bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the integration of artificial intelligence in math education: Preservice Teachers’ experiences and reflections on problem‐posing activities with ChatGPT
Authors: Kim Young Rae , Park Mi Sun , Joung Eunmi
Published: January 2025

This study addresses the need for research that incorporates educational perspectives and theories to understand the impact of Artificial Intelligence (AI) on learning and teaching. Utilizing AI‐integrated mathematical problem‐posing (AIM) activities and the AI‐powered scaffolding (AIS) strategy, the research investigated preservice teachers’ (PTs’) experiences with AI and their capacity for error recognition and correction in problems posed by ChatGPT. The findings reveal that while the PTs excelled at verifying error‐free problems, they struggled significantly with identifying and correcting errors, indicating a gap in their instructional preparedness. The study demonstrates that AIM activities are effective tools for assessing and developing PTs’ error recognition and correction skills. Additionally, AIM activities support the transfer of mathematical knowledge to pedagogical and instructional practices, contributing to PTs’ growth as adaptable educators. The research highlights the need to integrate AI‐based activities into PT training to build robust mathematical knowledge and teaching skills. Focusing on learning, pedagogy, and the human aspects of technology use, AIM activities and the AIS strategy enable PTs to engage critically with AI outputs and enhance their metacognitive skills. These insights emphasize the importance of incorporating AI‐integrated methods into teacher preparation programs to better equip future educators for an AI‐driven educational landscape.
Exploring the interactions among instructor, prospective teachers and AI in facilitating mathematics learning
Authors: Yılmaz Zuhal , Galanti Terrie M. , Naresh Nirmala , Kanbir Sinan
Published: January 2025

Mathematics teacher educators (MTEs) have an important obligation to prepare prospective elementary mathematics teachers (PEMTs) to use artificial intelligence (AI) in their classrooms. To better understand how AI can mediate the interactions between students, teachers, and mathematics, we examined PEMTs' perceptions of AI‐integrated learning sessions in a foundational content course. We employed inductive and deductive thematic analysis to categorize these perceptions along three edges of a didactic tetrahedron for teaching and learning (AI–PEMT interactions, PEMT–instructor interactions, and AI–instructor interactions). The instructor's use of Khanmigo as an AI tutor to facilitate small‐group problem‐solving yielded several experiences categorized along the AI–PEMT and instructor–PEMT edges of the didactic tetrahedron. AI–PEMT interactions created robust opportunities to communicate and construct mathematical knowledge with Khanmigo. Instructor–PEMT interactions provided a mathematical and technological “safety net”, mitigating challenges PEMTs faced in communicating with AI. Limited evidence of PEMT descriptions of AI–instructor interactions suggests MTEs should intentionally model their instructional decision‐making and partner with AI to facilitate their lessons. PEMTs can benefit from discussing how teachers foster meaningful student engagement with AI beyond getting answers to problems. Implications for recognizing challenges and realizing the affordances of using AI to deepen mathematics learning in content courses for PEMTs are offered.
Full Genomic Sequence of the HLA‐DQB1*06:304N Allele Identified by Next Generation Sequencing
Authors: Liacini Abdelhamid , Geier Steven
Published: January 2025

The full‐length sequence of HLA‐DQB1*06:304N covers the 5′‐untranslated region (UTR), all introns and exons, and the 3′ UTR.
Exploring student profiles in statistical performance based on self‐regulation, attitudes toward statistics and computer self‐efficacy
Authors: O'Connor Patrick A. , Graham Agnieszka J.
Published: January 2025

Understanding factors influencing students' success in statistics is crucial, as many psychology students struggle with the subject, affecting their academic confidence and career readiness. This study examines profiles of undergraduate psychology students learning statistics, focusing on attitudes, IT self‐efficacy, and statistical performance. A sample of 175 first‐year students completed assessments on attitudes toward statistics, academic delay of gratification, test anxiety, and computer self‐efficacy, plus an end‐of‐year exam. Latent profile analysis identified two groups: “Motivated Performers” with higher positive attitudes toward statistics, greater computer self‐efficacy, and lower statistical anxiety, and “Anxious Learners,” who scored lower in these areas. Although Motivated Performers outperformed Anxious Learners on the exam, the difference was nonsignificant. Academic delay of gratification was the only significant predictor of performance, regardless of profile membership. These findings emphasize promoting positive attitudes and I.T. confidence in statistics and highlight the importance of self‐regulatory academic behaviors in preparing students for statistics exams.
Spatial Performance Approach to Machine Learning Algorithms: A GIS‐Based Comparison Analysis for Real Estate Valuation
Authors: Genc Nihal , Colak H. Ebru , Ozbilgin Ferdi
Published: January 2025

Machine learning algorithms are frequently used in mass valuation activities today. These algorithms are believed to perform differently depending on various factors such as different functions, model parameters, data quantity, and quality. Another factor that is often overlooked is location. In this study, the performance of a set of machine learning algorithms in predicting real estate values was evaluated from a spatial perspective. To highlight the spatial performance of the algorithms, a study area was chosen where the factors affecting value are spatially heterogeneous. Value predictions were made using Linear Regression, Random Forest, Support Vector Machine, Regression Trees, Gaussian Process Regression, Artificial Neural Network, and Least‐Squares Boosting algorithms. Bayesian Optimization was used to improve the performance of the algorithms. The performances of the algorithms were compared using R2, RMSE, MSE, MAPE, and MAE metrics. The Random Forest model showed the best performance according to these metrics. Spatial predictions were made in the GIS environment using the IDW spatial interpolation method based on test data. The spatial distribution of the predictions and actual housing values were shown by producing maps. The spatial distribution of the algorithms was compared both with the actual values and with each other. It was found that, aside from the Random Forest model, other models also performed quite well in some locations and even produced better results than the Random Forest model. This demonstrates that location affects the performance of ML algorithms and that performance may vary depending on location. This study is expected to contribute to many fields of science where ML algorithms are used, especially in real estate valuation, and to bring a new perspective to the literature.
An experimental comparison and user evaluation of three different dried plasma products
Authors: Ehn Kristina , Skallsjö Gabriel , Romlin Birgitta , Sandström Göran , Sandgren Per , Wikman Agneta
Published: January 2025

Background and Objectives

Access to blood components in pre‐hospital bleeding resuscitation is challenging. Dried plasma is a logistically superior alternative, and new products are emerging. Therefore, we aimed to evaluate laboratory and practical differences in three differently produced dried plasma products.

Materials and Methods

Single‐donor lyophilized LyoPlas®, pooled‐donor, lyophilized and pathogen‐reduced OctaplasLG Powder®, and single‐donor sprayed‐dried FrontlineODP™ along with fresh plasma (in‐house, pre‐FrontlineODP and OctaplasLG) as controls were analysed (n = 8). Laboratory tests included measurements of various coagulation factors and thromboelastography. The practical evaluation of the dried plasma products included preparation time, time to dissolve the dried plasma and total time, together with subjective opinions from eight clinical users.

Results

The coagulation factor content was within human reference ranges for all dried plasma, with approximately 10%–20% loss compared with fresh plasma. More variations were observed in the single‐donor products compared with the pooled products. Clot formation analysed by thromboelastography showed normal graphs. Reconstitution time was similar, ranging from on average 7–9 min. In the user evaluation, the reconstitution time and the possibility of using a plastic bag for the transfusion were emphasized as important, the latter fulfilled by two of the products.

Conclusion

The study supports that dried plasma may be produced with lyophilization or spray‐drying technique, as well as with the addition of pathogen reduction, with preserved coagulation capability. The products were reconstituted in acceptable time and deemed feasible for pre‐hospital use by eighth test users.
Implementation of Flow Control Methods for Design of Connecting Duct of Annular Sector Cascade Tunnel
Authors: Bhavsar Hardikkumar , Mistry Chetan S.
Published: January 2025

The present study discusses the effect of various flow control methods implemented to develop an intermediate turbine duct (ITD), providing a continuous flow path between the contraction duct of the wind tunnel and the annular sector cascade (ASC) test section to deliver the required flow. The S-shaped diverging passage of the ITD with continuously increasing mean radius imposes a major challenge to achieving the required inlet flow angle with periodicity at the entry of the ASC. The numerical study was performed in ansyscfx to analyze the effect of active and passive flow control methods on the ITD exit flow delivered to the ASC test section. It was found that inlet guide vanes (IGVs), incorporated within the ITD as a passive flow control method, direct the flow through ITD, and approximately required inlet flow condition with reasonable periodicity was achieved at the entry of the ASC test section. However, the opening slot on the casing endwall, an active flow control method, shows the adverse effect on the flow angle distribution at the entry of the ASC test section. The change in axial spacing between IGVs and the test vane cascade shows a negligible effect on the cascade entry flow field. The experimental flow field measurement performed using a five-hole pressure probe showed that IGVs successfully directed the flow through the ITD, precisely meeting the requirements at the test section. The surface oil flow visualization confirms the formation of various flow features captured in the computational study.
A Force-Sensor-Less Approach for Rapid Young’s Modulus Identification of Heterogeneous Soft Tissue
Authors: Wang Zhen , Xu Tian , Shen Mengruo , Lei Yong
Published: January 2025

Due to individual differences, accurate identification of tissue elastic parameters is essential for biomechanical modeling in surgical guidance for hepatic venous injections. This paper aims to acquire the absolute Young’s modulus of heterogeneous soft tissues during endoscopic surgery with two-dimensional (2D) ultrasound images. First, we introduced a force-sensor-less approach that utilizes a precalibrated soft patch with a known Young’s modulus and its ultrasound images to calculate the external forces exerted by the probe on the tissue. Second, we introduced a Kriging-based inverse algorithm to identify the relative Young’s modulus (RYM) between the inclusion and the background tissue. The RYM was estimated based on 2D plane strain approximation and mapped to the RYM of three-dimensional (3D) soft tissue through a trained Kriging model. Finally, we developed a direct method to identify the background Young’s modulus (BYM) based on calculated external forces and RYM. The simulation results demonstrate the high efficiency and robustness of the Kriging-based inverse algorithm in identifying RYM. Physical experiments on the three phantoms show that the errors of the identified BYM and RYM are all below 15%. The proposed methodology for Young’s modulus identification is feasible and achieves satisfactory accuracy and computational efficiency in both simulations and physical experiments.
Improved Augmented Lagrangian Relaxation-Assisted Analytical Target Cascading for Multidisciplinary Design Optimization
Authors: Zhou Xiaowei , Li Wei
Published: January 2025

Analytical target cascading (ATC) is an optimization strategy designed for multilevel and multidisciplinary design optimization (MDO) problems. Its core aim is to enhance the overall convergence of the system by reducing the inconsistency between different levels. In previous studies, although the augmented Lagrangian relaxation method can achieve rapid and accurate positioning of the optimal solution, it is highly sensitive to the penalty parameters, which can easily cause instability in numerical calculation. In contrast, the Lagrangian duality theory effectively reduces the numerical instability by adaptively adjusting the parameters, but this method is at the expense of increasing the computational time and the number of iterations. This study proposes an analytical target cascading combined with the Maclaurin series method (ATC-MAC), which aims to reduce parameter sensitivity and accelerate convergence to the optimal solution. The method uses the Maclaurin series to approximate the cross terms in the augmented Lagrangian function to reduce its interference with the main function. Meanwhile, the step size updating strategy is optimized by combining the duality theory and the multiplier method. Through the application in three numerical cases and one engineering case, the effectiveness and practicability of the ATC-MAC method are verified.
Compliant Toggle-Linkage Mechanisms: A New Type of Displacement–Force Amplification Principle
Authors: Wu Shilei , Ling Mingxiang
Published: January 2025

A compliant toggle-linkage mechanism with the dual functions of displacement amplification and reduction is proposed. A series of compliant amplification mechanisms are examined by combining multi-group flexure toggle linkages, showcasing a flexible design with modular flexure toggle-linkage building blocks. A compliant toggle-lever mechanism is then investigated in detail as a displacement amplifier and a reducer for piezoelectric actuators by exchanging the input and output ports. Its kinetostatic and dynamic performances are captured using an improved dynamic stiffness matrix modeling procedure with high prediction accuracy and robustness, which shifts the end nodes of all adjacent flexure hinge/beam members to be coincident in order to deal with the irregular connection of building blocks. It is interestingly observed that the output displacements with forward and reverse motion directions can be simultaneously achieved with such a compliant toggle-lever mechanism by changing the structural parameters. Finally, the relationship of displacement amplification and reduction ratios between the input and output ports is clarified and discussed by comparing the results among the dynamic stiffness matrix model, finite element simulation, and experimental testing.
Maximum Stress Minimization Via Data-Driven Multifidelity Topology Design
Authors: Kato Misato , Kii Taisei , Yaji Kentaro , Fujita Kikuo
Published: January 2025

The maximum stress minimization problem is among the most important topics for structural design. The conventional gradient-based topology optimization methods require transforming the original problem into a pseudo-problem by relaxation techniques. Since their formulation methods and the parameter settings significantly influence optimization, a method is required to accurately solve the original maximum stress minimization problem without using relaxation techniques. This paper focuses on this challenge and compares solutions obtained by gradient-based topology optimization with those obtained by solving the original maximum stress minimization problem without relaxation techniques. We employ data-driven multifidelity topology design (MFTD), a gradient-free topology optimization based on evolutionary algorithms. The basic framework involves generating candidate solutions by solving a low-fidelity optimization problem, evaluating these solutions through high-fidelity forward analysis, and iteratively updating them using a deep generative model without sensitivity analysis. In this study, data-driven MFTD incorporates the optimized designs obtained by solving a gradient-based topology optimization problem with the p-norm stress measure in the initial solutions and solves the original maximum stress minimization problem based on a high-fidelity analysis with a body-fitted mesh. We demonstrate the effectiveness of our proposed approach through the benchmark of L-bracket. As a result of solving the original maximum stress minimization problem with data-driven MFTD, a volume reduction of up to 22.6% was achieved under the same maximum stress value, compared to the initial solution.
A Robust Algorithm for Solving Heterogeneous Systems of Equations Arising in Kinetostatics of Compliant Mechanisms
Authors: Tari Hafez
Published: January 2025

Design and analysis of compliant mechanisms draw constraints from both kinematics and statics, resulting in heterogenous systems of equations. This heterogeneity makes the system numerically ill conditioned and not amenable to the entire solution set (conversely seen for rigid mechanisms), thus burdening Jacobian-based solution procedures and the underlying design or analysis. This article proposes a robust restrained line search for Newton’s method for the numerical solution of such heterogeneous systems. This novel line search (i) prioritizes accuracy of the underlying function approximation over the widely used minimization of the functional residual error and (ii) employs a dual objective function definition with closed-form Hessian formulation to maximize performance. It addresses gaps existing in the classical Newton’s method and makes the method truly localized, even more than the MATLAB’s nonlinear solver “fsolve.” Examples from 2D inverse and 14D coupled kinetostatics of compliant mechanisms are presented to demonstrate the robustness of the proposed algorithm, rendering it into a black-box solver for kinetostatic problems.
Soft Robot Kinematic Control Via Manipulability-Aware Redundancy Resolution
Authors: Azizkhani Milad , Ha Junhyoung , Gunderman Anthony L. , Chen Yue
Published: January 2025

This article addresses the kinematic control of a redundant soft robotic arm. Full pose kinematic control of soft robots is challenging because direct application of the classical controllers developed based on rigid robots to soft robots could lead to unreliable or infeasible motions. In this study, we explore the manipulability property of a soft robotic arm and develop an advanced resolved-rate controller that prioritizes position over orientation control and switches its modes and gains based on position and orientation manipulabilities, enabling stable motion even when the robot is close to the singular configurations. The simulation and experimental results indicate that our proposed method outperforms previous methods in terms of both accuracy and smoothness during operation.
Enhanced Thermal Regulation of Lithium-Ion Batteries Using Composite Phase Change Material–Fin Structures for High Heat Dissipation
Authors: Shehabaz S. M. D. , Gugulothu S. K. , Muthyala Raju , Barmavatu Praveen
Published: January 2025

Poor thermal conductivity is common in batteries that use phase change material (PCM)-based thermal management systems (BTMS). This study introduces cylindrical rings and longitudinal fins to improve heat transfer. The thermal performance of several BTMS configurations is the primary focus of this analysis. The results show that the PCM–fin system offers superior temperature management compared to both pure PCM and pure battery systems. To understand the mechanisms, numerical simulations were compared against experimental data available in the literature. Numerical analysis shows that the fin shapes increase heat transmission and create a thermal conductive network inside the PCM, improving battery thermal performance. The study indicates that the effectiveness of thermal management is influenced by the number of extended surfaces and rings, as well as the heat generation rate. One cylindrical ring and eight longitudinal fins, with a dimensionless spacing of 0.2 between the battery and the ring, are recommended. The PCM–fin technology also effectively controls the battery's temperature rise at 20 W, proving its durability in high-heat conditions.
Evaluation of CRDi Engine Fueled With Binary and Ternary Blends of Biodiesel, Butanol, and Diesel
Authors: Amba Prasad Rao G. , Vinod Babu M.
Published: January 2025

An automotive-type four-cylinder turbocharged common rail direct injection (CRDi) engine has been considered to utilize a higher proportion of biodiesel beyond 20% while effectively addressing the NOx–soot engine performance trade-off with biodiesel, butanol, and petro-diesel fuel blends. Mixed feedstock obtained from Sterculia foetida oil and used palm oil in equal proportions to prepare biodiesel, and three binary and three ternary blends, prepared in different proportions, have been considered. Fuels were prepared with butanol blended with biodiesel and petro-diesel in different proportions. Investigations were carried out at various speed and load conditions similar to idling, urban, and highway drive conditions by varying the main injection timing and boost pressure, keeping other parameters at optimized values. The speed test conditions are chosen from a modified Indian driving cycle to simulate real driving conditions. The results obtained with different blends are compared against engine operation with neat petro-diesel operation. The engine is incorporated with a variable geometry turbine for increasing intake air and an open electronic control unit (ECU) for setting the operating parameters. For facilitating split injections, a dwell period (time between start of pilot and start of main injection) of 27° crank angle (CA) [i.e., with pilot injection timing (PIT) at 28 deg before top dead center (bTDC) and main injection timing (MIT) at 1 deg bTDC], pilot injection quantity (PIQ) of 11%, and fuel injection pressure (FIP) of 61.4 MPa are recommended for the speed and load conditions under consideration and the given engine configuration. Among the tested ternary blends, B20Bu10D70 and B30Bu10D60 showed improvement in NOx and smoke emissions, with low-temperature combustion-like conditions observed. The use of renewable fuels will effectively address UNO's sustainable development goals.
The meninges host a distinct compartment of regulatory T cells that preserves brain homeostasis
Authors: Marin-Rodero Miguel , Cintado Elisa , Walker Alec J. , Jayewickreme Teshika , Pinho-Ribeiro Felipe A. , Richardson Quentin , Jackson Ruaidhrí , Chiu Isaac M. , Benoist Christophe , Stevens Beth , Trejo José Luís , Mathis Diane
Published: January 2025

Our understanding of the meningeal immune system has recently burgeoned, particularly regarding how innate and adaptive effector cells are mobilized to meet brain challenges. However, information on how meningeal immunocytes guard brain homeostasis in healthy individuals remains limited. This study highlights the heterogeneous, polyfunctional regulatory T cell (T
reg
) compartment in the meninges. A T
reg
subtype specialized in controlling interferon-γ (IFN-γ) responses and another dedicated to regulating follicular B cell responses were substantial components of this compartment. Accordingly, punctual T
reg
ablation rapidly unleashed IFN-γ production by meningeal lymphocytes, unlocked access to the brain parenchyma, and altered meningeal B cell profiles. Distally, the hippocampus assumed a reactive state, with morphological and transcriptional changes in multiple glial cell types. Within the dentate gyrus, neural stem cells underwent more death and were blocked from further differentiation, which coincided with impairments in short-term spatial-reference memory. Thus, meningeal T
regs
are a multifaceted safeguard of brain homeostasis at steady state.
Restoring ceftolozane susceptibility: a role for diazabicyclooctane β-lactamase inhibitors?
Authors: Dorazio Ava J. , Kline Ellen G. , Squires Kevin M. , Pogue Jason M. , Van Tyne Daria , Shields Ryan K.
Published: January 2025

Paired baseline and post-exposure isolates from 34 patients who developed ceftolozane–tazobactam (TOL-TAZ) resistance following treatment of multidrug-resistant (MDR)
Pseudomonas aeruginosa
infections were analyzed to determine if ceftolozane with an alternative β-lactamase inhibitor could restore susceptibility. The median baseline TOL-TAZ MIC was 2 mg/L; 88% of post-exposure isolates harbored new
ampC
mutations. Median MIC fold-increase from baseline was 32-, 24-, 16-, and 6-fold for ceftolozane–tazobactam, ceftolozane–avibactam (AVI), ceftolozane–relebactam (REL), and ceftolozane–durlobactam (DUR), respectively. Enhanced ceftolozane–durlobactam activity was evident in specific
ampC
mutations.
mSphere of Influence: Seeking the unseen fungi in tumors
Authors: Liu Ning-Ning
Published: January 2025

Ningning Liu works in the field of fungal infection and cancer progression, with a particular focus on the mechanism of host-pathogen interaction. In this mSphere of influence article, he reflects on how papers entitled “The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL,” by B. Aykut, S. Pushalkar, R. Chen, Q. Li, et al. (Nature 574:264–267, 2019,
https://doi.org/10.1038/s41586-019-1608-2
), and “A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors,” by A. B. Dohlman, J. Klug, M. Mesko, I. H. Gao, et al. (Cell 185:3807–3822.E12, 2022,
https://doi.org/10.1016/j.cell.2022.09.015
), emphasized the non-negligible role of fungi in the host and demonstrated a connection between fungi and cancer. These researches arouse his interest in seeking the novel fungal pathogen lurking inside tumors and understanding the unexplored mechanisms behind the severe fungal infections in cancer patients.
Systematic analyses uncover robust salivary microbial signatures and host-microbiome perturbations in oral squamous cell carcinoma
Authors: Han Zewen , Hu Yichen , Lin Xin , Cheng Hongyu , Dong Biao , Liu Xuan , Wu Buling , Xu Zhenjiang Zech
Published: January 2025

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy in the oral-maxillofacial region with a poor prognosis. Oral microbiomes play a potential role in the pathogenesis of this disease. However, findings from individual studies have been inconsistent, and a comprehensive understanding of OSCC-associated microbiome dysbiosis remains elusive. Here, we conducted a large-scale meta-analysis by integrating 11 publicly available data sets comprising salivary microbiome profiles of OSCC patients and healthy controls. After correcting for batch effects, we observed significantly elevated alpha diversity and distinct beta-diversity patterns in the OSCC salivary microbiome compared to healthy controls. Leveraging random effects models, we identified robust microbial signatures associated with OSCC across data sets, including enrichment of taxa such as
Streptococcus
,
Lactobacillus
,
Prevotella
,
Bulleidia moorei
, and
Haemophilus
in OSCC samples. The machine learning models constructed from these microbial markers accurately predicted OSCC status, highlighting their potential as non-invasive diagnostic biomarkers. Intriguingly, our analyses revealed that the age- and gender-associated signatures in normal saliva microbiome were disrupted in the OSCC, suggesting perturbations in the intricate host-microbe interactions. Collectively, our findings uncovered complex alterations in the oral microbiome in OSCC, providing novel insights into disease etiology and paving the way for microbiome-based diagnostic and therapeutic strategies. Given that the salivary microbiome can reflect the overall health status of the host and that saliva sampling is a safe, non-invasive approach, it may be worthwhile to conduct broader screening of the salivary microbiome in high-risk OSCC populations as implications for early detection.

IMPORTANCE

The oral cavity hosts a diverse microbial community that plays a crucial role in systemic and oral health. Accumulated research has investigated significant differences in the saliva microbiota associated with oral cancer, suggesting that microbiome dysbiosis may contribute to the pathogenesis of oral squamous cell carcinoma (OSCC). However, the specific microbial alterations linked to OSCC remain controversial. This meta-analysis reveals robust salivary microbiome alterations. Machine learning models using differential operational taxonomic units accurately predicted OSCC status, highlighting the potential of the salivary microbiome as a non-invasive diagnostic biomarker. Interestingly, age- and gender-associated signatures in the normal salivary microbiome were disrupted in OSCC, suggesting perturbations in host-microbe interactions.
Novel PiuC, PirA, and PiuA mutations leading to
in vivo
cefiderocol resistance progression in IMP-16- and KPC-2-producing
Pseudomonas aeruginosa
from a leukemic patient
Authors: Viñes Joaquim , Herrera Sabina , Vergara Andrea , Roca Ignasi , Vila Jordi , Aiello Tommaso Francesco , Martínez José Antonio , del Río Ana , Lopera Carlos , Garcia-Vidal Carolina , Casals-Pascual Climent , Soriano Àlex , Pitart Cristina
Published: January 2025

Pseudomonas aeruginosa
is an opportunistic pathogen capable of causing severe infections in immunocompromised individuals, who often require prolonged antibiotic therapy. The emergence of carbapenemase-producing
P. aeruginosa
has further complicated the management of nosocomial infections, limiting therapeutic options. Cefiderocol has recently emerged as a promising antipseudomonal agent, using the bacterial iron transport system to gain entry into the cell; however, there have been reports of
P. aeruginosa
resistant to cefiderocol. We describe the
in vivo
cefiderocol resistance progression of four consecutive
P. aeruginosa
isolates from one patient with T-cell acute lymphoblastic leukemia. Analysis of potential genes involved in cefiderocol transport resulted in three genes mutated in two resistant isolates. One isolate presented a S116F substitution in PiuC, and the other presented a deletion of 29 amino acids in the signal peptide of PiuA and a STOP substitution in PirA, resulting in the deletion of a piece of the channel. These mutations increased 24- and 64-folds the cefiderocol minimum inhibitory concentration, respectively. The mutations in the aforementioned genes may directly impact siderophore internalization, thereby contributing to an elevation in the MIC of the antibiotic.

IMPORTANCE

Carbapenem-resistant
Pseudomonas aeruginosa
poses a significant challenge due to its broad antibiotic resistance. Cefiderocol is a novel antibiotic aimed at combating infections caused by such organisms. However, if these pathogens develop resistance to this new drug, it hinders treatment efficacy and options. Therefore, it is crucial to identify and describe mutations in the genes involved in the uptake of cefiderocol to find better treatment strategies for patients infected with multidrug-resistant
P. aeruginosa
.
Characterization of spike S1/S2 processing and entry pathways of lentiviral pseudoviruses bearing seasonal human coronaviruses NL63, 229E, and HKU1 spikes
Authors: Neerukonda Sabari Nath , Vassell Russell , Lusvarghi Sabrina , Liu Shufeng , Akue Adovi , Kukuruga Mark , Wang Tony T. , Weiss Carol D. , Wang Wei
Published: January 2025

Although much has been learned about the entry mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many details of the entry mechanisms of seasonal human coronaviruses (HCoVs) remain less well understood. In the present study, we used 293T cell lines stably expressing angiotensin converting enzyme (ACE2), aminopeptidase N (APN), or transmembrane serine protease 2 (TMPRSS2), which support high-level transduction of lentiviral pseudoviruses bearing spike proteins of seasonal HCoVs, HCoV-NL63, -229E, or -HKU1, respectively, to compare spike processing and virus entry pathways among these viruses. Our results showed that the entry of HCoV-NL63, -229E, and -HKU1 pseudoviruses into cells is sensitive to endosomal acidification inhibitors (chloroquine and NH
4
Cl), indicating entry via the endocytosis route. Although TMPRSS2 expression on target cell surface was required for HCoV-HKU1 spike-mediated entry and cell–cell fusion, we found that only the serine protease domain of TMPRSS2 and not the serine protease activity of TMPRSS2 was required for viral entry via endocytic route. However, the serine protease activity of TMPRSS2 and a furin processing site (RKRR) at the S1/S2 junction were essential for efficient HCoV-HKU1 spike-mediated cell–cell fusion. Additionally, we show that dibasic and monobasic arginine residues at the S1/S2 junctions of spike proteins of HCoV-NL63 and -229E are essential for virus entry, but multi-basic furin processing site at the S1/S2 junction was dispensable for HCoV-HKU1 viral entry. Our findings highlight features of the entry mechanisms of seasonal HCoVs that may support the development of novel treatment strategies.

IMPORTANCE

Details of the entry mechanisms of seasonal human coronaviruses (HCoVs) remain to be fully explored. To investigate spike-mediated virus entry of HCoV-NL63, -229E, and -HKU1 CoVs, we employed 293T cells that stably express angiotensin converting enzyme (ACE2), aminopeptidase N (APN), or transmembrane serine protease 2 (TMPRSS2) to study entry mechanisms of pseudoviruses bearing spike proteins of HCoV-NL63, -229E, and -HKU1, respectively. We found that HCoV-NL63, -229E, and -HKU1 pseudoviruses entered cells via the endocytic route independently of cellular serine protease activity and therefore likely depended on endosomal cathepsin activity. Furthermore, we showed that arginine amino acids in S1/S2 junctions of HCoV-NL63 and -229E spikes were essential for entry but not essential for HCoV-HKU1 entry. Our results provide new insights into the S1/S2 junctional residues, cellular receptors, and protease requirements for seasonal HCoV pseudovirus entry into cells that may support the development of novel inhibitors.
Postauricular feather foreign body in an infant
Authors: Hemmad Aayushi , Tabaksert Ayla Serena , Lowe David Ashley
Published: January 2025

A male infant presented with reduced oral intake, low-grade fever and postauricular erythema. Clinical examination revealed a soft, tender swelling posteroinferior to the mastoid tip with a dull tympanic membrane on otoscopy. Cross-sectional imaging did not show any evidence of middle ear infection or mastoiditis. However, there was minimal change in clinical status despite trialling various intravenous antibiotics. One week after admission, a thin, white foreign body self-extruded from the upper part of the postauricular skin, recognised by the child’s parents as a feather from their sofa cushion. The suspected mechanism was the penetration of the feather into the skin when the child was lying on the sofa. While incredibly rare, soft tissue foreign bodies should be considered in paediatric patients with postauricular swelling not responding to antibiotics.
Non-bacterial thrombotic endocarditis in a patient with high-grade serous ovarian carcinoma: diagnostic challenges and management insights
Authors: Altaher Hibatallah , Saleem Maaham , Coulson Daniel , Abiola Olukayode
Published: January 2025

Non-bacterial thrombotic endocarditis (NBTE) is characterised by sterile vegetations on heart valves and often emerges in hypercoagulable states like malignancy. It is frequently underdiagnosed and only comes to light during postmortem examination. Early diagnosis and treatment with anticoagulation can help lower mortality. We present a case of a woman in her 60s with marantic endocarditis, secondary to ovarian malignancy. She presented with a 4 week history of headache, confusion and abdominal discomfort. Examination revealed cyanosis, splinter haemorrhages and abdominal tenderness. Echocardiogram showed impaired left ventricular function and suspicion of a small vegetation at the tip of the anterior mitral valve. Further investigation revealed multiple cerebellar infarcts, pulmonary embolism, splenic infarct, ascites and a pelvic mass. A biopsy of the pelvic mass and analysis of ascitic fluid was consistent with high-grade serous carcinoma of tubo-ovarian origin. Following discussion at the gynaecology multidisciplinary team meeting, she was scheduled for chemotherapy treatment.
Sellar spine: a rare midline osseous spur
Authors: Rampersad Fidel , Diljohn Jason , Seepersad Sati , Cassim Nicolette
Published: January 2025

A sellar spine is a rare midline osseous spur, which arises from the dorsum sellae and projects into the pituitary fossa. It can be found incidentally on imaging or may present with symptoms related to optic chiasm compression or hormonal disturbances.

Herein, we present the case of an incidentally detected sellar spine in a patient presenting with sudden onset headaches.
Equity in medical devices: a socio-technical approach
Authors: Ensor Jonathan , Farnan Robert , Johnson Steven
Published: January 2025

Medical devices risk reinforcing societal inequalities unless we rethink how they are designed, developed and deployed. The UK government’s recent independent review on Equity in Medical Devices highlights how biases in the design and use of medical devices can lead to solutions that fail to equitably distribute benefits or can further exacerbate health inequalities. In this paper, we draw attention to how wider social, cultural, political and economic factors can also shape the way medical devices are designed, developed and deployed, and how individuals can access or come to be excluded from the associated benefits. Using the example of continuous glucose monitoring devices, we show the potential for medical devices to undermine patient well-being, to occlude patient expertise, and to reflect the priorities of politics rather than patients. These systemic failures highlight the urgent need to reconsider innovation and to develop processes where equity is a fundamental goal and moral responsibility. Here, we suggest a framework for equitable innovation that combines a process of co-design that accounts for knowledge, power and social differences among stakeholders, with considerations of technical needs alongside the institutional arrangements that mediate how devices are deployed in different social contexts.
Prevalence, predictors and selected outcomes of early sexual initiation among adolescents in secondary schools in Lugbe, Abuja, Nigeria: a mixed methods study
Authors: Okonta Uchechi Grace
Published: January 2025

Background

Early sexual initiation is the onset of sexual intercourse below 15 years. Despite many negative effects of early sexual initiation, its prevalence has kept increasing globally over the past decades.

Objective

This study aims to determine the burden, identify risk factors and examine the selected outcomes of early sexual initiation among secondary school adolescents.

Design

The study was a school-based descriptive cross-sectional survey which employed quantitative and qualitative methods.

Method

A descriptive cross-sectional survey was conducted among 300 in-school adolescents aged 15–19 in Lugbe, Abuja. Data were collected using an interviewer-administered questionnaire. Focus group discussion was also conducted in six schools using a structured FGD Guide. The prevalence of early sexual initiation was determined. Descriptive and inferential statistical analysis was done including a binary logistic regression to determine the predictive factors and outcomes of early sexual initiation with statistical inference made at p value <0.05.

Results

The prevalence of early sexual initiation was 11%; 80% of the respondents who had initiated sex did so before age 15, while 20% had first sex at ages between 15 and 19. Gender, academic performance, communication with parents and peer pressure were significantly associated predictive factors. Pregnancy, abortion, sexually transmitted infections, loss of self-confidence, expulsion from school, poor academic performance and depression were associated outcomes. Four main themes were identified from the qualitative data: being in a romantic relationship, peer pressure, media and lack of parental communication and monitoring.

Conclusion

The study concluded that there is high prevalence of early sexual initiation among those who had initiated sex. Predictive factors such as peer pressure, parental communication and media influence can be addressed by the inclusion of sex education in school curriculum and training of peer educators, advocacy and health education for parents of adolescents.
Understanding patient safety during earthquakes: a phenomenological study of disaster response
Authors: Palteki Tunçay , Salimi Saleh , Younas Ahtisham , Taylan Selahattin , Aydın Emre
Published: January 2025

Background

Natural hazards, such as earthquakes, pose a significant risk to both the public and healthcare professionals, jeopardising patient safety due to the disruption of healthcare systems and services. This study aimed to explore the lived experiences of healthcare professionals concerning patient safety during natural hazards, specifically earthquakes.

Methods

Employing a descriptive phenomenological approach, the study followed the Consolidated Criteria for Reporting Qualitative Research guidelines. 23 participants, including doctors, nurses and paramedics, were interviewed using purposive sampling. Data were gathered through semistructured interviews, which were audio recorded and transcribed. Ethical approval was obtained, and Colaizzi’s method was used for data analysis, with findings validated through researcher consensus and participant feedback.

Results

Nine overarching themes emerged, such as the emotional toll of communication breakdowns, struggles with patient identification, stress due to resource scarcity, operational chaos, ethical dilemmas and psychological impacts on both patients and staff. The study found that these factors collectively influenced patient safety during the earthquake.

Conclusion

The emotional strain caused by communication failures, patient identification issues and resource shortages compounded the challenges of providing safe care during the earthquake. Strengthening disaster preparedness through improved communication systems, resource management, psychological support, interagency coordination and regular realistic disaster drills is essential for safeguarding patient safety in future disasters.
Impact of changes in primary care attachment: a scoping review
Authors: Godfrey Leanda , St-Amant Antoine , Premji Kamila , Fitzsimon Jonathan
Published: January 2025

Objectives

Primary care attachment represents an inclusive, equitable and cost-effective way of enhancing health outcomes globally. However, the growing shortage of family physicians threatens to disrupt patient–provider relationships. Understanding the consequences of these disruptions is essential for guiding future research and policy. The objectives of this study were to map the existing evidence on the impacts of changes in primary care attachment, identify research gaps and recommend areas for further investigation.

Design

Scoping review following Joanna Briggs Institute (JBI) guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist. Two researchers conducted all stages of screening, and study quality was assessed using JBI critical appraisal tools. Key themes included causes of attachment change, direction of change and outcomes aligned with the quintuple aim framework. Both qualitative and quantitative findings were synthesised narratively.

Eligibility criteria

Peer-reviewed, English-language articles published between 1999 and 2024 on primary care attachment changes.

Information sources

PubMed, Scopus and Web of Science.

Results

Of 2045 studies screened, 31 met inclusion criteria, with 60% published after 2020. Most studies originated from high-income countries, particularly the USA (35%) and Canada (29%). Attachment losses and transfers were the most frequently studied, while attachment and unattachment durations were less explored. These changes in attachment were consistently shown to impact patients, providers, clinics and the healthcare system, influencing all aims of the quintuple aim framework, including clinical outcomes, healthcare utilisation, costs, equity and patient experience. Commonly assessed outcomes included clinical impact (68%), health equity (48%), patient experience (32%) and costs (23%), with no study assessing provider experience.

Conclusions

This scoping review maps the published literature on changes in primary care attachment and introduces clarifying terminology. Key research gaps include geographical diversity (lack of studies from low- and middle-income countries), attachment gain (limited research on strategies to reconnect unattached patients), attachment duration (insufficient evidence on long-term health outcomes), economic implications (underexplored costs of physician turnover and disruption), provider experiences (lack of studies on how changes in primary care attachment impact provider burnout, job satisfaction and workload) and patient health outcomes (focus on healthcare utilisation rather than direct health outcomes). These findings underscore the need for further research and offer valuable insights for future studies and policy development.
Chinese expert consensus on vaginal self-sampling with high-risk human papillomavirus testing for cervical cancer screening
Authors: Li Jingran , Wu Ruifang , Li Mingzhu , Du Hui , Sui Long , Kong Beihua , Zhao Fanghui , Wang Linhong , Zhao Yun , Qu Xinfeng , Ma Ding , Wei Lihui
Published: January 2025

Cervical cancer is one of the most common cancers in women globally and remains the leading cause of cancer-related death among women in low- and middle-income countries. It is more prevalent in populations that are unscreened or underscreened. Improving screening coverage presents a global challenge. Self-collected cervical cancer screening allows women to collect samples for high-risk human papillomavirus (HR-HPV) testing on PCR-based tests, effectively increasing screening rates for cervical cancer. In light of the push for HR-HPV testing as a primary cervical cancer screening strategy and considering the current status of cervical cancer screening in China, experts from five academic societies developed a consensus that including the definition, value, advantages, applicable people, screening proposal, tools and methods, process, sampler distribution form, organisational screening model, HPV DNA testing, abnormal results management of vaginal self-sampling, information system construction, management quality control and so on, aims to guide the standardised application of vaginal self-sampling screening, enhance cervical cancer screening coverage in China and advance the efforts to eliminate cervical cancer in the country.