bluuebunny/crossref_metadata_2025_split huggingface dataset:
The upregulation of NLRP3 inflammasome in dorsal root ganglion by ten-eleven translocation methylcytosine dioxygenase 2 (TET2) contributed to diabetic neuropathic pain in mice
Authors: Chen Wen , Wang Xiaotong , Sun Qingyu , Zhang Yurui , Liu Jing , Hu Tingting , Wu Weihua , Wei Chao , Liu Meng , Ding Yumeng , Liu Dianxin , Chong Yingzi , Wang Peipei , Zhu Hongwei , Cui Weihua , Zhang Jiannan , Li Qian , Yang Fei 
Published: December 2022

Abstract
Background
The nucleotide oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) in dorsal root ganglion (DRG) contributes to pain hypersensitivity in multiple neuropathic pain models, but the function of the NLRP3 in diabetic neuropathic pain (DNP) and the regulation mechanism are still largely unknown. Epigenetic regulation plays a vital role in the controlling of gene expression. Ten-eleven translocation methylcytosine dioxygenase 2 (TET2) is a DNA demethylase that contributes to transcriptional activation. TET2 is also involved in high glucose (HG)-induced pathology.

Methods
DNP was induced in mice via the intraperitoneal injection of streptozotocin (STZ) for five consecutive days and the mechanical threshold was evaluated in STZ-diabetic mice by using von Frey hairs. The expression level of the NLRP3 pathway and TET2 in DRG were determined through molecular biology experiments. The regulation of the NLRP3 pathway by TET2 was examined in in vitro and in vivo conditions.

Results
In the present research, we first established the DNP model and found that NLRP3 pathway was activated in DRG. The treatment of NLRP3 inhibitor MCC950 alleviated the mechanical allodynia of DNP mice. Then we revealed that in STZ-diabetic mice DRG, the genomic DNA was demethylated, and the expression of DNA demethylase TET2 was increased evidently. Using RNA-sequencing analysis, we found that the expression of Txnip, a gene that encodes a thioredoxin-interacting protein (TXNIP) which mediates NLRP3 activation, was elevated in the DRG after STZ treatment. In addition, knocking down of TET2 expression in DRG using TET2-siRNA suppressed the mRNA expression of Txnip and subsequently inhibited the expression/activation of NLRP3 inflammasome in vitro and in vivo as well as relieved the pain sensitivity of DNP animals.

Conclusion
The results suggested that the upregulation of the TXNIP/NLRP3 pathway by TET2 in DRG was involved in the pain hypersensitivity of the DNP model.
A detailed analysis of F-MuLV- and SFFV-infected cells in Friend virus-infected mice reveals the contribution of both F-MuLV- and SFFV-infected cells to the interleukin-10 host response
Authors: Podschwadt Philip , Malyshkina Anna , Windmann Sonja , Werner Tanja , Hansen Wiebke , Bayer Wibke 
Published: December 2022

AbstractBackgroundFriend virus (FV) is a complex of the Friend murine leukemia virus (F-MuLV) and the replication-defective, pathogenic spleen focus forming virus (SFFV). In the past, we used a fluorescently labeled F-MuLV to analyze FV target cells. To build on these findings, we have now created a double-labeled FV that contains a Katushka-labeled F-MuLV and an mTagBFP-labeled SFFV, which we have used to study the infection by the two individual viruses in the FV infection of highly susceptible BALB/c mice.ResultsOur data show that the target cells of SFFV largely mirror those of F-MuLV, with the highest virus loads in erythroblasts, B cells and myeloid cells. The early phase of infection was dominated by cells infected by either SFFV or F-MuLV, whereas double-infected cells became dominant later in the course of infection with increasing viral loads. In the late phase of infection, the frequency of double-infected cells was similarly high as the frequencies of SFFV or F-MuLV single-infected cells, and single- and double-infected cells outnumbered the uninfected cells in the most highly infected cell populations such as erythroblasts. FV and retroviruses in general have been shown to induce interleukin 10 (IL-10) as a means of suppressing immune responses. Interestingly, we found in infected IL-10-eGFP reporter mice that SFFV-infected cells contributed to the IL-10-producing cell pool much more significantly than F-MuLV-infected cells, suggesting that the truncated SFFV envelope protein gp55 might play a role in IL-10 induction. Even though BALB/c mice mount notoriously weak immune responses against FV, infection of mice with an ablation of IL-10 expression in T cells showed transiently lower viral loads and stronger T cell activation, suggesting that IL-10 induction by FV and by SFFV in particular may contribute to a suppressed immune response in BALB/c mice.ConclusionOur data provide detailed information about both F-MuLV- and SFFV-infected cells during the course of FV infection in highly susceptible mice and imply that the pathogenic SFFV contributes to immune suppression.
Astragaloside IV attenuates IL-1β-induced intervertebral disc degeneration through inhibition of the NF-κB pathway
Authors: Tian Yueyang , Chu Xu , Huang Qia , Guo Xing , Xue Yuan , Deng Weimin 
Published: December 2022

Abstract
Background
Intervertebral disc degeneration (IDD) is the main cause of low back pain. Patients with low back pain may experience significant socio-economic burdens and decreased productivity. Previous studies have shown that inflammation is one of the main causes of IDD. Astragaloside IV (AS IV), a traditional Chinese medicine, has been reported to have therapeutic effects on many inflammation-related diseases; however, the effectiveness of AS IV as the treatment for IDD has not been studied.

Methods
Nucleus pulposus (NP) cells from patients with IDD were used for the experiments. Cell counting kit 8 (CCK8) was used to evaluate the effect of AS IV on the viability of NP cells (NPCs). To mimic IDD in vitro, NPCs were divided into the following groups: control group, interleukin 1β (IL-1β) group, and AS IV + IL-1β group. To analyse the effect of AS IV on IL-1β-induced IDD, Western blotting, RT-qPCR, flow cytometry, and immunofluorescence assays were performed. To evaluate the effect of AS IV in vivo, a rat model of puncture-induced IDD was established.

Results
AS IV effectively alleviated IL-1β-induced inflammation, apoptosis, and extracellular matrix degeneration in NPCs. We also observed that AS IV decreased the IL-1β-induced phosphorylation of inhibitor of kappa B-alpha (p-IκBα) in the cytosol, and reduced nuclear translocation of NF-κB p65, indicating that AS IV inhibited the NF-κB pathway. Using the puncture-induced rat IDD model, our results showed that AS IV had a protective effect against the progression of IDD, suggesting that AS IV could alleviate IDD in vivo.

Conclusions
Our results demonstrated that AS IV effectively alleviated IDD in vivo and in vitro, indicating that it could be used as a therapeutic to treat IDD.
Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom study
Authors: Sgroi Dennis C. , Treuner Kai , Zhang Yi , Piper Tammy , Salunga Ranelle , Ahmed Ikhlaaq , Doos Lucy , Thornber Sarah , Taylor Karen J. , Brachtel Elena , Pirrie Sarah , Schnabel Catherine A. , Rea Daniel , Bartlett John M. S. 
Published: December 2022

Abstract
Background
Multiple clinical trials demonstrate consistent but modest benefit of adjuvant extended endocrine therapy (EET) in HR + breast cancer patients. Predictive biomarkers to identify patients that benefit from EET are critical to balance modest reductions in risk against potential side effects of EET. This study compares the performance of the Breast Cancer Index, BCI (HOXB13/IL17BR, H/I), with expression of estrogen (ER), progesterone (PR), and androgen receptors (AR), and Ki67, for prediction of EET benefit.

Methods
Node-positive (N+) patients from the Trans-aTTom study with available tissue specimen and BCI results (N = 789) were included. Expression of ER, PR, AR, and Ki67 was assessed by quantitative immunohistochemistry. BCI (H/I) gene expression analysis was conducted by quantitative RT-PCR. Statistical significance of the treatment by biomarker interaction was evaluated by likelihood ratio tests based on multivariate Cox proportional models, adjusting for age, tumor size, grade, and HER2 status. Pearson’s correlation coefficients were calculated to evaluate correlations between BCI (H/I) versus ER, PR, AR, Ki67 and AR/ER ratio.

Results
EET benefit, measured by the difference in risk of recurrence between patients treated with tamoxifen for 10 versus 5 years, is significantly associated with increasing values of BCI (H/I) (interaction P = 0.01). In contrast, expression of ER (P = 0.83), PR (P = 0.66), AR (P = 0.78), Ki67 (P = 0.87) and AR/ER ratio (P = 0.84) exhibited no significant relationship with EET benefit. BCI (H/I) showed a very weak negative correlation with ER (r = − 0.18), PR (r = − 0.25), and AR (r = − 0.14) expression, but no correlation with either Ki67 (r = 0.04) or AR/ER ratio (r = 0.02).

Conclusion
These findings are consistent with the growing body of evidence that BCI (H/I) is significantly predictive of response to EET and outcome. Results from this direct comparison demonstrate that expression of ER, PR, AR, Ki67 or AR/ER ratio are not predictive of benefit from EET. BCI (H/I) is the only clinically validated biomarker that predicts EET benefit.
Internet delivered, non-inferiority, two-arm, assessor-blinded intervention comparing mindfulness-based stress reduction and cognitive-behavioral treatment for insomnia: a protocol study for a randomized controlled trial for nursing staff with insomnia
Authors: Li Yaling , Nazari Nabi , Sadeghi Masoud 
Published: December 2022

Abstract
Background
Insomnia and poor sleep quality are highly prevalent conditions related to coronavirus disease 2019 (COVID-19) complications among clinical nurses. Although cognitive behavioral therapy for insomnia (CBT-I) is a first-line treatment, CBT-I suffers from several major drawbacks. This study investigates whether the application of the internet-delivered mindfulness-based stress reduction (iMBSR) intervention will produce effects that are non-inferior to the internet-delivered CBT-I (iCBT-I) intervention in reducing the severity of insomnia in clinical nurses with insomnia at the end of the study.

Methods
This study protocol presents an internet-delivered, parallel-groups, assessor-blinded, two-arm, non-inferiority randomized controlled trial. The primary outcome is sleep quality, assessed by the Insomnia Severity Index. Secondary outcomes include depression, dysfunctional beliefs, five facets of mindfulness, and client satisfaction.

Conclusion
It is expected that this study may address several gaps in the literature. The non-inferiority study design is a novel approach to evaluating whether a standardized, complementary treatment (i.e., MBSR) is as practical as a gold standard treatment rather than its potential benefits. This approach may lead to expanded evidence-based practice and improve patient access to effective treatments.

Trial registration
Trial registration number: ISRCTN36198096. Registered on 24th May 2022.
Spatial–temporal regulation of fatty alcohol biosynthesis in yeast
Authors: Gao Ning , Gao Jiaoqi , Yu Wei , Kong Sijia , Zhou Yongjin J. 
Published: December 2022

Abstract
Background
Construction of efficient microbial cell factories is one of the core steps for establishing green bio-manufacturing processes. However, the complex metabolic regulation makes it challenging in driving the metabolic flux toward the product biosynthesis. Dynamically coupling the biosynthetic pathways with the cellular metabolism at spatial–temporal manner should be helpful for improving the production with alleviating the cellular stresses.

Results
In this study, we observed the mismatch between fatty alcohol biosynthesis and cellular metabolism, which compromised the fatty alcohol production in Saccharomyces cerevisiae. To enhance the fatty alcohol production, we spatial-temporally regulated fatty alcohol biosynthetic pathway by peroxisomal compartmentalization (spatial) and dynamic regulation of gene expression (temporal). In particular, fatty acid/acyl-CoA responsive promoters were identified by comparative transcriptional analysis, which helped to dynamically regulate the expression of acyl-CoA reductase gene MaFAR1 and improved fatty alcohol biosynthesis by 1.62-fold. Furthermore, enhancing the peroxisomal supply of acyl-CoA and NADPH further improved fatty alcohol production to 282 mg/L, 2.52 times higher than the starting strain.

Conclusions
This spatial–temporal regulation strategy partially coordinated fatty alcohol biosynthesis with cellular metabolism including peroxisome biogenesis and precursor supply, which should be applied for production of other products in microbes.
Manure and mosquitoes: life history traits of two malaria vector species enhanced by larval exposure to cow dung, whilst chicken dung has a strong negative effect
Authors: Hardy Harrison , Hopkins Richard , Mnyone Ladslaus , Hawkes Frances M. 
Published: December 2022

AbstractBackgroundMalaria vectors have a strong ecological association with rice agroecosystems, which can provide abundant aquatic habitats for larval development. Climate-adapted rice cultivation practices, such as the System of Rice Intensification (SRI), are gaining popularity in malaria-endemic countries seeking to expand rice production; however, the potential impact of these practices on vector populations has not been well characterised. In particular, SRI encourages the use of organic fertilisers (OFs), such as animal manures, as low-cost and environmentally friendly alternatives to industrially produced inorganic fertilisers. We therefore set out to understand the effects of two common manure-based OFs on the life history traits of two major African malaria vectors,Anopheles arabiensisandAnopheles gambiaesensu stricto (s.s.).MethodsLarvae ofAn. arabiensisandAn. gambiaes.s. were reared from first instar to emergence in water containing either cow or chicken dung at one of four concentrations (0.25, 0.5, 0.75, and 1.0 g/100 ml), or in a clean water control. Their life history traits were recorded, including survival, development rate, adult production, and adult wing length.ResultsExposure to cow dung significantly increased the development rate ofAn. gambiaes.s. independent of concentration, but did not affect the overall survival and adult production of either species. Chicken dung, however, significantly reduced survival and adult production in both species, with a greater effect as concentration increased. Interestingly,An. arabiensisexhibited a relative tolerance to the lowest chicken dung concentration, in that survival was unaffected and adult production was not reduced to the same extent as inAn. gambiaes.s. The effects of chicken dung on development rate were less clear in both species owing to high larval mortality overall, though there was some indication that it may reduce development rate. Adult wing lengths in males and females increased with higher concentrations of both cow and chicken dung.ConclusionsOur findings suggest that manure-based OFs significantly alter the life history traits ofAn. gambiaes.s. andAn. arabiensis.In both species, exposure to cow dung may improve fitness, whereas exposure to chicken dung may reduce it. These findings have implications for understanding vector population dynamics in rice agroecosystems and may inform the use of OFs in SRI, and rice agriculture more widely, to avoid their adverse effects in enhancing vector fitness.Graphical Abstract
Efficient generation of epigenetic disease model mice by epigenome editing using the piggyBac transposon system
Authors: Horii Takuro , Morita Sumiyo , Kimura Mika , Hatada Izuho 
Published: December 2022

Abstract
Background
Epigenome-edited animal models enable direct demonstration of disease causing epigenetic mutations. Transgenic (TG) mice stably expressing epigenome-editing factors exhibit dramatic and stable changes in target epigenome modifications. Successful germline transmission of a transgene from founder mice to offspring will yield a sufficient number of epigenome-edited mice for phenotypic analysis; however, if the epigenetic mutation has a detrimental phenotypic effect, it can become difficult to obtain the next generation of animals. In this case, the phenotype of founder mice must be analyzed directly. Unfortunately, current TG mouse production efficiency (TG founders per pups born) is relatively low, and improvements would increase the versatility of this technology.

Results
In the current study, we describe an approach to generate epigenome-edited TG mice using a combination of both the dCas9–SunTag and piggyBac (PB) transposon systems. Using this system, we successfully generated mice with demethylation of the differential methylated region of the H19 gene (H19-DMR), as a model for Silver–Russell syndrome (SRS). SRS is a disorder leading to growth retardation, resulting from low insulin-like growth factor 2 (IGF2) gene expression, often caused by epimutations at the H19-IGF2 locus. Under optimized conditions, the efficiency of TG mice production using the PB system was approximately threefold higher than that using the conventional method. TG mice generated by this system showed demethylation of the targeted DNA region and associated changes in gene expression. In addition, these mice exhibited some features of SRS, including intrauterine and postnatal growth retardation, due to demethylation of H19-DMR.

Conclusions
The dCas9–SunTag and PB systems serve as a simple and reliable platform for conducting direct experiments using epigenome-edited founder mice.
Multi-region sequencing with spatial information enables accurate heterogeneity estimation and risk stratification in liver cancer
Authors: Yang Chen , Zhang Senquan , Cheng Zhuoan , Liu Zhicheng , Zhang Linmeng , Jiang Kai , Geng Haigang , Qian Ruolan , Wang Jun , Huang Xiaowen , Chen Mo , Li Zhe , Qin Wenxin , Xia Qiang , Kang Xiaonan , Wang Cun , Hang Hualian 
Published: December 2022

Abstract

Background
Numerous studies have used multi-region sampling approaches to characterize intra-tumor heterogeneity (ITH) in hepatocellular carcinoma (HCC). However, conventional multi-region sampling strategies do not preserve the spatial details of samples, and thus, the potential influences of spatial distribution on patient-wise ITH (represents the overall heterogeneity level of the tumor in a given patient) have long been overlooked. Furthermore, gene-wise transcriptional ITH (represents the expression pattern of genes across different intra-tumor regions) in HCC is also under-explored, highlighting the need for a comprehensive investigation.

Methods
To address the problem of spatial information loss, we propose a simple and easy-to-implement strategy called spatial localization sampling (SLS). We performed multi-region sampling and sequencing on 14 patients with HCC, collecting a total of 75 tumor samples with spatial information and molecular data. Normalized diversity score and integrated heterogeneity score (IHS) were then developed to measure patient-wise and gene-wise ITH, respectively.

Results
A significant correlation between spatial and molecular heterogeneity was uncovered, implying that spatial distribution of sampling sites did influence ITH estimation in HCC. We demonstrated that the normalized diversity score had the ability to overcome sampling location bias and provide a more accurate estimation of patient-wise ITH. According to this metric, HCC tumors could be divided into two classes (low-ITH and high-ITH tumors) with significant differences in multiple biological properties. Through IHS analysis, we revealed a highly heterogenous immune microenvironment in HCC and identified some low-ITH checkpoint genes with immunotherapeutic potential. We also constructed a low-heterogeneity risk stratification (LHRS) signature based on the IHS results which could accurately predict the survival outcome of patients with HCC on a single tumor biopsy sample.

Conclusions
This study provides new insights into the complex phenotypes of HCC and may serve as a guide for future studies in this field.
Effect of proton pump inhibitors in infants with esophageal atresia on the gut microbiome: a pilot cohort
Authors: Brusselaers Nele , Pereira Marcela , Alm Johan , Engstrand Lars , Engstrand Lilja Helene 
Published: December 2022

Abstract
Background
The effects of proton-pump inhibitors (PPIs) on the infant microbiome remain unclear. Swedish pilot cohort study to assess the longitudinal effect of long-term PPI on the infant gut microbiome, including ten newborn infants operated for esophageal atresia exposed to PPIs (mean 57 weeks), compared to healthy one-year-old controls. All children were born vaginally and were otherwise healthy. Within- and between sample diversity of the fecal microbiome was assessed using untargeted whole genome Shotgun metagenomics which sequences all the DNA in the sample and can capture genes rather than a taxonomic fingerprint.

Results
A longer duration of PPI-use was associated with considerable changes in evenness and high variation on diversity within samples compared to a shorter duration of use. The limited difference between baseline samples and controls suggests that this shift was most likely due to the drug exposure and not the underlying alterations on the microbiome. We found no associations with the number of antibiotic treatment episodes among the PPI-users.

Conclusion
Prolonged PPI-use may alter the early infant gut microbiome composition, especially those with the most prolonged duration of use.
Coronary artery aneurysm presenting as ST-elevation myocardial infarction in a man with coronavirus disease 2019: a case report
Authors: Alao David O. , Alabdouli Amani , Jalabi Ala 
Published: December 2022

Abstract
Background
Patients with underlying cardiovascular risk factors have worse clinical outcomes when they have coronavirus disease. In addition, a reduced workload of cardiovascular emergencies has been reported during the coronavirus pandemic due to patients’ reluctance to attend hospitals for fear of contracting the disease. Regional health service reorganization, separating hospitals into coronavirus and non-coronavirus can mitigate this effect. However, the effectiveness of this approach on outcomes and patient satisfaction is unknown.

Case presentation
A 35-year-old Pakistani man with acute ST myocardial infarction was found to have thrombosis of the right coronary artery aneurysm and concomitant coronavirus disease. He had percutaneous coronary angiography and thrombus removal, and was transferred to a coronavirus hospital for the management of the infection. Due to the large size of the aneurysm, he was considered for surgical intervention. Following discharge from the coronavirus hospital and a period of stay at the isolation center, he failed to keep his cardiology follow-up appointment.

Conclusion
This case illustrates an unusual cause of myocardial infarction in a patient with coronavirus infection whose care may have been adversely affected by the healthcare system restructuring.