bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainable fabrication of Fe2O3/C nanoparticles via Acacia nilotica extract for enhanced supercapacitor performance
Authors: Parveen Nazish , Da’na Enshirah , Taha Amel
Published: December 2024

This research investigates the eco-friendly production of iron oxide nanoparticles and their combination with carbon to create the FeC-1 and FeC-2 NPs, using seedless pods of Acacia nilotica. These pods, rich in tannins and flavonoids, serve as a natural reducing, stabilizing, and carbon source. The study details the synthesis of FeC NPs through a non-toxic, green method and examines the influence of varying concentrations of A. nilotica extract (ANE) on the electrochemical characteristics of the resulting n FeC-1 and FeC-2 electrodes. Both FeC-1 and FeC-2 NPs were tested extensively using cyclic voltammetry and galvanostatic charge-discharge methods to evaluate their pseudocapacitive properties in a three-electrode setup. The FeC-2 electrodes showed much better performance, achieving a specific capacitance of 482.85 F g−1, compared to FeC-1’s 155.71 F g−1 . This enhanced capacity is attributed to an optimal content that notably boosts conductivity. Additionally, FeC-2 showed impressive cyclic stability, retaining approximately 80% capacity at a constant current density. These findings underscore the potential of using ANE for developing cost-effective and environmentally benign FeC-1 and FeC-2 NPs with promising applications in high-performance supercapacitors.
Turing instability-induced oscillations in coupled reaction–diffusion systems
Authors: Wang 王 Nan 楠 , Tong 仝 Yuan 源 , Liu 刘 Fucheng 富成 , Li 李 Xiaoxuan 晓璇 , He 贺 Yafeng 亚峰 , Fan 范 Weili 伟丽
Published: December 2024

A new type of localized oscillatory pattern is presented in a two-layer coupled reaction–diffusion system under conditions in which no Hopf instability can be discerned in either layer. The transitions from stationary patterns to asynchronous and synchronous oscillatory patterns are obtained. A novel method based on decomposing coupled systems into two associated subsystems has been proposed to elucidate the mechanism of formation of oscillating patterns. Linear stability analysis of the associated subsystems reveals that the Turing pattern in one layer induces the other layer locally, undergoes a supercritical Hopf bifurcation and gives rise to localized oscillations. It is found that the sizes and positions of oscillations are determined by the spatial distribution of the Turing patterns. When the size is large, localized traveling waves such as spirals and targets emerge. These results may be useful for deeper understanding of pattern formation in complex systems, particularly multilayered systems.
Impurity sputtering model for ICRF edge plasma–surface interactions
Authors: Zhang 张 Quan-Zhi 权治 , Liu 刘 Ze-Xuan 泽璇 , Ma 马 Fang-Fang 方方 , Zhang 张 Lei-Yu 雷宇 , Matyakubov Nosir
Published: December 2024

One of the primary concerns associated with ion cyclotron resonance heating (ICRH) is the enhanced impurity sputtering resulting from radio frequency (RF) sheath formation near plasma-facing components (PFCs), such as limiters. Developing a sputtering model integrated with RF sheath simulations allows for a more comprehensive understanding of the kinetic behavior of incident ions and their interactions with the limiter surface. We accordingly develop an impurity sputtering model “PMSAD”, which computes the sputtering yield (amount of impurity) on the limiter surface based on incident ion characteristics and predicts the spatial distribution of impurities. The model provides a robust method for understanding and analyzing the impurity sputtering process from limiter surfaces, which is crucial for preventing ICRH surface erosion and reducing edge and core plasma contamination.
SNSAlib: A python library for analyzing signed network
Authors: Li 李 Ai-Wen 艾纹 , Lu 陆 Jun-Lin 俊霖 , Fan 樊 Ying 瑛 , Xu 许 Xiao-Ke 小可
Published: December 2024

The unique structure of signed networks, characterized by positive and negative edges, poses significant challenges for analyzing network topology. In recent years, various statistical algorithms have been developed to address this issue. However, there remains a lack of a unified framework to uncover the nontrivial properties inherent in signed network structures. To support developers, researchers, and practitioners in this field, we introduce a Python library named SNSAlib (Signed Network Structure Analysis), specifically designed to meet these analytical requirements. This library encompasses empirical signed network datasets, signed null model algorithms, signed statistics algorithms, and evaluation indicators. The primary objective of SNSAlib is to facilitate the systematic analysis of micro- and meso-structure features within signed networks, including node popularity, clustering, assortativity, embeddedness, and community structure by employing more accurate signed null models. Ultimately, it provides a robust paradigm for structure analysis of signed networks that enhances our understanding and application of signed networks.
Three-body physics under dissipative spin–orbit coupling
Authors: Zhao 赵 Xi 茜
Published: December 2024

We study the trimer state in a three-body system, where two of the atoms are subject to Rashba-type spin–orbit coupling and spin-dependent loss while interacting spin-selectively with the third atom. The short-time conditional dynamics of the three-body system is effectively governed by a non-Hermitian Hamiltonian with an imaginary Zeeman field. Remarkably, the interplay of non-Hermitian single particle dispersion and the spin-selective interaction results in a Borromean state and an enlarged trimer phase. The stability of trimer state can be reflected by the imaginary part of trimer energy and the momentum distribution of trimer wave function. We also show the phase diagram of the three-body system under both real and imaginary Zeeman fields. Our results illustrate the interesting consequence of non-Hermitian spectral symmetry on the few-body level, which may be readily observable in current cold-atom experiments.
Nanomedicine in cancer treatment - an overview
Authors: Dhanabalan Dharanidharan , Shanmugam Narkunaraja
Published: December 2024

Cancer remains a formidable global health challenge, with millions of lives lost annually and a projected increase in cases, particularly in regions like South Central Asia, Europe, Eastern Europe, etc, Traditional cancer treatments, including chemotherapy, radiotherapy, and surgery, face limitations in effectively managing the complex tumor microenvironment and addressing the diverse characteristics of cancer cells. Nano-oncology has emerged as a promising frontier in cancer therapy, utilizing nanoscale materials to deliver therapeutic agents with precision and efficacy. The benefits of nanoparticle-based drug delivery systems are the ability to target tumor cells while minimizing adverse effects and overcoming multidrug resistance. Advancements in hybrid nanoparticle development have further enhanced the stability and performance of drug delivery systems, offering new avenues for cancer treatment. Moreover, nanoparticle-based therapies hold the potential to modulate the immunosuppressive tumor microenvironment and improve outcomes in immunotherapy. The review provides a comprehensive overview of nanotherapeutic products currently in various preclinical and clinical study stages, focusing on their success rates in lung and breast cancers compared to conventional chemotherapeutic drugs. By elucidating the landscape of nano-oncology and evaluating its efficacy in specific cancer types, this review aims to shed light on the transformative potential of nanoparticle-based approaches in cancer treatment and diagnosis. They are exploring nano-oncology promises to pave the way for innovative strategies in combating cancer and improving patient outcomes globally.
MnCo2O4 nanorods-based electrochemical sensing platform for ultrasensitive detection of copper (II) ions in drinking water samples
Authors: Nguyen Ngoc Huyen , Ngo Xuan Dinh , Hoang Van Thanh , Mai Vu Thi Huong , Phan Vu Ngoc , Pham Duc Thang , Anh-Tuan Le
Published: December 2024

MnCo2O4 nanorods (MCO) are successfully fabricated by microwave-assisted hydrothermal method. MCO is coated on the commercial screen-printed electrode (SPE), aiming for effective detection of copper (II) ions (Cu2+). The morphological and structural characteristics are investigated through x-ray diffraction (XRD), Raman spectra, and scanning electron microscope (SEM) analysis. Besides, electrochemical properties and performance to detect Cu2+ on the modified electrode (MCO/SPE) are studied in detail using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and differential pulse anodic stripping voltammetry (DPASV) measurements. The results show the MCO/SPE display magnificent enhancements in dynamic linear range, sensitivity, limit of detection (LOD), selectivity, and stability. Under optimized conditions, the prepared electrochemical sensor had a linear range of 0.001–100 μM, corresponding to LOD of 0.72 nM. Notably, the achieved results point out the great potential of the developed sensor based on MnCo2O4 nanorods for heavy metal ion detection.
Effect of inlet sub-cooling on heat transfer and flow stability in a hybrid heat sink
Authors: Joshi Vipul , Pratihar A K
Published: December 2024

Inlet sub-cooling of fluid has significant influence on stability and heat transfer process during flow boiling in microchannel heat sinks for devices generating high heat flux. A computational study of a hybrid microchannel-microgap heat sink section has been performed for constant high heat flux condition with varying water inlet sub- cooling. Results of the transient two-phase analysis reveal that at saturated inlet condition (∆Tin = 0 K), heat sink shows better temperature uniformity and hotspot mitigation capabilities but had high pressure fluctuations due to flow reversal resulting in flow boiling instability. By increasing sub-cooling (∆Tin = 5 K and ∆Tin = 10 K), the pressure fluctuations reduced considerably but developed non-uniform, high surface temperatures in heat sink due to delay in onset of boiling, which can cause hotspots. Increasing the subcooling also resulted in increase in heat transfer coefficient (h) in heat sink, particularly in downstream microgap section. The study corroborated the importance and effect of inlet sub-cooling on heat transfer performance and flow stability of a hybrid heat sink with two-phase flow.
GADIFF: a transferable graph attention diffusion model for generating molecular conformations
Authors: Wang Donghan , Dong Xu , Zhang Xueyou , Hu LiHong
Published: December 2024

The diffusion generative model has achieved remarkable performance across various research fields. In this study, we propose a transferable graph attention diffusion model, GADIFF, for a molecular conformation generation task. With adopting multiple equivariant networks in the Markov chain, GADIFF adds GIN (Graph Isomorphism Network) to acquire local information of subgraphs with different edge types (atomic bonds, bond angle interactions, torsion angle interactions, long-range interactions) and applies MSA (Multi-head Self-attention) as noise attention mechanism to capture global molecular information, which improves the representative of features. In addition, we utilize MSA to calculate dynamic noise weights to boost molecular conformation noise prediction. Upon the improvements, GADIFF achieves competitive performance compared with recently reported state-of-the-art models in terms of generation diversity(COV-R, COV-P), accuracy (MAT-R, MAT-P), and property prediction for GEOM-QM9 and GEOM-Drugs datasets. In particular, on the GEOM-Drugs dataset, the average COV-R is improved by 3.75% compared with the best baseline model at a threshold (1.25 Å). Furthermore, a transfer model named GADIFF-NCI based on GADIFF is developed to generate conformations for noncovalent interaction (NCI) molecular systems. It takes GADIFF with GEOM-QM9 dataset as a pre-trained model, and incorporates a graph encoder for learning molecular vectors at the NCI molecular level. The resulting NCI molecular conformations are reasonable, as assessed by the evaluation of conformation and property predictions. This suggests that the proposed transferable model may hold noteworthy value for the study of multi-molecular conformations. The code and data of GADIFF is freely downloaded from https://github.com/WangDHg/GADIFF.
RNA-ModX: a multilabel prediction and interpretation framework for RNA modifications
Authors: Yuge Chelsea Chen , Hang Ee Soon , Mamtha Madasamy Ravi Nadar , Vishwakarma Shashikant , Wang Sijia , Wang Cheng , Le Nguyen Quoc Khanh
Published: December 2024

Accurate prediction of RNA modifications holds profound implications for elucidating RNA function and mechanism, with potential applications in drug development. Here, the RNA-ModX presents a highly precise predictive model designed to forecast post-transcriptional RNA modifications, complemented by a user-friendly web application tailored for seamless utilization by future researchers. To achieve exceptional accuracy, the RNA-ModX systematically explored a range of machine learning models, including Long Short-Term Memory (LSTM), Gated Recurrent Unit, and Transformer-based architectures. The model underwent rigorous testing using a dataset comprising RNA sequences containing the four fundamental nucleotides (A, C, G, U) and spanning 12 prevalent modification classes (m6A, m1A, m5C, m5U, m6Am, m7G, Ψ, I, Am, Cm, Gm, and Um), with sequences of length 1001 nucleotides. Notably, the LSTM model, augmented with 3-mer encoding, demonstrated the highest level of model accuracy. Furthermore, Local Interpretable Model-Agnostic Explanations were employed to facilitate result interpretation, enhancing the transparency and interpretability of the model’s predictions. In conjunction with the model development, a user-friendly web application was meticulously crafted, featuring an intuitive interface for researchers to effortlessly upload RNA sequences. Upon submission, the model executes in the backend, generating predictions which are seamlessly presented to the user in a coherent manner. This integration of cutting-edge predictive modeling with a user-centric interface signifies a significant step forward in facilitating the exploration and utilization of RNA modification prediction technologies by the broader research community.
Testing for a difference in means of a single feature after clustering
Authors: Chen Yiqun T , Gao Lucy L
Published: December 2024

For many applications, it is critical to interpret and validate groups of observations obtained via clustering. A common interpretation and validation approach involves testing differences in feature means between observations in two estimated clusters. In this setting, classical hypothesis tests lead to an inflated Type I error rate. To overcome this problem, we propose a new test for the difference in means in a single feature between a pair of clusters obtained using hierarchical or k-means clustering. The test controls the selective Type I error rate in finite samples and can be efficiently computed. We further illustrate the validity and power of our proposal in simulation and demonstrate its use on single-cell RNA-sequencing data.
Spatial proteomics reveals sirtuin 1 to be a determinant of T-cell infiltration in human melanoma
Authors: Placke Jan-Malte , Bottek Jenny , Váraljai Renata , Shannan Batool , Scharfenberg Sarah , Krisp Christoph , Spangenberg Philippa , Soun Camille , Siemes Devon , Borgards Lars , Hoffmann Franziska , Zhao Fang , Paschen Anette , Schlueter Hartmut , von Eggeling Ferdinand , Helfrich Iris , Rambow Florian , Ugurel Selma , Tasdogan Alpaslan , Schadendorf Dirk , Engel Daniel R , Roesch Alexander
Published: December 2024

Background

The tumour microenvironment significantly influences the clinical response of patients to therapeutic immune checkpoint inhibition (ICI), but a comprehensive understanding of the underlying immune-regulatory proteome is still lacking.

Objectives

To decipher targetable biologic processes that determine tumour-infiltrating lymphocytes (TiLs) as a cellular equivalent of clinical response to ICI.

Methods

We mapped the spatial distribution of proteins in TiL-enriched vs. TiL-low compartments in melanoma by combining microscopy, matrix-assisted laser desorption mass spectrometry imaging and liquid chromatography–mass spectrometry, as well as computational data mining. Pharmacological modulation of sirtuin 1 (SIRT1) activity in syngeneic mouse models was used to evaluate the efficacy of pharmacological SIRT1 activation in two syngeneic melanoma mouse models, one known to be α-programmed cell death protein 1 (PD-1) sensitive and the other α-PD-1 resistant.

Results

Spatial proteomics and gene ontology-based enrichment analysis identified > 145 proteins enriched in CD8high tumour compartments, including negative regulators of mammalian target of rapamycin signalling such as SIRT1. Multiplexed immunohistochemistry confirmed that SIRT1 protein was expressed more in CD8high than in CD8low compartments. Further analysis of bulk and single-cell RNA sequencing data from melanoma tissue samples suggested the expression of SIRT1 by different lymphocyte subpopulations (CD8+ T cells, CD4+ T cells and B cells). Furthermore, we showed in vivo that pharmacological SIRT1 activation increased the immunological effect of α-PD-1 ICI against melanoma cells in mice, which was accompanied by an increase in T-cell infiltration and T-cell-related cytokines, including interferon (IFN)-γ, CCL4, CXCL9, CXCL10 and tumour necrosis factor-α. In silico analysis of large transcriptional data cohorts showed that SIRT1 was positively associated with the proinflammatory T-cell chemokines CXCL9, CXCL10 and IFN-γ, and prolonged overall survival of patients with melanoma.

Conclusions

Our study deciphers the proteomics landscape in human melanoma, providing important information on the tumour microenvironment and identifying SIRT1 as having important prognostic and therapeutic implications.
Rapid Selection of Human Immunodeficiency Virus-2 Capsid Mutations in Salvage Therapy With Lenacapavir-containing Regimen
Authors: Montrouge Thomas , Bertine Mélanie , Peytavin Gilles , Saint-Joannis Thibault , Bachelard Antoine , De Truchis Pierre , Lariven Sylvie , Morlat Philippe , Pouderoux Cécile , Damond Florence , Sayre Naomi , Tubiana Roland , Valin Nadia , Charpentier Charlotte , Descamps Diane , Ghosn Jade , Le Hingrat Quentin
Published: December 2024

Lenacapavir is the first capsid inhibitor and its use is currently approved for multidrug-resistant human immunodeficiency virus-1 infection. We report that, despite the initial efficacy of a lenacapavir-containing regimen in patients with multidrug-resistant human immunodeficiency virus-2 viruses, virological suppression was not achieved after a year and most patients selected capsid drug resistance–associated mutations.
Associations between iron markers with hemoglobin and outcomes in peritoneal dialysis patients-results from the PDTAP study
Authors: Wang Zi , Liu Guiling , Hao Li , Li Shaomei , Pei Huaying , Zhao Jinghong , Zhang Ying , Xiong Zibo , Liao Yumei , Li Ying , Lin Qiongzhen , Hu Wenbo , Li Yulin , Zheng Zhaoxia , Duan Liping , Fu Gang , Guo Shanshan , Zhang Beiru , Yu Rui , Sun Fuyun , Ma Xiaoying , Zhao Zhanzheng , Xiao Jing , Shen Yulan , Zhang Yong , Du Xuanyi , Ji Tianrong , Wang Caili , Deng Lirong , Yue Yingli , Chen Shanshan , Ma Zhigang , Li Yingping , Zuo Li , Zhao Huiping , Zhang Xianchao , Wang Xuejian , Liu Yirong , Gao Xinying , Chen Xiaoli , Li Hongyi , Du Shutong , Zhao Cui , Xu Zhonggao , Zhang Li , Chen Hongyu , Li Li , Wang Lihua , Yan Yan , Ma Yingchun , Wei Yuanyuan , Zhou Jingwei , Li Yan , Dong Jie
Published: December 2024

Iron metabolism markers, such as Transferrin Saturation (TSAT) and ferritin, are crucial in anemia management in patients with chronic kidney disease (CKD) and those undergoing dialysis, yet optimal levels remain unelucidated. We conducted a prospective multicenter cohort study using data from the nationwide Peritoneal Dialysis Telemedicine-based Management Platform (PDTAP) to analyze TSAT, ferritin, and hemoglobin (Hb) levels, and their associations with mortality in the peritoneal dialysis (PD) population. Our study included 4429 PD patients, analyzing data through restricted cubic splines and Cox regression models, adjusted for multiple confounders. Nonlinear associations between Hb levels and TSAT/ferritin were observed. Hb levels increased with TSAT up to 40%, then plateaued, whereas ferritin levels increased with the decline of Hb. Further, ferritin levels above 200 ng/mL were independently linked to increased mortality risk (hazard ratio [HR] 1.207, 95% confidence interval [CI]: 1.134–1.286), with this effect decreasing as high-sensitivity C-reactive protein (hsCRP) levels rose. This risk was notably significant in patients with a history of cardiovascular disease (CVD). At last, ferritin/Hb ratio more than 2 was associated with increased risk of mortality after adjusting for demographic, nutritional factors and erythropoiesis agents (HR 1.219, 95% CI: 1.144–1.299). The ferritin/Hb ratio demonstrated superior predictive ability for iron responsiveness compared to ferritin alone, monitoring the ferritin/Hb ratio may help assess the relative iron content in the body and provide reference for iron supplementation among patients undergoing PD.
A systematic review of applications, manipulations and manipulation checks of construal level theory in advertising
Authors: Saeed Muhammad Rashid , Khan Hiba , Khan Huda , Lee Richard
Published: December 2024

Advertising research has increasingly applied construal level theory (CLT) to predict advertising effectiveness. This study systematically reviews and synthesizes CLT-based advertising research by focusing on the theoretical tenets of CLT, construal-level manipulations, and construal-level manipulation checks applied in this research domain. This is the first systematic review of CLT-based advertising research involving psychological distance, which is the distance from self, here, and now. The review identified 86 relevant articles published in top-ranked journals between 2009 and 2023, retrieved from seven electronic academic databases. It found that CLT-based advertising studies are primarily anchored on the theoretical tenets of matching effect, categorization effect, and psychological distance. It further identified and classified the construal-level manipulations used in CLT-based advertising research into three categories: psychological-distance dimensions, psychological manipulations, and marketing-related factors. Finally, this review highlights the critical gaps in existing research and offers avenues for future research.
Wolbachia pipientis modulates germline stem cells and gene expression associated with ubiquitination and histone lysine trimethylation to rescue fertility defects in Drosophila
Authors: Kagemann Catherine H , Bubnell Jaclyn E , Colocho Gabriela M , Arana Daniela C , Aquadro Charles F
Published: December 2024

Wolbachia pipientis are maternally transmitted endosymbiotic bacteria commonly found in arthropods and nematodes. These bacteria manipulate reproduction of the host to increase their transmission using mechanisms, such as cytoplasmic incompatibility, that favor infected female offspring. The underlying mechanisms of reproductive manipulation by W. pipientis remain unresolved. Interestingly, W. pipientis infection partially rescues female fertility in flies containing hypomorphic mutations of bag of marbles (bam) in Drosophila melanogaster, which plays a key role in germline stem cell daughter differentiation. Using RNA-seq, we find that W. pipientis infection in bam hypomorphic females results in differential expression of many of bam's genetic and physical interactors and enrichment of ubiquitination and histone lysine methylation genes. We find that W. pipientis also rescues the fertility and germline stem cell functions of a subset of these genes when knocked down with RNAi in a wild-type bam genotype. Our results show that W. pipientis interacts with ubiquitination and histone lysine methylation genes which could be integral to the mechanism by which W. pipientis modulates germline stem cell gene function.
Pharmacists’ perceptions of the impact of Objective Structured Clinical Examination on professional development and competence: a cross-sectional study in Qatar
Authors: Nasr Ziad G , Shehzad Hafsa , Wilby Kyle J
Published: December 2024

Objectives

The Objective Structured Clinical Examination (OSCE) is a key tool in healthcare education, assessing clinical skills and competencies. This study explores OSCE’s impact on pharmacists’ competence, confidence, and practice readiness, focusing on its role in professional development and long-term practice improvement.

Methods

A cross-sectional survey was conducted among Qatar University pharmacy graduates with at least a year of practice experience. The survey included 10 items on a 4-point Likert scale to capture quantitative data, along with open-ended questions for more detailed reflections and qualitative insights. Quantitative data were analyzed using SPSS, and qualitative data were thematically analyzed through an inductive approach, with two researchers independently coded responses and identifying themes.

Key findings

Out of 75 eligible pharmacists, 46 responded (61.3% response rate). Over 85% reported that OSCE improved communication and interprofessional collaboration skills, and 80% felt it helped apply essential professional skills effectively. However, opinions varied on making OSCE a licensure requirement. Six main themes emerged: (i) Enhanced Interprofessional Collaboration Skills, (ii) Application of Professional Skills, (iii) Practical Application of Pharmacy Education, (iv) Adaptability for Evolving Healthcare Challenges, (v) Enhancement of Patient-Facing Communication Skills, and (vi) Identification of Personal Strengths and Weaknesses.

Conclusions

This study demonstrates that OSCEs enhance pharmacists’ clinical skills, communication, and practice readiness. Pharmacy programs should continue integrating OSCEs alongside other assessments for comprehensive evaluation. Policymakers are encouraged to explore OSCEs for licensure, ensuring standardization and evaluator training. Future research should assess OSCE’s long-term impact on pharmacists’ career development and patient outcomes.
A Core Glycolipid Vaccine Elicits Cross-reactive Antibodies Against Salmonella Species and Protects Against Invasive Nontyphoidal Salmonella Disease in Mice
Authors: Baliban Scott M , Shridhar Surekha , Luo Kun , Kolasny Jacqueline , Hyun Sang , Zhao Zhiyong , Tennant Sharon M , Cross Alan S
Published: December 2024

Background

Enteric fever caused by Salmonella enterica serovars Typhi and Paratyphi A in addition to gastroenteritis and invasive disease, predominantly attributable to nontyphoidal Salmonella serovars Typhimurium and Enteritidis, are major causes of death and disability across the globe. A broad-spectrum vaccine that protects against disease caused by typhoidal and nontyphoidal serovars of Salmonella is not available for humans but would prevent a considerable burden of disease worldwide.

Methods

We previously developed a broad-spectrum vaccine for gram-negative bacteria that is based on the inner core domain of detoxified Escherichia coli O111, Rc (J5) mutant lipooligosaccharide, a highly conserved antigen across gram-negative bacteria, complexed with an outer membrane protein of group B Neisseria meningitidis. In this study, mice and rabbits were immunized with the J5 core/outer membrane protein subunit vaccine. We assessed the cross-reactivity of antisera with various Salmonella species lipopolysaccharides and the protective efficacy of passive and active immunization with J5 vaccine against experimental nontyphoidal Salmonella infection in mice.

Results

Vaccination with J5 induced IgG responses that strongly recognized lipopolysaccharide from both typhoidal and nontyphoidal Salmonella and imparted a survival benefit against lethal heterologous challenges with S. Typhimurium and S. Enteritidis. Additionally, passive transfer studies with rabbit hyperimmune sera raised against the J5 vaccine revealed that anti-core antibodies were protective against lipopolysaccharide challenge in D-galactosamine–sensitized mice.

Conclusions

Our findings support the development of core glycolipids as a novel Salmonella vaccine candidate. Further investigation is warranted to determine the efficacy of the J5 core/outer membrane protein vaccine against other Salmonella serovars of concern.
Antifungal stewardship in the UK: where are we now?
Authors: Schelenz Silke , Agrawal Samir , Brady Aaron , Kiely Gillian , Riaz Zeshan , Howes Emilie , Felton Tim , Micallef Christianne , Tyler Netta , Bicanic Tihana , White P Lewis
Published: December 2024

Background

Antifungal stewardship (AFS) is the judicious use of today’s antifungal agents with the aim of improving patient outcomes and preserving their future effectiveness. Antifungal resistance (AFR) is increasing globally, with more patients at risk of Invasive Fungal Disease (IFD), highlighting the urgent need to standardize AFS practices in the UK. The aim of this position paper is to understand the current AFS landscape in the UK.

Methods

A virtual panel discussion was held from September to October 2023 on an online platform followed by a virtual meeting with nine healthcare professionals from across the UK selected for their expertise on IFD management and AFS. The discussion was structured across four topics: current AFS landscape, key elements of an AFS programme, diagnostics and diagnostic stewardship, and unmet needs in education and training. A thematic analysis was carried out. The results represent the collated and summarized views from these activities.

Results and discussion

Participants reported barriers to implementing AFS and its integration within antimicrobial stewardship (AMS) programmes in the UK. The primary challenge identified was a lack of resources, including funding and staff time. Sub-optimal fungal diagnostics and limited mycology expertise was reported as a barrier to AFS, clinical IFD and AFR surveillance. Approaches to combatting these challenges may include investing in formal mycology networks to serve as centres of clinical expertise and diagnostic hubs.

Conclusion

National standards for AFS services and associated outcome metrics need to be established to set a benchmark for centres to improve AFS.
Implementing an inclusive digital health ecosystem for healthy aging: a case study on project SingaporeWALK
Authors: Lee Edmund Wei Jian , Bao Huanyu , Singh Navrag B , Pai Sai G S , Pham Ben Tan Phat , Meena Siva Subramaniam Sowmiya , Theng Yin-Leng
Published: December 2024

Objective

To pilot a digital health technologies ecosystem known as project SingaporeWALK (Wearables and Apps for Community Living and Knowledge) that build capacity in older adults, senior center managers, health coaches, and caregivers in using health technologies (eg, wearables, apps, exergames) collaboratively in a gamified way for active aging.

Materials and Methods

The SingaporeWALK ecosystem was set up through 3 initiatives: (1) co-developing technologies with stakeholders; (2) raising digital literacy and capacity building; and (3) cultivating community and intergenerational bonding for active aging through gamified technology use.

Results

Significant improvements in older adults’ self-reported physical and mental health post-intervention were observed.

Discussion

The SingaporeWALK project demonstrated that digital health technologies, when designed with inclusivity and community engagement, could significantly empower active aging.

Conclusion

This project underscored the necessity of a collective and community-centered approach to maximize the efficacy of digital health technologies to support older adults in active aging globally.
Managed honeybees and soil nitrogen availability interactively modulate sunflower production in intensive agricultural landscapes of China
Authors: Wu Panlong , Zhao Yi , Yang Jinyi , Wu Keyuan , Bai Jinrui
Published: December 2024

Insects provide important pollination services for cops. While land use intensification has resulted in steep declines of wild pollinator diversity across agricultural landscapes, releasing managed honeybees has been proposed as a countermeasure. However, it remains uncertain whether managed honeybees can close the pollination gap of sunflower (Helianthus annuus L. [Asterales: Asteraceae]) in areas lacking wild pollinators, and how the benefits of honeybees to sunflower production are modulated by soil nutrients. We investigated the effects of 3 pollination treatments (open, self and hand pollination) on sunflower yield parameters. We also estimated the pollination efficiency of managed honeybees (Apis mellifera L. [Hymenoptera: Apidae]), and analyzed the effects of honeybee visitation and soil nitrogen on sunflower yield parameters. Insect pollinators contributed 73% of seed set and 69% of the weight of filled seeds per head in the open pollination of sunflowers, but large pollination deficits still existed. Insect pollination may enhance sunflower yield by augmenting the number and weight of filled seeds per head, but not by altering the total number of seeds. Except for the total number of seeds per head, yield parameters increased significantly with the number of honeybee visits. Low nitrogen accelerated the positive effect of honeybee pollination on sunflowers, and alleviated the negative effect of distance of beehives on honeybee visitation rate. We conclude that managed honeybees could be used to pollinate sunflowers in areas with the shortage of wild pollinators, and sunflower production may benefit from shortening the distance of beehives and lowing of nitrogen fertilizer inputs.
A method for screening functional anti-Treg antibodies using a Treg-like cell line
Authors: Pfeffer Kirsten , Ho Thai H , Ruiz Yvette , Lake Douglas F
Published: December 2024

Regulatory T cells can suppress activated T cell proliferation by direct cell-contact, although the exact mechanism is poorly understood. Identification of a Treg-specific cell surface molecule that mediates suppression would offer a unique target for cancer immunotherapy to inhibit Treg immunosuppressive function or deplete Tregs in the tumor microenvironment. In this study, we explored a method of whole cell immunization using a Treg-like cell line (MoT cells) to generate and screen monoclonal antibodies that bound cell surface proteins in their native conformations and functionally reversed Treg-mediated suppression. From the 105 hybridomas that bound to the MoT cell surface, a functional screen utilizing conventional Treg suppression assays revealed 32 candidate antibodies that exhibited functional activity (reversed or enhanced suppressive activity). As an example, we characterized one anti-MoT mAb, 12E7, that exhibited strong binding to MoT cells and conventional Treg cell surfaces. This candidate antibody was subsequently found to bind to a potential suppressive target, CD44, and demonstrated the ability to partially reverse MoT and conventional human Treg-mediated suppression.
FCN4Flare: fully convolution neural networks for flare detection
Authors: Jia Minghui , Luo A-Li , Qiu Bo
Published: December 2024

Stellar flares offer invaluable insights into stellar magnetic activity and exoplanetary environments. Automated flare detection enables exploiting vast photometric data sets from missions like Kepler. This paper presents FCN4Flare, a deep learning approach using fully convolutional networks (FCN) for precise point-to-point flare prediction regardless of light-curve length. Key innovations include the NaN Mask to handle missing data automatedly, and the Mask Dice loss to mitigate severe class imbalance. Experimental results show that FCN4Flare significantly outperforms previous methods, achieving a Dice coefficient of 0.64 compared to the state-of-the-art of 0.12. Applying FCN4Flare to Kepler-LAMOST data, we compile a catalogue of 30 285 high-confidence flares across 1426 stars. Flare energies are estimated and stellar/exoplanet properties analysed, identifying pronounced activity for an M-dwarf hosting a habitable zone planet. This work overcomes limitations of prior flare detection methods via deep learning, enabling new scientific discoveries through analysis of photometric time-series data. Code is available at https://github.com/NAOC-LAMOST/fcn4flare
Identification and characterization of a human MORC2 DNA binding region that is required for gene silencing
Authors: Fendler Nikole L , Ly Jimmy , Welp Luisa , Lu Dan , Schulte Fabian , Urlaub Henning , Vos Seychelle M
Published: December 2024

The eukaryotic microrchidia (MORC) protein family are DNA gyrase, Hsp90, histidine kinase, MutL (GHKL)-type ATPases involved in gene expression regulation and chromatin compaction. The molecular mechanisms underlying these activities are incompletely understood. Here, we studied the full-length human MORC2 protein biochemically. We identified a DNA binding site in the C-terminus of the protein, and we observe that this region can be phosphorylated in cells. DNA binding by MORC2 reduces its ATPase activity and MORC2 can entrap multiple DNA substrates between its N-terminal GHKL and C-terminal coiled coil 3 dimerization domains. Finally, we observe that the MORC2 C-terminal DNA binding region is required for gene silencing in cells. Together, our data provide a model to understand how MORC2 engages with DNA substrates to mediate gene silencing.
Novel anti-HER2 ADCs vs dual anti-HER2 antibody for HER2-positive metastatic breast cancer failed to tyrosine kinase inhibitor
Authors: Li Feng , Li Jianbin , Ji Chenchen , Wu Song , Zhang Shaohua , Wang Tao , Bian Li , Jiang Zefei
Published: December 2024

Background

Both novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) and pertuzumab and trastuzumab (HP) combined with chemotherapy(C) regimens are the choice of treatment for HER2 positive metastatic breast cancer (MBC) after tyrosine kinase inhibitors (TKIs). Our team’s previous research has shown significant therapeutic effects of novel anti-HER2 ADCs in patients with TKIs treatment failure. Unfortunately, there is currently no data available to compare novel anti-HER2 ADCs with HP combined with chemotherapy regimens. This study was conducted to compare the efficacy and safety of novel anti-HER2 ADCs with that of the HP combined with chemotherapy regimen in patients for whom TKI treatment failed.

Materials and methods

HER2-positive MBC who used novel anti-HER2 ADCs and HP combined with a chemotherapy regimen from January 2019 to August 2023 were included, and all patients received TKIs. The primary study endpoint was progression-free survival (PFS), while the secondary study endpoints were objective response rate (ORR), clinical benefit rate (CBR), and safety.

Results

A total of 150 patients, of which 83 are in the novel anti-HER2 ADCs group and 67 are in the HP combined with chemotherapy. Among these novel anti-HER2 ADCs, 36 patients received treatment with trastuzumab deruxtecan (T-Dxd), and 47 patients received treatment with other new types of ADCs. The median PFS of the novel anti-HER2 ADCs group and HP combined with the chemotherapy group were 7.0 months and 8.9 months, respectively, with ORR of 51.8% and 26.9%, and CBR of 69.9% and 65.7%, respectively. In subgroup, patients receiving T-Dxd showed improvement in PFS compared to the HP combined with chemotherapy group. The most common grade 3-4 adverse events in the novel anti-HER2 ADCs group and the HP combined with chemotherapy group were neutropenia and gastrointestinal symptoms.

Conclusions

In HER2-positive MBC for whom TKI treatment has failed, novel anti-HER2 ADCs and the HP combined with chemotherapy regimen both showed moderate efficacy and tolerable toxicity. Novel anti-HER2 ADCs are the preferred treatment recommendation for TKI failure patients. Meanwhile, based on the results of this study, the HP combined with chemotherapy regimen may also be an option, especially for patients with low accessibility.
Current perspectives on the dynamic culture of mesenchymal stromal/stem cell spheroids
Authors: Ohori-Morita Yumi , Ashry Amal , Niibe Kunimichi , Egusa Hiroshi
Published: December 2024

Mesenchymal stromal/stem cells (MSCs) are promising candidates for regenerative medicine owing to their self-renewal properties, multilineage differentiation, immunomodulatory effects, and angiogenic potential. MSC spheroids fabricated by 3D culture have recently shown enhanced therapeutic potential. MSC spheroids create a specialized niche with tight cell-cell and cell-extracellular matrix interactions, optimizing their cellular function by mimicking the in vivo environment. Methods for 3D cultivation of MSCs can be classified into 2 main forms: static suspension culture and dynamic suspension culture. Numerous studies have reported the beneficial influence of these methods on MSCs, which is displayed by increased differentiation, angiogenic, immunomodulatory, and anti-apoptotic effects, and stemness of MSC spheroids. Particularly, recent studies highlighted the benefits of dynamic suspension cultures of the MSC spheroids in terms of faster and more compact spheroid formation and the long-term maintenance of stemness properties. However, only a few studies have compared the behavior of MSC spheroids formed using static and dynamic suspension cultures, considering the significant differences between their culture conditions. This review summarizes the differences between static and dynamic suspension culture methods and discusses the biological outcomes of MSC spheroids reported in the literature. In particular, we highlight the advantages of the dynamic suspension culture of MSC spheroids and contemplate its future applications for various diseases.
Direct Induction of Buprenorphine Extended-Release: A Case Report
Authors: Azar Pouya , Wong James S.H. , Machado Jessica , Nikoo Mohammadali , Li Victor W. , Ignaszewski Martha J. , Mathew Nickie , Krausz Reinhard M. , Herring Andrew A. , Mullen Rodney , Montaner Julio S.G. , Maharaj Anil R.
Published: December 2024

Buprenorphine has superior safety in opioid use disorder compared with alternatives due to its action as a partial opioid agonist, which limits its ability to cause respiratory depression. There is a risk of precipitated opioid withdrawal after buprenorphine exposure in someone using full opioid agonists. Buprenorphine induction strategies that avoid precipitated withdrawal remain a crucial component for starting buprenorphine in individuals actively using opioids. These strategies start with low doses of buprenorphine increasing over time, which may avoid precipitated withdrawal at the cost of an extended initiation period, potentially discouraging patients and increasing healthcare costs.

A 55-year-old male with severe opioid use disorder and unregulated fentanyl use presented after an overdose, was admitted due to a cerebral venous sinus thrombosis and anemia (hemoglobin of 4.4 g/dL), and was given 300 mg of buprenorphine injection depot subcutaneously without any prior buprenorphine stabilization. Prior to injection, he was taking 30 mg of methadone and 96 mg of oral hydromorphone equivalents daily. Over the 6 hours after injection, he received another 272 mg oral hydromorphone equivalents and experienced a maximum Clinical Opiate Withdrawal Scale score of 7. Over the next 18 hours, he received no additional hydromorphone, and his Clinical Opiate Withdrawal Scale was a maximum of 1.

This case illustrates a buprenorphine induction method without precipitated withdrawal by relying on the elution of buprenorphine from the subcutaneous depot alongside full agonist opioids that are given as needed. If these results are readily replicable, this approach may have significant implications for the accessibility and acceptability of buprenorphine for patients and providers.
Hyperacusis and Tinnitus in Vestibular Migraine Patients
Authors: Haro-Hernandez Elisheba , Perez-Carpena Patricia , Di Berardino Federica , Lopez-Escamez Jose Antonio
Published: December 2024

Objectives:

To estimate the prevalence of tinnitus and hyperacusis in patients with vestibular migraine (VM), and to define the association with hearing loss, anxiety, and depression.

Design:

A cross-sectional, multicenter study including 51 adult patients with definite or probable VM, defined according to the Barany Society diagnostic criteria. Audiological examinations were performed by pure tones extended to high frequencies to assess hearing thresholds. Psychoacoustic (pitch, masking level, and residual inhibition) and psychometric assessment of tinnitus was performed in all patients that reported tinnitus with the following questionnaires: Tinnitus Handicap Inventory (THI), Hypersensitivity to Sound Questionnaire and Hospital Anxiety Depression Scale. Correlation and regression analyses were used to assess the relationship between THI scores hyperacusis, anxiety, and depression in patients with VM.

Results:

Forty-five of 50 VM patients (90%) were females; 38 out of 50 (75%) patients reported tinnitus. In our series, the most common frequency (pitch) for tinnitus was 8000 Hz. Tinnitus was not associated with hearing loss in patients with VM and the hearing thresholds were similar in VM patients with or without tinnitus. Hyperacusis was reported in 35 (60%) individuals, and in patients with tinnitus, the THI scores were associated with higher scores in Hypersensitivity to Sound Questionnaire, and anxiety and depression subscales of Hospital Anxiety Depression Scale. There were differences in the distribution of hearing loss in patients with hyperacusis, however both groups did not exceed the normal hearing threshold (17.18 ± 13.43 patients with hyperacusis and 11.66 ± 5.41, p = 0.023 in patients without hyperacusis).

Conclusions:

Tinnitus is a common symptom in patients with VM and it is not related to hearing loss in the standard audiogram. Hyperacusis was associated with tinnitus, anxiety, and depression, but it was not associated with hearing thresholds.