bluuebunny/crossref_metadata_2025_split huggingface dataset:
Truncated FRMD7 proteins in congenital Nystagmus: novel frameshift mutations and proteasomal pathway implications
Authors: Su Yuqing , Zhang Juntao , Gao Jiahui , Ding Guoqing , Jiang Heng , Liu Yang , Li Yulei , Yang Guohua 
Published: January 2024

AbstractIdiopathic congenital nystagmus (ICN) manifests as involuntary and periodic eye movements. To identify the genetic defect associated with X-linked ICN, Whole Exome Sequencing (WES) was conducted in two affected families. We identified two frameshift mutations in FRMD7, c.1492dupT/p.(Y498Lfs*15) and c.1616delG/p.(R539Kfs*2). Plasmids harboring the mutated genes and qPCR analysis revealed mRNA stability, evading degradation via the NMD pathway, and corroborated truncated protein production via Western-blot analysis. Notably, both truncated proteins were degraded through the proteasomal (ubiquitination) pathway, suggesting potential therapeutic avenues targeting this pathway for similar mutations. Moreover, we conducted a comprehensive analysis, summarizing 140 mutations within the FRMD7 gene. Our findings highlight the FERM and FA structural domains as mutation-prone regions. Interestingly, exons 9 and 12 are the most mutated regions, but 90% (28/31) mutations in exon 9 are missense while 84% (21/25) mutations in exon 12 are frameshift. A predominant occurrence of shift code mutations was observed in exons 11 and 12, possibly associated with the localization of premature termination codons (PTCs), leading to the generation of deleterious truncated proteins. Additionally, our conjecture suggests that the loss of FRMD7 protein function might not solely drive pathology; rather, the emergence of aberrant protein function could be pivotal in nystagmus etiology. We propose a dependence of FRMD7 protein normal function primarily on its anterior domain. Future investigations are warranted to validate this hypothesis.
Bimodal DNA self-origami material with nucleic acid function enhancement
Authors: He Songlin , Deng Haotian , Li Peiqi , Tian Qinyu , Yang Yongkang , Hu Jingjing , Li Hao , Zhao Tianyuan , Ling Hongkun , Liu Yin , Liu Shuyun , Guo Quanyi 
Published: January 2024

Abstract
Background
The design of DNA materials with specific nanostructures for biomedical tissue engineering applications remains a challenge. High-dimensional DNA nanomaterials are difficult to prepare and are unstable; moreover, their synthesis relies on heavy metal ions. Herein, we developed a bimodal DNA self-origami material with good biocompatibility and differing functions using a simple synthesis method. We simulated and characterized this material using a combination of oxDNA, freeze–fracture electron microscopy, and atomic force microscopy. Subsequently, we optimized the synthesis procedure to fix the morphology of this material.

Results
Using molecular dynamics simulation, we found that the bimodal DNA self-origami material exhibited properties of spontaneous stretching and curling and could be fixed in a single morphology via synthesis control. The application of different functional nucleic acids enabled the achievement of various biological functions, and the performance of functional nucleic acids was significantly enhanced in the material. Consequently, leveraging the various functional nucleic acids enhanced by this material will facilitate the attainment of diverse biological functions.

Conclusion
The developed design can comprehensively reveal the morphology and dynamics of DNA materials. We thus report a novel strategy for the construction of high-dimensional DNA materials and the application of functional nucleic acid–enhancing materials.

Graphical Abstract
Comparative proteomics reveals different protein expression in platelets in patients with alcoholic liver cirrhosis
Authors: Haji Begli Nima , Freund Cora , Weiss Karl-Heinz , Gotthardt Daniel , Wannhoff Andreas 
Published: January 2024

Abstract
Background
The role of platelets in disease progression as well as the function of platelets as part of the haemostatic and immunological system in patients with liver cirrhosis is only incompletely understood. This is partly due to difficulties in assessing platelet function. Proteome analyses of platelets have been used to further investigate the role of platelets in other diseases.

Aim
To assess possible changes in the platelet proteome during different stages of alcohol induced liver cirrhosis compared to healthy donors.

Patients and methods
A 45 ml blood sample was drawn from 18 participants aged 18–80 years evenly divided into three groups of healthy donors, patients with less advanced alcohol induced liver cirrhosis (Child-Pugh < 7) and patients with advanced liver cirrhosis (Child-Pugh > 10). The blood was processed to isolate platelets and perform subsequent two-dimensional gel-electrophoresis using a SYPRO™ Ruby dye. After computational analysation significantly in- or decreased protein spots (defined as a two-fold abundance change between different study cohorts and ANOVA < 0.05) were identified via liquid chromatography–mass spectrometry (LCMS) and searching against human protein databases.

Results
The comparative analysis identified four platelet proteins with progressively decreased protein expression in patients with liver cirrhosis. More specifically Ras-related protein Rab-7a (Rab-7a), Ran-specific binding protein 1 (RANBP1), Rho GDP-dissociation inhibitor 1 (RhoGDI1), and 14–3-3 gamma.

Conclusion
There is significant change in protein expression in the platelet proteome throughout the disease progression of alcohol induced liver cirrhosis. The identified proteins are possibly involved in haemostatic and immunoregulatory function of platelets.
Impaired bisecting GlcNAc reprogrammed M1 polarization of macrophage
Authors: He Xin , Wang Bowen , Deng Wenli , Cao Jinhua , Tan Zengqi , Li Xiang , Guan Feng 
Published: January 2024

AbstractThe functions of macrophages are governed by distinct polarization phenotypes, which can be categorized as either anti-tumor/M1 type or pro-tumor/M2 type. Glycosylation is known to play a crucial role in various cellular processes, but its influence on macrophage polarization is not well-studied. In this study, we observed a significant decrease in bisecting GlcNAc during M0-M1 polarization, and impaired bisecting GlcNAc was found to drive M0-M1 polarization. Using a glycoproteomics strategy, we identified Lgals3bp as a specific glycoprotein carrying bisecting GlcNAc. A high level of bisecting GlcNAc modification facilitated the degradation of Lgals3bp, while a low level of bisecting GlcNAc stabilized Lgals3bp. Elevated levels of Lgals3bp promoted M1 polarization through the activation of the NF-кB pathway. Conversely, the activated NF-кB pathway significantly repressed the transcription of MGAT3, leading to reduced levels of bisecting GlcNAc modification on Lgals3bp. Overall, our study highlights the impact of glycosylation on macrophage polarization and suggests the potential of engineered macrophages via glycosylated modification.
EXO1/P53/SREBP1 axis-regulated lipid metabolism promotes prostate cancer progression
Authors: Wang Zefeng , Chao Zheng , Wang Qi , Zou Fan , Song Tianbao , Xu Lizhe , Ning Jinzhuo , Cheng Fan 
Published: January 2024

AbstractProstate cancer (PCa) is one of the most common malignant tumors affecting the male genitourinary system. However, there is currently a lack of effective treatments for patients with advanced prostate cancer, which significantly impacts men’s overall health. Exonuclease 1 (EXO1), a protein with mismatch repair and recombination functions, has been found to play a vital role in various diseases. In our study, we discovered that EXO1 acts as a novel biomarker of PCa, which promotes prostate cancer progression by regulating lipid metabolism reprogramming in prostate cancer cells. Mechanistically, EXO1 promotes the expression of SREBP1 by inhibiting the P53 signaling pathway. In summary, our findings suggest that EXO1 regulated intracellular lipid reprogramming through the P53/SREBP1 axis, thus promoting PCa progression. The result could potentially lead to new insights and therapeutic targets for diagnosing and treating PCa.
Immune-related lncRNAs signature and radiomics signature predict the prognosis and immune microenvironment of glioblastoma multiforme
Authors: Luan Jixin , Zhang Di , Liu Bing , Yang Aocai , Lv Kuan , Hu Pianpian , Yu Hongwei , Shmuel Amir , Zhang Chuanchen , Ma Guolin 
Published: January 2024

Abstract
Background
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. This study aimed to construct immune-related long non-coding RNAs (lncRNAs) signature and radiomics signature to probe the prognosis and immune infiltration of GBM patients.

Methods
We downloaded GBM RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) project database, and MRI data were obtained from The Cancer Imaging Archive (TCIA). Then, we conducted a cox regression analysis to establish the immune-related lncRNAs signature and radiomics signature. Afterward, we employed a gene set enrichment analysis (GSEA) to explore the biological processes and pathways. Besides, we used CIBERSORT to estimate the abundance of tumor-infiltrating immune cells (TIICs). Furthermore, we investigated the relationship between the immune-related lncRNAs signature, radiomics signature and immune checkpoint genes. Finally, we constructed a multifactors prognostic model and compared it with the clinical prognostic model.

Results
We identified four immune-related lncRNAs and two radiomics features, which show the ability to stratify patients into high-risk and low-risk groups with significantly different survival rates. The risk score curves and Kaplan–Meier curves confirmed that the immune-related lncRNAs signature and radiomics signature were a novel independent prognostic factor in GBM patients. The GSEA suggested that the immune-related lncRNAs signature were involved in L1 cell adhesion molecular (L1CAM) interactions and the radiomics signature were involved signaling by Robo receptors. Besides, the two signatures was associated with the infiltration of immune cells. Furthermore, they were linked with the expression of critical immune genes and could predict immunotherapy’s clinical response. Finally, the area under the curve (AUC) (0.890,0.887) and C-index (0.737,0.817) of the multifactors prognostic model were greater than those of the clinical prognostic model in both the training and validation sets, indicated significantly improved discrimination.

Conclusions
We identified the immune-related lncRNAs signature and tradiomics signature that can predict the outcomes, immune cell infiltration, and immunotherapy response in patients with GBM.
Differentiation between depression and bipolar disorder in child and adolescents by voice features
Authors: Luo Jie , Wu Yuanzhen , Liu Mengqi , Li Zhaojun , Wang Zhuo , Zheng Yi , Feng Lihui , Lu Jihua , He Fan 
Published: January 2024

Abstract
Objective
Major depressive disorder (MDD) and bipolar disorder (BD) are serious chronic disabling mental and emotional disorders, with symptoms that often manifest atypically in children and adolescents, making diagnosis difficult without objective physiological indicators. Therefore, we aimed to objectively identify MDD and BD in children and adolescents by exploring their voiceprint features.

Methods
This study included a total of 150 participants, with 50 MDD patients, 50 BD patients, and 50 healthy controls aged between 6 and 16 years. After collecting voiceprint data, chi-square test was used to screen and extract voiceprint features specific to emotional disorders in children and adolescents. Then, selected characteristic voiceprint features were used to establish training and testing datasets with the ratio of 7:3. The performances of various machine learning and deep learning algorithms were compared using the training dataset, and the optimal algorithm was selected to classify the testing dataset and calculate the sensitivity, specificity, accuracy, and ROC curve.

Results
The three groups showed differences in clustering centers for various voice features such as root mean square energy, power spectral slope, low-frequency percentile energy level, high-frequency spectral slope, spectral harmonic gain, and audio signal energy level. The model of linear SVM showed the best performance in the training dataset, achieving a total accuracy of 95.6% in classifying the three groups in the testing dataset, with sensitivity of 93.3% for MDD, 100% for BD, specificity of 93.3%, AUC of 1 for BD, and AUC of 0.967 for MDD.

Conclusion
By exploring the characteristics of voice features in children and adolescents, machine learning can effectively differentiate between MDD and BD in a population, and voice features hold promise as an objective physiological indicator for the auxiliary diagnosis of mood disorder in clinical practice.
Mechanisms of Bushen Tiaoxue Granules against controlled ovarian hyperstimulation-induced abnormal morphology of endometrium based on network pharmacology
Authors: Zhang Jia-Cheng , Zhang Hao-Lin , Xin Xi-Yan , Zhu Yu-Tian , Mao Xin , Hu Hang-Qi , Jin Yu-Xin , Fan Rui-Wen , Zhang Xiao-Hui , Ye Yang , Li Dong 
Published: January 2024

AbstractBushen Tiaoxue Granules (BTG) is an empirical Chinese herbal formula that has been used for the treatment of subfertility. The protective effect of BTG on controlled ovarian hyperstimulation (COH)-induced impaired endometrial receptivity has been reported in our previous study. This study aims to explore the mechanisms of BTG on ameliorating abnormal morphology of endometrium based on network pharmacology. Active compounds of BTG were identified via the traditional Chinese medicine systems pharmacology and UPLC-MS technology. The SwissTargetPrediction platform and HERB database were used to screen out the putative targets of BTG. Potential targets of endometrial dysfunction caused by COH were obtained from three GEO databases. Through the STRING database, the protein–protein interaction was carried out according to the cross-common targets of diseases and drugs. GO terms and KEGG pathways enrichment analyses were conducted via the Metascape database. AutoDock Vina was used for docking validation of the affinity between active compounds and potential targets. Finally, in vivo experiments were used to verify the potential mechanisms derived from network pharmacology study. A total of 141 effective ingredients were obtained from TCMSP and nine of which were verified in UPLC-MS. Six genes were selected through the intersection of 534 disease related genes and 165 drug potential targets. Enrichment analyses showed that BTG might reverse endometrial dysfunction by regulating adherens junction and arachidonic acid metabolism. Hematoxylin–eosin staining revealed that BTG ameliorated the loose and edematous status of endometrial epithelium caused by COH. The protein expression of FOXO1A, β-Catenin and COX-2 was decreased in the COH group, and was up-regulated by BTG. BTG significantly alleviates the edema of endometrial epithelium caused by COH. The mechanisms may be related to adheren junctions and activation of arachidonic acid metabolism. The potential active compounds quercetin, taxifolin, kaempferol, eriodictyol, and isorhamnetin identified from the BTG exhibit marginal cytotoxicity. Both high and low concentrations of kaempferol, eriodictyol, and taxifolin are capable of effectively ameliorating impaired hESC cellular activity.
DON in pediatric cerebral malaria, a phase I/IIA dose-escalation safety study: study protocol for a clinical trial
Authors: Nampota-Nkomba Nginache , Nyirenda Osward M. , Mallewa Jane , Chimalizeni Yamikani , Dzabala Nettie , Fay Michael P. , Gopalakrishnan Mathangi , Laurens Matthew B. , O’Brien Nicole F. , Miller Louis H. , Pierce Susan K. , Riggle Brittany A. , Postels Douglas G. 
Published: January 2024

Abstract
Background
Despite treatment with highly effective antimalarial drugs, malaria annually claims the lives of over half a million children under 5-years of age in sub-Saharan Africa. Cerebral malaria (CM), defined as Plasmodium falciparum infection with coma, is the severe malaria syndrome with the highest mortality. Studies in the CM mouse model suggest that a T cell-mediated response underlies CM pathology, opening a new target for therapy in humans. This trial aims to establish the preliminary safety of one such novel therapy, the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON).

Methods
In this phase I/IIa dose-escalation clinical trial, a single dose of intravenous (IV) DON is administered to three participants groups—healthy adults and adults with uncomplicated malaria, then pediatric participants with CM—to primarily assess safety. The secondary objective of this trial is to assess pharmacokinetics of DON over a range of doses. The open-label adult portion of the trial enrolls 40 healthy adults concurrently with 40 adults with uncomplicated malaria. Cohorts of 10 participants receive a single IV dose of DON with doses escalating between cohorts from 0.1 mg/kg, 1.0 mg/kg, 5.0 mg/kg, to 10 mg/kg. Following subsequent safety review, a randomized, double-blind, and placebo-controlled pediatric study enrolls 72 participants aged 6 months to 14 years with CM. The pediatric portion of the study minimally spans three malaria seasons including a planned interim analysis after 50% of pediatric enrollments. The first half of pediatric participants receive DON 0.1 mg/kg, 1.0 mg/kg, or placebo. Dosing for the second half of pediatric participants is informed by the safety and preliminary efficacy results of those previously enrolled. The pediatric portion of the study has an exploratory outcome evaluating the preliminary efficacy of DON. Efficacy is assessed by diagnostics predictive of CM outcome: electroencephalography (EEG), magnetic resonance imaging (MRI), and transcranial doppler (TCD), measured before and after DON administration. All participants with malaria receive standard of care antimalarials in accordance with local guidelines, regardless of study drug dose group.

Discussion
This preliminary safety and efficacy study evaluates DON, a candidate adjunctive therapy for pediatric CM. If results support DON preliminary safety and efficacy, follow-up phase II and III clinical trials will be indicated.

Trial registration
This trial was registered on ClinicalTrials.gov on 28 July 2022 (NCT05478720).
Preventing Respiratory Viral Illness Invisibly (PRiVII): protocol for a pragmatic cluster randomized trial evaluating far-UVC light devices in long-term care facilities to reduce infections
Authors: Nix Hayden P. , Meeker Samantha , King Caroline E. , Andrew Melissa , Davis Ian R. C. , Koto Prosper S. , Sim Meaghan , Murdoch Jennifer , Patriquin Glenn , Theriault Chris , Reidy Stephanie , Rockwood Michael , Sampalli Tara , Searle Samuel D. , Rockwood Kenneth 
Published: January 2024

Abstract
Background
Respiratory viral illness (RVI)—e.g., influenza, COVID-19—is a serious threat in long-term care (LTC) facilities. Standard infection control measures are suboptimal in LTC facilities because of residents’ cognitive impairments, care needs, and susceptibility to loneliness and mental illness. Further, LTC residents living with high degrees of frailty who contract RVIs often develop the so-called atypical symptoms (e.g., delirium, worse mobility) instead of typical cough and fever, delaying infection diagnosis and treatment. Although far-UVC (222 nm) light devices have shown potent antiviral activity in vitro, clinical efficacy remains unproven.

Methods
Following a study to assay acceptability at each site, this multicenter, double-blinded, cluster-randomized, placebo-controlled trial aims to assess whether far-UVC light devices impact the incidence of RVIs in LTC facilities. Neighborhoods within LTC facilities are randomized to receive far-UVC light devices (222 nm) or identical placebo light devices that emit only visible spectrum light (400–700 nm) in common areas. All residents are monitored for RVIs using both a standard screening protocol and a novel screening protocol that target atypical symptoms. The 3-year incidence of RVIs will be compared using intention-to-treat analysis. A cost-consequence analysis will follow.

Discussion
This trial aims to inform decisions about whether to implement far-UVC light in LTC facilities for RVI prevention. The trial design features align with this pragmatic intent. Appropriate additional ethical protections have been implemented to mitigate participant vulnerabilities that arise from conducting this study. Knowledge dissemination will be supported through media engagement, peer-reviewed presentations, and publications.

Trial registration
ClinicalTrials.gov NCT05084898. October 20, 2021.
Geographic expansion of the introduced Aedes albopictus and other native Aedes species in the Democratic Republic of the Congo
Authors: Vulu Fabien , Futami Kyoko , Sunahara Toshihiko , Mampuya Pitshou , Bobanga Thierry L. , Mumba Ngoyi Dieudonne , Minakawa Noboru 
Published: January 2024

Abstract
Background
Aedes albopictus has been reported in several Central African countries, including the Democratic Republic of the Congo (DRC). The establishment of this mosquito species poses a serious threat as a vector of various infectious diseases. Although Ae. albopictus has been reported in the western region of the DRC, information about its distribution is still scarce in the country. The aim of this study was to investigate the current nationwide distribution of the invasive Ae. albopictus, as well as other native Aedes mosquitoes, in the DRC and to identify suitable areas for its future expansion.

Methods
Two entomological surveys were conducted in 2017–2019 and 2022. Based on the occurrence sites of Ae. albopictus, important environmental variables were identified. Then, geographical areas suitable for Ae. albopictus establishment were determined using the maximum entropy model. The distribution and abundance of Ae. albopictus were also compared with those of the major native Aedes species.

Results
Aedes albopictus was found in the western, northern, central, and eastern regions of the DRC, but it was not found in the southeastern region. The maximum entropy model predicted that most parts of the DRC are suitable for the establishment of this mosquito. The unsuitable areas encompassed the eastern highlands, known for their low temperatures, and the southeastern highlands, which experience both low temperatures and a long dry season. The native Aedes species found were Aedes aegypti, Aedes simpsoni, Aedes africanus, and Aedes vittatus. Aedes albopictus dominated in the western and northern regions, while Ae. aegypti was more prevalent in other regions.

Conclusions
Aedes albopictus has been well established in the western and northern regions of the DRC. This mosquito is expanding its distribution while replacing the native Aedes species. Most of the country is suitable for the establishment of this mosquito species, except the highlands of the eastern and the southeastern regions.

Graphical Abstract