Cod (USA). Genomic DNA was sequenced using paired-end Illumina technologies. Here, we report the classification and genome statistics of
Mycobacterium
sp. SA01. A strain of
Mycobacterium
was isolated from seedlings of
Sporobolus alterniflorus
germinated under in vitro conditions after surface sterilization. The seeds were collected in Little Swippewisett Marsh, Barnstable, MA, USA.
Supplemental Material: Closure of the Paleo-Asian Ocean and amalgamation of the northern part of the East Asian continent in the latest Paleozoic: Evidence from the Xingshuwa ophiolitic mélange in southeastern Inner Mongolia
Authors: Liu Jianfeng , al. et
Published: January 2025

Supplemental Text S1, Figures S1–S3, and Tables S1–S4.
Supplemental Material: Decoupling of precipitation and temperature in North China across the Pliocene–Pleistocene transition
Authors: Zhang Ze , al. et
Published: January 2025

Lithologic description of the Huangdigou section and detailed proxies testing and interpretation.
Trial of alginates in throat symptoms: protocol for a pragmatic, multicentre, placebo controlled, double blind, parallel, randomised controlled trial of liquid alginate (Gaviscon Advance) for the treatment of persistent throat symptoms
Authors: Morton Miranda , Smith Hesther , Fouweather Tony , Joyce Richard , Evans Lysbeth , Thompson Julie , Wood Ruth , Teare Dawn , Maier Rebecca , McGlashan Julian , Hamilton David , O’Hara James
Published: January 2025

Introduction

Persistent throat symptoms (PTS) are indicators for over 60 000 new patient referrals to NHS secondary care annually. PTS have been attributed to manifestation of gastro-oesophageal reflux disease (GORD) with the hypothesis that gastric refluxate damages and irritates the mucosa of the upper aerodigestive tract. Symptoms of PTS and GORD are commonly treated with proton pump inhibitors (PPIs) or alginates are often, incorrectly, advocated. The Trial of PPIs in Throat Symptoms trial definitively demonstrated that lansoprazole is no more effective than placebo in treating symptoms of PTS, indicating that empirical PPI treatment for PTS should be discouraged. The impact of this is an anticipated increase in prescriptions of alginates for PTS, however, there is a lack of evidence of the efficacy of alginates in treating this condition. Trial of alginates in throat symptoms aims to compare symptomatic response of the symptoms of PTS in liquid alginate (Gaviscon Advance) in comparison to a near matched placebo over an 8-week period to provide definitive evidence of the use of alginates in treating PTS.

Methods and analysis

This is a multicentre, pragmatic, double blind, parallel, randomised controlled trial. 250 adults with PTS will be recruited from NHS secondary care sites and randomised to either liquid alginate (Gaviscon Advance) or near matched placebo in a 1:1 ratio. The primary objective is to compare the symptomatic response in patients with PTS to liquid alginate (Gaviscon Advance) compared with placebo using the outcome measure of total Reflux Symptom Index questionnaire score at 8 weeks.

Ethics and dissemination

Favourable ethical opinion was received from the East Midlands—Leicester South Research Ethics Committee (reference: 22/EM/0205). All participants will provide informed consent prior to any trial specific activity taking place. Results will be disseminated in peer reviewed publications, at national and international conferences, in peer reviewed journals and to participants and the public (using lay language).

Trial registration number

ISRCTN13949559
Neutropenic event incidence in women with early-stage breast cancer receiving neoadjuvant or adjuvant chemotherapy: a retrospective study
Authors: Englund Elin , Strandéus Michael , Engvall Kristina , Oliva Delmy
Published: January 2025

Objectives

To assess the incidence of neutropenia, febrile neutropenia, documented infection with neutropenia and fever associated with early-stage breast cancer (BC) in a real-life setting.

Methods

A retrospective study that includes 88 women with BC who received a first dose of Epirubicin plus Cyclophosphamide with or without 5-Fluorouracil, in the county hospital of Ryhov, Sweden. The patients were included continuously from May 2017 to November 2020 and were ≥18 years old. All data was collected in a form and the G-CSF prophylaxis was checked to ensure that it was given during the treatments.

Results

The median age among the patients was 59 (min 27-82max) years. 79 patients were treated with primary prophylaxis with Granulocyte-colony stimulating factor (G-CSF) support. Seven (8.0%) patients were affected by a neutropenic episode, including one (1.1%) patient with FN and two (2.3%) patients with documented infection (online supplemental table 1).

Conclusion

The incidence of neutropenic events in this study is relatively low. A higher incidence of neutropenic episodes is observed in patients ≥ 60 years old compared with younger patients, despite lower doses of chemotherapy for the elderly. The use of G-CSF in the elderly, regardless of the dose of chemotherapy, may be needed to decrease the incidence of neutropenia and its consequences. The adverse effects of G-CSF and its cost-effectiveness are important perspectives which should be included in the treatment.
Application of Optimized Support System-Based Large Deformation Control Technology in Plate Suture Zone Tunnels: A Case Study of the China-Laos Railway
Authors: Tan Zhongsheng , Yang Yang , Zhao Jinpeng , Hu Xuelong , Wang Jianjun
Published: January 2025

The Luang Prabang Suture Zone, characterized by its unique amalgamation of terranes from varied microcontinents, exhibits distinct metamorphic and paleogeographic histories, impacting the stability of infrastructure such as tunnels. This study addresses the challenges posed by complex tectonic stress patterns and the inherent weakness of rock masses in the suture zones, particularly influencing the China-Laos Railway tunnels. We conducted comprehensive tests including tectonic stress assessments, rock strength measurements, tunnel loosening zone evaluations, and primary support stress analyses. Our findings reveal that the predominant crustal stress pattern, σH>σh>σv, promotes thrust fault development, with significant deformations observed in carbonaceous slate exhibiting lump structures at suture boundaries. These deformations are primarily manifested through asymmetric sidewall squeezing, exacerbated by the expansion of surrounding rock loosening zones. In response, we propose a novel active control technology, verified through field application. This involves optimizing tunnel cross-sections, refining excavation techniques, employing a strategic long-short bolt system, and enhancing the stiffness of primary supports. Our research not only provides practical solutions for tunnel stability in similar complex geological environments but also extends the theoretical understanding of such geological settings. Future work will focus on refining these innovative control technologies for broader application in challenging tunneling scenarios.
Blind quantum computation with fewer quantum and delegated cost of client
Authors: Yan Yu-Zhan , Yang Zhen , Wu Guang-Yang , Luo Yuan-Mao , Bai Ming-Qiang , Mo Zhi-Wen
Published: January 2025

Blind quantum computation (for measuring the client Alice) protocol changes the role of the client from state preparation to measurement. In order to further save the quantum cost and delegated cost of Alice, two protocols are proposed to complete a certain single-qubit gate with fewer measurements and qubits while remaining loss tolerant in this paper. Finally, the protocols are feasibility from three aspects: blindness, correctness and universality.
Molecular Dynamics (ReaxFF MD) Simulation of Hydrogen Effects on Air Heater Combustion
Authors: Miaoe Liu , Chibing Shen
Published: January 2025

As a fuel commonly used by air heaters for ground tests of high-speed aircraft, the combustion mechanism of ethanol in air heaters is still unclear, especially the atomic-level chemical mechanism of important intermediate products represented by hydrogen in maintaining stable flame combustion needs to be further studied. In this paper, the combustion process of ethanol/oxygen mixtures under different hydrogen additions was simulated using the reactive force field (ReaxFF) molecular dynamics (MD) method. The results show that increasing the proportion of hydrogen in the mixed gas can not only reduce the ignition delay time of ethanol combustion but also promote the consumption of ethanol and accelerate the progress of the combustion reaction. It was also found that hydrogen and ethanol produced a competitive relationship for oxygen, which changed the ideal stoichiometric ratio (1:3) of complete combustion of ethanol and oxygen and significantly affected the intermediate products and reaction paths of ethanol and oxygen. In addition, increasing the combustion reaction temperature will affect the reaction path of ethanol/oxygen, and the number of intermediate products produced will reach the peak faster and then decompose. Theoretical support for a deeper understanding of the intermediate product hydrogen in the combustion of the three-component air heater of ethanol/liquid oxygen/air and also for improving the combustion efficiency of liquid rocket engine fuel are provided in this study.
A new extended metric space and solution of rocket’s ascending motion
Authors: Alam Khairul Habib , Rohen Yumnam , Tomar Anita , Ahmad Junaid
Published: January 2025

In this work, we introduce extended [Formula: see text]-metric space and extended [Formula: see text]-metric space with a focus on their topological notions including relations between [Formula: see text]-metric, extended [Formula: see text]-metric and extended [Formula: see text]-metric. By challenging the conventional assumption of zero self-distance, we investigate novel postulates to establish the existence and uniqueness of fixed point theorems in these domains and pave the way for more accurate mathematical models applicable to real-world scenarios. Our findings are supported by illustrative examples. Additionally, using our result we explore the problem that indicates the ascending motion of a rocket. Consequently, our research contributes not only to a deeper comprehension of mathematical concepts but also to practical utility across various scientific domains.
Electromechanical hysteresis and relaxation processes in relaxor piezoceramics
Authors: Konstantinova M. G. , Shvetsov I. A. , Shvetsova N. A. , Petrova E. I. , Rybyanets A. N.
Published: January 2025

This paper studies the relaxation processes and electromechanical hysteresis in relaxor piezoceramics based on the PZT system. Measurements and analysis of the electric displacement and mechanical strain hysteresis loops recorded in bipolar AC electric fields in the frequency range 0.001–5[Formula: see text]Hz were performed by means of the electromechanical response characterization system (STEPHV) and program (STEP). It was found that the coercive field, remnant and saturation electric displacement, area of hysteresis loops and relative mechanical strain values are strongly dependent on frequency. As a result of this study, complete sets of parameters characterizing the switching and ferroelectric hysteresis processes in relaxor piezoceramics were obtained.
Machine Learning Copper Price Predictions: Evidence Based on Gaussian Process Regressions Tuned with Cross-Validation and Bayesian Optimization
Authors: Jin Bingzi , Xu Xiaojie
Published: January 2025

For a considerable amount of time, many market participants have placed great importance on price forecasts for major metal commodities. To tackle the problem, our study looks at the price of copper recorded on a daily basis. The sample under inquiry spans more than 10 years, from 01/02/2014 to 04/12/2024, and the price series under examination has substantial financial implications. In this instance, Gaussian process regression models are built using cross-validation techniques and Bayesian optimization methodologies, and the resultant strategies are employed to provide price estimations. The relative root-mean-square error of 1.3880% indicates that our empirical prediction approach produces reasonably accurate price estimates for the out-of-sample assessment period of 04/11/2022–04/12/2024. Models for predicting prices give investors and governments the information they require to make wise choices about the copper market.