bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of itaconic acid production on Neurospora crassa in consolidated bioprocessing of cellulose
Authors: Zhao Jiajia , Ma Caihong , Mei Yaojie , Han Jingjing , Zhao Chen 
Published: February 2023

AbstractA system for itaconic acid synthesis from cellulose by Neurospora crassa was established, resulting in the highest yield of itaconic acid was 354.08 + 35.99 mg/L. Meanwhile, cellulase activity increased significantly, without any strain modifications for improved cellulase production. Multi-omics analyses showed that itaconic acid synthesis reduced energy production, leading to decreases in trehalose, cell wall, fatty acids synthesis and downregulations in MAPK signaling pathway, cell cycle and meiosis. More importantly, the low-energy environment enhanced the energy-efficient cellobionic acid/gluconic acid pathway, and the cellulase composition also changed significantly, manifested as the up-regulation of LPMOs and the down-regulation of β-glucosidases. Enhancing LPMOs-cellobionic acid/gluconic acid system has the potential to reduce energy consumption of the consolidated bioprocessing. These findings offer an overview of resource allocations by N. crassa in response to itaconic acid synthesis and highlight a series of intriguing connections between itaconic acid synthesis and cellulase synthesis in consolidated bioprocessing.
Low muscle mass in lung cancer is associated with an inflammatory and immunosuppressive tumor microenvironment
Authors: Cury Sarah Santiloni , de Moraes Diogo , Oliveira Jakeline Santos , Freire Paula Paccielli , dos Reis Patricia Pintor , Batista Miguel Luiz , Hasimoto Érica Nishida , Carvalho Robson Francisco 
Published: February 2023

Abstract
Background
Computed tomographies (CT) are useful for identifying muscle loss in non-small lung cancer (NSCLC) cachectic patients. However, we lack consensus on the best cutoff point for pectoralis muscle loss. We aimed to characterize NSCLC patients based on muscularity, clinical data, and the transcriptional profile from the tumor microenvironment to build a cachexia classification model.

Methods
We used machine learning to generate a muscle loss prediction model, and the tumor's cellular and transcriptional profile was characterized in patients with low muscularity. First, we measured the pectoralis muscle area (PMA) of 211 treatment-naive NSCLC patients using CT available in The Cancer Imaging Archive. The cutoffs were established using machine learning algorithms (CART and Cutoff Finder) on PMA, clinical, and survival data. We evaluated the prediction model in a validation set (36 NSCLC). Tumor RNA-Seq (GSE103584) was used to profile the transcriptome and cellular composition based on digital cytometry.

Results
CART demonstrated that a lower PMA was associated with a high risk of death (HR = 1.99). Cutoff Finder selected PMA cutoffs separating low-muscularity (LM) patients based on the risk of death (P-value = 0.003; discovery set). The cutoff presented 84% of success in classifying low muscle mass. The high risk of LM patients was also found in the validation set. Tumor RNA-Seq revealed 90 upregulated secretory genes in LM that potentially interact with muscle cell receptors. The LM upregulated genes enriched inflammatory biological processes. Digital cytometry revealed that LM patients presented high proportions of cytotoxic and exhausted CD8+ T cells.

Conclusions
Our prediction model identified cutoffs that distinguished patients with lower PMA and survival with an inflammatory and immunosuppressive TME enriched with inflammatory factors and CD8+ T cells.
Spermatogenesis associated serine rich 2 like plays a prognostic factor and therapeutic target in acute myeloid leukemia by regulating the JAK2/STAT3/STAT5 axis
Authors: Li Fenglin , Ye Wenle , Yao Yiyi , Wei Wenwen , Lin Xiangjie , Zhuang Haihui , Li Chenying , Li Xia , Ling Qing , Hu Chao , Huang Xin , Qian Yu , Mao Shihui , Huang Jiansong , Lu Ying , Jin Jie 
Published: February 2023

Abstract
Background
Spermatogenesis associated serine rich 2 like (SPATS2L) was highly expressed in homoharringtonine (HHT) resistant acute myeloid leukemia (AML) cell lines. However, its role is little known in AML. The present study aimed to investigate the function of SPATS2L in AML pathogenesis and elucidate the underlying molecular mechanisms.

Methods
Overall survival (OS), event-free survival (EFS), relapse-free survival (RFS) were used to evaluate the prognostic impact of SPATS2L for AML from TCGA database and ourcohort. ShRNA was used to knockdown the expression of SPATS2L. Apoptosis was assessed by flow cytometry. The changes of proteins were assessed by Western blot(WB). A xenotransplantation mice model was used to evaluate in vivo growth and survival. RNA sequencing was performed to elucidate the molecular mechanisms underlying the role of SPATS2L in AML.

Results
SPATS2L expression increased with increasing resistance indexes(RI) in HHT-resistant cell lines we had constructed. Higher SPATS2L expression was observed in intermediate/high-risk patients than in favorable patients. Meanwhile, decreased SPATS2L expression was observed in AML patients achieving complete remission (CR). Multivariate analysis showed high SPATS2L expression was an independent poor predictor of OS, EFS, RFS in AML. SPATS2L knock down (KD) suppressed cell growth, induced apoptosis, and suppressed key proteins of JAK/STAT pathway, such as JAK2, STAT3, STAT5 in AML cells. Inhibiting SPATS2L expression markedly enhanced the pro-apoptotic effects of traditional chemotherapeutics (Ara-c, IDA, and HHT).

Conclusions
High expression of SPATS2L is a poor prognostic factor in AML, and targeting SPATS2L may be a promising therapeutic strategy for AML patients.
Inducible co-stimulatory molecule (ICOS) alleviates paclitaxel-induced neuropathic pain via an IL-10-mediated mechanism in female mice
Authors: Sankaranarayanan Ishwarya , Tavares-Ferreira Diana , Mwirigi Juliet M. , Mejia Galo L. , Burton Michael D. , Price Theodore J. 
Published: February 2023

AbstractChemotherapy-induced peripheral neuropathy (CIPN) is a primary dose-limiting side effect caused by antineoplastic agents, such as paclitaxel. A primary symptom of this neuropathy is pain. Currently, there are no effective treatments for CIPN, which can lead to long-term morbidity in cancer patients and survivors. Neuro-immune interactions occur in CIPN pain and have been implicated both in the development and progression of pain in CIPN and the resolution of pain in CIPN. We investigated the potential role of inducible co-stimulatory molecule (ICOS) in the resolution of CIPN pain-like behaviors in mice. ICOS is an immune checkpoint molecule that is expressed on the surface of activated T cells and promotes proliferation and differentiation of T cells. We found that intrathecal administration of ICOS agonist antibody (ICOSaa) alleviates mechanical hypersensitivity caused by paclitaxel and facilitates the resolution of mechanical hypersensitivity in female mice. Administration of ICOSaa reduced astrogliosis in the spinal cord and satellite cell gliosis in the DRG of mice previously treated with paclitaxel. Mechanistically, ICOSaa intrathecal treatment promoted mechanical hypersensitivity resolution by increasing interleukin 10 (IL-10) expression in the dorsal root ganglion. In line with these observations, blocking IL-10 receptor (IL-10R) activity occluded the effects of ICOSaa treatment on mechanical hypersensitivity in female mice. Suggesting a broader activity in neuropathic pain, ICOSaa also partially resolved mechanical hypersensitivity in the spared nerve injury (SNI) model. Our findings support a model wherein ICOSaa administration induces IL-10 expression to facilitate neuropathic pain relief in female mice. ICOSaa treatment is in clinical development for solid tumors and given our observation of T cells in the human DRG, ICOSaa therapy could be developed for combination chemotherapy—CIPN clinical trials.
Evaluation of post-discharge engagement for emergency department patients with opioid use history who received telehealth recovery coaching services
Authors: Watson Dennis P. , Phalen Peter , Medcalf Spencer , Messmer Sarah , McGuire Alan 
Published: February 2023

Abstract
Background
In recent years, emergency departments (EDs) across the nation have implemented peer recovery coach (PRC) services to support patients who use opioids. The majority of such interventions discussed in the literature follow an in-person modality where PRCs engage patients directly at the ED bedside. However, the use of telehealth services in EDs is becoming more popular. These services connect PRCs with ED patients in real-time via secure communications technology, and very little is known about the service- and clinical-based outcomes with which they are associated. The current study sought to assess factors associated with successful post-discharge follow-up of patients with a history of opioid use who received PRC telehealth services while in the ED.

Method
Data come from records for 917 patients who engaged with a telehealth PRC one or more times (1208 total engagements) at 1 of 13 EDs within the same health system. A multilevel Poisson regression model was used to assess the degree to which variables predicted successful post-discharge follow-up, defined as the number of times a PRC successfully spoke with the patient each month after ED discharge.

Results
At least one follow-up was successfully completed by a PRC for 23% of enrolled patients. Significant predictors of successful follow-up included patient employment at baseline (Incidence Rate Ratio [IRR]: 2.8, CI: 2.05–3.9), living in a rural area (IRR: 1.8, CI: 1.04–3.2), PRC provision of referrals (IRR: 1.7, CI: 1.2–2.2), number of ED encounters in the previous 365 days (IRR: 0.99, CI: 0.98–0.99), and duration of the initial PRC telehealth interaction (IRR: 0.87, CI: 0.85–0.88).

Conclusion
Given that relationship development is a key tool in the PRC profession, understanding successful follow-up associated with telehealth engagement has unique importance. The results have potential utility for planning and implementing peer telehealth services in EDs and other locations, which is needed for the development of the PRC profession and the likely expansion of peer telehealth services.
Finite element analysis of posterior acetabular column plate and posterior acetabular wall prostheses in treating posterior acetabular fractures
Authors: Huang Guixiong , Wan Yizhou , Chen Kaifang , Yin Zhenchun , Song Qinghua , Xu Yi , Guo Xiaodong 
Published: February 2023

Abstract
Background
The purpose of this study was to investigate the mechanical stability of the posterior acetabular column plate and different posterior acetabular wall prostheses used in treating posterior acetabular fractures with or without comminution.

Methods
The unilateral normal ilium was reconstructed, and a model of posterior acetabular wall fracture was established on this basis. The fracture fragment accounted for approximately 40% of the posterior acetabular wall. The posterior acetabular column plate and different posterior acetabular wall prostheses were also designed. Using static and dynamic analysis methods, we observed and compared the changes in the stress and displacement values of different models at different hip joint flexion angles under external forces.

Results
At different hip flexion angles, the stress of each model mainly fluctuated between 37.98 MPa and 1129.00 MPa, and the displacement mainly fluctuated between 0.076 and 6.955 mm. In the dynamic analysis, the nodal stress‒time curves of the models were nonlinear, and the stress changed sharply during the action time. Most of the nodal displacement‒time curves of the models were relatively smooth, with no dramatic changes in displacement during the action time; additionally, most of the curves were relatively consistent in shape.

Conclusions
For simple posterior acetabular wall fractures, we recommend using a posterior acetabular column plate. In the case of comminuted posterior acetabular fractures, we recommend the use of a nonflanked posterior acetabular prosthesis or a biflanked posterior acetabular prosthesis. Regarding the method of acetabular prosthesis design, we propose the concept of “Break up to Make up” as a guide.
The deficiency of Maged1 attenuates Parkinson's disease progression in mice
Authors: Wang Jie , Xu Sheng-Ye , Ye Zhi-Yuan , Sun Zhou-Na , Zhang Jia-Qi , Qi Cui , Liu Rui , Gao Xiang , He Chuan , You Wei-Yan , Gao Jun 
Published: February 2023

AbstractMelanoma-associated antigen D1 (Maged1) has critical functions in the central nervous system in both developmental and adult stages. Loss of Maged1 in mice has been linked to depression, cognitive disorder, and drug addiction. However, the role of Maged1 in Parkinson’s disease (PD) remains unclear. In this study, we observed that Maged1 was expressed in the dopaminergic (DA) neurons of the substantia nigra in mice and humans, which could be upregulated by the in vivo or in vitro treatment with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-Methyl-4-phenylpyridinium iodide (MPP+). Genetic ablation of Maged1 in mice attenuated motor deficits, the loss of DA neurons, and disease progression induced by MPTP. Moreover, Maged1 deficiency protected DA neurons against MPP+-induced toxicity in primary cultured cells. Mechanistically, loss of Maged1 upregulated the Akt signaling pathway and downregulated the mTOR signaling pathway in SH-SY5Y cells, which may in turn attenuate the cell apoptosis and impairment of autophagy. Consistent with it, the degeneration of midbrain and striatum among elderly Maged1 knockout mice was relatively mild compared to those in wild-type mice under physiological conditions. Taken together, this study suggested that Maged1 deficiency inhibited apoptosis and enhanced autophagy, which may provide a new potential target for the therapy of PD.
FBXO22 promotes leukemogenesis by targeting BACH1 in MLL-rearranged acute myeloid leukemia
Authors: Zhu Xiao-Na , Wei Yu-Sheng , Yang Qian , Liu Hao-Ran , Zhi Zhe , Zhu Di , Xia Li , Hong Deng-Li , Yu Yun , Chen Guo-Qiang 
Published: February 2023

Abstract
Background
Selectively targeting leukemia stem cells (LSCs) is a promising approach in treating acute myeloid leukemia (AML), for which identification of such therapeutic targets is critical. Increasing lines of evidence indicate that FBXO22 plays a critical role in solid tumor development and therapy response. However, its potential roles in leukemogenesis remain largely unknown.

Methods
We established a mixed lineage leukemia (MLL)-AF9-induced AML model with hematopoietic cell-specific FBXO22 knockout mice to elucidate the role of FBXO22 in AML progression and LSCs regulation, including self-renewal, cell cycle, apoptosis and survival analysis. Immunoprecipitation combined with liquid chromatography-tandem mass spectrometry analysis, Western blotting and rescue experiments were performed to study the mechanisms underlying the oncogenic role of FBXO22.

Results
FBXO22 was highly expressed in AML, especially in MLL-rearranged (MLLr) AML. Upon FBXO22 knockdown, human MLLr leukemia cells presented markedly increased apoptosis. Although conditional deletion of Fbxo22 in hematopoietic cells did not significantly affect the function of hematopoietic stem cells, MLL-AF9-induced leukemogenesis was dramatically abrogated upon Fbxo22 deletion, together with remarkably reduced LSCs after serial transplantations. Mechanistically, FBXO22 promoted degradation of BACH1 in MLLr AML cells, and overexpression of BACH1 suppressed MLLr AML progression. In line with this, heterozygous deletion of BACH1 significantly reversed delayed leukemogenesis in Fbxo22-deficient mice.

Conclusions
FBXO22 promotes MLLr AML progression by targeting BACH1 and targeting FBXO22 might be an ideal strategy to eradicate LSCs without influencing normal hematopoiesis.
Patterns of variation in equine strongyle community structure across age groups and gut compartments
Authors: Boisseau Michel , Mach Núria , Basiaga Marta , Kuzmina Tetiana , Laugier Claire , Sallé Guillaume 
Published: February 2023

Abstract
Background
Equine strongyles encompass more than 64 species of nematode worms that are responsible for growth retardation and the death of animals. The factors underpinning variation in the structure of the equine strongyle community remain unknown.

Methods
Using horse-based strongyle community data collected after horse deworming (48 horses in Poland, 197 horses in Ukraine), we regressed species richness and the Gini-Simpson index upon the horse’s age, faecal egg count, sex and operation of origin. Using the Ukrainian observations, we applied a hierarchical diversity partitioning framework to estimate how communities were remodelled across operations, age groups and horses. Lastly, strongyle species counts collected after necropsy (46 horses in France, 150 in Australia) were considered for analysis of their co-occurrences across intestinal compartments using a joint species distribution modelling approach.

Results
First, inter-operation variation accounted for > 45% of the variance in species richness or the Gini-Simpson index (which relates to species dominance in communities). Species richness decreased with horse’s age (P = 0.01) and showed a mild increase with parasite egg excretion (P < 0.1), but the Gini-Simpson index was neither associated with parasite egg excretion (P = 0.8) nor with horse age (P = 0.37). Second, within-host diversity represented half of the overall diversity across Ukrainian operations. While this is expected to erase species diversity across communities, community dissimilarity between horse age classes was the second most important contributor to overall diversity (25.8%). Third, analysis of species abundance data quantified at necropsy defined a network of positive co-occurrences between the four most prevalent strongyle genera. This pattern was common to necropsies performed in France and Australia.

Conclusions
Taken together, these results show a pattern of β-diversity maintenance across age classes combined with positive co-occurrences that might be grounded by priority effects between the major species.

Graphical Abstract
Ultrasound halo count in the differential diagnosis of atherosclerosis and large vessel giant cell arteritis
Authors: Monjo-Henry Irene , Fernández-Fernández Elisa , Mostaza José María , Lahoz Carlos , Molina-Collada Juan , de Miguel Eugenio 
Published: February 2023

Abstract
Objective
To determine the diagnostic discriminant validity between large vessel giant cell arteritis (LV-GCA) and atherosclerosis using ultrasound (US) intima-media thickness (IMT) measurements.

Methods
We included 44 patients with LV-GCA and 42 with high-risk atherosclerosis. US examinations of the axillary, subclavian, and common carotid arteries (CCA) were systematically performed using a MylabX8 system (Genoa, Italy) with a 4–15-MHz probe. IMT ≥ 1 mm was accepted as pathological.

Results
The LV-GCA cohort included 24 females and 20 males with a mean age of 72.8 ± 7.6 years. The atherosclerosis group included 25 males and 17 females with a mean age of 70.8 ± 6.5 years. The mean IMT values of all arteries included were significantly higher in LV-GCA than in atherosclerosis. Among LV-GCA patients, IMT ≥ 1 mm was seen in 31 axillary, 30 subclavian, and 28 CCA. In the atherosclerotic cohort, 17 (38.6%) had IMT ≥ 1 mm with axillary involvement in 2 patients, subclavian in 3 patients, carotid distal in 14 patients (5 bilateral), and isolated carotid proximal affectation in 1 case. A cutoff point greater than 1 pathological vessel in the summative count of axillary and subclavian arteries or at least 3 vessels in the count of six vessels, including CCA, showed a precision upper 95% for GCA diagnosis.

Conclusion
The IMT is higher in LV-GCA than in atherosclerosis. The proposed US halo count achieves an accuracy of > 95% for the differential diagnosis between LV-GCA and atherosclerosis. The axillary and subclavian arteries have higher discriminatory power, while carotid involvement is less specific in the differential diagnosis.
Relative age effects on speed trials in Brazilian athletics
Authors: Barboza-Neto Rui , Nobari Hadi , Aidar Felipe J. , Almeida-Neto Paulo Francisco , Silva Ana Filipa , Medeiros Radamés Maciel Vítor , Clemente Filipe Manuel , de Queiros Victor Sabino , de Matos Dihogo Gama , da Silva Luiz Felipe , Badicu Georgian , Dantas Paulo Moreira Silva , de Araújo Tinôco Cabral Breno Guilherme 
Published: February 2023

Abstract
Background
Relative age effect (RAE) is a concept related to the possible advantage that older athletes would have over younger ones within the same category. Although many studies have approached this subject in individual sports, there are few clippings by events within the sport. More detailed analyses are necessary for a better understanding of how RAE behaves in sports, especially in athletics, the subject of this study. The objective of this study was to analyze the RAE on speed in track and field events as a whole, separating the flat races from the hurdles races.

Methods
The Brazilian Ranking of Brazilian Athletics Confederation was used for data analysis, and the sample was composed of the 50 best-placed marks in the ranking of speed events in athletics in the categories Under(U)-16 and U-18 (female and male). Statistical analysis was calculated by chi-square, and the effect size was checked by Cramer’s V. Likelihood-ratio test (L-Ratio) assessed the probability of the RAE occurring in the total sample and by age groups.

Results
In the total sample the results pointed to the emergence of RAE in males in both categories (U-16: p < 0.001; V: 0.13; L-Ratio: 3.64, U-18: p < 0.001; V: 0.13; L-Ratio: 3.80), whereas in females no such effect was found in any category (U-16: p = 0.6; V: 0.09; L-Ratio: 0.09, U-18: p = 0.6; V: 0.07; L-Ratio: 0.12). When the results were separated by type of event, there was only a RAE in the shallow event in the U-18 female category (p = 0.3; V: 0.11; L-Ratio: 8.72).

Conclusion
The results allow us to conclude that there is a RAE in the speed trials of Brazilian athletics in the U16 and U18 categories for men, while this effect appears only in the shallow trials of the U18 category for women, indicating that the RAE has incidence when there is more participation and competition in the sport.