bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the effectiveness of continuous glucose monitoring compared with conventional monitoring in enhancing surgical outcomes for patients with diabetes: protocol for a multicentre, parallel-arm, randomised, pragmatic trial in China
Authors: Duan Yi , Ding Lin , Gao Zhifeng , Wang Yutong , Cao Han , Zhang Huan , Yao Lan
Published: February 2025

Introduction

The Comprehensive Complication Index (CCI) is an internationally recognised indicator of postoperative complications. During the perioperative period, patients with diabetes mellitus (DM) or impaired glucose tolerance (IGT) may experience a significant increase in the CCI associated with glucose-related complications and increased mortality. Continuous glucose monitoring (CGM) offers advantages such as portability, accuracy, real-time monitoring and rich information. However, few large-scale studies have investigated the effectiveness and safety of CGM in reducing CCI during major surgeries.

Methods and analysis

This study is a multicentre, parallel-arm, randomised pragmatic trial to investigate whether CGM improves clinical outcomes in patients with type 1 or type 2 DM or IGT undergoing major surgery relative to conventional monitoring. This study is planned to be conducted in 50 secondary or tertiary hospitals in China. Eligible patients aged 18 years or older with DM or IGT undergoing elective major surgery will be recruited during a baseline screening period of 3 days before surgery. Eligible patients will be randomly assigned to receive CGM or conventional monitoring in a 1:1 ratio. The primary endpoint measure is the CCI score within 30 postoperative days. The margin of superiority is −12.0. A total of 10 168 participants will achieve 90% power to detect a clinically important difference of −13.0 between the means in the primary outcome. This trial includes multiple statistical analysis steps. For the primary outcome, a covariance model will be used to compare the difference in CCI within 30 days postoperatively between the two groups after adjusting for baseline and centre effects.

Ethics and dissemination

This trial has been approved by the Ethics Committee of Beijing Tsinghua Changgung Hospital (No. 23684-0-02) and its corresponding branch centres. Informed consent will be obtained from all subjects involved in the study. The primary trial results will be submitted for publication to a peer-reviewed journal.

Trial registration number

NCT06331923.
Response to Jesudason on ethical problems with kindness in healthcare
Authors: Tan Charlene , Neo Ruth
Published: February 2025

In this paper, we respond to a recent article by Edwin Jesudason regarding the ethical problems associated with kindness in healthcare. Jesudason contends that kindness contributes to unkind outcomes such as discrimination and systemic problems in healthcare. We disagree with his above assertion by forwarding three arguments. First, we question his association of kindness with favouritism through his conflation of favour with favouritism. We counter that doing someone a favour does not necessarily mean that preferential treatment is involved. Second, we object to his interpretation of discretionary kindness as possessing ‘circumscribed scope’, that is, doing favours to the ingroup and leaving out others. We maintain that the discretionary element of kindness does not denote inclusivity and instead refers to the judgement and prudence needed for a person to act kindly in specific circumstances. Our third argument concerns Jesudason’s emphasis on kindness as an action. By focussing on kind acts, he has inadvertently overlooked kindness as a moral value, attitude and inclination of a person. Overall, Jesudason has provided an inadequate explanation of kindness as a virtue. We suggest that a kind person does not promote or condone unkind outcomes such as prejudice, abuses and structural problems in healthcare. Instead, such a person goes beyond discrete kind acts and ingroup loyalty to actively demonstrate compassion, generosity and assistance towards those in need in a spontaneous and consistent manner.
Early snowmelt accelerates bud break but has mixed effects on leaf area of understory woody plants in a heavily snow-covered deciduous forest in northern Japan
Authors: Kunishima Mayu , Yoshimura Kenichi
Published: February 2025

Climate change induces earlier snowmelt in most regions and extends growing seasons for woody plants. However, there is still limited understanding of how the relative impacts and interactions of light, temperature, and water conditions altered by early snowmelt affect phenological and morphological traits of understory plants. We conducted snow removal experiments in a heavily snow-covered forest. We compared bud break dates and leaf size developments with the effects of snow removal in understory Fagus crenata, Lindera umbellata, and Viburnum furcatum. Snow removal increased temperature and light conditions around buds but decreased the soil moisture during bud break. Removing snow one month before ambient snowmelt accelerated bud break but only by 5.9-11.9 days. Bud break in individuals with snow removal required more thawing degree days around buds than under ambient conditions. Leaf areas of V. furcatum in the snow removal were smaller than those in controls. Summarizing changes in light conditions and leaf area growth, the earlier bud break and leaf growth did not result in greater light capture potential over the spring period in L. umbellata and V. furcatum. Although earlier snowmelt accelerates bud break and leaf expansion in these plants, this may not result in greater carbon accumulation.
Construction of College Labor Education Evaluation System Based on Big Data and K-Means
Authors: Ying Zhao
Published: February 2025

The labor education evaluation system often has problems such as strong subjectivity and a single evaluation index, which makes it difficult to comprehensively and objectively reflect the students’ labor literacy and practical ability. Therefore, a college labor education evaluation system based on big data and [Formula: see text]-means is constructed. To enhance labor education, we first collect relevant data. An evaluation ratio threshold is then set to eliminate low-quality data. By leveraging big data and cloud computing technology, we build a personalized labor education and teaching evaluation system. Within this system, the [Formula: see text]-means clustering algorithm is employed to classify a vast amount of college labor education data. To optimize the clustering center, particle swarm optimization is introduced. Furthermore, a multi-level evaluation system is constructed using the AHP method. This approach enables a comprehensive and systematic assessment of the effectiveness of labor education. The experimental results show that the resource utilization efficiency of the design methods is more than 90%, the loss value is the lowest 0.39, the average iteration time is 4.462[Formula: see text]s, and the evaluation time is 15[Formula: see text]s. The data clustering results show higher clustering clarity.
Highly dispersive gap solitons with the Kaup–Newell in fiber Bragg grating with white noise effects
Authors: Zayed Elsayed M. E. , El-Shater Mona , Murad Muhammad Amin S. , Secer Aydin , Ozisik Muslum , Arnous Ahmed H.
Published: February 2025

This study introduces an innovative examination of the stochastic Kaup–Newell equation within the realm of fiber Bragg grating, signifying a pioneering effort in this area. The study uses two main methods for integration: the [Formula: see text]-expansion method and the enhanced direct algebraic method to find different one-step solutions to the Kaup–Newell equation. The outcomes of this research are multifaceted, revealing an array of optical soliton solutions such as dark, singular, bell-shaped, kink-shaped, bright, and straddled solitons. These findings contribute a novel perspective on the behavior of optical solitons in fiber Bragg gratings, which are essential for optical communications and signal processing. Additionally, applying numerical schemes to these analytically obtained solutions offers a detailed visualization of their characteristics and behaviors, enhancing our understanding of their potential in practical scenarios. This work extends the range of soliton solution types for application and paves the way for subsequent explorations in the field of nonlinear optical systems.
FlightKoopman: Deep Koopman for Multi-Dimensional Flight Trajectory Prediction
Authors: Lu Jing , Jiang Jingjun , Bai Yidan , Dai Wenxiang , Zhang Wei
Published: February 2025

Multi-dimensional Flight Trajectory Prediction (MFTP) in Flight Operations Quality Assessment (FOQA) refers to the estimation of flight status at the future time, accurate prediction future flight positions, flight attitude and aero-engine monitoring parameters are its goals. Due to differences between flight trajectories and other kinds trajectories and difficult access to data and complex domain knowledge, MFTP in FOQA is much more challenging than Flight Trajectory Prediction (FTP) in Air Traffic Control (ATC) and other trajectory prediction. In this work, a deep Koopman neural operator-based multi-dimensional flight trajectory prediction framework, called Deep Koopman Neural Operator-Based Multi-Dimensional Flight Trajectories Prediction (FlightKoopman), is first proposed to address this challenge. This framework is based on data-driven Koopman theory, enables to construct a prediction model using only data without any prior knowledge, and approximate operator pattern to capture flight maneuver for downstream tasks. The framework recovers the complete state space of the flight dynamics system with Hankle embedding and reconstructs its phase space, and combines a fully connected neural network to generate the observation function of the state space and the approximation matrix of the Koopman operator to obtain an overall model for predicting the evolution. The paper also reveals a virgin dataset Civil Aviation Flight University of China (CAFUC) that could be used for MFTP tasks or other flight trajectory tasks. CAFUC Datasets and code is available at this repository: https://github.com/CAFUC-JJJ/FlightKoopman . Experiments on the real-world dataset demonstrate that FlightKoopman outperforms other baselines.
Automated Program Repair: Emerging Trends Pose and Expose Problems for Benchmarks
Authors: Renzullo Joseph , Reiter Pemma , Weimer Westley , Forrest Stephanie
Published: February 2025

Machine learning (ML) pervades the field of Automated Program Repair (APR). Algorithms deploy neural machine translation and large language models (LLMs) to generate software patches, among other tasks. But, there are important differences between these applications of ML and earlier work, which complicates the task of ensuring that results are valid and likely to generalize. A challenge is that the most popular APR evaluation benchmarks were not designed with ML techniques in mind. This is especially true for LLMs, whose large and often poorly-disclosed training datasets may include problems on which they are evaluated.

This paper reviews work in APR published in the field’s top five venues since 2018, emphasizing emerging trends in the field, including the dramatic rise of ML models, including LLMs. ML-based papers are categorized along structural and functional dimensions, and a variety of issues are identified that these new methods raise. Importantly, data leakage and contamination concerns arise from the challenge of validating ML-based APR using existing benchmarks, which were designed before these techniques were popular. We discuss inconsistencies in evaluation design and performance reporting and offer pointers to solutions where they are available. Finally, we highlight promising new directions that the field is already taking.
Dynamic Per-Flow Queues in Shared Buffer TSN Switches
Authors: Wu Wenxue , Zhang Tong , Li Zhen , Feng Xiaoqin , Zhang Liwei , Ren Fengyuan
Published: February 2025

Time-Sensitive Networking (TSN), as an enhancement based on Ethernet, can ensure deterministic traffic transmission with low delays and minimal jitters. However, TSN switches have only eight priority queues inherited from Ethernet at each egress port, which limits the flexibility and efficiency of traffic scheduling, as well as the support for developing traffic management mechanisms. Although per-flow queues boost scheduling and Quality of Service (QoS), static per-flow hardware queues in switches are considered unpratical due to resource limits. In this paper, we leverage the limitation of buffer size on the number of concurrent flows in shared buffer TSN switches to design Dynamic Per-Flow Queues (DFQ). DFQ only maintains a fixed number of virtual queues determined by the buffer size and dynamically manages the mapping between virtual queues and active flows to provide the capability of per-flow queueing. By constructing Flow Mapping Table (FMT) with content-addressable memory (or hash bucket), DFQ can quickly match, create, and recycle queues to multiplex limited switch resource. We prototype DFQ on an FPGA switch and evaluate its performance in different scenarios. Experimental results show that DFQ can decrease the overhead of per-flow isolation with minimal impact on delay and throughput, indicating that DFQ is an effective per-flow queues solution.
Machine Learning and Deep Learning Models for Automated Protocoling of Emergency Brain MRI Using Text from Clinical Referrals
Authors: Huhtanen Heidi J. , Nyman Mikko J. , Karlsson Antti , Hirvonen Jussi
Published: February 2025

“Just Accepted” papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. Purpose To develop and evaluate machine learning and deep learning-based models for automated protocoling of emergency brain MRI scans based on clinical referral text. Materials and Methods In this single-institution, retrospective study of 1953 emergency brain MRI referrals from January 2016 to January 2019, two neuroradiologists labeled the imaging protocol and use of contrast agent as the reference standard. Three machine learning algorithms (Naïve Bayes, support vector machine, and XGBoost) and two pretrained deep learning models (Finnish BERT and GPT-3.5) were developed to predict the MRI protocol and need for contrast agent. Each model was trained with three datasets (100% of training data, 50% of training data, and 50% + augmented training data). Prediction accuracy was assessed with test set. Results The GPT-3.5 models trained with 100% of the training data performed best in both tasks, achieving accuracy of 84% (95% CI: 80%–88%) for the correct protocol and 91% (95% CI: 88%–94%) for contrast. BERT had an accuracy of 78% (95% CI: 74%–82%) for the protocol and 89% (95% CI: 86%–92%) for contrast. The best machine learning model in the protocol task was XGBoost (accuracy 78% [95% CI: 73%–82%]), and in the contrast agent task support vector machine and XGBoost (accuracy 88% [95% CI: 84%–91%] for both). The accuracies of two nonneuroradiologists were 80%–83% in the protocol task and 89%–91% in the contrast medium task. Conclusion Machine learning and deep learning models demonstrated high performance in automatic protocoling emergency brain MRI scans based on text from clinical referrals. Published under a CC BY 4.0 license.
Improving Sodium Manganese Hexacyanoferrate with Optimized Synthesis Conditions, Effective Drying, and Small Amounts of Nickel
Authors: Deshmukh Jay , Zhang Libin , Zhang Ning , Dutta Animesh , Ye Ziwei , Hijazi Hussein , Yue Meng , Tulloch Meredith , Johnson Michel , Metzger Michael
Published: February 2025

Prussian Blue Analogs are a promising class of positive electrode materials for sodium-ion batteries that can be synthesized at low temperatures using only Earth-abundant elements like sodium, iron, and manganese. Their open framework structure allows them to sustain high current densities but also makes them prone to absorption of moisture. We improve the specific capacity of sodium manganese hexacyanoferrate (MnHCF) by optimizing synthesis and processing conditions, enabling a material-level energy density of 562 Wh kg−1, which is on par with lithium iron phosphate. We remove interstitial water from these materials by rigorous drying. We also demonstrate a factor two improvement in cycling life of MnHCF by substituting only 3 at. % Ni for Mn and leaving some vacancies, which leads to 80% capacity retention after 3,500 h (∼5 months) of cycling in Na half cells at 0.2 C between 2.0 and 4.1 V and an ability to retain >85% capacity at a high current density of 10 C.
Biochemical Characterization and Antimicrobial Properties of Extracts From Four Food Plants Traditionally Used to Improve Drinking Water Quality in Rural Areas of Burkina Faso
Authors: Konkobo Frédéric Anderson , Barry Poussian Raymond , Zongo Sandrine , Ouédraogo Elisabeth Rakisewendé , Roamba Noëlle Edwige , Dakuyo Roger , Bazié David , Santara Balamoussa , Diao Mamounata , Savadogo Paul Windinpsidi , Dicko Mamoudou Hama
Published: February 2025

The use of local plant extracts in drinking water purification represents a sustainable alternative in the fight against diseases linked to unsafe water consumption in rural areas. The aim of this study was to evaluate the biochemical composition and antimicrobial activity of four local plant extracts used in rural areas of Burkina Faso to purify drinking water: Moringa oleifera seeds, Boscia senegalensis seeds, Opuntia ficus-indica cladodes, and Aloe vera leaves. These four extracts were then subjected to biochemical screening to identify phytocompounds, followed by quantification and evaluation of their antibacterial properties on ten pathogenic bacterial strains. The screening results revealed the presence of a variety of molecules (phenolic compounds, alkaloids, saponosides, etc.) in the different extracts studied. From a quantitative point of view, M. oleifera and B. senegalensis seeds showed a high total protein content (34.5 and 24.6 g/100 g DM). A. vera and O. ficus-indica extracts showed high levels of total carbohydrates (20.4 and 35.52 g/100 g DM) compared with total lipids and proteins. The same applies to phenolic compounds, which were also high in A. vera and O. ficus-indica extracts (17.42 and 26.5 mg GAE/100 mg DM) compared to M. oleifera and B. senegalensis seeds. In terms of antibacterial properties, the four extracts studied showed inhibition diameters ranging from 7.33 to 16.33 mm. These results reflect the ability of the different extracts to eliminate pathogenic microorganisms present in water. Overall, this study stands out for its innovative character, offering an in‐depth understanding of the biochemical composition and antimicrobial properties of four distinct extracts of local plants commonly used in traditional drinking water purification practices. It enriches existing knowledge by providing new data on the biochemical composition and bioactivity of these extracts. In particular, the study highlights the synergistic effects of the bioactive compounds present, underlining their essential role in improving the sanitary quality of water consumed in rural areas, where sustainable and accessible solutions are crucial.
Research on Reservoir Hydrocarbon‐Bearing Property Identification Method Based on Logging Data and Machine Learning
Authors: Yu Chunyong , Qu Kaixuan , Peng Li
Published: February 2025

The hydrocarbon‐bearing property of a reservoir is a crucial index for its evaluation. Although various evaluation methods based on well‐logging data can reasonably interpret the hydrocarbon‐bearing property of most reservoirs, these methods often exhibit significant randomness and ambiguity. This is due to various external influences, making it challenging to quickly and accurately evaluate the hydrocarbon‐bearing property of a reservoir. To address this issue, this study investigates the identification of hydrocarbon‐bearing properties in reservoirs based on well‐logging data and machine learning techniques. Initially, 1731 sets of well‐logging data with hydrocarbon‐bearing property identification result labels from 356 wells in the Shahejie Formation of the Bohai Bay Basin’s Qikou Sag were collected. The distribution of different hydrocarbon‐bearing property categories was analyzed on three types of well‐logging data: gas logging, quantitative fluorescence logging, and Rock‐Eval pyrolysis. Subsequently, seven model inputs were formed by combining these three types of well‐logging data, and their performance was evaluated in combination with three machine learning techniques: K‐nearest neighbor, random forest, and artificial neural networks. The influence of different inputs and models on classification performance was compared. Lastly, the importance of each input feature was analyzed. The results showed that the combination of quantitative fluorescence logging and Rock‐Eval pyrolysis as inputs with the random forest model could achieve the best classification performance, with a macro F1 score of 95.36%. This suggests that this method has sufficient precision for the identification of hydrocarbon‐bearing property categories in formations, providing a more efficient classification method for the hydrocarbon‐bearing property of reservoirs compared to manual identification.
“E‐Motional Navigators”: Italian Adaptation and Validation of the Socio‐Emotional e‐Competencies Questionnaire (e‐COM)
Authors: Cricenti C. , Lausi G. , Barchielli B. , Mari E. , Burrai J. , Giannini A. M. , Quaglieri A.
Published: February 2025

Given the importance of social–emotional skills in fostering highly prosocial behaviors and the increasing frequency by which relationships are established and maintained in cyberspace, several studies have been conducted focusing on the role of social‐emotional skills developed in the online environment. However, the instruments developed to date have mainly considered “face‐to‐face” interactions, without considering the unique features of the virtual environment. The purpose of the present study was to validate the Italian translation of the Socio‐Emotional e‐Competencies Questionnaire. This instrument has been constructed to assess the knowledge, skills, and attitudes necessary to understand and manage emotions in the online environment for fostering positive relationships (e‐competencies (e‐COM)). The final sample consisted of 1096 adults (53.0% men) aged between 18 and 73 years. Factor analyses confirmed the original five‐factor structure, which showed excellent fit indices (i.e., root mean square error of approximation (RMSEA), Tucker–Lewis index (TLI), and comparative fit index (CFI)). Correlation analyses with other instruments related to social–emotional competence (i.e., E‐motions Questionnaire, Brief Emotional Intelligence Scale, and Difficulties in Emotion Regulation Scales) confirmed the convergent validity of the scale. Gender differences were also explored, in which women scored higher than men in all dimensions of e‐COM except for emotional e‐independence. Overall, this study demonstrated that the Italian version of e‐COM is a reliable and valid tool for measuring social‐emotional competence in a virtual context.
A Hybrid Fault Diagnosis Model for Rolling Bearing With Optimized VMD and Fuzzy Dispersion Entropy
Authors: Xia Xin , Wang Xiaolu , Chen Weilin
Published: February 2025

The vibration signal of rolling beating is nonlinear and nonstationary, which makes feature extraction difficult for fault diagnosis. To improve the efficiency of feature extraction and fault diagnosis, a hybrid model based on optimized variational mode decomposition (VMD), fuzzy dispersion entropy (FDE), and a support vector machine (SVM) is proposed. Firstly, a parameter optimization method using the sparrow search algorithm (SSA) was applied to VMD to improve the decomposition ability. Subsequently, a feature vector based on the FDE was proposed as a fault‐diagnosis feature. Finally, SVM was applied with the proposed feature vector for the fault diagnosis of rolling bearings. The simulation and experimental study results indicate that the proposed method can obtain useful features for fault diagnosis, particularly in short‐length samples and noise conditions. The proposed method performed well in the fault diagnosis for different fault types and degrees of rolling bearings.
Delving Into the Interaction Between Exercise and Diabetes on Methylation of the FKBP5 Gene
Authors: Yang Teng-Chi , Tsai Jen Pi , Hsu Honda , Chen Yen-Chung , Liaw Yi-Chia , Hsu Shu Yi , Yang Hao Jan , Liaw Yung-Po
Published: February 2025

Objective: FKBP5 is a critical gene involved in regulating the hypothalamic–pituitary–adrenal (HPA) axis and stress response. Aberrant DNA methylation at FKBP5 cytosine–phosphate–guanine (CpG) sites, such as cg22363520 and cg00862770, has been implicated in mental health disorders and metabolic diseases, including Type 2 diabetes. Exercise is a modulator of DNA methylation and metabolic health. This study investigates the interaction between exercise, diabetes, and FKBP5 methylation at cg22363520 and cg00862770 and explores their implications for mental health and disease development.

Materials and Methods: FKBP5 methylation levels at cg22363520 and cg00862770 were analyzed in a cohort stratified by diabetes and exercise. Multiple linear regression models assessed the main effects and interactions of exercise and diabetes on FKBP5 methylation, with further stratified analyses for site‐specific effects.

Results: Exercise and diabetes showed significant and site‐specific effects on FKBP5 methylation at cg22363520 and cg00862770. At cg22363520, exercise significantly reduced methylation levels in nondiabetic participants (β = −0.00195, p = 0.0157), while no significant effect was observed in diabetic individuals. Conversely, at cg00862770, exercise significantly decreased methylation levels in diabetic participants (β = −0.00611, p = 0.0081), with no significant effect in the nondiabetic group. Diabetes itself was associated with increased FKBP5 methylation at both sites, particularly in individuals without regular exercise. Additionally, significant interaction effects between exercise and diabetes were identified for both cg22363520 (p = 0.0336) and cg00862770 (p = 0.0021), highlighting the interplay between metabolic status and physical activity in regulating FKBP5 methylation.

Conclusion: This study demonstrates that the effects of exercise on FKBP5 methylation are site‐specific and influenced by diabetes status. Exercise reduces methylation at cg22363520 in nondiabetics and at cg00862770 in diabetics, indicating its role in modulating epigenetic regulation of stress and metabolic pathways. These findings underscore the interplay between exercise, diabetes, and FKBP5 methylation, with potential implications for improving mental health and metabolic outcomes.
Ovicidal Activity of 2‐Hydroxy‐4‐Methoxybenzaldehyde, Derivatives and Structural Analogues on Anopheles gambiae Eggs
Authors: Andati Reu E. , Omolo Maurice O. , Ndiege Isaiah O.
Published: February 2025

Effective remedies for disrupting An. gambiae metamorphosis at the egg stage are crucial in suppression of the malaria vector populations that result in the reduction of disease burden. 2‐Hydroxy‐4‐methoxybenzaldehyde (the major component of Mondia whytei roots), its derivatives, structural analogues and their blends were evaluated against the eggs of An. gambiae in the search for ovicidal compounds with potential use in mosquito control programs. Mature roots were harvested from Mondia whytei (Hook) Skeels (Asclepiadaceous) plants grown in the Center for African Medicinal and Nutritional Flora and Fauna (CAMNFF) herbal medicinal garden and cleaned with distilled water. 2‐Hydroxy‐4‐methoxybenzaldehyde (1) was isolated by steam distillation of the chopped roots. The selected derivatives and/or analogues were prepared using established chemical procedures and their structures confirmed by NMR spectroscopy and ESI‐MS. Ovicidal activity of the pure compounds, derivatives, structural analogues and/or formulated blends was tested at 1, 10, 25 and 50 parts per million (ppm) on An. gambie eggs. Eleven mono‐substituted (3–7), di‐substituted (8–10), tri‐substituted (1-2) aromatic compounds were assayed for ovicidal activity against Anopheles gambiae eggs singly or as blends. Benzaldehyde (4) and 4‐methoxybenzaldehyde (9) were further converted into 2‐hydroxy‐1, 2‐diphenylethanone (11), 1, 5‐diphenylpenta‐1, 4‐diene‐3‐one (12) and 1, 5‐bis (4‐methoxyphenyl) penta‐1, 4‐diene‐3‐one (13) and evaluated for ovicidal activity individually or as blends. Of the 13 compounds evaluated individually, 2‐hydroxy‐4‐methoxybenzaldehyde (1) exhibited the highest ovicidal activity at LC50 0.7075 ppm while anisole had the lowest activity at LC50 40.342 ppm. The derivatives exhibited moderate activity: 2‐hydroxy‐1, 2‐diphenylethanone (LC50 10.599 ppm), 1, 5‐diphenylpenta‐1, 4‐diene‐3‐one (LC50 9.019 ppm) and 1, 5‐bis (4‐methoxyphenyl) penta‐1, 4‐diene‐3‐one (LC50 15.642 ppm). The blends exhibited intriguingly high ovicidal efficacy with the mixture of benzaldehyde and phenol showing the highest (LC50 0.332 ppm) while phenol and anisole exhibited the lowest activity (LC50 9.9909 ppm). From the activity of the blends, it is evident that anisole is antagonistic to the efficacy of phenol and benzaldehyde. It is also apparent that aldehyde and hydroxyl groups, when directly attached to the phenyl ring, provide the critical structural characteristics that contribute to the ovicidal activity of the aromatic compounds.
Spatial Transcriptomics of Intraductal Papillary Mucinous Neoplasms Reveals Divergent Indolent and Malignant States
Authors: Iyer Matthew K. , Fletcher Ashley , Okoye Jude Ogechukwu. , Shi Chanjuan , Chen Fengming , Kanu Elishama , Eckhoff Austin M. , Bao Matthew , Pasca di Magliano Marina , Frankel Timothy L. , Chinnaiyan Arul M. , Nussbaum Daniel P. , Allen Peter J.
Published: February 2025

Purpose: Intraductal papillary mucinous neoplasms (IPMN) occur in 5-10% of the population, but only a small minority progress to pancreatic ductal adenocarcinoma (PDAC). The lack of accurate predictors of high-risk disease leads both to unnecessary operations for indolent neoplasms as well as missed diagnoses of PDAC. Digital spatial RNA profiling (DSP-RNA) provides an opportunity to define and associate transcriptomic states with cancer risk. Experimental Design: We performed whole-transcriptome DSP-RNA profiling on 10 IPMN specimens encompassing the spectrum of dysplastic changes from normal duct to cancer. Epithelial regions within each tissue were annotated as normal duct (NL), low-grade dysplasia (LGD), high-grade dysplasia (HGD), or invasive carcinoma (INV). The resulting digital gene expression data were analyzed with R/Bioconductor. Results: Our analysis uncovered three distinct epithelial transcriptomic states – “normal-like” (cNL), “low-risk” (cLR), and “high-risk” (cHR) – which were significantly associated with pathologic grade. Furthermore, the three states were significantly correlated with the exocrine, classical, and basal-like molecular subtypes described in PDAC. Specifically, exocrine function diminished in cHR, classical activation distinguished neoplasia (cLR and cHR) from cNL, and basal-like genes were specifically upregulated in cHR. Intriguingly, markers of cHR were detected in NL and LGD regions from specimens with PDAC but not low-grade IPMN. Conclusions: DSP-RNA of IPMN revealed low-risk (indolent) and high-risk (malignant) expression programs that correlated with the activity of exocrine and basal-like PDAC signatures, respectively, and distinguished pathologically low-grade from malignant specimens. These findings contextualize IPMN pathogenesis and have the potential to improve risk stratification.
Table S4 from PARP Inhibitors Differentially Regulate Immune Responses in Distinct Genetic Backgrounds of High-Grade Serous Tubo-Ovarian Carcinoma
Authors: Doro Pereira Luiza , Wielgos-Bonvallet Monica , Misirlioglu Selim , Khodadai-Jamayran Alireza , Jelinic Petar , Levine Douglas A.
Published: February 2025

Supplementary Table 4 shows enriched gene sets upregulated in CAOV3 cells treated with veliparib .
Figure 1 from PARP Inhibitors Differentially Regulate Immune Responses in Distinct Genetic Backgrounds of High-Grade Serous Tubo-Ovarian Carcinoma
Authors: Doro Pereira Luiza , Wielgos-Bonvallet Monica , Misirlioglu Selim , Khodadai-Jamayran Alireza , Jelinic Petar , Levine Douglas A.
Published: February 2025

Pro-inflammatory genes are significantly upregulated in CAOV3 and OVCAR3 talazoparib-treated cells compared with control and veliparib-treated cells. Volcano plots highlighting fold change values of a small set of pro-inflammatory genes (FDR < 0.1) in (A and C) talazoparib-treated vs. DMSO-treated cells or (B and D) veliparib-treated vs. DMSO-treated cells. Red circles denote genes that were significantly upregulated, and blue circles represent genes that were significantly downregulated. Results shown are from three independent experiments. E–H, GSEA plots representative of the top upregulated pathway in each of the four comparisons. NES, normalized enrichment score.
Impact of Helicobacter pylori on Immune Checkpoint Inhibition in Hepatocellular Carcinoma: A Multicenter Study
Authors: Ben Khaled Najib , Schulz Christian , Alunni-Fabbroni Marianna , Bronny Kathrin , Jochheim Leonie S. , Kalali Behnam , Öcal Osman , Seidensticker Max , Piseddu Ignazio , Enssle Stefan , Karin Monika , Schneider Julia S. , Strasoldo-Graffemberg Theresa , Koch Nadine , Macke Lukas , Reiter Florian P. , Lange Christian M. , Wang Yinghong , De Toni Enrico N. , Gerhard Markus , Mayerle Julia , Ricke Jens , Malfertheiner Peter
Published: February 2025

Introduction: Immunomodulating effects of Helicobacter pylori (H. pylori) have been shown to inhibit antitumor immunity. Resistance to immune checkpoint inhibitor (ICI)-based therapies is common among patients with hepatocellular carcinoma (HCC). This study aimed to assess the effect of H. pylori on the outcomes of ICI in patients with HCC. Methods: We conducted a multicenter study in patients with HCC across a broad range of treatments. Patients received either ICI-based combination regimens or sorafenib-based therapy. H. pylori serostatus and virulence factors were determined and correlated with overall survival (OS), progression-free survival (PFS), and safety across the treatment modalities. Results: 180 patients with HCC were included; among these, 64 were treated with ICI-based regimen and 116 with sorafenib-based regimen. In patients treated with ICI, median OS was shorter in H. pylori-positive patients (10.9 months in H. pylori-positive vs. 18.3 months; p = 0.0384). H. pylori positivity was associated with a shorter PFS in ICI recipients (3.9 months vs. 6.8 months, p = 0.0499). In patients treated with sorafenib, median OS was not shorter among H. pylori-positive patients (13.4 months in H. pylori-positive vs. 10.6 months; p = 0.3353). Immune-related adverse events and rates of gastrointestinal bleeding were comparable between H. pylori-positive and -negative patients. Conclusion: H. pylori seropositivity was linked to poorer outcomes in patients with HCC treated with ICI. This association was not observed among patients receiving sorafenib-based therapies.
First trimester universal one-time serology screening for cytomegalovirus. A pilot study at two tertiary referral centers in Barcelona (Catalunya, Spain).
Authors: Castillo Karen P. , Guirado Laura , Cahuana Alex , Marcos María Angeles , Mercadé Imma , Casals Font Elena , Liu Qiqi , Medina Clara , López Marta , Gómez-Roig María Dolores , Figueras Francesc , Goncé Anna
Published: February 2025

Introduction
Congenital cytomegalovirus (cCMV) is the main infectious cause of sensorineural hearing loss and neurodevelopmental disability. First-trimester and periconceptional period are the most vulnerable times for fetal injury. Universal serological cytomegalovirus (CMV) screening in pregnant women is not currently recommended. After a recent randomized controlled clinical trial that demonstrated a 70% reduction of vertical transmission with high-dose valacyclovir (VCV), a pilot first-trimester screening program was launched at our setting.
Methods
This epidemiological surveillance study was conducted at two tertiary hospitals in Barcelona. The primary outcome was to evaluate the results of the first two years of implementation of a universal first-trimester CMV screening program. The secondary outcome was to assess maternal seroprevalence, and the burden of primary infection during the fetal risk period in this population. IgG and IgM antibodies were determined in first-trimester pregnant women at the time of the Combined Test for aneuploidy. In those with positive IgG and IgM, IgG avidity was performed through a fast alert system. Low or intermediate avidity was considered as primary infection in the first-trimester or periconceptional period, and women were offered VCV up to the time of amniocentesis. Infected fetuses were followed-up according to our clinical protocol.
Results
From February 2021 to August 2023, 2 777 first-trimester pregnant women between 8+0 and 13+6 gestational weeks were screened. Maternal IgG seroprevalence was 70.6%. Among these, 22 (0.8%) had IgM antibodies, four with low or intermediate avidity, suggesting a recent primary infection, and they received oral VCV 2g/6h. Vertical transmission occurred in one with a delayed start of VCV treatment and the family opted for termination of pregnancy.
Conclusions
Universal first-trimester CMV screening is feasible. A high seroprevalence was observed in our population. Larger studies will confirm whether screening is cost-effective in our setting.
Effect of Acupuncture on Dysphagia After Stroke: A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials
Authors: Zhang Jiongliang , Wu Minmin , Li Xinyue , Yu Donghui , Jia Huanhuan , Wang Binhan , Wang Yuting , Su Yumeng , Wei Xiangyu , Zhu Luwen
Published: February 2025

Introduction: Post-stroke dysphagia (PSD) is a highly prevalent dysfunction after stroke, characterized by high mortality and seriously affecting the quality of life of patients. Previous studies have shown that acupuncture improves symptoms of PSD. However, repeated tests of significance may exaggerate Type I errors. To update the evidence on the effectiveness and safety of acupuncture for PSD using a meta-analysis and trial sequential analysis (TSA).
Methods: A comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science was conducted to identify randomized controlled trials evaluating the effects of acupuncture on PSD. Trials published up to September 15, 2024, meeting the predetermined inclusion criteria, were included.
Results: Twenty studies involving 1,718 participants were included. Combined acupuncture with rehabilitation therapies significantly improved the Standard Swallowing Assessment (mean difference [MD] = -3.64, 95% confidence interval (CI): -4.72 to -2.56, p < 0.0001), Videofluoroscopic Swallowing Study scale (MD = 1.49, 95% CI: 0.89 to 2.09, p < 0.0001), Water Swallow Test (MD = -0.72, 95% CI: -0.96 to -0.47, p < 0.0001), and Swallowing Quality of Life Questionnaire (MD = 16.56, 95% CI: 9.94 to 23.18, p < 0.0001). TSA indicated that the sample size exceeded the required information size. In addition, acupuncture showed safety for PSD treatment (relative ratio [RR] = 1.23, 95% CI: 0.70 to 2.17, p = 0.48); however, the sample size was insufficient.
Conclusions: TSA demonstrated the positive effects of acupuncture on swallowing function in patients with PSD. Nonetheless, high-quality trials are needed to validate the safety of acupuncture.
Refractory subcutaneous panniculitis-like T-cell lymphoma with hemophagocytic syndrome treated with romidepsin and allogeneic hematopoietic cell transplantation
Authors: Ishizawa Yuki , Toubai Tomomi , Ichikawa Tsubasa , Himuro Masahito , Kato Mikiya , Nagano Yusuke , Takahashi Ryo , Hosokawa Masashi , Hosokawa Yuka , Yamada Akane , Suzuki Takuma , Aizawa Keiko , Ito Satoshi , Peltier Daniel , Yokoyama Hisayuki , Ishizawa Kenichi
Published: February 2025

Introduction: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous T-cell lymphoma (CTCL) that when refractory or complicated by hemophagocytic syndrome (HPS) has a poor prognosis. Romidepsin is a histone deacetylase inhibitor (HDACi), but its efficacy for SPTCL is unknown. The efficacy of allogeneic hematopoietic cell transplantation (allo-HCT) is also unclear. Herein, we report a case of refractory SPTCL with HPS that was successfully treated with romidepsin followed by consolidation with allo-HCT. Case Presentation: A 26-year-old female presented with fever, generalized painful erythema, pancytopenia, and hemophagocytosis. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) showed diffuse PET-avid infiltration of the subcutaneous adipose tissue found to be SPTCL via skin biopsy. Her SPTCL was refractory to conventional chemotherapy but complete metabolic response (CMR) was achieved after romidepsin. An allo-HCT was used for consolidation, and she remains in complete remission three years later. Conclusion: Romidepsin with allo-HCT consolidation may be an effective approach for refractory SPTCL..
A case: Thrombocytopenia in an EGFR 19 exon-deficient bilateral diffuse LUAD with ARDS treated with ECMO and Osimertinib
Authors: Liang Donghai , Zhou Fei , Xu Chen , Zou Lili , Jiang Tao , Lu Haijun , Meng Chunliu
Published: February 2025

Introduction: EGFR-sensitive mutations bilateral-diffuse lung adenocarcinoma (LUAD) complicated with acute respiratory distress syndrome (ARDS)is relatively rare. Whether EGFR-TKI can be simultaneously received when treating with extracorporeal membrane oxygenation (ECMO) and anti-infective therapy in these patients, and what adverse events should be noted?
Case Presentation: We report a case of EGFR 19 exon-deficient bilateral diffuse LUAD complicated with ARDS. When treated with ECMO and anti-infective therapy, the patient received oral Osimertinib anti-tumor therapy simultaneously. The tumor receded, but eventually irreversible thrombocytopenia developed.
Conclusion: For patients with severe lung cancer, anti-tumor efficacy and adverse events should be closely observed during anti-tumor therapy.
TXK Functional Variants Contribute to Asthma by Regulating Th1 and Th17 Cytokine Pathways
Authors: Sio Yang Yie , Liu Yu , Lam Terence Yin Weng , Say Yee-How , Reginald Kavita , Chew Fook Tim
Published: February 2025

Introduction
TXK is involved in the regulation of IFN-γ expression and T helper (Th)1 cell-mediated inflammation that underlies the development of neutrophilic asthma, however, its implication in asthma pathogenesis remains uncertain. This study aims to characterize the functional role of TXK single nucleotide polymorphism (SNP) contributing to asthma.
Methods
This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). Associations of TXK transcript expression with asthma phenotype, the transcript expression of IFN-γ and IL23A, and SNP genotype were assessed in peripheral blood mononuclear cell (PBMC) samples from n=658 individuals of the SMCSGES sub-cohort. Genetic associations of TXK SNPs with asthma were assessed in a case-control cohort of n=2407 individuals from the SMCSGES population. Functional effects of asthma-associated SNPs on TXK promoter activity were evaluated by in vitro promoter luciferase assay in THP-1 cells.
Results
We identified significant associations of upregulated TXK transcript expression with increased asthma risk (p<0.05) and the increased transcript expressions of both IFN-γ (p<0.0001) and IL23A (p<0.0001) in PBMC. A significant association between tag-SNP rs2661532 and TXK transcript expression was detected in PBMC: the allele “T” was significantly associated with a higher TXK expression than allele “C” (false discovery rate-adjusted p<0.05). The major allele “T” of rs2661532 is also significantly associated with a higher risk of asthma (p=0.0346, odds ratio=1.171, 95% confidence interval=1.011-1.357). The in vitro promoter luciferase assay showed the major alleles of rs6819804 and rs74513879 (tagged by rs2661532) are significantly associated with higher TXK promoter activity (p<0.05).
Conclusion
This study identified multiple TXK functional variants associated with asthma by regulating the transcript expression of TXK and downstream Th1 and Th17 cell-mediated inflammatory pathways. Our findings indicated the potential involvement of TXK functional variants in the development of neutrophilic asthma.
A review of sex differences in neurodegeneration and psychological comorbidities in MS and related disorders
Authors: Brasanac Jelena , Heine Josephine , Chien Claudia
Published: February 2025

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are chronic neuroinflammatory conditions that disproportionately affect women, with a 2:1 ratio in MS and up to 8.9:1 in NMOSD. Cognitive impairment is one of the earliest and most debilitating symptoms of MS, while mood disorders are common and significantly impact the quality of life and disease prognosis. Understanding sex differences in disease progression, particularly the potential differences in the mechanisms behind disability, is critical for advancing patient care. This review synthesizes current knowledge of sex-specific differences in MS and NMOSD, with a focus on neuroinflammation and neurodegeneration, as well as cognitive symptoms, and psychiatric comorbidities. The current state of research highlights the role of hormonal changes over the patient lifespan, such as estrogen and testosterone, as well as their role in modulating neuroinflammatory responses and subsequent neurodegeneration. Lastly, we discuss implications for disease monitoring and furthering knowledge in the field with a sex-specific lens, including recommendations for evaluating sex differences and personalized care in MS and NMOSD.
Da taça ao vinho: a linhagem literária de Machado de Assis
Authors: Jackson Kenneth David
Published: February 2025

In Riso e melancolia, Sérgio Paulo Rouanet enlightens the special literary qualities of Machado de Assis compared to European writers he read. Their varied expressions of melancholy and comichal qualities are complementary to the work of the Brazilian master. In this essay, starting with the book by Rouanet, we put forward instances of Machado’s originality, on the light of the authors he quotes in his work.