bluuebunny/crossref_metadata_2025 huggingface dataset:
Transplant Patients’ Perceptions About Participating in First‐in‐Human Pig Kidney Xenotransplant Clinical Trials: A Mixed Methods Study
Authors: Gordon Elisa J. , Maschke Karen J. , Gacki‐Smith Jessica , Brooks Hannah L. , Matthews Margaret M. , Traboulsi Karen , Manning Dahlya , Leventhal Joseph , Gusmano Michael K.
Published: February 2025

First‐in‐human pig xenotransplant clinical trials may soon begin, which raises ethical concerns about patients’ decision‐making to participate in such trials. We assessed kidney transplant candidates’ attitudes and hypothetical decision‐making about participating in xenotransplant trials through semi‐structured telephone interviews and an online survey. We analyzed qualitative data by thematic analysis and quantitative data by descriptive statistics. Twenty‐eight patients participated in interviews; 142 patients participated in the survey. Most interview and survey respondents were male (68%, 56%), White (54%, 61%), or Black (36%, 22%). Although interview participants appreciated xenotransplantation research's potential to advance science, they expressed concerns about infection transmission and graft function. Few survey respondents were willing to participate in a pig kidney trial to test the safety of pig kidneys (12.6%) or pig kidney function (16.9%). Interview participants would be more likely to participate in a first‐in‐human pig kidney trial if receiving a human kidney was unlikely and their health status declined. Willingness would also depend on how long the pig kidney would function. Most interview participants were receptive to long‐term monitoring, but not to family monitoring. Transplant programs planning xenotransplant trials should anticipate these types of concerns for optimizing human subject protections and conducting a robust informed consent process.
A Brief Review on the Tribological Effects of Electrically Induced Bearing Damage
Authors: Notay Rai Singh
Published: February 2025

Over the past two decades, the phenomenon of electrical stray currents in bearings has garnered significant attention from researchers and industry professionals. With the widespread adoption of electric motors and generators in applications like electric vehicles and sustainable energy sources, understanding and mitigating the potential bearing damage caused by these currents has become paramount. This paper provides a concise review of the sources of electrical bearing damage, failure modes, and their implications for critical tribological factors such as bearing life and lubrication. Special emphasis is placed on the challenges posed by elastohydrodynamic lubrication in the presence of electrical potential and the impact on durability, highlighting the need for further research. The paper concludes by emphasizing the importance of collaboration among original equipment manufacturers (OEMs), tier suppliers, lubrication additive companies, and academic institutions in advancing our understanding and effectively addressing electrically induced bearing damage. By exploring this complex topic, this paper aims to contribute to the broader scientific knowledge base and inspire future investigations in this field.
The Influence of Non-Gaussian Surface Topography and Contact Models on Mixed-Lubrication Parameters for Water-Lubricated Journal Bearings
Authors: Prajapati Deepak K. , Bjorling Marcus , Katiyar Jitendra Kumar
Published: February 2025

Greenwood and Williamson (GW) and Greenwood and Tripp (GT) elastic contact models have extensively been used previously for the mixed-lubrication analysis of water-lubricated journal bearings (WLJBs). The approximate expressions of a parabolic cylinder function involved in these contact models are available in the literature which makes these models easy to implement in the mixed-lubrication analysis. However, approximate expressions available so far are valid only for the Gaussian distribution of asperity heights. Moreover, elastic-plastic contact models with few exceptions have rarely been used in the mixed-lubrication analysis of WLJBs. The present work demonstrates a simple numerical procedure to predict the mixed-lubrication parameters for WLJBs. The average Reynolds equation considering non-Gaussian flow factors is solved along with film thickness and load balance equations in a coupled manner. A routine is developed to predict the pressure curve (a plot between average asperity pressure and rigid body displacement) for different contact models and non-Gaussian surface topography, and the asperity pressure for a particular surface topography is predicted utilizing the concept of a macro-micro approach. The effect of non-Gaussian surface topography on the tribological performance of WLJBs is discussed in detail. The influence of different contact models on the performance of WLJBs is also presented. It is shown that the GT elastic contact model fails to simulate the effect of kurtosis and skewness properly. However, the Kogut and Etsion (KE) elastic-plastic contact model which is based on finite element method (FEM)-based analysis excellently simulates the non-Gaussian effect on the performance of the WLJB.
A Combined Approach of Melt Pool Ultrasonic Vibration and Interpass Laser Remelting for Achieving Superior Mechanical Properties by Controlling Microstructure and Phases in L-DED of Inconel 625
Authors: Kumar Prabhat , Rao Shubham , Gollapudi Srikant , Bartarya Gaurav , Muvvala Gopinath , Mullick Suvradip
Published: February 2025

Laser direct energy deposition (DED) is an additive manufacturing technique used in aerospace, automotive, and nuclear industries. However, challenges such as porosity, cracks, microstructural inhomogeneity, and elemental segregation usually affect the mechanical properties of fabricated components. This study proposes the synergistic application of ultrasonic vibration and interpass laser remelting in DED of Inconel 625 to effectively address these issues. Ultrasonic vibration to the melt pool results in equiaxed structures and reduces micropores by inducing acoustic streaming and cavitation effects, whereas interpass laser remelting selectively melts the previously deposited layers and reduces porosity. Both techniques influence the formation and distribution of intermetallic within the deposition. A synergistic application of these methods led to minimal porosity and equiaxed grains with thinner grain boundaries. Phase analysis revealed the significant presence of similar intermetallic compounds in as-deposited and vibration-assisted samples, with (γ′) phase appearing specifically in remelted and combined techniques. Further, intermetallic compounds, which were randomly distributed in as-deposited and remelted conditions, were found predominantly near the grain boundaries when vibration was applied alone or with remelting, resulting in better mechanical properties. The synergistic effect led to ∼20% increase in microhardness, ∼75% reduction in wear-rate, ∼32% higher ultimate tensile strength, and ∼25% increase in strain, and it also significantly enhanced corrosion resistance compared to as-deposited samples. This study underscores the potential of using ultrasonic vibration and interpass remelting synergistically to enhance the overall performance of DED-fabricated Inconel 625 components, outperforming their individual effects.
A Numerical Study on the Buckling of Near-Perfect Spherical Shells
Authors: Ubamanyu Uba K. , Baizhikova Zheren , Le Jia-Liang , Ballarini Roberto , Reis Pedro M.
Published: February 2025

We present the results from a numerical investigation using the finite element method to study the buckling strength of near-perfect spherical shells containing a single, localized, Gaussian-dimple defect whose profile is systematically varied toward the limit of vanishing amplitude. In this limit, our simulations reveal distinct buckling behaviors for hemispheres, full spheres, and partial spherical caps. Hemispherical shells exhibit boundary-dominated buckling modes, resulting in a knockdown factor of 0.8. By contrast, full spherical shells display localized buckling at their pole with knockdown factors near unity. Furthermore, for partial spherical shells, we observed a transition from boundary modes to these localized buckling modes as a function of the cap angle. We characterize these behaviors by systematically examining the effects of the discretization level, solver parameters, and radius-to-thickness ratio on knockdown factors. Specifically, we identify the conditions under which knockdown factors converge across shell configurations. Our findings highlight the critical importance of carefully controlled numerical parameters in shell-buckling simulations in the near-perfect limit, demonstrating how precise choices in discretization and solver parameters are essential for accurately predicting the distinct buckling modes across different shell geometries.
Enhanced underwater three-dimensional imaging using acoustic orbital angular momentum waves and mode matching beamforming
Authors: Jia Yanqing , Hu Qing , Li Shengquan
Published: February 2025

Improving the underwater three-dimensional imaging resolution of a sonar system is of great significance to achieving high-precision ocean exploration results. Actually, improving the resolution can be considered from the perspective of information acquisition. The acoustic orbital angular momentum (AOAM) wave has a modal dimension and can carry more target information. However, there are few studies on the application of AOAM waves for underwater three-dimensional imaging. This paper establishes the related signal models of the AOAM wave in underwater imaging and examines the sound field characteristics from both simulation and underwater real test data. A method called mode matching beamforming (MMBF) is proposed, and a composite structure of uniform circular array (UCA) plus spiral array is combined to study the imaging performance of AOAM waves and plane waves. The simulation results indicate that, compared with the plane wave, the sidelobe in the AOAM wave imaging beam pattern reaches −22.43 and −29.10 dB in the azimuth and elevation angles, respectively, and the mainlobe widths are reduced by 1.70° and 0.40° in both directions. Finally, this paper uses the MMBF method to process the echo data of underwater real object and realizes the imaging of the corner reflector.
Repetitive Feeding-Challenge With Different Nutritional Densities on Markers of Gastrointestinal Function, Substrate Oxidation, and Endurance Exercise Performance
Authors: Martinez Isabel G. , Biesiekierski Jessica R. , Rauch Christopher E. , Costa Ricardo J.S.
Published: February 2025

Gut-training has been shown to improve gastrointestinal tolerance, circulatory glucose availability, and exercise performance. The study aimed to investigate the effects of a repetitive feeding-challenge using fat versus carbohydrate (CHO) on markers of gastrointestinal function, glucose availability, and subsequent performance when challenged with a high-CHO load (87 g/hr) during exercise. Forty-four endurance athletes (mean ± SD [9 females and 35 males]: body mass: 71.2 ± 9.2 kg, height: 173.6 ± 7.0 cm, : 55.0 ± 6.1 ml·kg−1·min−1) completed a preintervention gut-challenge trial (T1), involving a 2 hr run (60% ) while taking a CHO gel every 20 min (87 g/hr, 10% w/v), followed by a 1 hr self-paced distance test with ad libitum water. Participants were then randomized to a fat (fat feeding-challenge [FFC]; 20 g nut butter, 124 kcal, 11 g fat, 3 g protein, and 3 g CHO) or CHO supplement (CHO feeding-challenge [CFC]; 47 g CHO gel: 123 kcal, 29 g CHO) group to complete a 7-day repetitive feeding-challenge (1 hr exercise and supplement intake every 20 min with 290 ml water), followed by a gut-challenge retrial (T2). FFC did not differ from CFC in terms of resting orocecal transit time, feeding tolerance, or substrate oxidation during T1 and T2. Peak breath hydrogen was lower in FFC than CFC (p = .028) at T2. Total (FFC: 27%, p = .005 vs. CFC: 38%, p = .001) and upper gastrointestinal symptoms severity (FFC: 26%, p = .013 vs. CFC: 40%, p < .001) during exercise was reduced similarly between groups from T1 to T2. FFC covered more distance in T2 (11.51 ± 2.02 vs. 11.08 ± 2.02 km, p = .013), but not significantly different to CFC (p = .341). A repetitive feeding-challenge with fat does not enhance nor worsen gastrointestinal and fueling outcomes compared with a CHO repetitive feeding-challenge.
Fitness Profiles of Highly Trained Female Futsal Players According to Their Playing Positions
Authors: Albalad-Aiguabella Rafael , Mainer-Pardos Elena , Roso-Moliner Alberto , Lozano Demetrio , Vicente-Rodríguez Germán , Muniz-Pardos Borja
Published: February 2025

Purpose: Although women’s futsal has experienced great growth recently, few studies have analyzed the physical profiles of female futsal players. The objectives of this study were to determine the physical and anthropometric characteristics in elite women’s futsal using laboratory and field tests and to analyze the differences between the different playing positions. Methods: Forty-one female futsal players from the second division of the Spanish league (age 22.69 [4.76] y; body height 161.28 [6.03] cm; body mass 62.20 [10.34] kg) were evaluated for body composition with dual-energy X-ray absortiometry anthropometrically, lower-body power using a force platform (countermovement jump, squat jump, and drop jump), linear speed (5, 10, 15, and 25 m), changes of direction (505 modified, V-Cut, and L-Run), and repeated-sprint ability measured through photoelectric cells. Results: The results reveal that there are no significant differences between the physical profiles of players depending on playing position. Despite this, wingers seem to have the best physical profiles, and goalkeepers have the highest body mass index (26.9 [4.48] vs 23.3 [2.82]; P = .069) and fat percentage (31.9 [7.81] vs 29.96 [6.08]; P = .101), but they present very similar values to the other positions in all other tests performed, except for repeated-sprint ability (4.64 [0.45]; P = .009). Conclusion: Relevant descriptive data were presented to provide useful information for coaches to optimize their training programs, reporting that playing position does not identify different physical profiles in elite female futsal players.
Is an Activity Wristband-Based Intermittent Teaching Unit in the Physical Education Setting Effective for Increasing High School Students’ Weekly Steps? School-Fit Study
Authors: Guijarro-Romero Santiago , Viciana Jesús , Casado-Robles Carolina , Mayorga-Vega Daniel
Published: February 2025

Purpose: To examine the effect of an activity wristband-based intermittent teaching unit (TU) combined with other behavior modification strategies in the physical education setting on high school students’ weekly steps. Method: Seventy-one high school students (49.3% girls) aged 12–16 years performed an 8-week intermittent TU (last 15 min of each session) twice a week. The TU consisted of the following strategies: activity wristband (24 hr), educational counseling, and progressive step goals, among others. Results: The students improved their weekly steps from Week 1 to Weeks 4–8 (p ≤ .001; d = 0.45–0.58). There was a higher percentage of students who did at least an average of 10,000 steps per day at Week 8 compared with Week 1 (p = .031; Cramer’s V = 0.246). Conclusion: The studied intermittent TU increased students’ weekly steps and the proportion of students who did at least an average of 10,000 steps per day.
Impact of Increasing Levels of Obesity on Functional Capacity and Cardiorespiratory Fitness in Children
Authors: Ahmed Youssef E. , Wadowski Jeremy , Dhuper Sarita
Published: February 2025

Purpose: This study aims to evaluate the impact of increasing severity of childhood obesity on cardiorespiratory fitness (CRF) using cardiopulmonary exercise testing. Methods: A retrospective analysis of cardiopulmonary exercise testing data from patients <21 years of age was performed. Patients were categorized by body mass index percentile into 4 classes. CRF was assessed and compared between groups by relative peak VO2 and metabolic equivalents achieved at limit of tolerance. Results: A total of 204 patients were included in the study. Significantly lower relative peak VO2 and metabolic equivalents and higher adjusted peak VO2 were achieved with increasing obesity. Resting and recovery heart rates (HRs) were significantly higher in Class III compared with the nonobese patients (P = .001 and .003, respectively). Class III patients had a significantly greater HR at anaerobic threshold relative to maximum HR achieved compared with the nonobese patients (P = .002). There was no significant difference between groups in the rating of perceived exertion at peak exercise, peak O2 pulse, or maximum HR achieved. Conclusion(s): Our study has shown that CRF worsens with increasing levels of obesity. Cardiopulmonary exercise testing can be used as an objective measure to assess CRF as a target for intervention in childhood obesity for pediatricians. Improvement in fitness is an achievable outcome, which also translates into improved cardiometabolic health.
The
Silene latifolia
genome and its giant Y chromosome
Authors: Moraga Carol , Branco Catarina , Rougemont Quentin , Jedlička Pavel , Mendoza-Galindo Eddy , Veltsos Paris , Hanique Melissa , Rodríguez de la Vega Ricardo C. , Tannier Eric , Liu Xiaodong , Lemaitre Claire , Fields Peter D. , Cruaud Corinne , Labadie Karine , Belser Caroline , Briolay Jerome , Santoni Sylvain , Cegan Radim , Linheiro Raquel , Adam Gabriele , El Filali Adil , Mossion Vinciane , Boualem Adnane , Tavares Raquel , Chebbi Amine , Cordaux Richard , Fruchard Cécile , Prentout Djivan , Velt Amandine , Spataro Bruno , Delmotte Stephane , Weingartner Laura , Toegelová Helena , Tulpová Zuzana , Cápal Petr , Šimková Hana , Štorchová Helena , Krüger Manuela , Abeyawardana Oushadee A. J. , Taylor Douglas R. , Olson Matthew S. , Sloan Daniel B. , Karrenberg Sophie , Delph Lynda F. , Charlesworth Deborah , Muyle Aline , Giraud Tatiana , Bendahmane Abdelhafid , Di Genova Alex , Madoui Mohammed-Amin , Hobza Roman , Marais Gabriel A. B.
Published: February 2025

In many species with sex chromosomes, the Y is a tiny chromosome. However, the dioecious plant
Silene latifolia
has a giant ~550-megabase Y chromosome, which has remained unsequenced so far. We used a long- and short-read hybrid approach to obtain a high-quality male genome. Comparative analysis of the sex chromosomes with their homologs in outgroups showed that the Y is highly rearranged and degenerated. Recombination suppression between X and Y extended in several steps and triggered a massive accumulation of repeats on the Y as well as in the nonrecombining pericentromeric region of the X, leading to giant sex chromosomes. Using sex phenotype mutants, we identified candidate sex-determining genes on the Y in locations consistent with their favoring recombination suppression events 11 and 5 million years ago.
Sequence-dependent activity and compartmentalization of foreign DNA in a eukaryotic nucleus
Authors: Meneu Léa , Chapard Christophe , Serizay Jacques , Westbrook Alex , Routhier Etienne , Ruault Myriam , Perrot Manon , Minakakis Alexandros , Girard Fabien , Bignaud Amaury , Even Antoine , Gourgues Géraldine , Libri Domenico , Lartigue Carole , Piazza Aurèle , Thierry Agnès , Taddei Angela , Beckouët Frédéric , Mozziconacci Julien , Koszul Romain
Published: February 2025

In eukaryotes, DNA-associated protein complexes coevolve with genomic sequences to orchestrate chromatin folding. We investigate the relationship between DNA sequence and the spontaneous loading and activity of chromatin components in the absence of coevolution. Using bacterial genomes integrated into
Saccharomyces cerevisiae
, which diverged from yeast more than 2 billion years ago, we show that nucleosomes, cohesins, and associated transcriptional machinery can lead to the formation of two different chromatin archetypes, one transcribed and the other silent, independently of heterochromatin formation. These two archetypes also form on eukaryotic exogenous sequences, depend on sequence composition, and can be predicted using neural networks trained on the native genome. They do not mix in the nucleus, leading to a bipartite nuclear compartmentalization, reminiscent of the organization of vertebrate nuclei.
Hidden cascades of seismic ice stream deformation
Authors: Fichtner Andreas , Hofstede Coen , Kennett Brian L. N. , Svensson Anders , Westhoff Julien , Walter Fabian , Ampuero Jean-Paul , Cook Eliza , Zigone Dimitri , Jansen Daniela , Eisen Olaf
Published: February 2025

Ice streams are major regulators of sea level change. However, standard viscous flow simulations of their evolution have limited predictive power owing to incomplete understanding of involved processes. On the Greenland ice sheet, borehole fiber-optic observations revealed a brittle deformation mode that is incompatible with viscous flow, over length scales similar to the resolution of modern ice sheet models: englacial ice quake cascades that are unobservable at the surface. Nucleating near volcanism-related impurities that promote grain boundary cracking, the ice quake cascades appear as a macroscopic form of crystal-scale wild plasticity. A conservative estimate indicates that seismic cascades are likely to produce strain rates that are comparable in amplitude with those measured geodetically, providing a plausible missing link between current ice sheet models and observations.
Supersaturation mutagenesis reveals adaptive rewiring of essential genes among malaria parasites
Authors: Oberstaller Jenna , Xu Shulin , Naskar Deboki , Zhang Min , Wang Chengqi , Gibbons Justin , Pires Camilla Valente , Mayho Matthew , Otto Thomas D. , Rayner Julian C. , Adams John H.
Published: February 2025

Malaria parasites are highly divergent from model eukaryotes. Large-scale genome engineering methods effective in model organisms are frequently inapplicable, and systematic studies of gene function are few. We generated more than 175,000 transposon insertions in the
Plasmodium knowlesi
genome, averaging an insertion every 138 base pairs, and used this “supersaturation” mutagenesis to score essentiality for 98% of genes. The density of mutations allowed mapping of putative essential domains within genes, providing a completely new level of genome annotation for any
Plasmodium
species. Although gene essentiality was largely conserved across
P. knowlesi
,
Plasmodium falciparum
, and rodent malaria model
Plasmodium berghei
, a large number of shared genes are differentially essential, revealing species-specific adaptations. Our results indicated that
Plasmodium
essential gene evolution was conditionally linked to adaptive rewiring of metabolic networks for different hosts.
Endothelial insulin resistance induced by adrenomedullin mediates obesity-associated diabetes
Authors: Cho Haaglim , Lai Chien-Cheng , Bonnavion Rémy , Alnouri Mohamad Wessam , Wang ShengPeng , Roquid Kenneth Anthony , Kawase Haruya , Campos Diana , Chen Min , Weinstein Lee S. , Martínez Alfredo , Looso Mario , Sanda Miloslav , Offermanns Stefan
Published: February 2025

Insulin resistance is a hallmark of obesity-associated type 2 diabetes. Insulin’s actions go beyond metabolic cells and also involve blood vessels, where insulin increases capillary blood flow and delivery of insulin and nutrients. We show that adrenomedullin, whose plasma levels are increased in obese humans and mice, inhibited insulin signaling in human endothelial cells through protein-tyrosine phosphatase 1B–mediated dephosphorylation of the insulin receptor. In obese mice lacking the endothelial adrenomedullin receptor, insulin-induced endothelial nitric oxide–synthase activation and skeletal muscle perfusion were increased. Treating mice with adrenomedullin mimicked the effect of obesity and induced endothelial and systemic insulin resistance. Endothelial loss or blockade of the adrenomedullin receptor improved obesity-induced insulin resistance. These findings identify a mechanism underlying obesity-induced systemic insulin resistance and suggest approaches to treat obesity-associated type 2 diabetes.
Probing the planet’s poles
Ends of the Earth: Journeys to the Polar Regions in Search of Life, the Cosmos, and Our Future
Neil Shubin
Dutton, 2025. 288 pp.
Authors: Boon Sarah
Published: February 2025

A paleontologist explores our intertwined fate with Earth’s most remote regions
The future of measles
Booster Shots: The Urgent Lessons of Measles and the Uncertain Future of Children’s Health
Adam Ratner
Avery, 2025. 288 pp.
Authors: Caplan Arthur
Published: February 2025

A pediatrician confronts the disease’s persistence in a world where eradication is possible
Relating DNA sequence, organization, and function
Authors: Fudenberg Geoffrey , Ramani Vijay
Published: February 2025

Cross-species mosaic genomes provide insight into synthetic chromosome design
Keeping our eye on the ball
Authors: May Willie E.
Published: February 2025

Unnerving. Concerning. Alarming. This is how many in the research community are describing the first weeks of the Trump administration.
In Other Journals
Authors: Simonti Corinne , Lavine Marc S. , Nusinovich Yevgeniya , Stern Peter , Uzogara Ekeoma , Jin Sumin , Yeston Jake S.
Published: February 2025

Editors’ selections from the current scientific literature
Trump orders cause chaos at science agencies
Authors: Mervis Jeffrey
Published: February 2025

Wild week of canceled meetings, program changes, and data purges creates high anxiety
New complexity emerges in Earth’s ‘boring’ middle region
Authors: Voosen Paul
Published: February 2025

Planetary CT scans and lab experiments reveal layering and intricate flows in the mantle
A new ‘mini-CRISPR’ flexes its editing power in monkey muscles
Authors: Couzin-Frankel Jennifer
Published: February 2025

The downsized DNA-slicing machinery may reach more tissues to take aim at more diseases
Pharmacokinetics and bioequivalence of a molnupiravir tablet formulation compared with the molnupiravir capsule formulation in healthy adult participants—a randomized, open-label, three-period, crossover study
Authors: Fiore Julie L. , Jin Yoon , Heimbach Tycho , Patel Shruti R. , Zhao Tian , Matthews Catherine Z. , Pagnussat Sandra , Maas Brian M. , Cheng Mickie H. , Stoch S. Aubrey
Published: February 2025

Molnupiravir, a prodrug of β-D-N
4
-hydroxycytidine (NHC), is administered orally as four 200 mg capsules twice daily for 5 days to treat COVID-19. This randomized, open-label, four-treatment sequence, three-period crossover study (NCT06615869) evaluated the bioequivalence of a new single 400 mg oral dose of the molnupiravir tablet Formulation 1 (F1) to a 400 mg oral dose of the currently authorized molnupiravir capsule formulation (administered as two 200 mg capsules) by comparing the plasma pharmacokinetics of NHC following administration to healthy participants. The effect of food on the plasma NHC pharmacokinetics following the administration of the molnupiravir F1 tablet, safety and tolerability of a single oral 400 mg dose of molnupiravir, and pharmacokinetics of a separate molnupiravir tablet Formulation 2 (F2) with a slower
in vitro
dissolution rate were also evaluated. The geometric mean ratio and 90% confidence intervals ([1 × 400-mg F1 tablet]/[2 × 200 mg reference capsules]) for plasma NHC area under the concentration-time curve (AUC) from time 0–infinity, AUC from time 0–last measurable time point, and maximum plasma concentration were 1.00 (0.97, 1.03), 1.00 (0.97, 1.03), and 0.98 (0.93, 1.03), respectively. All estimates were within prespecified limits (0.80, 1.25), demonstrating bioequivalence of the molnupiravir F1 tablet and reference capsules. Administration of the F1 tablet with a high-fat meal did not meaningfully impact the rate or extent of absorption. The pharmacokinetics of the F2 tablet were similar to the reference capsules. Administered in either formulation, molnupiravir was generally safe and well tolerated. In conclusion, a single 400 mg tablet of molnupiravir is bioequivalent to the reference capsule formulation in healthy adults.

CLINICAL TRIALS

This study was registered at ClinicalTrials.gov as
NCT06615869
.
Effects of Sup35 overexpression on the formation, morphology, and physiological functions of intracellular Sup35 assemblies
Authors: Feng Jianhui , Osmekhina Ekaterina , Timonen Jaakko V. I. , Linder Markus B.
Published: February 2025

The yeast prion protein Sup35 is aggregation-prone at high concentrations.
De novo
Sup35 prion formation occurs at a significantly increased rate after transient overexpression of Sup35 in the presence of another prion, [
PIN
+
], but it is still a rare event. Recent studies uncovered an additional and seemingly more prevalent role of Sup35: at its physiological level, it undergoes phase separation to form reversible condensates in response to transient stress. Stress-induced reversible Sup35 condensation in the [
psi
-
] strain enhances cellular fitness after stress ceases, whereas irreversible Sup35 aggregates in the [
PSI
+
] strain do not confer this advantage. However, how Sup35 overexpression, which could potentially lead to irreversible aggregation, affects its condensation under stress conditions remains unclear. In this study, we used a combinatorial method to examine how different levels of Sup35 overproduction and cellular conditions affect the nature, formation, and physical properties of Sup35 assemblies in yeast cells, as well as their impacts on cellular growth. We observed notable morphological distinctions between irreversible Sup35 aggregates and reversible Sup35 condensates, possibly indicating different formation mechanisms. In addition, Sup35 aggregation caused by a very high overexpression level can strongly inhibit cell growth, diminish the formation of stress-induced condensates when Sup35 is completely aggregated, and impair cellular recovery from stress. Together, this study advances our fundamental understanding of the physical properties and formation mechanism of different Sup35 assemblies and their impacts on cellular growth. We conclude that
in vivo
studies are sensitive to overexpression and can lead to assembly routes that strongly affect functions.

IMPORTANCE

The role of condensates in living cells is often studied by overexpression. For understanding their physiological role, this can be problematic. Overexpression can shift cellular functions, thereby changing the system under study, and overexpression can also affect the phase behavior of condensates by shifting the position of the system in the underlying phase diagram. Our detailed study of overexpression of Sup35 in
S. cerevisiae
shows the interplay between these factors and highlights basic features of intracellular condensation such as the balance between condensation and aggregation as well as how cellular localization and responsiveness depend on protein levels. We also apply super-resolution microscopy to highlight details within the cells.
Seneca Valley virus induces mitochondrial apoptosis by activating ER stress or the PERK pathway based on Ca
2+
transfer from ER to mitochondria
Authors: Hou Lei , Yang Xiaoyu , Liu Changzhe , Yu Ju , Wu Zhi , Wang Yong , Zeng Penghui , Guo Jinshuo , Shi Yongyan , Zhou Jianwei , Liu Jue
Published: February 2025

Seneca Valley virus (SVV), also known as Senecavirus A, a porcine pathogen that causes vesicular diseases, is prevalent in pig herds worldwide. SVV infection induces endoplasmic reticulum (ER) stress in PK-15 and BHK-21 cells, accompanied by activation of the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and activating transcription factor 6 (ATF6) pathways, which in turn facilitates SVV replication. ER stress is associated with the regulation of Ca
2+
homeostasis and mitochondrial apoptosis. However, the precise role of Ca
2+
in SVV-induced apoptosis remains unclear. In this study, western blotting, flow cytometry, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) detection revealed that either ER stress or the PERK pathway is involved in the apoptosis of SVV-infected cells treated with specific inhibitors. Furthermore, SVV-mediated ER stress markedly contributed to the transfer of Ca
2+
from the ER to mitochondria. The subsequent increase in mitochondrial Ca
2+
content was accompanied by an increased number of ER membranes near the mitochondria. Finally, the inhibition of mitochondrial Ca
2+
overload, ER stress, and the PERK pathway substantially attenuated SVV-mediated mitochondrial dysfunction, as evidenced by analyzing mitochondrial membrane potential (MMP), mitochondrial permeability transition poremPTP, reactive oxygen speciesROS, and adenosine 5′-triphosphate ATP, and the levels of mitochondrial apoptosis. These findings demonstrate that SVV induces mitochondrial apoptosis, which is dependent on ER stress-mediated transmission of Ca
2+
from the ER to the mitochondria.

IMPORTANCE

Viruses have developed multiple mechanisms to facilitate their proliferation or persistence through manipulating various organelles in cells. Seneca Valley virus (SVV), as a novel emerging pathogen associated with vesicular disease, is clinically and economically important infections that affect farm animals. Previously, we had confirmed that SVV-induced endoplasmic reticulum (ER) stress benefited for viral replication. Ca
2+
, as an intracellular signaling messenger mainly stored in the ER, is regulated by ER stress and then involved in apoptosis. However, the precise mechanism that Ca
2+
transfer induced by SVV infection triggered apoptosis remained unclear. Here, we found that SVV infection triggered the Ca
2+
transform from ER to mitochondria, resulting in mitochondrial dysfunction, and finally induced mitochondrial apoptosis. Our study shed light on a novel mechanism revealing how ER stress manipulates Ca
2+
homeostasis to induce mitochondrial apoptosis and regulate viral proliferation.
Genome sequences of
Klebsiella pneumoniae
bacteriophages SF_KL2 and SF_KL25
Authors: Lorenz Sophia , Abreu Gabriel , Oliveira Hugo
Published: February 2025

This report describes the genomes of
Klebsiella pneumoniae
phages SF_KL2 and SF_KL25, which infect the encapsulated multidrug-resistant
K. pneumoniae
known to cause nosocomial infections. SF_KL2 and SF_KL25 belong to the genus
Webervirus
(
siphovirus
morphotype) and have genomes of 48,737 and 49,170 bp, respectively. The phages were isolated from wastewater in northern Portugal.
Evaluation of the LDBio ICT IgG/IgM lateral flow assay versus the Bordier Elisa assay for the diagnosis of chronic pulmonary aspergillosis in Nigeria
Authors: Balogun O. J. , Oladele R. O. , Ajibola O. O. E. , Davies A. A. , Fashanu T. A. , Nwosu A. O. , Ekeng B. E. , Gangneux J. P.
Published: February 2025

The detection of anti-
Aspergillus
antibodies is key for diagnosing chronic pulmonary aspergillosis (CPA). Available techniques are limited and pose a considerable challenge in resource-limited settings. The objective of this study was to evaluate the performance of the point-of-care test LDBio ICT IgG/IgM lateral flow assay (LDBio) versus that of the Bordier Elisa assay in a field study in Nigeria. Of the 97 serum samples tested in the CPA patient group, 71 tested positive by the LDBio assay with 69.4% sensitivity. In the non-CPA group, 286 of the 289 sera tested negative by the LDBio assay with 98.7% specificity. The Bordier test was positive for 97 of the 97 CPA serum samples tested, showing 100% sensitivity, significantly different from the LDBio test in detecting
Aspergillus
antibodies (
P
< 0.0001). However, there was no significant difference in the specificity between the two tests (
P
= 0.617). The results were in agreement for 353 of the 386 samples tested (91.5%), with a Cohen’s kappa coefficient of 0.75, indicating substantial agreement between the LDBio and Bordier test results. The LDBio lateral flow assay (LFA) test is a simple and rapid point-of-care test that can be used in field studies in which the Elisa test is not available. The lower sensitivity of the LDBio LFA in our field study could have been due to
A. fumigatus
being the species involved in only 50%–60% of cases in Nigeria, with
A. flavus
being more frequent than in Northern countries.

IMPORTANCE

Available techniques for the detection of
Aspergillus
IgG are limited and pose a considerable challenge in resource-limited settings in terms of affordability, skilled personnel, equipment, and a regular power supply. A point-of-care test would address most of these challenges. The LDBio lateral flow assay (LFA) test is a simple and rapid point-of-care test that can be used in field studies in which the Elisa test is not available. When combined with clinical features, the LFA can be used as a screening tool for chronic pulmonary aspergillosis in settings such as ours; however, a lower sensitivity was observed compared to the Elisa.
UV radiation at 222, 254, and 282 nm inhibits sporulation and suppresses infectivity of
Eimeria acervulina
oocysts
Authors: Baumann Aaron A. , Myers Addison K. , Khajeh-Kazerooni Niloofar , Wise-Mitchell Ashley , Rosenthal Benjamin M. , Jenkins Mark C. , O'Brien Celia , Fuller Lorraine , Tremaine Samuel , Morgan Mark , Lenaghan Scott C.
Published: February 2025

Eimeria acervulina
is one of several apicomplexan parasites that can cause the economically important disease avian coccidiosis, which is transmitted
via
the fecal-oral route. It is also a valuable model for exploring interventions capable of reducing the public health risks posed by the related foodborne parasite
Cyclospora cayetanensis
. Unsporulated (noninfectious) oocysts are shed in the feces and sporulate in the environment to become infectious. In this study, the effect of UV radiation (UVR) on
E. acervulina
sporulation efficiency was evaluated. Nonstandard wavelengths including 222 and 282 nm have been established as alternatives to standard 254 nm UVR for sterilization. To address the disinfection capability of these nonstandard wavelengths,
E. acervulina
sporulation was scored following treatment under three wavelengths: 222, 254, or 282 nm. Each wavelength significantly (
P
< 0.05) reduced the sporulation rate relative to untreated controls, supporting the utility of nonstandard UVR treatments for coccidian inactivation. Furthermore, infectivity assays showed that chickens administered
E. acervulina
treated at each wavelength shed significantly fewer oocysts (
P
< 0.05) than those that received untreated oocysts, demonstrating a near 3-log reduction and verifying that these alternative wavelengths successfully break the transmission cycle. Owing to its biological similarity with the emerging enteric parasite
Cyclospora cayetanensis
, it is proposed that disinfection with 222 or 282 nm UVR will likewise be efficacious against
Cyclospora
.

IMPORTANCE

Coccidian parasites cause enteric disease in animals and people. For example,
Eimeria acervulina
imposes major economic burdens on the poultry industry and provides a surrogate for investigating means to mitigate the foodborne risk that
Cyclospora cayetanensis
poses to human health. Previous work established that UV radiation at 254 nm can inactivate the oocysts of
E. acervulina,
but radiation at this wavelength harms human skin and eyes. Since nonstandard UVR at wavelengths of 222 and 282 nm shows promise against pathogens like
Giardia
and
Cryptosporidium,
the present work sought to determine whether such exposures could arrest
E. acervulina
development and reduce their infectivity. These nonstandard wavelengths proved capable of disrupting transmission. Epidemiological evidence suggests
Cyclospora
transmission through the food chain; the use of nonstandard UV wavelengths represents a promising method to inactivate coccidian oocysts, thereby protecting produce supply chains while, specifically in the case of 222 nm, incurring less risk to occupational health.
Candida auris
isolates from New York outbreak are highly pathogenic with measurable experimental disease in
Galleria mellonella
Authors: Anower Md. Rokebul , Dennis Emily , Chaturvedi Sudha , Chaturvedi Vishnu
Published: February 2025

Candida auris
causes prolonged colonization and bloodstream infections in hospitalized patients. Different
C. auris
clades vary in their geographic origin, disease spectrum, and antifungal resistance, but biological basis underlying such variations needs further examination. Therefore, we investigated susceptible and multidrug-resistant
C. auris
isolates, obtained early in the New York outbreak, to benchmark their pathogenic potential in caterpillar worms of greater wax moth
Galleria mellonella
. Healthy
G. mellonella
worms responded to
C. auris
in a strain-specific, dose-responsive pattern. Three drug-resistant, clade I
C. auris
17-1, 18-1, and 18-2 isolates caused high mortality, while a control, drug-susceptible, clade II
C. auris
16-1 caused lower mortality (
P
< 0.001) with graded inocula (1 × 10
4
to 1 × 10
7
CFU). Virulence correlated with fungal growth in hemolymph as
C. auris
17-1, 18-1 and 18-2 reached high fungal cell load in the infected larvae, while
C. auris
16-1 multiplied less proficiently. The degree of melanization was higher in worms infected with more pathogenic
C. auris
. Hemocoel histopathology showed more fungal elements and about 50 granulomas per profile for
C. auris
17-1, 18-1 and 18-2 compared to 5 to 10 granulomas for
C. auris
16-1. With more pathogenic
C. auris
isolates, the expression of gallerimycin, ceropin, and galiomycin increased significantly (
P
< 0.05). Thus, the induction of
G. mellonella
immune effector peptides, histopathological responses, and melanization are proportionate to
C. auris
pathogenic potential. However,
G. mellonella
from different vendors showed unpredictable quality upon delivery that impacted feasibility and reproducibility of planned studies. Our results indicate utility of
G. mellonella
experimental model for screening of
C. auris
pathogenesis depending upon quality of worms commercially available in the USA.

IMPORTANCE

The New York metropolitan area continues to suffer from the largest, ongoing outbreak of drug-resistant
Candida auris
. It is necessary to gather more information to determine if
C. auris
isolates from this outbreak vary in their ability to cause more severe disease in affected patients. Therefore, we studied the experimental model of greater wax moth
Galleria mellonella
. We found that susceptible and drug-resistant NY
C. auris
isolates caused measurable disease in
G. mellonella
. There was a good correlation between pathogenic potential of
C. auris
and melanin in the infected worms, fungal elements in worm hemolymph, uptick in the genes involved in insect immunity, and histopathological changes. The worms sourced from various commercial vendors were of variable quality. We confirm that
G. mellonella
remains a facile model to study
C. auris
experimental disease.
Supplemental Material: The Neoproterozoic glacial broom
Authors: Kirkland Christopher L. , al. et
Published: February 2025

Methods, Figures S1–S2, and Dataset S1 (Tables 1–5). 
Microwave Activation of the [FeCl3·6H2O–TsOH·H2O]-Catalyzed Reaction of Norbornene with Organic Nitriles
Authors: Frolova K. S. , Zosim T. P. , Ramazanov I. R.
Published: February 2025

An efficient catalytic system consisting of 20 mol % FeCl3·6H2O and 20 mol % of p-toluenesulfonic acid has been proposed for the amidation of norbornene in toluene with organic nitriles under microwave irradiation at 95°C for 1 h. The corresponding N-(norbornan-2-exo-yl) carboxamides have been obtained with high yields. The efficiency of InCl3 in the amidation of norbornene with aryl cyanides has been demonstrated for the first time.
Abiotrophia defectiva endocarditis implicated in antineutrophil cytoplasmic antibody-negative glomerulonephritis
Authors: Santos Peter W , Lopez Yvette Y
Published: February 2025

We report a rare case of antineutrophil cytoplasmic antibody (ANCA)-negative pauci-immune necrotising glomerulonephritis (PING) inAbiotrophia defectiva(A. defectiva) endocarditis. A woman in her 50s presented to the hospital with acute kidney injury (AKI), pancytopenia, microscopic haematuria, proteinuria and maculopapular rash. She hadA. defectivasepsis and endocarditis. Serologies were positive for antinuclear antibody and low complement components 3 and 4 but negative for ANCA. A kidney biopsy revealed PING with minimal focal crescents, fibrinoid necrosis and tubulointerstitial fibrosis. She was managed with antibiotics and mitral valve replacement alone. Haemodialysis (HD) was initiated briefly until renal recovery. She remained in complete remission after 2 years. This case illustrates the complex immune response to bacterial endocarditis resulting in ANCA-negative PING. The appropriate use of antibiotics and surgical intervention without immunosuppression inA. defectivaendocarditis led to the resolution of AKI and maculopapular rash.
Investigating processes to support and improve informed financial consent in Australian cancer services: an implementation process mapping study and analysis
Authors: Mazariego Carolyn , Cox Raylene , Kennedy Elizabeth , Whittaker Kate , Taylor Natalie , Varlow Megan
Published: February 2025

Objectives

Through implementation process mapping and thematic analysis, this study aimed to understand existing pathways of established informed financial consent (IFC) processes to develop general recommendations for implementing IFC in various cancer care settings.

Design

Implementation science-based process mapping qualitative study. The Consolidated Framework for Implementation Research (CFIR) informed the development of interview questions and a process map outlining a normative process or workflow for patient consults was used during the interviews.

Setting

Australian cancer care provider health services.

Participants

Australian healthcare professionals who provide services to cancer patients and indicated having an IFC process or activities in their service were approached through existing networks to participate in a semistructured interview.

Results

Ten healthcare professionals who regularly worked with cancer patients were interviewed. IFC processes varied by professional specialty (ie, general practice, surgery, radiation oncology and medical oncology) and healthcare settings (eg, public and private). An aggregated process map that highlights the key components of IFC processes discussed was created and includes strategies such as centralised points of contact, consolidated information delivery, reiteration of information by others or at various time-points and the use of follow-up appointments to revisit the financial impact of treatment. Interview themes identified barriers and facilitators such as training, resources and templates that to support or hinder IFC in accordance with CFIR domains.

Conclusions

The themes and aggregated process map provide timely recommendations for healthcare professionals who provide services to cancer patients to facilitate IFC with their patients prior to treatment or as treatment changes. These practical actions will assist healthcare professionals and services providing cancer care to integrate IFC practices and processes into their routine patient interactions. Further work should identify implementation strategies to integrate and scale-up these evidence-based IFC processes and practices across the healthcare system.