bluuebunny/crossref_metadata_2025 huggingface dataset:
Training for Mindfulness Teachers: Benefits for Mindfulness, Well-being, and Emotion Regulation
Authors: Matiz Alessio , Chiesa Alberto , D’Antoni Fabio , Barbieri Rachele , Crescentini Cristiano
Published: February 2025

Objectives

This study examined the effects of a 9-month mindfulness teacher training (MTT) program on mindfulness skills, emotion regulation, and psychological well-being among future mindfulness instructors, compared to a control group.

Method

Eighty-seven mindfulness instructors-in-training participated in the MTT program. The control group consisted of age- and gender-matched individuals. Mindfulness skills, emotion regulation, and psychological well-being were assessed at baseline, mid-intervention, and post-intervention using validated measures.

Results

In comparison with the control group, participants in the MTT group showed significant improvements in most facets of mindfulness (i.e., observe, describe, non-react, and act with awareness). They also reported decreased rumination, as well as increased personal growth and purpose in life compared to the control group. However, there were no significant differences between the groups in other dimensions of emotion regulation or psychological well-being.

Conclusions

This study provides preliminary evidence that mindfulness teacher trainings positively affect mindfulness skills, as well as specific aspects of psychological well-being (personal growth and purpose in life), and emotion regulation (rumination). Future research should investigate the long-term effects of these trainings and how instructors’ well-being relates to their teaching effectiveness.

Preregistration

This study is not preregistered.
Experimental study to evaluate the impact of bubble defects on the interfacial bonding properties of the self-compacting concrete filling layer
Authors: Jiang Wei , Xie Youjun , Ni Yi-Qing , Wang Su-Mei , Fu Qiang , Liu He , Li Ning , Li Wenxu , Long Guangcheng
Published: February 2025

The current technical standards primarily relied on experience to judge the interfacial bonding properties between the self-compacting concrete filling layer and the steam-cured concrete precast slab in CRTS III slab ballastless track structure. This study sought to enhance technical standards for evaluating interfacial bonding properties by suggesting the use of the splitting tensile strength to evaluate the impact of bubble defects. Specimens were fabricated through on-site experiment. The percent of each area of 6 cm2 or more bubble defect was 0 in most of specimens. When the cumulative area of all bubble defects reached 12%, the splitting tensile strength value was 0.67 MPa, which exceeded the minimum required value of 0.5 MPa for ensuring bonding interface adhesion. Furthermore, when the cumulative area of all bubble defects reached 8%, the splitting tensile strength value was 0.85 MPa, which exceeded the minimum required value of 0.8 MPa, thereby overcoming the negative impact of each area of 10 cm2 or more bubble defect. Additionally, keeping the cumulative area of each area of 6 cm2 or more bubble defect below 6% ensured adequate bonding strength and reduced the occurrence of specimens with lower splitting tensile strength values.
Sleep Across the Lifespan: A Neurobehavioral Perspective
Authors: Simon Katharine C. , Cadle Chelsea , Shuster Alessandra E. , Malerba Paola
Published: February 2025

Purpose of Review

Sleep is dynamic across the lifespan, influenced by brain maturation, neurophysiology, hormones, and cognitive processes. Sleep behaviors influenced by physiological and external factors can also impact sleep health. As sleep plays a mechanistic role in health across the lifespan, understanding when and how to intervene to benefit health is essential.

Recent Findings

Recent research has advanced our understanding of sleep across three domains: patterns, neurophysiology, and behaviors. Highlights include (1) Early childhood nap cessation is thought to relate to medial temporal lobe network maturation and underlie long-term hippocampal-dependent memory development. (2) Chronotype misalignment is a key factor in sleep deficits and social jetlag. (3) Older adult daytime sleep has complex effects on health, at times beneficial while others, potentially maladaptive. (4) Longitudinal sleep oscillation trajectories are starting to be investigated and indicate neurophysiology could be interpreted as indicative of brain maturation in development. (5) In adults, sleep quality and macrostructure trajectories show high variability, emphasizing distinctive traits in shaping sleep and its lifespan trajectories. (6) Neighborhood and socioeconomic factors influence sleep health across all ages. (7) In older adults, associations between loneliness and poor sleep are being unpacked.

This recent research, while comprehensively describing our current understanding of sleep trajectories across the lifespan, emphasizes the need to expand current approaches to longitudinal measurement studies that cross age-spans. Expanding will enhance our ability to mechanistically determine the temporal and causal relations between the multiple dimensions of sleep (i.e., patterns, behaviors, and physiology) and outcomes in sleep health.
Laparoscopic-assisted colostomy with anorectal malformation: friend or foe?
Authors: Barros Ana Isabel , Correia Mário Rui , Cagigal Jorge , Carvalho Fátima , Carvalho Catarina
Published: February 2025

Purpose

The standard management of anorectal malformations (ARM) without perineal fistula involves fecal diversion via a sigmoid colostomy. This report aims to describe our initial experience and evaluate the feasibility and benefits of laparoscopically-assisted loop colostomy in a neonate with ARM without perineal fistula, addressing the question of whether this minimally invasive approach offers advantages over traditional open techniques.

Methods

We report the case of a full-term male newborn with an imperforate anus. A laparoscopic-assisted loop colostomy was performed on the second day of life. Three trocars were used: a 5 mm umbilical port for the laparoscope and two 3 mm ports on the flanks. The surgical technique, including trocar placement, bowel mobilization, stoma creation, and closure, is described. The postoperative course and long-term outcomes were monitored over 17 months, including subsequent anorectoplasty and stoma closure.

Results

The laparoscopic approach provided superior visualization of pelvic anatomy, enabling accurate identification of the fistula and optimal stoma placement. Postoperatively, the patient exhibited early stoma function, rapid recovery, and no complications such as urinary tract infections or stomal issues. Follow-up procedures, including anorectoplasty and colostomy closure, were performed without incident. The patient remains healthy and complication-free at 17 months of age

Conclusion

Laparoscopic-assisted colostomy offers distinct advantages over the open technique, including reduced complications, improved recovery, and favorable cosmetic outcomes. This minimally invasive method represents a promising alternative for ARM management, aligning with modern pediatric surgical advancements.
Tandem-repeat modules in phytopathogenic effectors driver their evolution and diversification
Authors: Li Hui
Published: February 2025

Plant pathogens deliver effector proteins into both the host apoplast and host cells. These effectors function to colonize the host typically by altering host physiology or by subverting plant immune responses. The host plants have evolved intracellular nucleotide-binding site leucine-rich repeat (NBS-LRR) immunoreceptors that directly or indirectly recognize specific effector(s) to trigger plant immunity that prevents colonization. To circumvent effector-triggered immunity, adapted pathogens rely on constantly effectors evolution to further enhance susceptible host colonization. During the past few years, evidence has arisen that many effectors containing tandem repeat modules are particularly prone to rapid evolution through module insertion/deletion/shuffling, point mutations or adoption of other function domains. In this review, we highlight the diverse function of two modular effectors: TAL effectors in prokaryotic bacteria, (L) WY effectors in eukaryotic oomycetes, focus on new insights and the potential role of modularity in effector evolution, and discuss avenues for future research.
Improving ice plant efficiency with Al2O3 nanoparticles and evaporative cooling techniques
Authors: Aher Nitin S. , Gurnani Umesh , Dhamande Laxmikant S. , Bornare Rakhi , Hamilton Anurag
Published: February 2025

This study focuses on reducing energy consumption in vapor compression refrigeration-based ice plants by incorporating nanoparticle in secondary refrigerants and evaporative cooling technique. Experimental evaluations were performed on a test rig using brine and ethylene glycol as secondary refrigerants. Results showed that brine outperformed glycol, reducing ice formation time by 15% when combined with evaporative cooling. Further enhancement was achieved by incorporating Al2O3 nanoparticles into the brine, which, combined with direct evaporative cooling, reduced ice formation time by 20% compared to glycol. The improved system demonstrated significant performance gains, lowering energy costs and enhancing the Coefficient of Performance (COP).
Towards an EU Charter of Digital Patients’ Rights in the Age of Artificial Intelligence
Authors: van Kolfschooten Hannah
Published: February 2025

The rapid advancement of digital health innovation, including Artificial Intelligence (AI), is transforming healthcare. The growing role the European Union (EU) plays in regulating the use of AI in healthcare renders national laws insufficient to safeguard patients from unique AI-related risks. This underscores the urgent need for the recognition of a canon of patients’ rights in the scope of EU law. This paper proposes the blueprint for an EU Charter for Digital Patients’ Rights, consolidating and adapting existing rights for patients to address these specific challenges. Traditional patients’ rights such as the right to privacy and the right to informed consent are interpreted in light of the challenges posed by AI. It also proposes novel rights for patients, such as the right not to be subject to automated medical decision-making and the right to meaningful human contact. This paper highlights the EU’s central role in protecting patients’ rights and outlines strategies for effective implementation. This comprehensive approach aims to address the current shortcomings and enhance the legal framework governing digital health in Europe.
Implications of plastic pollution on global carbon cycle
Authors: Yao Lifen , Zhao Shaoyan , Tremblay Louis A. , Wang Weiping , LeBlanc Gerald A. , AN Lihui
Published: February 2025

Plastic pollution represents a critical global issue. Massive plastic waste in the environment poses significant threats to ecosystems and human health while also negatively impacting carbon cycles through multiple pathways. In particular, the global carbon cycle is disrupted by the carbon budget imbalance, primarily due to the excessive production of fossil-based plastics in past years. Meanwhile, microplastics and nanoplastics resulting from the degradation and fragmentation of plastic waste in the environment also have significant implications for the carbon cycle within both terrestrial and aquatic ecosystems. Furthermore, the leaching of plastic additives from plastics not only contributes organic carbon to the environment but also poses significant adverse effects on the growth and development of various organisms. Therefore, developing innovative and comprehensive strategies to mitigate plastic pollution is imperative. This initiative should involve the development of effective policies and the application of advanced technologies, including strategies to close both the plastic loop and the carbon loop.

Graphical Abstract
Geometrization of the Satake transform for mod p Hecke algebras
Authors: Cass Robert , Xu Yujie
Published: February 2025

We geometrize the mod p Satake isomorphism of Herzig and Henniart–Vignéras using Witt vector affine flag varieties for reductive groups in mixed characteristic. We deduce this as a special case of a formula, stated in terms of the geometry of generalized Mirković–Vilonen cycles, for the Satake transform of an arbitrary parahoric mod p Hecke algebra with respect to an arbitrary Levi subgroup. Moreover, we prove an explicit formula for the convolution product in an arbitrary parahoric mod p Hecke algebra. Our methods involve the constant term functors inspired from the geometric Langlands program, and we also treat the case of reductive groups in equal characteristic. We expect this to be a first step toward a geometrization of a mod p Local Langlands Correspondence.
Relationship between nutrition knowledge and nutritional adequacy in Japanese university students: a cross-sectional study
Authors: Yanagihara Yatsuki , Narumi-Hyakutake Aiko
Published: February 2025

The aim of this study was to examine the relationship between nutrition knowledge and nutritional adequacy among Japanese university students. This cross-sectional study was conducted in 2018 at a university located in Hyogo Prefecture, Kobe, Japan, and 801 students from various academic disciplines were enrolled. Eligible participants were students aged more than 18 years, encompassing all years of study. Nutrition knowledge data were obtained using a nutrition knowledge questionnaire (NKQ) for Japanese adults. Participants were classified into three nutrition knowledge groups according to their total NKQ scores [mean ± standard deviation; all (64.7 ± 15.4%), low (48.1 ± 13.8%), medium (68.3 ± 2.8%), and high (78.5 ± 4.2%)]. Participants reported their dietary habits in the preceding month using a brief self-administered diet history questionnaire. Differences in nutritional adequacy among groups were determined using logistic regression and covariance analyses, adjusted for potential confounding factors. The adequacy of each nutrient was quantified as the proportion of participants with nutrient intake that fell outside the reference range. Although the intakes of only a few nutrients and foods were associated with nutrition knowledge, the total number of nutrients below the estimated average requirement was lower in the high nutrition knowledge group (3.1 ± 2.7) than in the low nutrition knowledge group (3.6 ± 2.9) (P = 0.046). In conclusion, the nutrition knowledge level of Japanese university students is associated with nutritional adequacy but may partially affect eating habits. Future longitudinal studies must clarify the causal and dose-response relationships between nutrition knowledge and dietary habits.
The poet Ulrich von Hutten (1488–1523) and the French disease: the records and human remains of a probable yaws patient
Authors: Gantenbein Urs Leo
Published: February 2025

Ulrich von Hutten (1488–1523), a renowned sixteenth-century German humanist, documented the symptoms of the epidemic that swept through Europe starting around 1495, commonly known as the French Disease. While it has traditionally been associated with venereal syphilis, Dutch tropical physician Willem F. R. Essed proposed in 1933, largely unnoticed to this day, that this new disease might instead be tropical yaws. This study establishes a clear link between Hutten’s reported symptoms and yaws, especially in its secondary and tertiary stages. The skeleton discovered in 1968 on Ufnau Island in Lake Zurich where Hutten died and was buried, exhibits distinct bone manifestations of ancient treponematosis with a pattern more consistent with yaws than syphilis. Furthermore, the correspondence between Hutten’s main symptoms and the lesions observable on the 1968 skeleton further confirms the identification of these human remains. The historical evidence of yaws significantly contributes to our understanding of this early modern epidemic.
Translating data into policy informing decisions: current and future perspectives from the European Food Safety Authority (EFSA)
Authors: Anastassiadou Maria , Devos Yann , Dujardin Bruno , Eskes Chantra , Kouloura Eirini , López-Gálvez Gloria , Rizzi Valentina , Gilsenan Mary B.
Published: February 2025

The European Food Safety Authority (EFSA) provides independent scientific advice to EU risk managers on a wide range of food safety issues and communicates on existing and emerging risks in the food chain. This advice helps to protect consumers, animals and the environment. Data are essential to EFSA’s scientific assessments. EFSA collects data from various sources including scientific literature, biological and chemical monitoring programmes, as well as food consumption and composition databases. EFSA also assesses data from authorisation dossiers for regulated products submitted by industry. To continue delivering the highest value for society, EFSA keeps abreast of new scientific, technological and societal developments. EFSA also engages in partnerships as an essential means to address the growing complexity in science and society, and to better connect and integrate knowledge, data and expertise across sectors. This paper provides insights into EFSA’s data related activities and future perspectives in the following key areas of EFSA’s 2027 strategy: one substance-one assessment, combined exposure to multiple chemicals, environmental risk assessment, new approach methodologies, antimicrobial resistance and risk-benefit assessment. EFSA’s initiatives to integrate societal insights in its risk communication are also described.
Intermittent theta-burst stimulation with adjunctive D-cycloserine rapidly resolves suicidal ideation and decreases implicit association with death/suicide
Authors: Sohn Myren N. , Cole Jaeden , Bray Signe L. , McGirr Alexander
Published: February 2025

Background

Depressive disorders are the most common diagnosis among individuals who die by suicide, and intermittent theta-burst stimulation (iTBS) is a noninvasive treatment for those with difficult-to-treat depression who are at higher risk for suicide. Previous data suggests that pairing iTBS with D-cycloserine, a partial N-methyl-D-aspartate (NMDA) receptor agonist, improves antidepressant outcomes. However, its impact on suicide risk is not known.

Methods

We examine suicidal ideation and implicit suicide risk after iTBS+D-cycloserine in two clinical trials (open-label trial [n = 12] and randomized placebo-controlled trial [RCT, n = 50]) involving adults with major depressive disorder and the acute effects of D-cycloserine on implicit suicide risk in a crossover trial (n = 18). Implicit suicide risk was assessed using the computerized death/suicide implicit association test (IAT), and depressive symptoms and suicidal ideation were assessed using the clinician-rated Montgomery–Asberg Depression Rating Scale (MADRS).

Results

Open-label iTBS+D-cycloserine was associated with a rapid reduction in suicidal ideation, and iTBS+D-cycloserine was superior to iTBS+placebo in reducing suicidal ideation. Similarly, open-label iTBS+D-cycloserine was associated with decreased implicit suicide risk as measured by the death/suicide IAT, and iTBS+D-cycloserine was associated with greater decreases in death/suicide IAT scores compared to iTBS+placebo. A single acute dose of D-cycloserine in the absence of iTBS had no effect on implicit suicide risk.

Conclusions

Adjunctive D-cycloserine with iTBS is a promising strategy to reduce suicidal ideation and implicit suicide risk in depression.
Effects of phonetic training and cognitive aptitude on the perception and production of non-native speech contrasts
Authors: Correia Susana , Rato Anabela , Ge Yuxin , Fernandes João Dinis , Kachlicka Magdalena , Saito Kazuya , Rebuschat Patrick
Published: February 2025

Research on second language (L2) speech learning suggests that incidental perception training can lead to the establishment of non-native phonological categories. The present study contributes to this line of enquiry by investigating how this training is mediated by individual differences in working memory capacity and domain-general auditory processing abilities. In our study, 130 native British English speakers without prior knowledge of Portuguese were randomly assigned to trained or untrained conditions. All participants completed a visual digit span task and an auditory processing test battery. We observed improvements from pretest to post-test in production only, but since both groups improved, these gains cannot be attributed to the incidental perception training. The analysis of the ID measures further confirms the important role played by auditory processing abilities in L2 speech learning. However, more research is needed to better understand the role of incidental perception training and the mediating role of cognitive aptitudes.
Evaluating the acceptability of a self-directed, self-management intervention for patients and caregivers facing advanced cancer
Authors: Wasserman Sydney , Ould Brahim Lydia , Laizner Andrea Maria , Mehta Anita , Côté José , Henry Melissa , Thibodeau Kimberly , Bitzas Vasiliki Bessy , Lambert Sylvie D.
Published: February 2025

Objectives

Coping-Together is a self-directed, self-management intervention initially developed for patients in early-stages of cancer and their caregivers. This study evaluated its acceptability among patients with advanced cancer and their caregivers.

Methods

Twenty-six participants (patients with advanced cancer n = 15 and their caregivers n = 11) were given the Coping-Together materials (6 booklets and a workbook) for 7 weeks. Participants were interviewed twice during this time to solicit feedback on the intervention’s content, design, and recommended changes. Audio-recorded interviews were transcribed verbatim, and thematic analysis was conducted.

Results

Participants found Coping-Together was mostly relevant. All (n = 26, 100%) participants expressed interest and a desire to improve their self-management skills. Perceived benefits included learning to develop SMARTTER (specific, measurable, attainable, relevant, timely, and done together) self-management plans, normalizing challenges, and enhancing communication within the dyad and with their healthcare team. Most (n = 25, 96%) identified strategies from the booklets that benefited them. Top strategies learned were skills to manage physical health (n = 20, 77%) (e.g., monitoring symptoms), emotional well-being (n = 21, 81%) (e.g., reducing stress by reframing thoughts), as well as social well-being (n = 24, 92%) (e.g., communicating with their healthcare team). Barriers included illness severity and time constraints. The unique advanced cancer needs that are to be integrated include support related to fear of death, uncertainty, palliative care and advanced care planning. Suggested modifications involved enhancing accessibility and including more advanced cancer information (e.g., end-of-life planning, comfort care, resources).

Significance of results

Participants reported several benefits from using Coping-Together, with minimal adaptations needed. Creating SMARTTER self-management plans helped them implement self-management strategies. Specific areas for improvement addressed the need for improved accessibility and more content related to advanced cancer. Findings demonstrate how Coping-Together is acceptable for those living with advanced cancer and their caregivers, offering much of the support needed to enhance day-to-day quality of life.
Study of low-profile near-field electromagnetic energy harvesting
Authors: Yadav Subash Chandra , Agrahari Rajan
Published: February 2025

In order to recover the magnetic energy that leaks from an induction cooktop, this study suggests a straightforward and cost-effective magnetic-field energy harvester (MFEH) circuit. With the aid of the intended circuitry, the acquired magnetic energy is transformed into DC electrical energy. We harvested the magnetic-field energy (MFE) from the induction cooktop at various heights and locations of the energy harvesting coil. With a load resister of 46.6 Ω and a capacitance of 1 mF, the developed MFEH circuit, when positioned 2 cm beneath the cooktop, can capture an average DC power of 1936 mW. Placing the energy-harvesting coil 7.5 cm beneath the induction cooktop lowers the power output to 142 mW. For a range of load resister values, the MFE gathered at various locations along the energy harvesting coils is examined. Batteries can be used to store the gathered energy for later use. Additionally, the suggested device is shown to be capable of wirelessly powering low-power Internet of things devices and charging mobile devices. The suggested device differs from the previously published magnetic harvesting circuits due to the induction cooktop’s superior performance and capacity to gather MFE.
Investigation of the Fresnel Scale From Ionospheric Scintillation Spectra
Authors: Song K. , Meziane K. , Hamza A. M. , Jayachandran P. T.
Published: February 2025

Trans‐ionospheric radio signals recorded on the ground exhibit random amplitude and phase fluctuations attributed to irregularities in the ionospheric electron density. Studying the ground‐based measurements of trans‐ionospheric radio signals can contribute to understanding plasma instability mechanisms leading to the development of ionospheric structures. In this regard, radio signals emitted from satellites, making up the Global Positioning System (GPS), and recorded by the Canadian High Arctic Ionospheric Network (CHAIN) GPS receivers, are analyzed to study the physical signatures of both amplitude and phase fluctuations. The current ionospheric scintillation paradigm posits that amplitude fluctuations arise from diffraction caused by Fresnel scale ionospheric structures, while refraction is responsible for signal phase variations. The amplitude power spectrum profile consistently displays a rollover frequency, which is not equal to the Fresnel frequency under the Taylor hypothesis. Phase screen theory is used to investigate this phenomenon further and identify an empirical relation between the rollover and Fresnel frequencies. Notably, we have found that the rollover frequency is consistently smaller than the Fresnel frequency. Furthermore, the Fresnel frequency extracted from two‐component phase spectra tends to be larger than the rollover frequency. Based on our results, we have concluded that the identified Fresnel frequencies are directly linked to the ionospheric irregularities causing scintillation.
Piercing the Martian Veil: A Statistical Study of Interplanetary Magnetic Field Reach Through Ionospheric Pressure Balance
Authors: Shaver S. R. , Andersson L. , Ramstad R. , Waghule Bhagyashree , Brain D. , Lillis R. , Cravens T. , Halekas J. , Xu S. , Hinton P. C. , Malaspina D. , Liemohn M. W. , Ledvina S. , Gruesbeck J. R. , Curry S.
Published: February 2025

Mars, being a small planet with a tenuous atmosphere, does not have a sharp boundary between regions dominated by solar wind plasma and planetary plasma. Instead, this transition is typically extended, allowing the interplanetary magnetic field (IMF) to penetrate into the Martian ionosphere. However, the depth of this penetration is not well understood. Using 6 years of MAVEN data, we statistically assess locations where a transition exists between the dominance of magnetic versus cold (1 eV), thermal plasma pressure to better understand the reach of the IMF. We identify the presence or absence of pressure transitions from 200 to 800 km altitude for each MAVEN orbit and find a clear transition in 55% of cases. The pressure transition locations are mapped in different coordinate systems that provide insight into the solar and planetary driving conditions that cause a detected transition region. Transitions are more likely to occur under weak‐to‐nominal solar wind conditions, away from strong crustal magnetic fields, near the terminator, on the dusk side of the planet compared to the dawn side, and in the negative solar wind motional electric field hemisphere. We speculate on possible causes for asymmetries that arise in the mapped locations of these pressure transitions and the effect that penetrated IMF may have on driving plasma dynamics in the Martian ionosphere.
Seasonal Wind Stress Direction Influences Source and Properties of Inflow to the Salish Sea and Columbia River Estuary
Authors: Brasseale Elizabeth , MacCready Parker
Published: February 2025

Estuaries in the northern California current system (NCCS) experience seasonally reversing wind stress, which is expected to impact the origin and properties of inflowing ocean water. Wind stress has been shown to affect the source of estuarine inflow by driving alongshelf currents. However, the effects of vertical transport by wind‐driven Ekman dynamics and other shelf and slope currents on inflow are yet to be explored. Variations in inflow to two NCCS estuarine systems, the Salish Sea and the Columbia River estuary, were studied using particle tracking in a hydrodynamic model. Particles were released in a grid extending two degrees of latitude north and south of each estuary every two weeks of 2017 and tracked for sixty days. Inflow was identified as particles that crossed the estuary mouths. Wind stress was compared with initial horizontal and vertical positions and physical properties of shelf inflow particles. Inflow to the Salish Sea came from Vancouver Island and Washington slope water upwelled through canyons during upwelling‐favorable wind stress, and from Washington slope water or Columbia River plume water during downwelling‐favorable wind stress. Inflow to the Columbia River estuary came from Washington shelf bottom water during upwelling‐favorable wind stress and Oregon shelf surface water during downwelling‐favorable wind stress. For both estuaries, upwelling‐favorable wind stress direction was significantly correlated with a denser and deeper shelf inflow source north of the estuary mouth. These results may help predict the source and properties of inflow to estuaries in other regions with known wind or shelf current patterns.
Improved Representations of Longwave Surface Emissivity to Reduce Surface and Atmospheric Heating Biases in Earth System Models
Authors: Manzo L. , Zender C. , Tolento J. , Whicker‐Clarke C. A.
Published: February 2025

Many Earth system models (ESMs) approximate surface emissivity as a broadband constant. This approximation reduces the computational burden, yet omits the spectral structure of emissivity and atmospheric absorption. Neglecting spectral variation in surface emission introduces biases in longwave (LW) atmospheric fluxes and heating. Biases are strongest over surfaces with strongly varying emissivity and minimal atmospheric opacity. We examine these biases over water, ice, and snow surfaces. We partition spectral emissivity into the 16 spectral bands utilized by a single‐column atmospheric radiative transfer model (RRTMG_LW) commonly used in ESMs. We quantify flux and heating biases introduced by broadband assumptions relative to the spectrally resolved case for standard atmospheric profiles over each surface type. Current assumptions tend to overestimate upwelling surface fluxes; for example, the greybody assumption overestimates flux by 1.6 W/m2 (0.52%) at the bottom of a mid‐latitude winter atmosphere over ice, and by 2.33  (1.0%) at the top of atmosphere. The blackbody assumption tends to artificially cool Earth's surface, stabilizing the lower troposphere. Interestingly, the optimal broadband emissivity can deviate from the Planck‐weighted mean by up to 3% depending on surface type and atmospheric profile. We investigate bias sensitivity to surface temperature, cloud water path, and atmospheric water vapor. Bias is most sensitive to water vapor content, and least sensitive to cloud water path. Lastly, we show that a modified greybody method with updated broadband values can reduce total surface flux bias up to 1.69 , comparable to a five‐band approach and at a fraction of the computational cost.
ELM‐Wet: Inclusion of a Wet‐Landunit With Sub‐Grid Representation of Eco‐Hydrological Patches and Hydrological Forcing Improves Methane Emission Estimations in the E3SM Land Model (ELM)
Authors: Yazbeck Theresia , Bohrer Gil , Scyphers Madeline E. , Missik Justine E. C. , Shchehlov Oleksandr , Ward Eric J. , Merino Sergio L. , Bordelon Robert , Taj Diana , Villa Jorge A. , Wrighton Kelly , Zhu Qing , Riley William J.
Published: February 2025

Wetlands are the largest emitters of biogenic methane (CH4) and represent the highest source of uncertainty in global CH4 budgets. Here, we aim to improve the realism of wetland representation in the U.S. Department of Energy's Exascale Earth System Model land surface model, ELM, thereby reducing uncertainty of CH4 flux predictions. We develop an updated version, ELM‐Wet, where we activate a separate landunit for wetlands that handles multiple wetland‐specific eco‐hydrological patch functional types. We introduce more realistic hydrological forcing through prescribing site‐level constraints on surface water elevation, which allows resolving different sustained inundation depth for different patches, and if data exists, prescribing inundation depth. We modified the calculation of aerenchyma transport diffusivity based on observed conductance per leaf area for different vegetation types. We use Bayesian Optimization to parameterize CO2 and CH4 fluxes in the developed wet‐landunit. Site‐level simulations of a coastal non‐tidal freshwater wetland in Louisiana were performed with the updated model. Eddy covariance observations of CO2 and CH4 fluxes from 2012 to 2013 were used to train the model and data from 2021 were used for validation. Patch‐specific chamber flux observations and observations of CH4 concentration profiles in the soil porewater from 2021 were used for evaluation of the model performance. Our results show that ELM‐Wet reduces the model's CH4 emission root mean squared error by up to 33% and is able to represent inter‐daily CO2 and CH4 flux variability across the wetland's eco‐hydrological patches, including during periods of extreme dry or wet conditions.
Targeting the splicing factor SNRPB inhibits endometrial cancer progression by retaining the POLD1 intron
Authors: Li Yingwei , Chen Zhongshao , Xiao Huimin , Liu Yanling , Zhao Chen , Yang Ning , Yuan Cunzhong , Yan Shi , Li Peng
Published: February 2025

Dysregulated alternative splicing has been closely linked to the initiation and progression of tumors. Nevertheless, the precise molecular mechanisms through which splicing factors regulate endometrial cancer progression are still not fully understood. This study demonstrated elevated expression of the splicing factor SNRPB in endometrial cancer samples. Furthermore, our findings indicate that high SNRPB expression is correlated with poor prognosis in patients with endometrial cancer. Functionally, SNRPB inhibition hindered the proliferative and metastatic capacities of endometrial cancer cells. Mechanistically, we revealed that SNRPB knockdown decreased POLD1 expression and that POLD1 intron 22 was retained after SNRPB silencing in endometrial cancer cells, as determined via RNA sequencing data analysis. The retained intron 22 of POLD1 created a premature termination codon, leading to the absence of amino acids 941–1,107 and the loss of the site of interaction with PCNA, which is essential for POLD1 enzyme activity. In addition, POLD1 depletion decreased the increase in the malignancy of endometrial cancer cells overexpressing SNRPB. Furthermore, miR-654-5p was found to bind directly to the 3′ untranslated region of SNRPB, resulting in SNRPB expression inhibition in endometrial cancer. Antisense oligonucleotide-mediated SNRPB inhibition led to a decrease in the growth capacity of a cell-derived xenograft model and a patient with endometrial cancer-derived xenograft model. Overall, SNRPB promotes the efficient splicing of POLD1 by regulating intron retention, ultimately contributing to high POLD1 expression in endometrial cancer. The oncogenic SNRPB–POLD1 axis is an interesting therapeutic target for endometrial cancer, and antisense oligonucleotide-mediated silencing of SNRPB may constitute a promising therapeutic approach for treating patients with endometrial cancer.
Phase 1 clinical trial of B-Cell Maturation Antigen (BCMA) NEX-T® Chimeric Antigen Receptor (CAR) T cell therapy CC-98633/BMS-986354 in participants with triple-class exposed multiple myeloma
Authors: Ravi Gayathri , Richard Shambavi , Kumar Shaji , Atrash Shebli , Liedtke Michaela , Kaur Gurbakhash , Derman Benjamin , Bergsagel P. Leif , Mailankody Sham , McCarthy Philip , Shrestha Alok , Kelly Lisa M. , Ly Thomas , Das Sharmila , Thorpe Jerill , Maier Alison , Varun Divya , Navarro Garnet , Burgess Michael R. , Hege Kristen , Koegel Ashley K. , Costa Luciano J.
Published: February 2025

BCMA-targeted CAR T-cells transformed the treatment of relapsed and refractory multiple myeloma (RRMM), yet improvements are needed in manufacturing, toxicity and efficacy. We conducted a phase 1 clinical trial of BMS-986354, an autologous BCMA CAR T manufactured using an optimized NEX-T® process, in participants with triple-class exposed, RRMM. The 65 participants had a median of 5 (range 3–13) prior regimens, 39% had cytogenetic high-risk, 91% triple-class refractory, and 43% extra-medullar disease. Part A (dose-escalation) of the study enrolled participants in cohorts receiving 20 (N = 7), 40 (N = 24), or 80 (N = 11)x 106 CAR + T-cells. In part B (expansion), an additional 23 participants were treated at the recommended phase 2 dose, 40 ×106 CAR + T cells. Across dose levels, cytokine release syndrome (CRS) occurred in 82% (2% grade ≥3), neurotoxicity in 8% (2% grade ≥3), and infections in 32% of participants (5% grade ≥ 3). The response rate was 95%, with 46% achieving complete responses. Median progression-free survival was 12.3 months (95% CI 11.3–16). Compared to orvacabtagene autoleucel (same CAR construct, conventional manufacturing), BMS-986354 had higher proportion of T central memory cells, were less differentiated and had enhanced potency and proliferative capacity, supporting the use of NEX-T® in future CAR T development.
Exploring BCL2 regulation and upstream signaling transduction in venetoclax resistance in multiple myeloma: potential avenues for therapeutic intervention
Authors: Fonseca Rodrigo , Zhu Yuan Xiao , Bruins Laura A. , Ahmann Joseph , de Bonolo Campos Cecilia , Braggio Esteban , Chen Xianfeng , Arribas Mariano , Darvish Susie , Welsh Seth , Meermeier Erin , Mangalaparthi Kiran K. , Kandasamy Richard K. , Ahmann Greg , Wiedmeier-Nutor J. Erin , Pandey Akhilesh , Chesi Marta , Bergsagel P. Leif , Fonseca Rafael
Published: February 2025

Investigating venetoclax (VTX) resistance in multiple myeloma (MM) is crucial for the development of novel therapeutic strategies to tackle resistance. We conducted a multi-omic characterization of established VTX-resistant isogenic human myeloma cell lines (HMCL) and primary MM patient samples pre- and post-VTX treatment. Transcriptomic and proteomic analysis revealed that resistance was largely associated with BCL-2 family protein dysregulation, including upregulation of anti-apoptotic proteins such as MCL-1, BCL-XL, BCL-2, and downregulation of pro-apoptotic members. Notably, the re-introduction of BIM into resistant cells restored VTX sensitivity and synergized with MCL-1 inhibitors. Upstream signaling pathways, including growth factor receptor tyrosine kinase (RTK) and phosphoinositide-3-kinase (PI3K) were implicated in this dysregulation. Simultaneous inhibition of MCL-1, BCL-XL, and upstream PI3K, RTK (FGF, EGF, and IGF1) mediated signaling enhanced VTX sensitivity. Post-translational modifications of MCL-1, particularly its stabilization via acetylation and phosphorylation, were investigated, although their inhibition only marginally increased VTX sensitivity. Lastly, the inhibition of AURKA and mitochondrial respiration also improved VTX sensitivity in some resistant HMCLs. Our findings suggest that combining VTX with MCL-1 and BCL-XL inhibitors or PIK3/RTK inhibitors holds potential for overcoming resistance. The study illustrates the importance of understanding molecular determinants of resistance to develop tailored therapeutic strategies.
Cell-associated galectin 9 interacts with cytotoxic T cells confers resistance to tumor killing in nasopharyngeal carcinoma through autophagy activation
Authors: Kam Ngar-Woon , Lau Cho Yiu , Lau Jeffrey Yan Ho , Dai Xin , Liang Yusi , Lai Syrus Pak Hei , Chung Michael King Yung , Yu Valen Zhuoyou , Qiu Wenting , Yang Mengsu , Smith Corey , Khanna Rajiv , Ng Kwan Ming , Dai Wei , Che Chi Ming , Lee Victor Ho-Fun , Kwong Dora L. W.
Published: February 2025

Immune effector cells, including cytotoxic T lymphocytes (CTLs) play essential roles in eliminating cancer cells. However, their functionality is often compromised, even when they infiltrate the tumor microenvironment (TME) or are transferred to cancer patients adoptively. In this study, we focused on galectin 9 (G9), an inhibitory ligand that we observed to be predominately positioned on the plasma membrane and readily interacts with CD8 + CTL in the TME of nasopharyngeal carcinoma (NPC). We discovered that cell-cell contact between activated effector CTLs and target tumor cells (TarTC) with G9 overexpression led to cellular death defects. Despite the formation of CTL–TarTC conjugates, there is no impact on the cell number nor viability of CTL, and the release of cytolytic content and associated activity were not completely abrogated. Instead, this interaction promoted autophagy and restricted necrosis in the TarTC. Furthermore, reducing G9 expression in tumor cells enhanced the suppressive effect on tumor growth upon adoptive transfer of activated effector CTL. Additionally, inhibiting autophagy effectively controlled tumor growth in cases of G9 overexpression. Therefore, we highlight the contribution of G9 in facilitating the resistance of NPC to CTL-mediated killing by inducing a selection-cell death state in tumor cells, characterized by increased autophagy and decreased necrosis.
A Markov model assessing the cost-effectiveness of various anti-vascular endothelial growth factor drugs and panretinal photocoagulation for the treatment of proliferative diabetic retinopathy
Authors: Luckham Kirsty , Tebbs Hannah , Claxton Lindsay , Burgess Philip , Dinah Christiana , Lois Noemi , Mohiuddin Syed
Published: February 2025

Background

Proliferative diabetic retinopathy (PDR) may lead to vision loss and blindness. The cost-effectiveness of various anti-vascular endothelial growth factor (anti-VEGF) drugs and panretinal photocoagulation (PRP) was assessed to supplement the NICE guideline for treating PDR.

Methods

A Markov model including eight levels of visual acuity (ranged between >85 and ≤25 letters) was developed to compare the cost-effectiveness of ranibizumab, aflibercept and bevacizumab with PRP (alone or in combination). Clinical inputs in the model were based on literature, while a published network meta-analysis (NMA) informed visual outcomes. Costs were estimated from a UK NHS perspective.

Results

Assuming initial treatment effects from the NMA continued to be applied for the remainder of lifetime, the probabilistic analysis resulted in bevacizumab plus PRP producing the highest net monetary benefit (NMB [95% CI]) of £221,374 [£203,941–£238,388] at £20,000 per quality-adjusted life-year. However, assuming initial treatment effects stabilised over time resulted in PRP alone producing the highest NMB of £223,416 [£209,318–£236,866]. Results were associated with large uncertainty due to wide confidence intervals around vision-based treatment effects of anti-VEGFs versus PRP, particularly for bevacizumab as data were drawn from trials with small sample size and high risk of bias. Using confidential prices for aflibercept and ranibizumab did not change the overall findings.

Conclusions

PRP is likely to be more cost-effective than anti-VEGFs for PDR. However, the results should be interpreted with caution given the scarcity of long-term visual outcomes with anti-VEGFs in this population. Further research on long-term visual outcomes may resolve these uncertainties.
Developing mRNA lipid nanoparticle vaccine effective for cryptococcosis in a murine model
Authors: Li Yeqi , Ambati Suresh , Meagher Richard B. , Lin Xiaorong
Published: February 2025

Cryptococcus neoformans is considered a critical fungal pathogen by the World Health Organization and developing a vaccine for cryptococcosis is a top priority. Here, we employed mRNAs encoding an antigen(s) packaged in lipid nanoparticles (LNPs) to develop vaccines for cryptococcosis. Remarkably, when coupled with capsule adjuvant, vaccination with CDA1-LNPs protected the vast majority of mice from the otherwise lethal cryptococcosis. These results support the promise of mRNA-LNP vaccines against fungal diseases.
A comprehensive spatio-cellular map of the human hypothalamus
Authors: Tadross John A. , Steuernagel Lukas , Dowsett Georgina K. C. , Kentistou Katherine A. , Lundh Sofia , Porniece Marta , Klemm Paul , Rainbow Kara , Hvid Henning , Kania Katarzyna , Polex-Wolf Joseph , Knudsen Lotte Bjerre , Pyke Charles , Perry John R. B. , Lam Brian Y. H. , Brüning Jens C. , Yeo Giles S. H.
Published: February 2025

The hypothalamus is a brain region that plays a key role in coordinating fundamental biological functions1. However, our understanding of the underlying cellular components and neurocircuitries have, until recently, emerged primarily from rodent studies2,3. Here we combine single-nucleus sequencing of 433,369 human hypothalamic cells with spatial transcriptomics, generating a comprehensive spatio-cellular transcriptional map of the hypothalamus, the ‘HYPOMAP’. Although conservation of neuronal cell types between humans and mice, as based on transcriptomic identity, is generally high, there are notable exceptions. Specifically, there are significant disparities in the identity of pro-opiomelanocortin neurons and in the expression levels of G-protein-coupled receptors between the two species that carry direct implications for currently approved obesity treatments. Out of the 452 hypothalamic cell types, we find that 291 neuronal clusters are significantly enriched for expression of body mass index (BMI) genome-wide association study genes. This enrichment is driven by 426 ‘effector’ genes. Rare deleterious variants in six of these (MC4R, PCSK1, POMC, CALCR, BSN and CORO1A) associate with BMI at population level, and CORO1A has not been linked previously to BMI. Thus, HYPOMAP provides a detailed atlas of the human hypothalamus in a spatial context and serves as an important resource to identify new druggable targets for treating a wide range of conditions, including reproductive, circadian and metabolic disorders.