bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating tumour DNA alterations: emerging biomarker in head and neck squamous cell carcinoma
Authors: Huang Xiaomin , Duijf Pascal H. G. , Sriram Sharath , Perera Ganganath , Vasani Sarju , Kenny Lizbeth , Leo Paul , Punyadeera Chamindie 
Published: August 2023

AbstractHead and Neck cancers (HNC) are a heterogeneous group of upper aero-digestive tract cancer and account for 931,922 new cases and 467,125 deaths worldwide. About 90% of these cancers are of squamous cell origin (HNSCC). HNSCC is associated with excessive tobacco and alcohol consumption and infection with oncogenic viruses. Genotyping tumour tissue to guide clinical decision-making is becoming common practice in modern oncology, but in the management of patients with HNSCC, cytopathology or histopathology of tumour tissue remains the mainstream for diagnosis and treatment planning. Due to tumour heterogeneity and the lack of access to tumour due to its anatomical location, alternative methods to evaluate tumour activities are urgently needed. Liquid biopsy approaches can overcome issues such as tumour heterogeneity, which is associated with the analysis of small tissue biopsy. In addition, liquid biopsy offers repeat biopsy sampling, even for patients with tumours with access limitations. Liquid biopsy refers to biomarkers found in body fluids, traditionally blood, that can be sampled to provide clinically valuable information on both the patient and their underlying malignancy. To date, the majority of liquid biopsy research has focused on blood-based biomarkers, such as circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and circulating microRNA. In this review, we will focus on ctDNA as a biomarker in HNSCC because of its robustness, its presence in many body fluids, adaptability to existing clinical laboratory-based technology platforms, and ease of collection and transportation. We will discuss mechanisms of ctDNA release into circulation, technological advances in the analysis of ctDNA, ctDNA as a biomarker in HNSCC management, and some of the challenges associated with translating ctDNA into clinical and future perspectives. ctDNA provides a minimally invasive method for HNSCC prognosis and disease surveillance and will pave the way in the future for personalized medicine, thereby significantly improving outcomes and reducing healthcare costs.
Use of the mCherry fluorescent protein to optimize the expression of class I lanthipeptides in Escherichia coli
Authors: Van Zyl Winschau F , Van Staden Anton D. , Dicks Leon M T. , Trindade Marla 
Published: August 2023

Abstract
Background
Lanthipeptides are a rapidly expanding family of ribosomally synthesized and post-translationally modified natural compounds with diverse biological functions. Lanthipeptide structural and biosynthetic genes can readily be identified in genomic datasets, which provides a substantial repository for unique peptides with a wide range of potentially novel bioactivities. To realize this potential efficiently optimized heterologous production systems are required. However, only a few class I lanthipeptides have been successfully expressed using Escherichia coli as heterologous producer. This may be attributed to difficulties experienced in the co-expression of structural genes and multiple processing genes as well as complex optimization experiments.

Results
Here, an optimized modular plasmid system is presented for the complete biosynthesis for each of the class I lanthipeptides nisin and clausin, in E. coli. Genes encoding precursor lanthipeptides were fused to the gene encoding the mCherry red fluorescent protein and co-expressed along with the required synthetases from the respective operons. Antimicrobially active nisin and clausin were proteolytically liberated from the expressed mCherry fusions. The mCherry-NisA expression system combined with in vivo fluorescence monitoring was used to elucidate the effect of culture media composition, promoter arrangement, and culture conditions including choice of growth media and inducer agents on the heterologous expression of the class I lanthipeptides. To evaluate the promiscuity of the clausin biosynthetic enzymes, the optimized clausin expression system was used for the heterologous expression of epidermin.

Conclusion
We succeeded in developing novel mCherry-fusion based plug and play heterologous expression systems to produce two different subgroups of class I lanthipeptides. Fully modified Pre-NisA, Pre-ClausA and Pre-EpiA fused to the mCherry fluorescence gene was purified from the Gram-negative host E. coli BL21 (DE3). Our study demonstrates the potential of using in vivo fluorescence as a platform to evaluate the expression of mCherry-fused lanthipeptides in E. coli. This allowed a substantial reduction in optimization time, since expression could be monitored in real-time, without the need for extensive and laborious purification steps or the use of in vitro activity assays. The optimized heterologous expression systems developed in this study may be employed in future studies for the scalable expression of novel NisA derivatives, or novel genome mined derivatives of ClausA and other class I lanthipeptides in E. coli.
Association of fine particulate matter and its constituents with hypertension: the modifying effect of dietary patterns
Authors: Huang Kun , Yu Dongmei , Fang Hongyun , Ju Lahong , Piao Wei , Guo Qiya , Xu Xiaoli , Wei Xiaoqi , Yang Yuxiang , Zhao Liyun 
Published: August 2023

Abstract
Background
Studies have shown that nutritional supplements could reduce the adverse effects induced by air pollution. However, whether dietary patterns can modify the association of long-term exposure to fine particulate matter (PM2.5) and its constituents with hypertension defined by the 2017 ACC/AHA guideline has not been evaluated.

Methods
We included 47,501 Chinese adults from a nationwide cross-sectional study. PM2.5 and five constituents were estimated by satellite-based random forest models. Dietary approaches to stop hypertension (DASH) and alternative Mediterranean diet (AMED) scores were calculated for each participant. Interactions between dietary patterns and air pollution were examined by adding a multiplicative interaction term to logistic models.

Results
Long-term exposure to PM2.5 and its constituents was associated with an increased risk of hypertension and stage 1–2 hypertension. The DASH and AMED scores significantly modified these associations, as individuals with higher scores had a significantly lower risk of air pollution-related hypertension and stage 1–2 hypertension (P-interaction < 0.05), except for interaction between PM2.5, sulfate, nitrate, ammonium, and AMED score on stage 1 hypertension. For each IQR increase in PM2.5, participants with the lowest DASH and AMED quintiles had hypertension risk with ORs (95%CI) of 1.20 (1.10, 1.30) and 1.19 (1.09, 1.29), whereas those with the highest DASH and AMED quintiles had lower risks with 0.98 (0.91, 1.05) and 1.04 (0.97, 1.11). The stratified analysis found modification effect was more prominent in the < 65 years age group. Consuming more fresh vegetables, fruits, whole grains, and dairy would reduce the risk of hypertension caused by PM2.5 and its constituents.

Conclusions
Dietary patterns rich in antioxidants can reduce long-term exposure to PM2.5 and its constituents-induced hypertension defined by the 2017 ACC/AHA guideline, especially in young and middle-aged individuals. Compared to the Mediterranean diet, the DASH diet offers superior dietary guidance to prevent stage 1 hypertension caused by air pollution.
Translation and evaluation of the HeartQoL in patients with coronary heart disease in Iceland
Authors: Svavarsdóttir Margrét Hrönn , Ingadottir Brynja , Oldridge Neil , Årestedt Kristofer 
Published: August 2023

Abstract
Background
Health-related quality of life (HRQoL) reflects an individual’s own perception of their symptom burden, functional limitations, prognosis, overall health and changes associated with treatment. The HeartQoL is a validated heart disease-specific questionnaire with a physical and an emotional subscale that is used internationally to assess HRQoL in patients with coronary heart disease (CHD). The aim of this study was to translate and evaluate the psychometric properties of the HeartQoL in patients with CHD in Iceland.

Methods
Patients ≥ 18 years (n = 396; mean age 64.4 ± 8.8 years; 79.6% male) admitted with CHD were recruited from two hospitals in Iceland and completed the Icelandic versions of the HeartQoL, Short-Form 12v2 Health Survey (SF-12v2), and Hospital Anxiety and Depression Scale (HADS). A subsample of 47 patients completed the HeartQoL 14 days later. Confirmatory factor analysis for ordinal data was used to evaluate the measurement model with a physical and an emotional subscale. Convergent and divergent validity, internal consistency, and test-retest reliability were evaluated.

Results
Overall, the hypothesized two-factor structure of the Icelandic version of the HeartQoL was supported. However, problems with cross-loadings and correlated error variances were identified. Convergent and divergent validity were supported in correlational analyses between HeartQoL, SF-12v2, and HADS. Internal consistency reliability, measured by ordinal alpha, was good for the physical (α = 0.96) and emotional (α = 0.90) subscale. According to intraclass correlations (ICC), acceptable test-retest reliability was demonstrated (ICC = 0.79–0.86).

Conclusion
With the two-factor structure confirmed, the Icelandic HeartQoL demonstrated satisfactory psychometric properties in the sample of patients with CHD. Users of the instrument can use the original scoring.
SARS-CoV-2-associated organs failure and inflammation: a focus on the role of cellular and viral microRNAs
Authors: Rasizadeh Reyhaneh , Aghbash Parisa Shiri , Nahand Javid Sadri , Entezari-Maleki Taher , Baghi Hossein Bannazadeh 
Published: August 2023

AbstractSARS-CoV-2 has been responsible for the recent pandemic all over the world, which has caused many complications. One of the hallmarks of SARS-CoV-2 infection is an induced immune dysregulation, in some cases resulting in cytokine storm syndrome, acute respiratory distress syndrome and many organs such as lungs, brain, and heart that are affected during the SARS-CoV-2 infection. Several physiological parameters are altered as a result of infection and cytokine storm. Among them, microRNAs (miRNAs) might reflect this poor condition since they play a significant role in immune cellular performance including inflammatory responses. Both host and viral-encoded miRNAs are crucial for the successful infection of SARS-CoV-2. For instance, dysregulation of miRNAs that modulate multiple genes expressed in COVID-19 patients with comorbidities (e.g., type 2 diabetes, and cerebrovascular disorders) could affect the severity of the disease. Therefore, altered expression levels of circulating miRNAs might be helpful to diagnose this illness and forecast whether a COVID-19 patient could develop a severe state of the disease. Moreover, a number of miRNAs could inhibit the expression of proteins, such as ACE2, TMPRSS2, spike, and Nsp12, involved in the life cycle of SARS-CoV-2. Accordingly, miRNAs represent potential biomarkers and therapeutic targets for this devastating viral disease. In the current study, we investigated modifications in miRNA expression and their influence on COVID-19 disease recovery, which may be employed as a therapy strategy to minimize COVID-19-related disorders.
Targeted mRNA demethylation in Arabidopsis using plant m6A editor
Authors: Fang Ruiqiu , Chen Xiaolong , Shen Jie , Wang Bin 
Published: August 2023

Abstract
Background
N6-methyladenosine (m6A) is an important epigenetic modification involved in RNA stability and translation regulation. Manipulating the expression of RNA m6A methyltransferases or demethylases makes it difficult to study the effect of specific RNA methylation.

Results
In this study, we report the development of Plant m6A Editors (PMEs) using dLwaCas13a (from L. wadei) and human m6A demethylase ALKBH5 catalytic domain. PMEs specifically demethylates m6A of targeted mRNAs (WUS, STM, FT, SPL3 and SPL9) to increase mRNAs stability. In addition, we discovered that a double ribozyme system can significantly improve the efficiency of RNA editing.

Conclusion
PMEs specifically demethylates m6A of targeted mRNAs to increase mRNAs stability, suggesting that this engineered tool is instrumental for biotechnological applications.
CircECE1 promotes osteosarcoma progression through regulating RAB3D by sponging miR-588
Authors: Liang Zhizhong , Shi Yuxia , Guan Zhe 
Published: August 2023

Abstract
Background
Circular RNAs (circRNAs) have been confirmed to be involved in cancer pathogenesis. However, the underlying mechanism of circRNA endothelin converting enzyme 1 (circECE1) in osteosarcoma (OS) development is still not understood.

Methods
The expression levels of circECE1, microRNA-588 (miR-588) and RAB3D, member RAS oncogene family (RAB3D) were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. OS cell proliferation was assessed by cell counting kit-8 (CCK-8) assay and 5-ethynyl-2’-deoxyuridine (EdU) assay. OS cell apoptosis rate and metastasis were identified by flow cytometry and transwell assay. Dual-luciferase reporter analysis and RNA immunoprecipitation (RIP) assay were performed to confirm the interactions among circECE1, miR-588 and RAB3D. Xenograft tumor models were established to explore circECE1 function in vivo. Immunohistochemistry (IHC) assay was applied to analyze RAB3D level after circECE1 knockdown.

Results
In OS, circECE1 expression was higher than that in normal chondroma tissues. High levels of circECE1 were positively linked to OS cell viability, proliferation, migration and invasion, and negatively linked to OS cell apoptosis rate. It was found that circECE1 was a miR-588 sponge, and miR-588 inhibitor abrogated the influence of si-circECE1 on OS cells. MiR-588 targeted RAB3D to further regulate the pathological process of OS. Moreover, silencing circECE1 blocked OS tumor growth in vivo.

Conclusion
We elucidated the function of a novel circECE1/miR-588/RAB3D axis in OS progression.
Macrophage-organoid co-culture model for identifying treatment strategies against macrophage-related gemcitabine resistance
Authors: Jiang Shengwei , Deng Tingwei , Cheng Huan , Liu Weihan , Shi Dan , Yuan Jiahui , He Zhiwei , Wang Weiwei , Chen Boning , Ma Li , Zhang Xianbin , Gong Peng 
Published: August 2023

Abstract
Background
Gemcitabine resistance (GR) is a significant clinical challenge in pancreatic adenocarcinoma (PAAD) treatment. Macrophages in the tumor immune-microenvironment are closely related to GR. Uncovering the macrophage-induced GR mechanism could help devise a novel strategy to improve gemcitabine treatment outcomes in PAAD. Therefore, preclinical models accurately replicating patient tumor properties are essential for cancer research and drug development. Patient-derived organoids (PDOs) represent a promising in vitro model for investigating tumor targets, accelerating drug development, and enabling personalized treatment strategies to improve patient outcomes.

Methods
To investigate the effects of macrophage stimulation on GR, co-cultures were set up using PDOs from three PAAD patients with macrophages. To identify signaling factors between macrophages and pancreatic cancer cells (PCCs), a 97-target cytokine array and the TCGA-GTEx database were utilized. The analysis revealed CCL5 and AREG as potential candidates. The role of CCL5 in inducing GR was further investigated using clinical data and tumor sections obtained from 48 PAAD patients over three years, inhibitors, and short hairpin RNA (shRNA). Furthermore, single-cell sequencing data from the GEO database were analyzed to explore the crosstalk between PCCs and macrophages. To overcome GR, inhibitors targeting the macrophage-CCL5-Sp1-AREG feedback loop were evaluated in cell lines, PDOs, and orthotopic mouse models of pancreatic carcinoma.

Results
The macrophage-CCL5-Sp1-AREG feedback loop between macrophages and PCCs is responsible for GR. Macrophage-derived CCL5 activates the CCR5/AKT/Sp1/CD44 axis to confer stemness and chemoresistance to PCCs. PCC-derived AREG promotes CCL5 secretion in macrophages through the Hippo-YAP pathway. By targeting the feedback loop, mithramycin improves the outcome of gemcitabine treatment in PAAD. The results from the PDO model were corroborated with cell lines, mouse models, and clinical data.

Conclusions
Our study highlights that the PDO model is a superior choice for preclinical research and precision medicine. The macrophage-CCL5-Sp1-AREG feedback loop confers stemness to PCCs to facilitate gemcitabine resistance by activating the CCR5/AKT/SP1/CD44 pathway. The combination of gemcitabine and mithramycin shows potential as a therapeutic strategy for treating PAAD in cell lines, PDOs, and mouse models.
Fibronectin fragments generated by pancreatic trypsin act as endogenous inhibitors of pancreatic tumor growth
Authors: Resovi Andrea , Persichitti Perla , Brunelli Laura , Minoli Lucia , Borsotti Patrizia , Garattini Giulia , Tironi Matteo , Dugnani Erica , Redegalli Miriam , De Simone Giulia , Pastorelli Roberta , Bani Maria Rosa , Piemonti Lorenzo , Mosher Deane F. , Giavazzi Raffaella , Taraboletti Giulia , Belotti Dorina 
Published: August 2023

Abstract
Background
The pancreatic microenvironment has a defensive role against cancer but it can acquire tumor-promoting properties triggered by multiple mechanisms including alterations in the equilibrium between proteases and their inhibitors. The identification of proteolytic events, targets and pathways would set the basis for the design of new therapeutic approaches.

Methods and results
Here we demonstrate that spheroids isolated from human and murine healthy pancreas and co-transplanted orthotopically with pancreatic ductal adenocarcinoma (PDAC) in mouse pancreas inhibited tumor growth. The effect was mediated by trypsin-generated fibronectin (FN) fragments released by pancreatic spheroids. Tumor inhibition was observed also in a model of acute pancreatitis associated with trypsin activation. Mass spectrometry proteomic analysis of fragments and mAb against different FN epitopes identified the FN type III domain as responsible for the activity. By inhibiting integrin α5β1, FAK and FGFR1 signaling, the fragments induced tumor cell detachment and reduced cell proliferation. Consistent with the mutual relationship between the two pathways, FGF2 restored both FGFR1 and FAK signaling and promoted PDAC cell adhesion and proliferation. FAK and FGFR inhibitors additively inhibited PDAC growth in vitro and in orthotopic in vivo models.

Conclusions
This study identifies a novel role for pancreatic trypsin and fibronectin cleavage as a mechanism of protection against cancer by the pancreatic microenvironment. The finding of a FAK-FGFR cross-talk in PDAC support the combination of FAK and FGFR inhibitors for PDAC treatment to emulate the protective effect of the normal pancreas against cancer.
Relationship between insecticide resistance profiles in Anopheles gambiae sensu lato and agricultural practices in Côte d’Ivoire
Authors: Kouadio France-Paraudie A. , Wipf Nadja C. , Nygble Angele S. , Fodjo Behi K. , Sadia Christabelle G. , Vontas John , Mavridis Konstantinos , Müller Pie , Mouhamadou Chouaïbou S. 
Published: August 2023

Abstract
Background
Insecticide-based malaria vector control is increasingly undermined due to the development of insecticide resistance in mosquitoes. Insecticide resistance may partially be related to the use of pesticides in agriculture, while the level and mechanisms of resistance might differ between agricultural practices. The current study aimed to assess whether phenotypic insecticide resistance and associated molecular resistance mechanisms in Anopheles gambiae sensu lato differ between agricultural practices.

Methods
We collected An. gambiae s.l. larvae in six sites with three different agricultural practices, including rice, vegetable and cocoa cultivation. We then exposed the emerging adult females to discriminating concentrations of bendiocarb (0.1%), deltamethrin (0.05%), DDT (4%) and malathion (5%) using the standard World Health Organization insecticide susceptibility test. To investigate underlying molecular mechanisms of resistance, we used multiplex TaqMan qPCR assays. We determined the frequency of target-site mutations, including Vgsc-L995F/S and Vgsc-N1570Y, and Ace1-G280S. In addition, we measured the expression levels of genes previously associated with insecticide resistance in An. gambiae s.l., including the cytochrome P450-dependent monooxygenases CYP4G16, CYP6M2, CYP6P1, CYP6P3, CYP6P4, CYP6Z1 and CYP9K1, and the glutathione S-transferase GSTe2.

Results
The An. gambiae s.l. populations from all six agricultural sites were resistant to bendiocarb, deltamethrin and DDT, while the populations from the two vegetable cultivation sites were additionally resistant to malathion. Most tested mosquitoes carried at least one mutant Vgsc-L995F allele that is associated with pyrethroid and DDT resistance. In the cocoa cultivation sites, we observed the highest 995F frequencies (80–87%), including a majority of homozygous mutants and several in co-occurrence with the Vgsc-N1570Y mutation. We detected the Ace1 mutation most frequently in vegetable-growing sites (51–60%), at a moderate frequency in rice (20–22%) and rarely in cocoa-growing sites (3–4%). In contrast, CYP6M2, CYP6P3, CYP6P4, CYP6Z1 and CYP9K1, previously associated with metabolic insecticide resistance, showed the highest expression levels in the populations from rice-growing sites compared to the susceptible Kisumu reference strain.

Conclusion
In our study, we observed intriguing associations between the type of agricultural practices and certain insecticide resistance profiles in the malaria vector An. gambiae s.l. which might arise from the use of pesticides deployed for protecting crops.

Graphical Abstract
Sex differences in metabolic phenotype and hypothalamic inflammation in the 3xTg-AD mouse model of Alzheimer’s disease
Authors: Robison Lisa S. , Gannon Olivia J. , Salinero Abigail E. , Abi-Ghanem Charly , Kelly Richard D. , Riccio David A. , Mansour Febronia M. , Zuloaga Kristen L. 
Published: August 2023

AbstractBackgroundAlzheimer’s disease (AD) is notably associated with cognitive decline resulting from impaired function of hippocampal and cortical areas; however, several other domains and corresponding brain regions are affected. One such brain region is the hypothalamus, shown to atrophy and develop amyloid and tau pathology in AD patients. The hypothalamus controls several functions necessary for survival, including energy and glucose homeostasis. Changes in appetite and body weight are common in AD, often seen several years prior to the onset of cognitive symptoms. Therefore, altered metabolic processes may serve as a biomarker for AD, as well as a target for treatment, considering they are likely both a result of pathological changes and contributor to disease progression. Previously, we reported sexually dimorphic metabolic disturbances in ~ 7-month-old 3xTg-AD mice, accompanied by differences in systemic and hypothalamic inflammation.MethodsIn the current study, we investigated metabolic outcomes and hypothalamic inflammation in 3xTg-AD males and females at 3, 6, 9, and 12 months of age to determine when these sex differences emerge.ResultsIn agreement with our previous study, AD males displayed less weight gain and adiposity, as well as reduced blood glucose levels following a glucose challenge, compared to females. These trends were apparent by 6–9 months of age, coinciding with increased expression of inflammatory markers (Iba1, GFAP, TNF-α, and IL-1β) in the hypothalamus of AD males.ConclusionsThese findings provide additional evidence for sex-dependent effects of AD pathology on energy and glucose homeostasis, which may be linked to hypothalamic inflammation.