bluuebunny/crossref_metadata_2025 huggingface dataset:
Residents’ willingness and awareness to participate in internet+nursing service in China: A meta-analysis
Authors: Xu Xiaotao , Li Nan , Gao Fang , Wen Xianxiu , Zhang Qin , Hu Rong , Wang Yun , Xiao Li
Published: January 2025

Background:

The internet + nursing service is an important initiative for implementing the strategy of healthy China and actively responding to the aging of the population. However, the current literature on residents’ awareness and willingness to participate is insufficient and presents large variations and limitations. Therefore, this study aims to systematically evaluate the awareness and willingness of Chinese residents to participate in internet + nursing service to comprehensively understand the level of awareness and acceptance of this emerging service model among Chinese residents and to provide strong support for relevant policy formulation and service optimization.

Methods:

The PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang Data, SinoMed, and VIP databases were electronically searched to collect cross-sectional studies related to the awareness and willingness of Chinese residents to participate in internet + nursing service from inception to January 2024. Two reviewers independently screened the literature, extracted the data, and assessed the risk of bias of the included studies.

Results:

A total of 27 cross-sectional studies involving 11,761 subjects were included. The results of the meta-analysis showed that the percentage of Chinese residents willing to participate in internet + nursing service was 76.3% (95% CI [71.2%, 81.3%]). The results of the subgroup analysis showed that residents who lived in Western regions (82.1%), had employee medical insurance (85.9%), were suffering from other diseases (89.2%), were under the age of 60 (87.8%), were not married (78.9%), and had an undergraduate degree or above (85.5%) had a relatively high willingness to participate in internet + nursing service. The rate of awareness of internet + nursing service among Chinese residents was 48.6% (95% CI [24.1%, 73.2%]), which shows a downwards trend over time (67.4% in 2019, 56.1% in 2020, and 45.1% in 2021).

Conclusion:

The willingness to participate in internet + nursing service among Chinese residents is high, but the awareness rate is low. It is necessary to improve the awareness and willingness of Chinese residents to use internet + nursing service through various channels and aspects of publicity and promotion to achieve the goal of innovating the health service model, accurately connecting with the diverse health needs of people, and actively responding to the aging population.
Progress in investigating pituitary stalk lesions: A review
Authors: Zhang Zaidong , Wang Jinlin , Shi Yaru , Zhao Yahui , Hu Yanli , Wang Wentao , Chen Zonglan
Published: January 2025

Pituitary stalk lesions are uncommon and are typically identified through pituitary magnetic resonance imaging and screening for causes of diabetes insipidus. Recent literature indicates that pituitary stalk lesions primarily manifest as pituitary stalk interruption syndrome and thickening of the pituitary stalk. The etiology of these lesions is complex and can be divided into major categories: congenital disorders, inflammatory or infectious diseases, and tumors. Therefore, achieving accurate diagnosis, differential diagnosis, and treatment for pituitary stalk lesions is crucial. This article aims to classify pituitary stalk lesions and delve into the latest research on their etiology, pathological mechanisms, clinical manifestations, diagnosis, and treatment of associated diseases.
Causal relationship between rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and risk of prostate cancer: Multivariable and bidirectional Mendelian-randomization analyses
Authors: Ye Shihua , Chen Ru , Yao Yi , Chen Guangbing , Li Guomin
Published: January 2025

Previous studies have suggested an association between autoimmune diseases (AIDs) and the risk of prostate cancer (PCa). However, the causal relationship between AID and PCa remained unclear. The purpose of this study was to investigate the causal association between 3 common AIDs, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS), and the risk of PCa. We used genome-wide association studies summary statistics to conduct forward and reverse Mendelian randomization (MR) in a two-sample framework. We also incorporated risk factors, including smoking and obesity, in the multivariable MR analysis. Multiple sensitivity analysis methods have been adopted to test the robustness of our results. Our univariable MR analysis showed that genetically predicted RA was associated with an increased risk of PCa (odds ratio: 1.036, 95% CI: 1.022–1.049, P < .001). However, there was no significant association between SLE or AS and PCa. The multivariable MR analysis adjusted for smoking and obesity confirmed the positive association between RA and PCa, but not for the other 2 autoimmune diseases. In the reverse MR analysis, we did not find any significant inverse causal associations between PCa and the 3 autoimmune diseases. Our study suggested that genetically predicted RA was likely causally associated with an increased risk of PCa, while there is no significant causal relationship between SLE or AS and PCa. These findings provided new insights into the relationship between autoimmune diseases and PCa and might inform future research and clinical practice.
Causal relationship between immune cells and heart failure: A Mendelian randomization study
Authors: Lu Shenghua , Yu Yunfeng , Zhu Zheqin , Wang Min , Liu Rongzhen , Liu Jianhe
Published: January 2025

This study aimed to evaluate the causal effects of different immune cells on heart failure (HF) using Mendelian randomization (MR). Datasets for immune cell phenotypes and HF were obtained from European Bioinformatics Institute and FinnGen. Then, single nucleotide polymorphisms were screened according to the basic assumptions of MR. Subsequently, inverse variance weighted was used as primary tool for MR analysis, and Cochran Q and leave-one-out analyses were used to assess heterogeneity and robustness, respectively. MR analysis showed that cluster of differentiation (CD) 66b++ myeloid cell absolute count (AC) (odds ratio [OR] 1.043, 95% confidence interval [CI] 1.001–1.088, P = .045), human leukocyte antigen D-related on CD14– CD16+ monocyte (OR 1.030, 95% CI 1.005–1.056, P = .019), IgD on unsw mem (OR 1.046, 95% CI 1.015–1.078, P = .003), CD4 on CD4+ (OR 1.039, 95% CI 1.009–1.070, P = .011), CD24 on IgD+ CD38– (OR 1.026, 95% CI 1.000–1.052, P = .046), CD20 on CD24 + CD27+ (OR 1.032, 95% CI 1.003–1.061, P = .029), CD19 on CD20– (OR 1.037, 95% CI 1.005–1.071, P = .023), CD62L– CD86 + myeloid dendritic cell %DC (OR 1.032, 95% CI 1.004–1.061, P = .027), human leukocyte antigen D-related + CD4 + AC (OR 1.037, 95% CI 1.003–1.072, P = .032), and effector memory CD8br AC (OR 1.048, 95% CI 1.021–1.076, P < .001) were associated with increased genetic susceptibility to HF. Cochran Q and sensitivity analyses showed that the results had no heterogeneity and were robust. This MR analysis revealed 10 immune cell phenotypes associated with increased genetic susceptibility to HF. These findings provide new directions for understanding the pathogenesis of HF and developing novel therapies.
Anesthetic management for upper arm amputation in a patient with acute rapid atrial fibrillation and a large thyroid goiter: A case report
Authors: Teng Yue , Wei He , Hao Siqi , Nan Yongshan
Published: January 2025

Rationale:

Patients with atrial fibrillation and a large goiter have high perioperative risks and often cannot tolerate general anesthesia, making it necessary for us to explore new safe and effective anesthesia methods.

Patient concerns:

The patient presented with atrial fibrillation accompanied by rapid ventricular rate, a thrombus attached to the left atrial appendage, and a massive thyroid goiter compressing the airway.

Diagnosis:

After the left humerus fracture surgery, the patient’s internal fixation loosened and fractured, accompanied by infection, formation of sinus tracts, and suppuration. Consequently, an emergency left upper arm amputation was performed.

Interventions:

An ultrasound-guided subclavian brachial plexus block combined with intercostobrachial nerve block via the axillary region was performed on a high-risk elderly patient.

Outcomes:

We opted for a multi-regional block technique, which allowed us to avoid the numerous risks associated with general anesthesia. The surgery proceeded smoothly, the patient reported no significant discomfort, and was discharged 1 week postoperatively.

Lessons:

This case demonstrates that a well-executed multi-regional block can provide satisfactory anesthesia, offering a viable alternative for managing anesthesia in high-risk patients.
Maternal X chromosome pericentric inversion resulting in the genetic analysis of offspring pedigrees with deletions at Xp22.33 and Xp22.33p11.3, and duplications at Xq27.3q28: Case report
Authors: Deng Guo-Sheng , Lai Yu-Qing , Luo Bo-Wen , Luo Yu-Di , Zhu Ling-Ling , Yang Zeng-Yu , Feng Keng , Li De-Rong , Li Xiang
Published: January 2025

Rationale:

This study investigates the genetic cause of primary infertility and short stature in a woman, focusing on maternal X chromosome pericentric inversion and its impact on offspring genetic outcomes, including deletions at Xp22.33 and Xp22.33p11.3, and duplications spanning Xq27.3 to the distal end of the X chromosome’s long arm.

Patient concerns:

The proband presented with primary infertility, menstrual irregularities, and ultrasound findings indicating a small uterus.

Diagnoses:

Peripheral blood G-banded karyotype analysis and single nucleotide polymorphism array analysis revealed a 46,X,rec(X)dup(Xq)inv(X)(p11.3q27)dmat karyotype in the proband, inherited from her mother. Genetic testing identified pathogenic deletions at Xp22.33 and Xp22.33p11.3, and a pathogenic duplication at Xq27.3q28.

Interventions:

Genetic counseling and pedigree analysis were conducted to trace the maternal origin of the pericentric inversion and assess recurrence risks.

Outcomes:

The study confirmed the maternal X chromosome pericentric inversion caused the observed genetic abnormalities, with a 50% recurrence risk for X-linked inheritance.

Lessons:

Maternal X chromosome pericentric inversion significantly affects offspring genetic outcomes. Assisted reproductive technologies, including in vitro fertilization with preimplantation genetic testing, are recommended to reduce recurrence risks in future pregnancies. Prenatal genetic testing is advised for natural conception to ensure fetal genetic health.
Factors influencing antiretroviral therapy switching in people with virologically suppressed HIV-1: a cross-sectional multicenter study in France
Authors: Pourcher Valérie , Robineau Olivier , Parienti Jean-Jacques , Loubet Paul , Palacios Christia , Jacomet Christine , Benachir Haydar , Mariot Philippe , Spire Bruno , Slama Laurence
Published: January 2025

Introduction:

In France, over 90% of people living with HIV-1 (PLWH) achieve virological suppression with effective combination of antiretroviral therapies (ART), but limited data exist on the motivation for switching ART.

Objective:

To describe the reasons and determinants for switching ART, with a particular focus on doravirine-based regimens, in routine clinical practice in France.

Design:

This analysis of cross-sectional baseline data is part of the DoraVIH study, a French, multicenter (15 sites), two-step observational cohort study that includes prospective follow-up for a subset of participants.

Methods:

Eligible participants were PLWH under ART regimen, virologically suppressed for at least 6-months, doravirine-naïve and switching ART regimen. Sociodemographic and clinical data, ART history, and reasons for switching ART were assessed at baseline.

Results:

Inclusions occurred between December 13, 2021 and September 21, 2022. Of the 291 PLWH included whose data were analyzed, 143 switched to doravirine-based regimen (DOR PLWH) and 148 to another combined regimen (non-DOR PLWH). Mean age was 51.6 years and 206 participants (70.8%) were men. At baseline, 35 (25.0%) DOR PLWH and 15 (10.6%) non-DOR PLWH had Body Mass Index (BMI) ≥30 kg/m2 (p = 0.007). The most common reasons for switching were treatment simplification, tolerability and drug-drug interactions, accounting for 79.7% of all reasons. Among the 68 participants with prior tolerability issues, 47 (69.1%) switched to doravirine-based regimen.

Conclusions:

Primary reasons for switch were treatment simplification and tolerability. Participants with obesity were more likely to switch to doravirine, reflecting physicians’ favorable perception of doravirine potential benefits, particularly in managing weight gain.
Cost-effective and Flexible Preimplantation Genetic Testing (PGT) Using Adaptive Sampling-based Targeted Nanopore Sequencing (ASTN-seq)
Authors: Zhang Zhiqiang , He Shujing , Ding Taoli , Liang Xiaoyan , Fang Cong , Zeng Haitao , Xu Linan , Li Xiaolan , Jia Lei , Zhang Shihui , Su Wenlong , Sun Peng , Yang Ji , Ren Jun , Lu Sijia , Ren Zi
Published: January 2025

Genetic diseases encompass a spectrum of disorders resulting from DNA variations. Preimplantation genetic testing (PGT) is a critical strategy for preventing recurrent miscarriage, foetal malformations, and the birth of children affected by chromosomal abnormalities and monogenic disorders. Traditional PGT techniques necessitate comprehensive pedigree genetic data for haplotype linkage analysis, whereas PGT employing third-generation sequencing (TGS) has distinct advantages, particularly in cases of incomplete pedigree information,de novomutations, and complex pathogenic variants. Nevertheless, the widespread application of TGS-based PGT in clinical practice encounters hurdles owing to its high costs. Targeted sequencing technologies present a promising solution by selectively enriching regions of interest while disregarding nontargeted areas, offering a more cost-effective and flexible alternative. In this study, we employed next-generation sequencing (NGS) and adaptive sampling-based targeted nanopore sequencing (ASTN-seq) to analyse samples from five couples who carried balanced translocations andHBBgene pathogenic mutations, as well as three additional couples with monogenic diseases caused by mutations inPKD1,ASNS, orALPL. ASTN-seq successfully identified various mutations and facilitated haplotype linkage analysis, confirming its accuracy and reliability. Successful embryo transfer and subsequent prenatal diagnosis in certain families underscore the potential of ASTN-seq in assisted reproduction. Compared with traditional NGS-based PGT techniques, our work highlights that ASTN-seq is a promising tool for PGT, offering cost-effective solutions for PGT, especially for incomplete pedigrees andde novomutations.
Evaluating Regional Diversity in Scientific Communication: A Comparative Analysis of COVID-19 Preprints and Peer-Reviewed Publications
Authors: Kim Dong Hyun , Jeon Kyu Lee , You Seng Chan
Published: January 2025

Background

The unprecedented COVID-19 pandemic has triggered extensive global research, leading to an overwhelming surge in publications with surge of preprints. Despite the proliferation of preprints during the pandemic, the specific details of their implications for global diversity, along with their utility, remain underexplored. In this study, we assess the contribution of COVID-19 preprints in diverse aspects.

Methods

We collected COVID-19-related peer-reviewed papers and preprints from SCOPUS and MedRxiv, respectively, between December 2019 to November 2022. We analyzed four key aspects of scientific communication: 1) international co-authorship patterns using network analysis and eigenvector centrality, 2) publication patterns through relative ratio analysis comparing preprint to peer-reviewed paper counts, 3) social media dissemination through analysis of X (formerly Twitter) post quotations, and 4) citation impact by comparing citation counts between peer-reviewed papers with and without preprint history. All analyses were stratified by country income levels and geographical regions.

Results

Network analysis revealed higher co-authorship diversity in preprints, with Sub-Saharan Africa, Latin America, and the Caribbean showing 3.9 to 4.5 times higher eigenvector centrality compared to peer-reviewed papers. Countries with lower GDP showed significantly higher preprint publication ratios (correlation coefficient: −0.38, p-value < 0.001). Social media analysis demonstrated higher engagement with preprints, as evidenced by higher median numbers of social media quotations for preprints across all income groups. Peer-reviewed papers with preprint history received significantly higher citations (median: 10, IQR: 3-30) compared to those without (median: 5, IQR: 1-15, p-value < 0.001), particularly pronounced in low- and middle-income countries.

Conclusion

This study demonstrates the significant role of preprints in advancing regional diversity in scientific communication during the COVID-19 pandemic. Our findings show enhanced international collaboration through preprints, particularly benefiting researchers from lower-income regions, higher social media engagement across income groups, and increased citation impact for papers with preprint history. These results highlight preprints as an important tool for promoting more equitable global scientific discourse.
A Broad Survey and Functional Analysis of Immunoglobulin Loci Variation in Rhesus Macaques
Authors: Peres Ayelet , Upadhyay Amit A. , Klein Vered , Saha Swati , Rodriguez Oscar L. , Vanwinkle Zachary M. , Karunakaran Kirti , Metz Amanda , Lauer William , Lin Mark C. , Melton Timothy , Granholm Lukas , Polak Pazit , Peterson Samuel M , Peterson Eric J , Raju Nagarajan , Shields Kaitlyn , Schultze Steven , Ton Thang , Ericsen Adam , Lapp Stacey A. , Villinger Francois , Ohlin Mats , Cottrell Christopher A. , Amara Rama R. , Derdeyn Cynthia A. , Crotty Shane , Schief William R. , Karlsson Hedestam Gunilla B. , Smith Melissa L. , Lees William , Watson Corey T. , Yaari Gur , Bosinger Steven E.
Published: January 2025

Rhesus macaques (RMs) are a vital model for studying human disease and invaluable to pre-clinical vaccine research, particularly for the study of broadly neutralizing antibody responses. Such studies require robust genetic resources for antibody-encoding genes within the immunoglobulin (IG) loci. The complexity of the IG loci has historically made them challenging to characterize accurately. To address this, we developed novel experimental and computational methodologies to generate the largest collection to date of integrated antibody repertoire and long-read genomic sequencing data in 106 Indian origin RMs. We created a comprehensive resource of IG heavy and light chain variable (V), diversity (D), and joining (J) alleles, as well as leader, intronic, and recombination signal sequences (RSSs), including the curation of 1474 novel alleles, unveiling tremendous diversity, and expanding existing IG allele sets by 60%. This publicly available, continually updated resource (https://vdjbase.org/reference_book/Rhesus_Macaque) provides the foundation for advancing RM immunogenomics, vaccine discovery, and translational research.
PSI Atlas: a comprehensive knowledgebase of plant self-incompatibility
Authors: Wang Chen , Zhao Hong , Zhang Hongkui , Sun Sijie , Xue YongBiao
Published: January 2025

Self-incompatibility (SI) is an important genetic mechanism in angiosperms that prevents inbreeding and promotes outcrossing. Although significant progress has been made in understanding SI, its molecular underpinnings and evolutionary origins remain elusive in many plant families. In eudicots, SI is typically regulated by a singleS-locus with diverseS-haplotypes, while in grasses, it is controlled by two separateSandZloci. Genome assemblies of SI plants have greatly facilitated the identification and evolutionary analysis ofS-loci. However, a comprehensive database that integrates information on the diverseS-loci has been lacking. To fill this gap, we create the Plant Self-Incompatibility Atlas (PSIA,http://www.plantsi.cn), a knowledgebase that offers an extensive compilation of plant SI, including genomic resources for assembled SI species, the origins and evolution ofSgenes, and the molecular mechanisms of the eight known SI types. In our most recent release, we have obtained more than 500 genome assemblies across 469 SI species. We have also collected 1275 nucleotide and 1130 protein sequence accessions ofSgenes from public databases, with a total of 3095Sgenes manually identified and curated. PSIA not only thoroughly explores theS-locus information of the assembled SI species but also enables users to efficiently browse, perform BLAST searches, analyze, and downloadSgenes. Additionally, PSIA acts as a comprehensive platform for comparative genomic studies ofS-loci, aiding in the exploration of the dynamic processes involved in the origin, loss, and regain of SI. Consequently, PSIA is poised to significantly enhance our understanding of angiosperm SI and offer new perspectives on plant mating systems.
Investigating The Potential of Division of Labour in Synthetic Bacterial Communities for the Production of Violacein
Authors: Mehta Harman , Jimenez Jose , Ledesma-Amaro Rodrigo , Stan Guy-Bart
Published: January 2025

With advancements in synthetic biology and metabolic engineering, microorganisms can now be engineered to perform increasingly complex functions, which may be limited by the resources available in individual cells. Division of labour in synthetic microbial communities offers a promising approach to enhance metabolic efficiency and resilience in bioproduction. By distributing complex metabolic pathways across multiple subpopulations, the resource competition and metabolic burden imposed on an individual cell is reduced, potentially enabling more efficient production of target compounds. Violacein is a high-value pigment with anti-tumour properties that exemplifies such a challenge due to its complex bioproduction pathway, imposing a significant metabolic burden on host cells. In this study we investigated the benefits of division of labour for violacein production by splitting the violacein bioproduction pathway between two subpopulations ofEscherichia colibased synthetic communities. We tested several pathway splitting strategies and reported that splitting the pathway into two subpopulations expressing VioABE and VioDC at a final composition of 60:40 yields a 2.5 fold increase in violacein production as compared to a monoculture. We demonstrated that the coculture outperforms the monoculture when both subpopulations exhibit similar metabolic burden levels, resulting in comparable growth rates, and when both subpopulations are present in sufficiently high proportions.
Micromorphology and ammonium transmembrane transport characteristics in roots of rice seedlings
Authors: Zhang Xiaoguo , Xu Yanan , Chen Song , Chu Guang , Xu Chunmei , Yang Yongjie , Wang Danying
Published: January 2025

During the seedling stage, rice root exhibit rapid growth and absorb significant quantities of nutrients. This study involved cultivating rice seedlings in two different seedling-raising mediums characterized by high ammonium concentration (HN, NH4+1.2 mg g−1) and low ammonium concentration (LN, NH4+0.006 mg g−1). The morphology of distinct root zones (root cap, meristematic zone, elongation zone, and maturation zone) was observed under a microscope throughout root development, and variations in transmembrane flux rates of NH4+in different root zones were assessed using Non-invasive micro-test technology (NMT). Results showed that the root caps of both seminal and adventitious roots became separated from the root tip between 9 and 12 days after root emergence. During this time, the root tip transformed from a sharp to a round shape, and the distance from the maturation zone to the root tip progressively decreased from over 900 μm on 6 days after sowing (DAS) to under 500 μm on DAS12. The meristematic zone was the primary site for NH4+absorption in new root and proved to be particularly sensitive to environmental NH4+concentration. At DAS 6, the net NH4+flux rate was highest in the meristematic zone under both HN and LN treatments. Additionally, the external NH4+concentration influenced the direction of NH4+flux in the meristematic zone at DAS9, with HN being a net NH4+influx and LN being an NH4+efflux, and the net NH4+influx in the meristematic zone persisted for 3 days longer in the HN treatment compared to the LN treatment. In mature roots, the root hair zone emerged as the primary site of NH4+uptake, exhibiting an infNH4+influx rate of 40−140 pmol cm−1s−1, and this low rate of uptake could be sustained for up to 12 days after root emergence. By DAS15, a net NH4+efflux was observed in the entire seminal root, signaling the loss of NH4+absorption function 15 days post-emergence. A similar trend was noted in adventitious roots, where NH4+uptake remained functional for 12-15 days after root emergence. As rice seedlings continued to grow, new adventitious roots replaced old ones, facilitating ongoing NH4+uptake.
Contrasting dynamics and biotic association networks in estuarine microbenthic communities along an environmental disturbance gradient
Authors: Garate Leire , Chariton Anthony A. , Abad-Recio Ion L. , Bissett Andrew , Lanzén Anders
Published: January 2025

Estuarine ecosystems experience a range of anthropogenic pressures. Consequently, robust monitoring tools are essential for their management and protection. Utilising environmental DNA in routine monitoring programs enables the inclusion of benthic microorganisms, which are not only good indicators of environmental condition, but also play critical roles in ecosystem functioning. In this study we collect eDNA from sediment samples across time in six estuaries, from the Basque coast (Spain), under varying degrees of disturbance. To identify potential indicators of biotic integrity (environmental health status), we used time series data to examine the prokaryotic microbial communities and consensus networks associated with different levels of pollution. In general, sediment communities were relatively temporally stable, with the moderately and heavily disturbed sites showing more variation. The consensus networks also differed significantly in their topologies, with more impacted estuaries having fewer nodes, edges and connectance, among others, and higher modularity compared to those less impacted. Moreover, the potential keystone taxa and predicted functional profiles differed between consensus networks. This illustrates how modelled association networks can reveal new insights regarding the state of estuarine ecosystems and their potential functional processes.
NERINE reveals rare variant associations in gene networks across multiple phenotypes and implicates anSNCA-PRL-LRRK2subnetwork in Parkinson’s disease
Authors: Nazeen Sumaiya , Wang Xinyuan , Morrow Autumn , Strom Ronya , Ethier Elizabeth , Ritter Dylan , Henderson Alexander , Afroz Jalwa , Stitziel Nathan O. , Gupta Rajat M. , Luk Kelvin , Studer Lorenz , Khurana Vikram , Sunyaev Shamil R.
Published: January 2025

Gene networks encapsulate biological knowledge, often linked to polygenic diseases. While model system experiments generate many plausible gene networks, validating their role in human phenotypes requires evidence from human genetics. Rare variants provide the most straightforward path for such validation. While single-gene analyses often lack power due to rare variant sparsity, expanding the unit of association to networks offers a powerful alternative, provided it integrates network connections. Here, we introduce NERINE, a hierarchical model-based association test that integrates gene interactions that integrates gene interactions while remaining robust to network inaccuracies. Applied to biobanks, NERINE uncovers compelling network associations for breast cancer, cardiovascular diseases, and type II diabetes, undetected by single-gene tests. For Parkinson’s disease (PD), NERINE newly substantiates several GWAS candidate loci with rare variant signal and synergizes human genetics with experimental screens targeting cardinal PD pathologies: dopaminergic neuron survival and alpha-synuclein pathobiology. CRISPRi-screening in human neurons and NERINE converge onPRL, revealing an intraneuronal α-synuclein/prolactin stress response that may impact resilience to PD pathologies.
The secreted Nimrod NimB1 negatively regulates early steps of apoptotic cell phagocytosis inDrosophila
Authors: Dolgikh Asya , Rommelaere Samuel , Ghanem Aseel , Petrignani Bianca , Poidevin Mickael , Kurant Estee , Lemaitre Bruno
Published: January 2025

Efferocytosis, the efficient clearance of apoptotic cells (ACs) by phagocytes, is vital for maintaining tissue homeostasis. Here, we reveal the role of the secreted protein NimB1 in reducing apoptotic cell recognition and binding in the early stages of efferocytosis. NimB1 is expressed in macrophages (also called plasmatocytes) and binds to ACs in a phosphatidylserine-dependent manner. Structural analysis shows that NimB1 shares striking similarities with the bridging molecule NimB4, and possesses two phosphatidylserine-binding motifs, supporting its role in efferocytosis. Larval macrophages of NimB1 null mutants display a hyper-phagocytic phenotype characterized by increased engulfment of ACs. Confocal imaging reveals that NimB1 specifically inhibits early steps in internalization of ACs, but does not impact phagosome maturation. We find that NimB1 is a secreted factor that negatively regulates efferocytosis, antagonizing the role of NimB4. Our study and the analogous opposing roles of Draper Isoforms II and I in efferocytosis suggest that a balance of negative and positive regulators allows optimization of the rate of apoptotic cell clearance by macrophages.
Anillin directly cross-links microtubules with filamentous actin
Authors: Bareja Ilina , Kučera Ondřej , Petitjean Irene Istúriz , Sabo Jan , Braun Marcus , Lansky Zdenek , Koenderink Gijsje H. , Dogterom Marileen
Published: January 2025

Complex morphogenetic processes such as cell division require a tight coordination of the activities of microtubules and actin filaments. There is evidence that anillin, conventionally known as an actin-binding and bundling protein, regulates microtubule-actin crosstalk during cell division. However, it is unknown whether anillin binds directly to microtubules and whether it is sufficient to establish crosslinking between microtubules and actin filaments. Here we address both questions by developing an in-vitro system to observe anillin-mediated interactions with actin filaments and dynamic microtubules using total internal reflection fluorescence microscopy. We find that anillin can interact directly with microtubules and promote microtubule bundling. We confirm that anillin binds and bundles actin filaments and find that it has a strong preference for actin bundles over individual filaments. Moreover, we show that anillin can directly crosslink microtubules and actin filaments, can cause sliding of actin filaments on the microtubule lattice, and can transport actin filaments by the growing microtubule tip. Our findings indicate that anillin can potentially serve as a direct regulator of microtubule-actin crosstalk, e.g. during cell division.
Harnessing Computational Insights to Identify Potent Inhibitors for Human Metapneumovirus (HMPV): A Synergistic Approach with Natural Compounds
Authors: Dubey Amit , Kumar Manish , Tufail Aisha , Dwivedi Vivek Dhar
Published: January 2025

Human metapneumovirus (HMPV), a leading cause of acute lower respiratory tract infections, has emerged as a global health challenge due to its high prevalence, particularly among children, the elderly, and immunocompromised individuals. Despite its significant impact, no targeted antivirals or vaccines are available. This study employs a comprehensive computational pipeline to identify and evaluate potential inhibitors of the HMPV matrix protein (PDB: 5WB0). Natural compounds such as epigallocatechingallate (EGCG), rutin, and quercetin, along with control drugs, were screened for their therapeutic potential.Virtual screening identified EGCG (−9.1 kcal/mol), rutin (−9.0 kcal/mol), and quercetin (−8.8 kcal/mol) as top binders, surpassing standard drugs like ribavirin (−8.9 kcal/mol). Molecular docking revealed stable binding interactions, including hydrogen bonding with residues Arg143 and Glu186. Molecular dynamics (MD) simulations over a 1000 ns trajectory confirmed the stability of these complexes, with EGCG displaying the lowest RMSD (2.1 Å) and consistent hydrogen bonding throughout the simulation. Density Functional Theory (DFT) calculations highlighted favorable electronic properties, with EGCG showing a low band gap (3.29 eV) and high dipole moment (3.12 D), indicative of strong reactivity and binding potential. ADMET profiling revealed excellent oral bioavailability for EGCG (84%) and quercetin (88%), with minimal toxicity risks. The Molecular Electrostatic Potential (MESP) mapping identified highly reactive regions on the molecular surface, correlating with nucleophilic and electrophilic binding capabilities. The findings position EGCG, rutin, and quercetin as promising candidates for HMPV therapy, providing a strong foundation for further experimental validation and preclinical development.
Genome structural variation in natural Caenorhabditis elegans populations
Authors: Lesack Kyle J. , Wasmuth James D.
Published: January 2025

Structural variation, involving large alterations in chromosome structure, drives genetic diversification and the emergence of new phenotypes. These changes are widespread in natural populations and play an important role in adaptation and speciation. For many species, research has been limited to laboratory adapted strains and experimental evolution, which may not reflect the diversity of structural variants in the wild. Furthermore, technological limitations have proved to be a major barrier to accurate and comprehensive variant calling. In this study, we used PacBio sequencing data from 14 wildCaenorhabditis elegansstrains to characterize structural variants in a natural population. With long-reads, we overcame limitations associated with short-read approaches and leveraged population-level data to further refine the accuracy of variant calls. We found that large, rapidly evolving gene families, such as GPCR, F-Box, and C-Type lectin, were prominent among the variants predicted to have phenotypic consequences. These results shed light on the significant role of structural variants in the evolution ofCaenorhabditis elegansin its wild habitats and the limitations of treating N2 as the reference wild-type.
Exosomes derived from highly scalable and regenerative human progenitor cells promote functional improvement in a rat model of ischemic stroke
Authors: Lee Jieun , Var Susanna R. , Chen Derek , Natera-Rodriguez Dilmareth E. , Hassanipour Mohammad , West Michael D. , Low Walter C. , Grande Andrew W. , Larocca Dana
Published: January 2025

Globally, there are 15 million stroke patients each year who have significant neurological deficits. Today, there are no treatments that directly address these deficits. With demographics shifting to an older population, the problem is worsening. Therefore, it is crucial to develop feasible therapeutic treatments for stroke. In this study, we tested exosomes derived from embryonic endothelial progenitor cells (eEPC) to assess their therapeutic efficacy in a rat model of ischemic stroke. Importantly, we have developed purification methods aimed at producing robust and scalable exosomes suitable for manufacturing clinical grade therapeutic exosomes. We characterized exosome cargos including RNA-seq, miRNAs targets, and proteomic mass spectrometry analysis, and we found that eEPC-exosomes were enhanced with angiogenic miRNAs (i.e., miR-126), anti-inflammatory miRNA (i.e., miR-146), and anti-apoptotic miRNAs (i.e., miR-21). The angiogenic activity of diverse eEPC-exosomes sourced from a panel of eEPC production lines was assessedin vitroby live-cell vascular tube formation and scratch wound assays, showing that several eEPC-exosomes promoted the proliferation, tube formation, and migration in endothelial cells. We further applied the exosomes systemically in a rat middle cerebral artery occlusion (MCAO) model of stroke and tested for neurological recovery (mNSS) after injury in ischemic animals. The mNSS scores revealed that recovery of sensorimotor functioning in ischemic MCAO rats increased significantly after intravenous administration of eEPC-exosomes and outpaced recovery obtained through treatment with umbilical cord stem cells. Finally, we investigated the potential mechanism of eEPC-exosomes in mitigating ischemic stroke injury and inflammation by the expression of neuronal, endothelial, and inflammatory markers. Taken together, these data support the finding that eEPCs provide a valuable source of exosomes for developing scalable therapeutic products and therapies for stroke and other ischemic diseases.
Niacin protects against vascular calcification via enhanced SIRT1 and SIRT6 signaling and promoted VSMC autophagy
Authors: Kong Chao-hua , Wu Li-da , Sun Yue , Jiang Xiao-min , Shi Yi , Wang Feng , Wang Dong-chen , Gu Yue , Zhou Wen-ying , Luo Jin-que , Chao Yue-lin , Chen Shao-liang
Published: January 2025

Background

Vascular calcification (VC) is a common pathologic state that often accompanies calcium-phosphorus metabolism disorder and chronic kidney diseases (CKDs) in aging individuals. Vascular smooth muscle cell (VSMC) has been widely acknowledged as one of the main cell types that involved in this process. Niacin, a lipid-lowering reagent, has been demonstrated to be beneficial in atherosclerotic disease. The correlation and mechanism between niacin and vascular calcification have not been reported so far.

Methods and results

RCS analysis based on large clinical databases indicated that diet that riches in niacin can protect against abdominal artery calcification (AAC). Our data showed that niacin treatment remarkably reduced VSMC osteogenic differentiation and senescence-associated markers under osteogenic stimulation. Moreover, niacin treatment alleviated CKD and vitamin D3-induced vascular calcification in C57BL/6J mice. Mechanistically, we for the first time demonstrated that niacin supplementation inhibited vascular calcification via maintaining both Sirtuin 1 (SIRT1) and Sirtuin 6 (SIRT6) levels. Moreover, we verified that niacin activated SIRT1 and SIRT6 promoted VSMC autophagy flux.

Conclusions

These findings may help to develop novel therapeutic strategies in the treatment and prevention of vascular calcification.
A biological growth model using continued fraction of straight lines
Authors: S Shruti I , S Vijay Prakash
Published: January 2025

S-shaped curves are ubiquitous in biology especially when it comes to growth of a population or even an individual. Growth models such as the classical Verhulst-Pearl logistic growth equation and its extensions effectively model such S-shaped growth curves. Most of these models are parametrised by three or more parameters. In this work, continued fraction of straight lines has been applied to model S-shaped curves of biological growth through the use of only two parametersaandm. Here,mis the maximum growth rate andais the parameter restricting the growth rate. The parametersaandmhelp to better interpret the data when compared to the logistic growth model sincemrepresents factors promoting growth whilearepresents the constraints on growth. This model is effective for modeling both population as well as individual growth, especially around the phase of rapid growth.
Soluble Immune Checkpoint Protein and Lipid Network Associations with All-Cause Mortality Risk: Trans-Omics for Precision Medicine (TOPMed) Program
Authors: Rodriguez Annabelle , Yang Chaojie , Gan Wenqi , Karlinsey Keaton , Zhou Beiyan , Rich Stephen S. , Taylor Kent D. , Guo Xiuqing , Rotter Jerome I. , Johnson W. Craig , Cornell Elaine , Tracy Russell P. , Durda J. Peter , Gerszten Robert E. , Clish Clary B. , Blackwell Thomas , Papanicolaou George J. , Lin Honghuang , Raffield Laura M. , Vargas Jose D. , Vasan Ramachandran , Manichaikul Ani
Published: January 2025

Adverse cardiovascular events are emerging with the use of immune checkpoint therapies in oncology. Using datasets in the Trans-Omics for Precision Medicine program (Multi-Ethnic Study of Atherosclerosis, Jackson Heart Study [JHS], and Framingham Heart Study), we examined the association of immune checkpoint plasma proteins with each other, their associated protein network with high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and the association of HDL-C- and LDL-C-associated protein networks with all-cause mortality risk. Plasma levels of LAG3 and HAVCR2 showed statistically significant associations with mortality risk. Colocalization analysis using genome wide-association studies of HDL-C or LDL-C and protein quantitative trait loci from JHS and the Atherosclerosis Risk in Communities identified TFF3 rs60467699 and CD36 rs3211938 variants as significantly colocalized with HDL-C; in contrast, none colocalized with LDL-C. The measurement of plasma LAG3, HAVCR2, and associated proteins plus targeted genotyping may identify patients at increased mortality risk.
Performance management and development system in South Africa, a necessary evil. Qualitative study
Authors: Ibeziako Ozo J
Published: January 2025

Performance management, primarily developmental-oriented, improves individual and organisational performance as key enablers of improved services. Accomplishing performance management’s objectives are critical in the current global challenges of the shortage of healthcare workers and providing equitable, quality healthcare for all. The weakened South African district-based primary healthcare system is strongly linked to poor leadership and governance. This study aims to understand how doctors in primary health care experience the performance management and development system. The objectives explored what medical officers know about it and their experiences. Emerging themes could provide insights into improving its implementation. The study used a qualitative, interpretive phenomenological research design. Data was collected through Focus Group Discussions with semi-structured interview guide. Stratified purposive sampling was used, and thematic analysis was performed. The overarching theme was Performance Management and Development System, a necessary evil with benefits and challenges. The subthemes included understanding its multiple components, understanding clinic systems to improve service outcomes, promoting employee-supervisor interactions and interconnectedness, creating a performance and learning culture, and personal and professional growth. Effective and efficient implementation of the Performance Management and Development System at the coalface demands that managers and supervisors drive this process in an informed and strategic manner. Managers and supervisors entrusted with clinical governance should invest time in personal development to understand the process and creatively consider a fit-for-purpose implementation tool.
“Our kids are our future”: Barriers and facilitators to vaccine uptake and timeliness among Aboriginal children aged under five years in Boorloo (Perth), Western Australia
Authors: Puca Carla , Wood-Kenney Paige , Nelson Naomi , Hansen Jordan , Mathews Judy , van der Helder Erin , Kickett Justin , Robinson Melanie , Attwell Katie , Phillips Anastasia , Swift Valerie , Blyth Christopher C. , Carlson Samantha J.
Published: January 2025

Introduction

Rates of several vaccine preventable diseases, and associated hospitalisation, are higher among Aboriginal and/or Torres Strait Islander children than non-Indigenous children. Western Australia has among the lowest childhood vaccine coverage in Australia, particularly among Aboriginal and/or Torres Strait Islander children. Delayed vaccination is also more common in this population. This project aimed to understand the barriers and facilitators to vaccine uptake and timeliness among Aboriginal and/or Torres Strait Islander children aged under five years in Boorloo (Perth).

Methods

The Tailoring Immunisation Programs method was used to determine the barriers and facilitators to vaccination. Between March – November 2023, in-depth interviews were conducted with 18 parents/carers of Aboriginal and/or Torres Strait Islander children in Boorloo who were currently or previously overdue for one or more childhood vaccines. Qualitative data were analysed in NVivo 14 using deductive and inductive coding following the Capability-Opportunity-Motivation-Behaviour model.

Results

The majority of participants believed vaccines are safe, effective and supported vaccination as a means to strengthen the next generation of Aboriginal and/or Torres Strait Islander children. Barriers to on-time vaccination related to access and ineffective reminder systems. Participants expressed limited knowledge about additional vaccines recommended for Aboriginal and/or Torres Strait Islander children under Australia’s National Immunisation Program.

Conclusion

An increase in vaccine coverage and timeliness will optimise protection and decrease the burden of disease in Aboriginal and/or Torres Strait Islander children in Boorloo. This can be supported by policy interventions to better cater for the needs of families, including addressing transport challenges, being mindful of the wider network of kin and care relationships, ensuring the funding of Aboriginal health services, and co-designing culturally appropriate resources. The federal government should use the Centrelink system to notify all eligible families of pending vaccines due.
Protein Structure Description with ρ, θ and ϕ: A Case Study with Caenopore-5
Authors: Li Wei
Published: January 2025

Since its establishment in 1971, the Protein Data Bank (PDB) has been using Cartesian coordinate system (CCS) as the standard framework for protein structure description withx, y, z. Despite the interconvertibility of CCS and spherical coordinate systems (SCS, ρ, θ and ϕ), CCS remains to date the default and the only framework for protein structure description in PDB. Recent advances in protein structure prediction (e.g., AlphaFold) revolutionized the field by integrating deep learning algorithms with experimental structural data, achieving unprecedented accuracy of protein structure prediction and relying on Cartesian representation of protein structures to extract geometric features, such as inter-residue distances and dihedral angles, which are essential for building and visualizing protein structures withx, y, z. To this end, questions remain about the potential for further improvement in the performance of protein structure prediction, i.e., what is going to drive the next stage of its continued development with improved accuracy and efficiency. Therefore, this article introduces an alternative coordinate system for protein structure description and feature extraction. Using Caenopore-5 as an example, this article redefines protein backbone structures using atomic bonding networks (ABN) within the SCS framework (ABN-SCS), leading to the extraction of a set of spherical parameters (ρ, θ and ϕ) from the NMR ensemble of Caenopore-5, encompassing 477 covalent bonds and 80 peptide bonds within its backbone for each structural model in its NMR ensemble. Overall, this work offers an alternative spherical framework (ABN-SCS), i.e., a new language (ρ, θ, ϕ), for protein structure description and ABN-SCS-based extraction of spherical geometric features for protein structure prediction, aiming to contribute a little bit to its performance and application in drug discovery and design.