bluuebunny/crossref_metadata_2025_split huggingface dataset:
Second‐Trimester Inflammatory Markers in Predicting Fetal Growth Restriction: A Retrospective Analysis
Authors: Aktemur Gizem , Çakır Betül Tokgöz , Karabay Gülşan , Filiz Ahmet Arif , Seyhanlı Zeynep , Sucu Serap Topkara , Tonyalı Nazan Vanlı , Çelen Şevki 
Published: January 2025

ABSTRACTProblem:Fetal growth restriction (FGR) is a critical pregnancy complication linked to increased perinatal morbidity and mortality. Inflammation plays a key role in FGR's pathophysiology, and systemic inflammation markers may serve as predictors. This study evaluates the role of various inflammation indices; systemic immune‐inflammation index (SII), systemic inflammatory response index (SIRI), pan‐immune‐inflammation value (PIV), neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), monocyte‐to‐lymphocyte ratio (MLR), lymphocyte‐to‐platelet ratio (LMR), monocyte‐to‐platelet ratio (MPR), aggregate systemic inflammation index (AISI), systemic coagulation inflammation index (SCII), and immature granulocyte percentage (IG%) in predicting FGR.Methods of StudyThis retrospective study included 403 pregnant women treated at Ankara Etlik City Hospital between August 2022 and May 2024. The study population comprised 202 women with uncomplicated pregnancies (control group) and 201 women diagnosed with FGR per the Delphi Consensus Criteria. Second‐trimester blood samples were used to calculate the inflammatory indices.ResultsSII and NLR levels were significantly higher in the FGR group compared to controls (p = 0.020, p = 0.028, respectively). However, no significant associations were found between these indices and adverse neonatal outcomes. Cut‐off values for SII and NLR were 896 and 3.91, respectively, with moderate sensitivity and specificity.ConclusionsSII and NLR, measured in the second trimester, may be useful in predicting FGR. Although these indices did not correlate with adverse neonatal outcomes, further prospective studies with larger populations are needed to validate their clinical utility.
Is germline genome‐editing person‐affecting or identity‐affecting, and does it matter?
Authors: McGee Andrew , Prince Sinead 
Published: January 2025

AbstractWriters have debated whether germline genome‐editing is person‐affecting or identity‐affecting. The difference is thought to be ethically relevant to whether we should choose genome‐editing or choose preimplantation genetic diagnosis and embryo selection, when seeking to prevent or produce bad conditions (e.g., cystic fibrosis, or deafness) in the individuals who will grow from the embryo edited or selected. We consider the very recent views of three prominent bioethicists and philosophers who have grappled with this issue. We claim that both sides are right, but that the sense in which genome‐editing is person‐affecting is less important, morally, when the aim is to have healthy children. Since this is the predominant objective of engaging in embryo selection and genome‐editing, and since there are certain risks, at least for now, with genome‐editing, it remains better, morally, to engage in embryo selection than genome‐editing.
Evolving interdependencies between two waves of gentrifiers in the wax and wane of a ‘Utopian Village’: A case study of Cenbu Village, Shanghai
Authors: Hao Jinwei , Zhu Jin , He Shenjing , Lu Junhua 
Published: January 2025

AbstractAmid the escalating rural gentrification, a diverse array of gentrifiers is precipitating the path from coexistence and cooperation to conflict and eventual displacement. Existing literature has primarily addressed gentrifiers as a homogeneous group and focuses on the displacement of indigenous villagers, while the staged interdependencies and the displacement of gentrifiers have remained largely understudied. Drawing on a longitudinal study of a Shanghai village on a path to rural super‐gentrification, this article investigates the complex interdependencies of two waves of gentrifiers, from commensal relations to exclusion, culminating in the eventual displacement of the first‐wave gentrifiers. The study further analyses the construction and deconstruction of a ‘Utopian Village’ and the role of the gentrifiers' divergent perceptions of rurality in this evolving process. First‐wave gentrifiers tend to value the authenticity of villages, and seek to construct a ‘Utopian Village’ through commensal socio‐economic relations and the maintenance of a sustainable ecosystem, while preserving the authenticity and openness of the landscape. Their efforts, however, attract a second wave of gentrifiers who hold differing views of rurality, and this misalignment results in the over‐consumption and alienation of rurality, characterised by introverted social networks and over‐decorative landscapes. The originally envisaged ‘Utopian Village’ is thus undermined, leading to the exclusion and displacement of the first‐wave gentrifiers. This research contributes to a deeper understanding of the evolving dynamics of rural gentrification, the super‐gentrification trend, the complex interdependencies of the different types of gentrifiers and the effects on the communities in question.
Effective Reduction of Transgene‐Specific Immune Response With rAAV Vectors Co‐Expressing miRNA‐UL112‐5p or ERAP1 shRNA
Authors: Huang Xiaoping , Wang Xiao , Sun Yaqi , Xie Xinrui , Xiao Luming , Xu Yihang , Yan Qiongshi , Xu Xianxiang , Li Ling , Xu Wentao , Weng Wenting , Wu Wenlin , Xie Xiaolan , Dai Congjie , Diao Yong 
Published: January 2025

ABSTRACTRecombinant adeno‐associated virus (rAAV) has emerged as one of the best gene delivery vectors for human gene therapy in vivo. However, the clinical efficacy of rAAV gene therapy is often hindered by the host immune response against its transgene products. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is specialised to process peptides presented by class I molecules of major histocompatibility complex. Therefore, we hypothesise that modulation of the ERAP1 activity in rAAV transduced cells may be favoured to evade immune response against transgene products. In this study, we incorporated either miRNA‐UL112‐5p or ERAP1 shRNA into rAAV vectors expressing full‐length ovalbumin (OVA) as a model antigen, and evaluated their effects for antigen presentation, cellular and humour immune response induced by OVA expression. The results indicated that silencing ERAP1 using miR‐UL112‐5p or ERAP1 shRNA did not affect the expression of OVA in cells, but inhibited the processing and presentation of OVA antigen peptide SIINFEKL in antigen presenting cells (APCs). Moreover, the rAAV vector co‐expressing ERAP1 shRNA maintains stable and high expression of OVA in vivo, while simultaneously suppressing the humoral immunity of OVA. In addition, experimental results demonstrated that rAAV vectors incorporated ERAP1 shRNA efficiently repress costimulatory signals in dendritic cells (DCs), significantly attenuated the cytotoxic T‐cell response, allowed for sustained transgene expression and reduced clearance of transduced muscle cells in mice. Moreover, our study suggested that the incorporation of miRNA‐UL112‐5p or ERAP1 shRNA into rAAV vectors effectively reduced transgene products induced immune response. The proposed method may potentially be applied in clinics to deliver therapeutic proteins safely and efficiently.
Anticancer Effects of MAPK6 siRNA‐Loaded PLGA Nanoparticles in the Treatment of Breast Cancer
Authors: Toruntay Ceyhun , Poyraz Fatma Sayan , Susgun Seda , Yucesan Emrah , Mansuroglu Banu 
Published: January 2025

ABSTRACTsiRNA‐loaded nanoparticles open new perspectives for cancer treatment. MAPK6 is upregulated in breast cancer and is involved in cell growth, differentiation and cell cycle regulation. Herein, we aimed to investigate the anticancer effects of MAPK6 knockdown by using MAPK6 siRNA‐loaded PLGA nanoparticles (siMAPK6‐PLGA‐NPs) in MCF‐7 breast cancer cells. After the synthesis and characterisation of nanoparticles, treatment concentrations were determined with cytotoxicity assay. Subsequently, MAPK6 knockdown and anticancer effects of siMAPK6‐PLGA‐NPs were evaluated by in vitro assays. siMAPK6‐PLGA‐NPs have been determined to suppress MAPK6 expression efficiently. In vitro studies revealed that siMAPK6‐PLGA‐NPs significantly reduced the migration, proliferation and colony‐forming ability and enhanced the apoptosis in MCF‐7 cells. Taken together, siMAPK6‐PLGA‐NPs exhibited robust and promising anticancer effects against MCF‐7 cells. Our findings demonstrated that siRNA‐loaded PLGA nanoparticles have great potential for breast cancer treatment and MAPK6 gene may be the therapeutic target in breast cancer.
In‐Depth Examination of TPBG as a New Predictive Indicator for Gastric Cancer
Authors: Yang Lianlei , Weng Chunyan , Zhang Yaping , Zhao Yu , Chen Kexin , Li Guodong , Zhong Xueqing , He Chenghai 
Published: January 2025

ABSTRACTTrophoblast glycoprotein (TPBG) plays a significant part in the growth of specific cancers, yet its connection to gastric cancer (GC) remains uncertain. This research seeks to analyse the fluctuation in TPBG levels in GC and evaluate how TPBG expression relates to the prognosis of GC patients. TPBG expression in GC and normal gastric tissues was investigated in The Cancer Genome Atlas (TCGA) and Genotype‐Tissue Expression (GTEx) database, further extracting the immunohistochemistry images from HPA database and validating by Western blot. The connection between TPBG and GC patients' survival rates was investigated by Kaplan–Meier and COX regression analysis. Genes related to TPBG were enriched using GO and KEGG data. In vitro and in vivo tumour models were utilised to evaluate the function of TPBG in GC. Western blot analysis was performed to detect the expression of PI3K/AKT signalling pathway proteins following TPBG knockdown. Immune infiltration was analysed using the CIBERSOFT and ssGSEA methods. The association between TPBG and immune cells that infiltrate tumours was evaluated through the utilisation of GSVA. TPBG expression increased in several tumour tissues (including GC) more than in adjacent noncancerous tissues. Elevated TPBG level predicted worse outcomes, such as poorer overall survival, pathological stage, and therapy response in GC. Enrichment analysis primarily focused on biological processes like the organisation of external encapsulating structures, extracellular structure, and collagen metabolism. Biological experiments further demonstrated that TPBG knockdown successfully inhibits the progression, migration, and invasion of GC cells. Western blot analysis revealed that TPBG knockdown inhibits the PI3K/AKT signalling pathway. Furthermore, TPBG is associated with the infiltration of immune cells in GC, which correlates with the expression of macrophage cells. There is a positive relationship between TPBG and malignant behaviour of GC tissues and cells, suggesting that TPBG can be useful for diagnosing and prognosing GC.
Diagnostic Power of MicroRNAs in Melanoma: Integrating Machine Learning for Enhanced Accuracy and Pathway Analysis
Authors: Rafiepoor Haniyeh , Ghorbankhanloo Alireza , Soleimani Dorcheh Soroush , Angouraj Taghavi Elham , Ghanadan Alireza , Shirkoohi Reza , Aryanian Zeinab , Amanpour Saeid 
Published: January 2025

ABSTRACTThis study identifies microRNAs (miRNAs) with significant discriminatory power in distinguishing melanoma from nevus, notably hsa‐miR‐26a and hsa‐miR‐211, which have exhibited diagnostic potential with accuracy of 81% and 78% respectively. To enhance diagnostic accuracy, we integrated miRNAs into various machine‐learning (ML) models. Incorporating miRNAs with AUC scores above 0.70 significantly improved diagnostic accuracy to 94%, with a sensitivity of 91%. These findings underscore the potential of ML models to leverage miRNA data for enhanced melanoma diagnosis. Additionally, using the miRNet tool, we constructed a network of miRNA–miRNA interactions, revealing 170 key genes in melanoma pathophysiology. Protein–protein interaction network analysis via Cytoscape identified hub genes including MYC, BRCA1, JUN, AURKB, CDKN2A, DDX5, MAPK14, DDX3X, DDX6, FOXM1 and GSK3B. The identification of hub genes and their interactions with miRNAs enhances our understanding of the molecular mechanisms driving melanoma. Pathway enrichment analyses highlighted key pathways associated with differentially expressed miRNAs, including the PI3K/AKT, TGF‐beta signalling pathway and cell cycle regulation. These pathways are implicated in melanoma development and progression, reinforcing the significance of our findings. The functional enrichment of miRNAs suggests their critical role in modulating essential pathways in melanoma, suggesting their potential as therapeutic targets.
ALBA3 maintains male fertility under heat stress in plants
Authors: Ci Dong , Liu Yi , Wang Lishuan , Zhu Ruixian , Chen Yong , Bai Ge , Xu Ziyan , Zhou Huanbin , Zhou Xueping , Fan Liu‐Min , Qian Weiqiang 
Published: January 2025

ABSTRACTHeat stress (HS) at the reproductive stage detrimentally affects crop yields and seed quality. However, the molecular mechanisms that protect reproductive processes in plants under HS remain largely unknown. Here, we report that Acetylation Lowers Binding Affinity 3 (ALBA3) is crucial for safeguarding male fertility against HS in Arabidopsis. ALBA3 is highly expressed in pollen, and ALBA3 is localized in the cytoplasm of both sperm and vegetative cells. Mutants lacking functional ALBA3 exhibit hypersensitivity to HS, with reduced silique length and fertility due to defects in pollen germination, pollination, pollen tube growth, and fertilization under HS. ALBA3 binds and stabilizes a subset of messenger RNAs (mRNAs) essential for pollen function, thereby protecting male fertility. Two residues in the Alba domain, K46 and L90, are critical for ALBA3's ability to bind and stabilize mRNAs and are necessary for its proper function. Interestingly, the loss of rice ALBA3 also leads to severe pollen abortion and male sterility under HS, highlighting the conserved role of ALBA3 in protecting male fertility across plant species. This study uncovers a conserved mechanism by which ALBA3 safeguards male fertility during HS by stabilizing specific mRNAs crucial for pollen function.
Angiostrongylus cantonensis Meningo‐Encephalitis in Children—Heightened Awareness Needed During Prolonged Wet Weather Conditions
Authors: Hasan Nadia , Nourse Clare , Heney Claire , Lee Rogan , Kapoor Vishal , Berkhout Angela 
Published: January 2025

ABSTRACTAimAngiostrongylus cantonensis, the leading cause of eosinophilic meningoencephalitis, is well established in eastern Australia. Prolonged wet weather in Queensland during 2021–2022 coincided with anecdotal reports of increased neuroangiostrongyliasis cases, prompting an evaluation of paediatric cases from 2013 to 2022.MethodsThis retrospective observational study reviewed children (0–16 years) with cerebrospinal fluid (CSF) eosinophilia (≥ 10% of the total CSF leukocyte count) and/or A. cantonensis testing (serology or polymerase chain reaction) between 01/01/2013 and 31/12/2022, using statewide laboratory data and patient records.ResultsEighty children were identified: 59 (74%) had CSF eosinophilia without A. cantonensis testing, 9 (11%) had CSF eosinophilia with A. cantonensis testing, and 12 (15%) had A. cantonensis testing without CSF eosinophilia. Neuroangiostrongyliasis was either proven or probable in seven children: five (71%) during 2021–2022, coinciding with prolonged wet weather. A significant positive correlation was observed between rainfall and case numbers (r = 0.88, p < 0.01). Median age of diagnosed children was 4 years (IQR 1.8–8.5, range 1.5–13 years) and five (71%) were male. Snail or slug exposure was reported in four (57%) children. All children presented with vomiting, and six also had a headache and focal neurology (86%). Abnormal neuroimaging was noted in six (86%) cases. Five children received corticosteroid therapy alone (71%), while two (29%) were managed conservatively. There were no deaths, but one child had persistent focal neurological abnormalities at discharge.ConclusionAwareness of A. cantonensis and exposure risks is crucial, especially during prolonged wet weather conditions. While most children in this study had good outcomes, this is not always the case.
Resetting of the Human Circadian Melatonin Rhythm by Ambient Hypoxia
Authors: Post Titiaan E. , De Gioannis Riccardo , Schmitz Jan , Wittkowski Martin , Schäper Tina Martin , Wrobeln Anna , Fandrey Joachim , Schmitz Marie‐Therese , Takahashi Joseph S. , Jordan Jens , Elmenhorst Eva‐Maria , Aeschbach Daniel 
Published: January 2025

ABSTRACTCircadian clocks in the body drive daily cycles in physiology and behavior. A master clock in the brain maintains synchrony with the environmental day–night cycle and uses internal signals to keep clocks in other tissues aligned. Work in cell cultures uncovered cyclic changes in tissue oxygenation that may serve to reset and synchronize circadian clocks. Here we show in healthy humans, following a randomized controlled single‐blind counterbalanced crossover study design, that one‐time exposure to moderate ambient hypoxia (FiO2 ~15%, normobaric) for ~6.5 h during the early night advances the dim‐light onset of melatonin secretion by 9 min (95% CI: 1–16 min). Exposure to moderate hypoxia may thus be strong enough to entrain circadian clocks to a 24‐h cycle in the absence of other entraining cues. Together, the results provide direct evidence for an interaction between the body's hypoxia‐sensing pathway and circadian clocks. The finding offers a mechanism through which behaviors that change tissue oxygenation (e.g., exercise and fasting/eating) can affect circadian timing and through which hypoxia‐related diseases (e.g., obstructive sleep apnea and chronic obstructive pulmonary disease) can result in circadian misalignment and associated pathologies.Trial Registration: Registration number: DRKS00023387; German Clinical Trials Register: http://www.drks.de
Genotype–Phenotype Correlation in Progressive External Ophthalmoplegia: Insights From a Retrospective Analysis
Authors: Wang Jiayin , Lin Yan , Zhuang Xingyu , Zhao Dandan , Li Busu , Zhao Ying , Xu Zhe , Liu Fuchen , Dai Tingjun , Li Wei , Jiang Min , Yan Chuanzhu , Zhao Yuying , Ji Kunqian 
Published: January 2025

ABSTRACTBackgroundProgressive external ophthalmoplegia (PEO) is a classic manifestation of mitochondrial disease. However, the link between its genetic characteristics and clinical presentations remains poorly investigated.MethodsWe analysed the clinical, pathological and genetic characteristics of a large cohort of patients with PEO, based on the type of their mtDNA variations. Eighty‐two PEO patients were enrolled and grouped into three categories: mtDNA single large‐scale deletions (SLDs), multiple deletions (MulDs) and the m.3243A > G point variant. Patients in the SLD category were further divided into ‘common deletion’ and ‘noncommon deletion’ groups based on the presence or absence of a 4977‐bp deletion. The mutational load of deleted mtDNA of these patients was comprehensively detected by real‐time polymerase chain reaction (RT‐PCR).ResultsSLD Patients showed the highest proportion of cytochrome C oxidase‐negative (COX‐n) fibres on muscle biopsy. The mutational load of deleted mtDNA exhibited an inverse relationship with deletion length and a direct relationship with the COX‐n fibre ratio. Compared with patients having noncommon deletions, those with common deletions tend to have other muscle involvement, lower body mass index (BMI) scores (17 ± 3 vs. 22 ± 4 kg/m2), higher mutational load in muscle (63% ± 22% vs. 46% ± 24%), more COX‐n fibres (26% vs. 9%, interquartile range [IQR]: 15%–32% vs. 6%–26%) and higher growth and differentiation factor 15 (GDF15) levels (2583 vs. 1472, IQR: 1746–4081 vs. 924–2155 pg/mL). MulDs patients displayed milder symptoms, especially compared to patients with m.3243A > G variant, as indicated by their later age of onset (31 vs. 13, IQR: 27–49 vs. 6–29 years), higher BMI scores (24.0 ± 4 vs. 16.5 ± 3.4 kg/m2), lower lactate (1.6 ± 1.1 vs. 6.3 ± 6.0 mmol/L) levels and lower proportion of ragged‐blue fibres (RBFs) (3 vs. 16, IQR: 1%–9% vs. 7%–27%).ConclusionThe m.3243A > G variant group exhibits more severe symptoms compared to other subgroups, particularly MulDs patients. In the SLD group, those with common deletions experience more severe clinical and pathological manifestations. These findings enhance our understanding of PEO, facilitating its diagnosis, prognosis and genetic counselling.
Insights into the subdaily variations in methane, nitrous oxide and carbon dioxide fluxes from upland tropical tree stems
Authors: Bréchet Laëtitia M. , Salomόn Roberto L. , Machacova Katerina , Stahl Clément , Burban Benoît , Goret Jean‐Yves , Steppe Kathy , Bonal Damien , Janssens Ivan A. 
Published: January 2025

Summary
Recent studies have shown that stem fluxes, although highly variable among trees, can alter the strength of the methane (CH4) sink or nitrous oxide (N2O) source in some forests, but the patterns and magnitudes of these fluxes remain unclear. This study investigated the drivers of subdaily and seasonal variations in stem and soil CH4, N2O and carbon dioxide (CO2) fluxes.
CH4, N2O and CO2 fluxes were measured continuously for 19 months in individual stems of two tree species, Eperua falcata (Aubl.) and Lecythis poiteaui (O. Berg), and surrounding soils using an automated chamber system in an upland tropical forest. Subdaily variations in these fluxes were related to environmental and stem physiological (sap flow and stem diameter variations) measurements under contrasting soil water conditions.
The results showed that physiological and climatic drivers only partially explained the subdaily flux variations. Stem CH4 and CO2 emissions and N2O uptake varied with soil water content, time of day and between individuals. Stem fluxes decoupled from soil fluxes.
Our study contributes to understanding the regulation of stem greenhouse gas fluxes. It suggests that additional variables (e.g. internal gas concentrations, wood‐colonising microorganisms, wood density and anatomy) may account for the remaining unexplained variability in stem fluxes, highlighting the need for further studies.
Two reductases complete steroidal glycoalkaloids biosynthesis in potato
Authors: Akiyama Ryota , Terami Daiki , Noda Aozora , Watanabe Bunta , Umemoto Naoyuki , Muranaka Toshiya , Saito Kazuki , Sugimoto Yukihiro , Mizutani Masaharu 
Published: January 2025

Summary
Steroidal glycoalkaloids (SGAs) are specialized metabolites primarily produced by Solanaceae plants such as potatoes and tomatoes. Notably, α‐solanine and α‐chaconine are recognized as toxic substances in potatoes. While the biosynthetic pathways of SGAs are largely understood, the final steps of α‐solanine and α‐chaconine biosynthesis remained elusive.
In this study, we discovered that two reductase‐encoding genes, reductase for potato glycoalkaloid biosynthesis 1 (RPG1) and RPG2, complete SGA biosynthesis in potato. Knockout of both RPG1 and RPG2 in potato hairy roots halted α‐solanine production, leading to the accumulation of zwittersolanine.
We analyzed the catalytic function of recombinant enzymes and conducted structural determination of the reaction products by nuclear magnetic resonance. As a result, RPG1 converted zwittersolanine to 16‐iminiumsolanine, and RPG2 further converted it to α‐solanine. RPG2 also transformed zwittersolanine to 22‐iminiumsolanine, which RPG1 then converted to α‐solanine. Similar processes were observed for α‐chaconine synthesis from zwitterchaconine. Due to differences in enzymatic reaction efficiency, the biosynthetic pathway via 16‐iminiumsolanine/16‐iminiumchaconine was suggested to be predominant in potato.
Our results could pave the way for tailoring SGA structures within Solanum plants, enabling the development of Solanum crop varieties with reduced toxicity or enhanced resistance to diseases and pests.