bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenomic Prediction Can Be Improved by Optimization of NIRS Preprocessing
Authors: Braun Vincent , Zhu Xintian , Meyenberg Carina , Hahn Volker , Maurer Hans Peter , Würschum Tobias , Thorwarth Patrick
Published: February 2025

In recent years, phenomic prediction has emerged as a new method in plant breeding that has been shown to have great potential. However, there are still many open questions regarding its practical application. For example, in the field of spectroscopy, it is standard practice to optimize the preprocessing of spectra, which so far has only been done to a limited extent for phenomic prediction. In this study, we therefore used three different data sets of soybean, triticale and maize to identify the best combinations of Savitzky–Golay filter parameters for preprocessing near‐infrared spectra for phenomic prediction. We tested 677 combinations of polynomial order, derivative and window size and evaluated them with Monte Carlo cross‐validation. Our results showed that the predictive ability can be improved with the right settings. However, there was no global optimum that gave the best results for all data sets. Even for different traits within the same data set, different combinations of parameters were necessary to achieve the highest predictive ability. Nevertheless, we show that some combinations generally result in a very low predictive ability and should not be used for preprocessing. In addition, we used the normalized discounted cumulative gain to assess whether preprocessing affected the ranking of individuals, which revealed no major changes in the top 1%, 10% or 20% of predicted individuals. Taken together, our results show the potential of preprocessing near‐infrared spectroscopy data to improve the phenomic predictive ability, but there appears to be no global optimum of parameter settings across data sets and traits.
Unexpected Palatal Lesion: Pistachio Shell Mimicking a Palatal Tumor
Authors: Dikmen Adile , Akdeniz Hande
Published: February 2025

A 17‐month‐old child presented with a suspected nodule on the hard palate, initially diagnosed as a possible teratoma or adenoma. MRI showed a mucosal mass limited to the submucosa, leading to an excisional biopsy under general anesthesia. The lesion was ultimately identified as a pistachio shell, emphasizing the challenge of diagnosing foreign bodies in atypical locations. This case highlights the need for vigilance among clinicians in identifying uncommon presentations of foreign body ingestion.
An adversarial risk analysis framework for software release decision support
Authors: Soyer Refik , Ruggeri Fabrizio , Insua David Rios , Pierce Cason , Guevara Cesar
Published: February 2025

Recent artificial intelligence (AI) risk management frameworks and regulations place stringent quality constraints on AI systems to be deployed in an increasingly competitive environment. Thus, from a software engineering point of view, a major issue is deciding when to release an AI system to the market. This problem is complex due to, among other features, the uncertainty surrounding the AI system's reliability and safety as reflected through its faults, the various cost items involved, and the presence of competitors. A novel general adversarial risk analysis framework with multiple agents of two types (producers and buyers) is proposed to support an AI system developer in deciding when to release a product. The implementation of the proposed framework is illustrated with an example and extensions to cases with multiple producers and multiple buyers are discussed.
Benefits Conditionality in the United Kingdom: Is It Common, and Is It Perceived to Be Reasonable?
Authors: Geiger Ben Baumberg , Scullion Lisa , Edmiston Daniel , de Vries Robert , Summers Kate , Ingold Jo , Young David
Published: February 2025

Programme‐level data suggest that increasing numbers of claimants are subject to work‐related behavioural requirements in countries like the United Kingdom. Likewise, academic qualitative research has suggested that conditionality is pervasive within the benefits system, and is often felt to be unreasonable. However, there is little quantitative evidence on the extent or experience of conditionality from claimants' perspectives. We fill this gap by drawing on a purpose‐collected survey of UK benefit claimants (n = 3801). We find that the stated application of conditionality was evident for a surprisingly small proportion of survey participants—even lower than programme‐level data suggest. Unreasonable conditionality was perceived by many of those subject to conditionality, but not a majority, with, for example, 26.2% believing that work coaches do not fully take health/care‐related barriers into account. Yet, alongside this, a substantial minority of claimants not currently subject to conditionality (22.4%) report that conditionality has negatively affected their mental health. We argue that reconciling this complex set of evidence requires a more nuanced understanding of conditionality, which is sensitive to methodological assumptions, the role of time and implementation and the need to go beyond explicit requirements to consider implicit forms of conditionality. In conclusion, we recommend a deeper mixed‐methods agenda for conditionality research.
The cis‐prenyltransferase protein family in Taraxacum koksaghyz
Authors: Müller Boje , Niephaus Eva , Eisenreich Wolfgang , Bröker Jan Niklas , Twyman Richard M. , Prüfer Dirk , Schulze Gronover Christian
Published: February 2025

The cis‐prenyltransferase (cisPT) enzyme family is involved in diverse biological processes that require the synthesis of linear isoprenoid compounds. Taraxacum koksaghyz is a rubber‐producing species and potential crop that has eight cisPT homologs (TkCPT1–8) but their distribution and functions are unclear. We compared the structural organization and sequence homology of the proteins, and defined two groups: TkCPT and TkCPT‐like (TkCPTL) proteins that form heteromeric cisPT enzymes (TkCPT1–4), and TkCPT proteins that function as homomeric cisPTs (TkCPT5–8). We found that TkCPT1 and TkCPT2 are predominantly expressed in latex whereas TkCPT3 and TkCPT6‐8 are predominantly expressed in leaves. TkCPT4 was constitutively expressed in all T. koksaghyz tissues and TkCPT5 mRNA was detected in flowers. The TkCPT1–4 subunits localized to the endoplasmic reticulum whereas TkCPT5–7 were located in chloroplasts. TkCPT1‐4 interacted with TkCPTL1‐2, forming heteromeric complexes that complemented yeast lacking cisPT. Homomeric TkCPT6 could also complement yeast lacking cisPT but we observed no cisPT activity for TkCPT5, TkCPT7, or TkCPT8 in yeast functional complementation assays. TkCPT1/TkCPTL1 and TkCPT2/TkCPTL1 expressed in yeast produced extra‐long‐chain polyisoprenes, whereas TkCPT3/TkCPTL1 and TkCPT4/TkCPTL1 produced long‐chain dolichols and polyisoprenes, TkCPT5 and TkCPT6 produced medium‐chain polyisoprenes, and TkCPT7 and TkCPT8 catalyzed the formation of nerol. The complexity of cisPT proteins in T. koksaghyz suggests that they synthesize different metabolites in a tissue‐specific manner, and thus play distinct roles in isoprenoid metabolism. This is the first comprehensive analysis of the localization, interactions, and products of the entire T. koksaghyz cisPT family in vivo, also revealing a novel pentaprenol found specifically in flowers.
Accuracy and safety of two landmark‐guided techniques for arthrocentesis and intra‐articular injection of the shoulder in dogs
Authors: McClean Brónach , P. McNally Turlough , Pozzi Antonio , Evans Richard , C. Cuddy Laura
Published: February 2025

Objective

To determine the accuracy and safety of two landmark‐guided techniques for shoulder arthrocentesis and injection.

Study design

Ex vivo prospective study.

Animals

A total of 36 paired canine cadaver forelimbs.

Methods

An electronic survey was used to assess the prevalence of injection technique amongst surgeons in clinical practice. Thoracic limbs were randomized to technique for shoulder arthrocentesis and injection (subacromial [SA], n = 18, or supratubercular [ST], n = 18). Repositions, attempts, and the acquisition of synovial fluid was recorded. After the needle was placed, contrast was injected into the joint to determine accuracy of position. The radiographic presence of intra‐articular contrast was judged as an accurate injection. Shoulders were disarticulated and India ink assay performed to assess for iatrogenic articular cartilage injury (IACI).

Results

Both SA and ST techniques were not accurate. Completely accurate injection was identified in 50% SA and 44% ST (p = .80). IACI was identified in 50% SA versus 11% ST (p = .027). There were no significant differences in repositions, attempts, presence of synovial fluid (p = .5, p = .6, p = .7).

Conclusion

Landmark‐guided shoulder injections performed via SA and ST approaches in cadaveric dog shoulders are overall inaccurate. If performing landmark‐guided shoulder injection, ST technique carries a lower risk of IACI than SA in cadaveric shoulders.

Clinical significance

Landmark‐guided shoulder injections are inaccurate in dogs and may result in treatment failure. A ST approach may be considered preferable due to the lower risk of cartilage damage. Future studies should assess ultrasound‐guided techniques to improve accuracy and safety.
Nutritional Characterization of Moringa oleifera as a Potential Equine Feed and Human Application
Authors: Matriffin Maisarah Madihah , Panadi Mira , Md. Khudzari Ahmad Zahran
Published: February 2025

The demand for high-quality horse feed in Malaysia has led to a reliance on imported products. Locally grown Moringa oleifera is a promising protein source for horse feed and possible human application. Hence, this study aimed to characterize Moringa oleifera as a potential horse feed, projecting into possible human use. In this study, Moringa pellets were formulated to compose of rice bran, molasses, corn meal, palm kernel cake (PKC), calcium carbonate, mineral premix and salt. The formulation was designed based on the nutritional needs of maintenance horses (11% CP and 11 MJ/kg DM ME). The production process involved drying Moringa leaves, weighing of ingredients according to formulation followed by mixing, and pelletizing of the components. The nutritional composition of the Moringa pellets was analyzed following standard Association of Official Analytical Chemists (AOAC). It was found that the Moringa pellets contained 90.4% dry matter (DM), 11.7% crude protein (CP), 9.7% crude fiber (CF), and 4.9% ether extract (EE). The Moringa pellets have met the requirement for maintenance horse. Hence, the use of locally sourced ingredients ensures that the Moringa pellets provide balanced nutrition, supporting the overall health and wellness of horses while reducing dependence on imported feed ingredients. The individual protein and fibers compositions are also useful for human applications such as for topical use and oral consumption. However, further exploration and modification should be done for the purpose of human application.
Innovative Approaches to Gas Sensing: Bridging Theory and Human Applications
Authors: Mahmoud Osama Gamal , Noramli Nur Athirah Syafiqah , Abdul Rahim Herlina
Published: February 2025

In this study, a comprehensive analysis of gas sensor technology was conducted, focusing on various types and their applications in industrial instrumentation. The technical characteristics of different gas sensors, both static and dynamic, are explored, along with an examination of working principles. Connection methods with other devices were demonstrated using simulation software for wiring diagrams and microcontroller programming. An analysis of circuit characteristics was presented, with a focus on input-output relations such as amplitude and sensitivity. Additionally, a conceptual design for a new type of gas sensor was proposed, utilizing existing components. This study not only contributes to the understanding of current gas sensor technologies but also outlines key directions for future innovations, specifically focusing on optimizing sensor efficiency for human-based technology applications.
Review on Fundamental of Electroencephalography and Detection Techniques in Substance and Behavioral Addiction
Authors: Saleem Kbah Sadeem Nabeel , Tan Tian Swee , Sheikh Jahanzeb , Al-Qazzaz Noor Kamal , Mohamad Salim Maheza Irna , Hum Yan Chai , Tan Michael Loong Peng , Qiu Fujie
Published: February 2025

Addiction is a chronic relapsing brain disease associated with substantial individual and societal burden. It includes complex phyco-physiological conditions and can be recognized by compulsive and harmful behaviors towards a substance or activity, despite negative consequences or “bio-psycho-social-spiritual” disorder. This paper aims to comprehensively review previous research which applied machine learning to electroencephalography (EEG) signals for automatic detection of addiction. A systematic search was done on 200 relevant papers published between 2018 - 2023. The previous studies applied a variety of machine learning algorithms including support vector machines, neural networks, logistic regressions and brain networks to classify addicted individuals against controls based on resting state, cue-reactivity paradigms and neurofeedback tasks. The features utilized spectral power, functional and effective connectivity, graph theoretical measures and event-related potentials. The output accuracy often exceeded 95% across multiple substances including alcohol, nicotine, cannabis and opioids. In this review, the challenges and open questions around data quality, model interpretation and transition to clinical settings were also discussed. In overall, automatic EEG analysis shows significant potential as an objective and accessible tool for addiction diagnosis, treatment monitoring and relapse prevention that projects worthy of continued refinement and validation.
Digital Immersion in Melaka: Enhancing Historical Learning through Technology on the Malaccan Sultanate
Authors: Sulaiman Hamzah Asyrani , Toh Darren Chia Yen , Che Ku Mohd Che Ku Nuraini
Published: February 2025

This article presents an evaluation on the “Enjoy Melaka” game, which aims to create an engaging educational tool that informs and enlightens the public society on the historical riches of Malaccan Sultanate. The main objectives of this study were to develop an interactive three-dimensional (3D) game that provides an immersive learning experience and to assess its effectiveness as a medium for disseminating historical information. The game was set around the Melaka River attraction site, allowing human players to explore a virtual world filled with historical landmarks and facts. The game was designed for the players to collect items to activate in-game checkpoints that displayed educational content about the Malaccan Empire. There were four checkpoints, each elaborating on different historical aspects of the Sultanate. The accumulated scores allowed the players to progress through the game until they achieved the maximum score. The game development involved creating a detailed 3D environment and integrating educational content into the gameplay. Data were collected through testing activities conducted with a target group of public users. This group provided feedback on the game's effectiveness in making historical information more engaging compared to traditional textual forms such as books, brochures, newspapers and online articles. The important contribution of this study is highlighted through the interactive 3D games which can serve as a more engaging and effective medium for historical education. By transforming the approach in conveying information about the Malaccan Sultanate, the “Enjoy Melaka” game has the potential to enhance public interest and understanding on historical period.
High-Speed Visualization and Characterization of Bubbles in a Bubble Absorber with Swirl-Induced Flow of Refrigerant
Authors: Sanikommu Narasimha Reddy , Mani Dr. A. , Tiwari Shaligram
Published: February 2025

The present study experimentally investigates the hydrodynamic characteristics of air bubbles within a glass bubble absorber. A swirl generator designed based on the cavity profile introduces swirl motion to the air entering the water column, and high-speed visualization techniques are employed to analyze the resulting bubble behavior. The optimal swirl generator geometry is determined by performing numerical simulations. The present study considers still, co-current and counter current water flow conditions relative to the airflow. Experiments are also conducted to explore the impact of air and water flow rates on bubble characteristics, such as departure diameter, departure time, rise velocity, etc. Visualization studies revealed that the bubble formation phenomenon can be categorized into three different stages: initiation, growth, and detachment. It is observed that the direction of water flow has a significant effect on bubble characteristics. Based on the experimental data, empirical correlations for non-dimensional departure bubble diameter have been proposed, which can help estimate the primitive bubble size in a bubble absorber.
Transition Wave Interference in Multistable Mechanical Metamaterials
Authors: Bonthron Michael , Tubaldi Eleonora
Published: February 2025

Mechanical metamaterials with multiple stable configurations offer a promising avenue for the design and development of adaptable materials with unprecedented levels of control over physical properties. Specifically, arrays of bistable beam elements represent a unique metamaterial platform with tunable transition waves offering means of passive control, sensing, and memory effects of environmental conditions. Although previous studies have mainly investigated transition waves triggered by a static input in nonlinear metamaterials, the dynamic properties of these structures and the interference of colliding waves are still unknown. Here, we investigate the dynamic properties of arrays of bistable beam elements which are important keys in the further development of applications of these metastructures. We determine the critical force and the optimal location to apply a force to trigger a transition wave and characterize the natural frequencies of the metamaterial. Moreover, we study the interference between two transition waves simultaneously actuated at both ends of the one-dimensional multistable array. Our new insights on the nonlinear dynamic responses of multistable metamaterials pave the way for the ability to design and program adaptable structures with enhanced energy absorption, vibration isolation, and wave steering capabilities.
Embedded Fused Filament Fabrication of Thermoplastics for Biomedical Applications
Authors: Mitchell Kellen , Shackleford Aidan , Bandala Erick , Zhang Chen , Chai Guangrui , Jin Yifei
Published: February 2025

Utilizing material extrusion three-dimensional printing methods, particularly fused filament fabrication (FFF), allows for the creation of complex architectures. Nevertheless, FFF-fabricated structures often suffer from inadequate mechanical properties and elevated surface roughness. In this study, we developed an embedded FFF (e-FFF) approach to produce thermoplastic products with enhanced mechanical characteristics and improved surface quality. This approach was achieved through the development of a thermostable yield-stress fluid made from fumed silica particles and sunflower oil. By tuning the rheological properties of the support bath, thermoplastic filaments were effectively supported in a molten state throughout printing. Biocompatible and biodegradable polycaprolactone (PCL) was selected as the exemplary thermoplastic polymer in this work. Filaments, single-layer sheets, and tensile test samples were printed to fine-tune the printing parameters, assess surface morphology, and certify the mechanical properties of structures printed by e-FFF. To demonstrate the potential biomedical applications of the approach, an orbital implant model was designed using numerical simulation to evaluate mechanical integrity. Then, the orbital implant was printed and measured to confirm the effectiveness of the proposed e-FFF approach. Lastly, cells were successfully incubated on the PCL implant, which was affixed to a mock orbital fracture to confirm that patient-specific orbital implants could be fabricated.
Presenting Hackathon Data for Design Research: A Transcript Dataset
Authors: Flus Meagan , Litster Gregory , Olechowski Alison
Published: February 2025

Hackathons are intensive design experiences during which teams identify a problem and rapidly develop prototypes of solutions. These events offer a promising venue for studying collaborative design: they are naturalistic, short-term, and contained, which mitigate many of the drawbacks of traditional investigations in design research. The objective of this technical brief is to present and describe a transcript dataset of conversations collected from a hackathon team. The dataset includes a transcript of the verbal communication between a four-person hackathon team in the first 2 hours and 9 minutes of their collaboration. This portion of the design process, totalling 908 segments of speech, details the team's problem exploration, brainstorming, idea selection, and premature team dissolution. This brief outlines the advantages of having rich transcript data freely available, with a specific focus on new research directions and impact. We demonstrate the potential for this dataset in an example analysis of premature team dissolution, using inductive coding to explore goal misalignment as a possible explanation. We aim for this brief to encourage the use of this data for future investigations of design, teamwork, and hackathon phenomena, as well as act as an exemplar for future publications of open-access datasets.
Impact localization on a metal plate using matched field processing and a microphone array
Authors: King Allison M. , Dowling David R.
Published: February 2025

Acoustic waves are well-suited for remote sensing applications and structural health monitoring because they convey information about their source and can be recorded using non-contacting methods. An important structural health monitoring task is localization of an impact excitation. However, traditional array signal processing techniques for source localization are ill-suited for many structural engineering applications because of geometrical complexity, dispersive acoustic wave propagation in structures, and the coupling of the vibrating structure and the surrounding medium. Plus, many traditional methods use contacting sensors, which can permanently alter the structure. This study utilizes Bartlett matched field processing (MFP), a localization technique initially developed for underwater acoustics, to localize an impact source on a metal plate. A 14-microphone array recorded the sound radiated by a 0.64-cm-thick 91.4-cm-diameter round aluminum plate after the impact of a 1.3-cm-diameter stainless-steel ball bearing. MFP and a physics-based finite-element acoustic environment model were used to localize the impact on the plate. Results are presented as ambiguity surfaces where the predicted source location was typically found to be within 1.1 cm of the true source location. Localization performance was also assessed in a noisy environment, with success down to a signal-to-noise ratio of −7.5 dB.
Applying deep learning for underwater broadband-source detection using a spherical array
Authors: Cao Huaigang , Pan Yue , Wang Qiang , Wang Zhen , Yang Jiaming
Published: February 2025

For improving passive detection of underwater broadband sources, a source-detection and direction-of-arrival-estimation method is developed herein based on a deep neural network (DNN) using a spherical array. Spherical Fourier transform is employed to convert the element pressure signals into spherical Fourier coefficients, which are used as inputs of the DNN. A Gaussian distribution with a spatial-spectrum-like form is adopted to design labels for the DNN. A physical model coupling underwater acoustic propagation and the spherical array is established to simulate array signals for DNN training. The introduction of white noise into the training data considerably enhances the detection capability of the DNN and effectively suppresses false estimation. The model's performance is evaluated based on its detection rate at a constant false alarm rate. Notably, the model does not rely on prior knowledge of the source's spectral features. Further, this study demonstrates that a DNN trained by one source can achieve multisource detection to a certain extent. The simulation and experimental processing results validate the broadband detection capability of the proposed method at varying signal-to-noise ratios.
Disparities in Pedestrian and Cyclist Crashes by Social Vulnerability Across South Carolina
Authors: Hallum Shirelle H. , Chupak Anna L. , Thomas Kelsey M. , Looney Erin N. , Witherspoon Eleanor , Huynh Nathan H. , Kaczynski Andrew T.
Published: February 2025

Background: Little crash equity research has controlled for active transportation rates, examined the Southeastern United States, or used composite sociodemographic metrics. This study analyzed disparities in pedestrian and cyclist crashes and crash severity according to level of social vulnerability (SV) across South Carolina. Methods: Data about SV and its 4 dimensions (socioeconomic status, household composition and disability, minority status and language, and housing type and transportation) were compiled for all census tracts (N = 1103) within South Carolina. Data for all crashes involving a pedestrian (n = 10,688) and/or cyclist (n = 4802) from 2011 to 2021 were obtained from the South Carolina Department of Transportation and geocoded to the respective census tract. Total average pedestrian and cyclist crash severity (Equivalent Property Damage Only) were also calculated for each tract. Crash frequency and severity scores were adjusted using the average number of walking and cycling trips in the census tract per year using StreetLight Data. Mixed-model linear regression analyzed the relationships between overall SV and the 4 SV dimensions and 4 crash measures—pedestrian and cyclist frequency and severity. Stratified analyses were conducted for urban and rural tracts. Results: Overall SV was positively and significantly associated with all 4 crash outcomes in urban areas: pedestrian crashes per trip (B = 0.048, SE = 0.012, P < .001), pedestrian crash severity per trip (B = 9.018, SE = 2.516, P < .001), cyclist crashes per trip (B = 0.093, SE = 0.029, P < .01), and cyclist crash severity per trip (B = 16.370, SE = 5.482, P < .01). In urban areas, greater SV was associated with more severe pedestrian and cyclist crash outcomes. Conclusions: Targeted policy and programmatic and infrastructure interventions are needed to improve active transportation safety and public health.
Instant variable stiffness in cardiovascular catheters based on fiber jamming
Authors: Sun Yi , Piskarev Yegor , Hofstetter Etienne H. , Fischer Cedric , Boehler Quentin , Stárek Zdeněk , Nelson Bradley J. , Floreano Dario
Published: February 2025

Variable stiffness (VS) has revolutionized miniature surgical instruments, including cardiovascular catheters for minimally invasive surgeries (MISs), enabling advanced capabilities in stiffness modulation and multi-curvature bending. However, existing VS catheters with phase-changing materials are slow in softening and stiffening rates (≈90 s), which can lead to substantial increase in surgery duration. To address the slow stiffness change, we propose a VS catheter based on fiber jamming (FJ) that achieves instant stiffness changes (≤300 ms), enabling seamless catheter operations without delays. Moreover, our catheter, incorporating hundreds of ultrathin fibers into a slender 2.3-mm catheter body, achieves up to 6.5-fold stiffness changes. With adequate stiffness change, our two-segment catheter achieves complex bending profiles within seconds. In addition, the FJ-based design does not require electric currents or heating inside the human body, minimizing patient risks. This FJ-based VS catheter, with instantaneous response, adequate stiffness change, and enhanced safety, can potentially establish benchmarks in MIS, allowing medical practitioners to effectively address formidable diseases.
Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma
Authors: Lutz Raphael , Poos Alexandra M. , Solé-Boldo Llorenç , John Lukas , Wagner Johanna , Prokoph Nina , Baertsch Marc A. , Vonficht Dominik , Palit Subarna , Brobeil Alexander , Mechtersheimer Gunhild , Hildenbrand Nina , Hemmer Stefan , Steiger Simon , Horn Sabrina , Pepke Wojciech , Spranz David M. , Rehnitz Christoph , Sant Pooja , Mallm Jan-Philipp , Friedrich Mirco J. , Reichert Philipp , Huhn Stefanie , Trumpp Andreas , Rippe Karsten , Haghverdi Laleh , Fröhling Stefan , Müller-Tidow Carsten , Hübschmann Daniel , Goldschmidt Hartmut , Willimsky Gerald , Sauer Sandra , Raab Marc S. , Haas Simon , Weinhold Niels
Published: February 2025

The bone marrow microenvironment plays a crucial role in the development of multiple myeloma. As the disease progresses, malignant myeloma cells can evolve to survive outside the bone marrow. However, the processes underlying bone marrow independence and their consequences for immune control remain poorly understood. Here, we conducted single-cell and spatial multiomics analyses of bone marrow–confined intramedullary disease and paired breakout lesions that disrupt the cortical bone. These analyses revealed a distinct cellular microenvironment and architectural features of breakout lesions, characterized by extensive areas of malignant plasma cells interspersed with lesion-specific solitary natural killer and macrophage populations, as well as focal accumulations of immune cell agglomerates. Within these agglomerates, spatially confined T cell clones expanded alongside various immune cells, coinciding with the local genomic evolution of tumor cells. These analyses identify breakout lesions as a hotspot for tumor-immune cell interactions and diversification, representing a key event in myeloma pathogenesis.
Xpert MTB/RIF Ultra-resistant and MTBDR
plus-
susceptible rifampicin results in people with tuberculosis: utility of FluoroType MTBDR and deep sequencing
Authors: Ghebrekristos Yonas , Ahmed Aysha , Beylis Natalie , Singh Sarishna , Opperman Christoffel , Naufal Fahd , Folkerts Megan , Engelthaler David , Auma Erick , Venter Rouxjeane , Booley Ghowa , Metcalfe John , Warren Robin , Theron Grant
Published: February 2025

Xpert MTB/RIF Ultra (Ultra)-detected rifampicin-resistant tuberculosis (TB) is often programmatically confirmed using MTBDR
plus
. There are limited data on discordant results, including when re-tested using newer methods, like FluoroType MTBDR (FT-MTBDR) and targeted deep sequencing. MTBDR
plus
rifampicin-susceptible isolates from people with Ultra rifampicin-resistant sputum were identified from a South African programmatic laboratory. FT-MTBDR and single molecule-overlapping reads (SMOR;
rpoB
,
inhA
,
katG
) on isolate DNA were done (SMOR was used as a reference standard). Between 1 April 2021 and 30 September 2022, 8% (109/1347) of Ultra rifampicin-resistant specimens were MTBDR
plus
-susceptible. Of 89% (97/109) isolates with a sequenceable
rpoB
, SMOR resolved most in favor of Ultra (79% [77/97]). Sputum with lower mycobacterial load was associated with Ultra false-positive resistance (46% [11/24] of “very low” Ultra had false resistance vs 12% [9/73;
P
= 0.0004] of ≥“low”), as were Ultra heteroresistance calls (all wild-type probes, ≥1 mutant probe) (62% [23/37 vs 25% 15/60] for Ultra without heteroresistance calls;
P
= 0.0003). Of the 91% (88/97) of isolates successfully tested by FT-MTBDR, 55% (48/88) were FT-MTBDR rifampicin-resistant and 45% (40/88) susceptible, translating to 69% (47/68) sensitivity and 95% (19/20) specificity. In the 91% (99/109) of isolates with
inhA
and
katG
sequenced, 62% (61/99) were SMOR isoniazid-susceptible. When Ultra and MTBDR
plus
rifampicin results are discordant, Ultra is more likely to be correct, and FT-MTBDR agrees more with Ultra than MTBDR
plus
; however, lower load and the Ultra heteroresistance probe pattern were risk factors for Ultra false rifampicin-resistant results. Most people with Ultra–MTBDR
plus
discordant resistance results were isoniazid-susceptible. These data have implications for drug-resistant TB diagnosis.
Evaluation of two gradient diffusion tests to determine susceptibility to aztreonam and ceftazidime–avibactam in combination
Authors: Khan Ayesha , Manuel Carmila , Maynard Richard , Humphries Romney M.
Published: February 2025

The combination of aztreonam and ceftazidime–avibactam (ATM–CZA) is a last resort regimen against recalcitrant infections caused by metallo-β-lactamase (MBL)-producing organisms. Susceptibility testing is warranted due to emerging resistance to the combination, but there are no widely implemented methods for use in clinical laboratories. Here, we used a cohort of 100 Enterobacterales
, Pseudomonas aeruginosa
, and
Stenotrophomonas maltophilia
strains, including 68 MBL producers, to evaluate the performance of two ETEST strip-based synergy testing methods: the side-by-side (SS) method with an ATM ETEST placed next to a CZA ETEST (10 mm apart) and the strip cross (SX) method with a CZA ETEST placed perpendicularly on top of the ATM ETEST (at the 8 µg/mL mark). By reference broth microdilution (BMD), 89.1% (41/46) of the Enterobacterales, 15% (3/20) of the
P. aeruginosa
, and 97.1% (33/34) of the
S. maltophilia
isolates tested susceptible to the ATM–CZA combination. The SS method yielded 72% categorical agreement with BMD and 28 major errors (ME, 36.4%). Initial testing with the SX method yielded three ME , of which one was resolved upon repeat testing, yielding a final categorical agreement of 98% with BMD with two ME (2.6%). The SX method also yielded 100% reproducibility across three brands of Mueller Hinton agar (BD, Hardy, Remel). Our study demonstrates that the SX method is accurate, precise, and feasible for clinical laboratories to perform ATM–CZA susceptibility testing to guide use of the combination for treatment of multidrug-resistant gram-negative pathogens.
Enhancing
Acanthamoeba
diagnostics: rapid detection of viable
Acanthamoeba
trophozoites and cysts using viability PCR assay
Authors: Veugen J. M. J. , Savelkoul P. H. M. , Nuijts R. M. M. A. , Dickman M. M. , Wolffs P. F. G.
Published: February 2025

Acanthamoeba
keratitis (AK) is a sight-threatening corneal infection that is challenging to diagnose and treat due to the resistance of
Acanthamoeba
to standard antimicrobial agents. Current detection methods have limitations. This study aimed to develop and validate a sensitive viability PCR (v-PCR) assay using a photoreactive dye to distinguish viable from non-viable
Acanthamoeba
for rapid identification of viable
Acanthamoeba
trophozoites and cysts. Propidium monoazide (PMAxx) was used as a photoreactive dye. Mixtures containing decreasing percentages of viable
Acanthamoeba
, including reference strains
Acanthamoeba polyphaga
trophozoites and cysts,
Acanthamoeba castellanii
trophozoites, and
Acanthamoeba castellanii
trophozoites from a clinical sample, were prepared. Disinfectant efficacy against
Acanthamoeba
was also assessed. Samples were divided into PMAxx-treated and non-PMAxx-treated parts, and v-PCR assay was applied to both. The difference in viable
Acanthamoeba
was determined by subtracting the cycle threshold (Ct) value of the PMAxx-treated sample from the non-PMAxx-treated sample. Mixtures with decreasing concentrations of viable
Acanthamoeba
trophozoites and cysts showed increasingly lower delta Ct values as the percentage of viable
Acanthamoeba
decreased, as expected. This relationship was observed across all tested samples. Menicon Progent effectively eliminated
A. polyphaga
trophozoites and cysts, while propamidine, chlorhexidine, or their combination resulted in approximately 2-log reductions in
A. polyphaga
trophozoites and cysts. In the current study, a rapid v-PCR assay was developed that can distinguish between viable and non-viable
Acanthamoeba
, for both trophozoites and cysts, across multiple species. The presence of viable
Acanthamoeba
, as determined by v-PCR, allows monitoring of treatment response and efficacy in AK.

IMPORTANCE

The development of a sensitive viability PCR (v-PCR) assay using propidium monoazide (PMAxx) as a photoreactive dye marks a significant advancement in the diagnosis and treatment of
Acanthamoeba
keratitis (AK), a severe corneal infection notorious for its resistance to conventional antimicrobials. This innovative assay offers a rapid and accurate method to distinguish viable from non-viable
Acanthamoeba
trophozoites and cysts, addressing a critical need in the field. By effectively distinguishing between viable and non-viable
Acanthamoeba
, this test enables monitoring of treatment response and efficacy, essential for guiding clinical interventions in AK cases. The successful validation of this v-PCR assay across various
Acanthamoeba
species and its ability to assess disinfectant efficacy further underline its potential as a valuable tool for improving diagnostic precision and therapeutic outcomes in the treatment of AK.
Supplemental Material: Insights into Cordilleran collisional processes: Early shared history of the Eocene Siletzia and Yakutat terranes as a ridge-centered oceanic plateau
Authors: Donaghy Erin E. , al. et
Published: February 2025

Sedimentologic characterization of sedimentary units discussed in manuscript text, detailed U-Pb zircon geochronology methods, and raw data. 
Supplemental Material: Wetland methane feedback during the early Eocene hyperthermals
Authors: Chen Zuoling , al. et
Published: February 2025

Compound-specific isotope data and biomarker distributions. 
Supplemental Material: Development of an intracontinental plate boundary transfer zone, Marlborough, Aotearoa New Zealand: A review and synthesis
Authors: Upton Phaedra , al. et
Published: February 2025

Three figures, five tables and analytical methods.
Supplemental Material: Fingerprints of El Niño-Southern Oscillation and solar activity cycles recorded in the middle Eocene Bohai Bay Basin (East China)
Authors: Han Yu , Liang Chao , et al.
Published: February 2025

R scripts for TimeOpt and eTimeOpt methods; Figures S1 to S10.
Supplemental Material: Formation of carbonatite-related giant rare earth element deposits by liquid immiscibility
Authors: Xue Shuo , Ling Ming-Xing , al. et
Published: February 2025

Tables S1–S8 and Figures S1–S10.
Nasal mask ventilator-delivered versus face maskT-piece resuscitator positive pressure ventilation during resuscitation of preterm neonates: a cohort study
Authors: Akhtar Nosheen , Hemani Aman , Jasani Bonny , Lindsay Brittany , Morgan Brent , Jain Amish , Baczynski Michelle
Published: February 2025

Objective

To evaluate the clinical impact of nasal mask ventilator-delivered positive pressure ventilation (PPV) versus face mask manual T-piece resuscitator PPV during resuscitation of preterm neonates.

Design

We conducted a pre-post cohort study in a tertiary neonatal unit, comparing consecutive neonates born 250/7–286/7weeks of gestational age (GA) who received PPV ≤10 min after birth, before and after changing the approach during resuscitation from face mask manual T-piece resuscitator PPV (epoch 1, April 2018–April 2020) to nasal mask ventilator-delivered PPV (epoch 2, May 2020–February 2022). The association between birth epoch and the primary outcome of emergent intubation (EI) during resuscitation was examined by multivariable logistic regression and inverse probability of treatment weighting models. Additional outcomes compared between epochs were rates of advanced resuscitation, and early (≤7 days) and late (>7 days) prematurity-related morbidities.

Results

Of 545 eligible births, 336 (62%) received PPV; 176 (58%) in epoch 1 and 160 (66%) in epoch 2. Neonates in epoch 1 had lower GA (26.7 (25.9–27.9) vs 27.4 (26.0–28.1) weeks; p=0.02) but similar birth weight (900 (730–1060) vs 880 (740–1085) g; p=0.53). Neonates in epoch 2 had lower rates of EI (16% vs 44%; p<0.001) and less use of post-resuscitation invasive ventilation (22% vs 59%; p<0.001). After accounting for confounders, nasal mask ventilator-delivered PPV remained associated with lower odds of EI (adjusted OR 0.23 (95% CI 0.13 to 0.42)). Secondary outcomes were similar between groups.

Conclusion

Nasal mask ventilator-delivered PPV may reduce EI during resuscitation of preterm neonates. Our observations support a large trial of nasal mask ventilator-delivered PPV in this context.
Responsible governance of genomics data and biospecimens in the context of broad consent: experiences of a pioneering access committee in Africa
Authors: Rebai Ahmed , Abayomi Akin , Andanda P , Kerr R , Herbst Kobus , Mabuka J , Wamuyu R , Bukini Daima , Dandara C
Published: February 2025

International collaboration in genomic research is gaining momentum in African countries and is often supported by external funding. Over the last decade, there has been an increased interest in African genomic data. The contribution of this rich data resource in understanding diseases predominant in both African and global populations has been limited to date. There has been some non-governmental funding dedicated to the advancement of genomic research and innovation by African-based and African-led research groups, but the impact of these initiatives is hard to quantify. However, there is now an opportunity for the global research community to leverage decades of genomic data and biospecimens originating from African populations. The experience we describe in this paper is of an access governance framework established under the Human, Heredity, and Health in Africa (H3A) consortium, given the task of managing wider access to the data and biospecimen resources collected via its various projects. The function of the Data and Biospecimen Access Committee (DBAC) is to facilitate the advancement of medicine and health while fostering the development of bioinformatics capabilities at Africa-based institutions or regional hubs. Our collective experiences and lessons learnt as a committee provide examples of nuanced considerations when evaluating access to African data. The committee was semi-autonomous in its establishment and had independence in decision-making. The DBAC continually advocates for the responsible use of genomic data and biospecimens that were obtained from African research participants, under broad consent, by primary researchers who no longer have oversight over the future use of these resources.
Biological embodiment of educational attainment and future risk of breast cancer: findings from a French prospective cohort
Authors: Berger Eloïse , Dudouet Richard , Dossus Laure , Baglietto Laura , Gelot Amandine , Boutron-Ruault Marie-Christine , Severi Gianluca , Castagné Raphaële , Delpierre Cyrille
Published: February 2025

Background

Women with higher educational attainment have a higher risk of developing breast cancer (BC). Despite the acknowledged impact of reproductive and lifestyle factors, some excess risks remain unexplained. Many studies support the hypothesis that education has a distinctive effect on physiological processes associated with health, independently of known risk factors.

Objectives

In this study, we aimed to determine whether the biological embodiment of education could be part of the observed social inequalities in BC risk. We focused on biomarkers from several physiological systems examined individually, and jointly through a biological health score (BHS).

Design

Prospective cohort study.

Setting

This study, based on a subsample of the French E3N cohort, included women with biological data from four nested case–control studies.

Participants

The study included 3048 postmenopausal women (17% BC).

Main outcome measures

We first evaluated the association between educational attainment and each biomarker, separately (N=11) and by combining them into a BHS, indicative of an augmented biological health hazard when elevated. Finally, we explored the relationships between the socially patterned biomarkers and BHS, and risk of incident BC.

Results

Women with higher educational attainment exhibited a lower BHS in comparison to those with lower educational attainment (β
high education
=−0.21 (95% CI −0.42; 0.01), model 2). Specific biomarkers associated with the cardiovascular (systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), high-density lipoprotein (HDL)), inflammatory (C reactive protein (CRP)) and hormonal systems (sex hormone-binding globulin (SHBG) and oestradiol) were found socially distributed (OR
CRP-high
=0.70 (95% CI 0.54; 0.91), OR
TG-high
=0.79 (95% CI 0.61; 1.04), OR
DBP-high
=0.69 (95% CI 0.53; 0.90), OR
SBP-high
=0.57 (95% CI 0.44; 0.74), OR
HDL-high
=0.79 (95% CI 0.60; 1.03), (OR
SHBG-high
=0.67 (95% CI 0.52; 0.88), OR
oestradiol-high
=1.34 (95% CI 1.00; 1.79); model 1). Associations persisted after adjustment for cofounders and a large set of potential mediators for two of the investigated cardiovascular markers (OR
DBP-high
=0.75 (95% CI 0.57; 1.00), OR
SBP-high
=0.61 (95% CI 0.46; 0.81); model 2). No associations were found between the socially stratified biomarkers and BHS with risk of BC.

Conclusion

Educational attainment has a direct impact on biological processes suggesting that the biological embodiment of the social environment could be a potential pathway that mediates the association between educational attainment and health. Further studies are needed to specifically investigate the relationships between socially stratified biomarkers and BC risk.