bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delineation and authentication of ferroptosis genes in ventilator-induced lung injury
Authors: Huang Enhao , Han Hanghang , Qin Ke , Du Xueke 
Published: January 2024

Abstract
Background
Mechanical ventilation, a critical support strategy for individuals enduring severe respiratory failure and general anesthesia, paradoxically engenders ventilator-induced lung injury (VILI). Ferrostatin-1 mitigates lung injury via ferroptosis inhibition, yet the specific ferroptosis genes contributing significantly to VILI remain obscure.

Methods
Leveraging the Gene Expression Omnibus database, we acquired VILI-associated datasets and identified differentially expressed genes (DEGs). To identify the hub genes, we constructed a protein–protein interaction network and used three parameters from CytoHubba. Consequently, we identified hub genes and ferroptosis genes as ferroptosis hub genes for VILI (VFHGs). We conducted enrichment analysis and established receiver operating characteristic (ROC) curves for VFHGs. Subsequently, to confirm the correctness of the VFHGs, control group mice and VILI mouse models, as well as external dataset validation, were established. For further research, a gene-miRNA network was established. Finally, the CIBERSORT algorithm was used to fill the gap in the immune infiltration changes in the lung during VILI.

Results
We identified 64 DEGs and 4 VFHGs (Il6,Ptgs2,Hmox1 and Atf3) closely related to ferroptosis. ROC curves demonstrated the excellent diagnostic performance of VFHGs in VILI. PCR and external dataset validation of the VILI model demonstrated the accuracy of VFHGs. Subsequently, the gene-miRNA network was successfully established. Ultimately, an Immune cell infiltration analysis associated with VILI was generated.

Conclusions
The results emphasize the importance of 4 VFHGs and their involvement in ferroptosis in VILI, confirming their potential as diagnostic biomarkers for VILI.
Plectin plays a role in the migration and volume regulation of astrocytes: a potential biomarker of glioblastoma
Authors: Žugec Maja , Furlani Borut , Castañon Maria J. , Rituper Boštjan , Fischer Irmgard , Broggi Giuseppe , Caltabiano Rosario , Barbagallo Giuseppe M. V. , Di Rosa Michelino , Tibullo Daniele , Parenti Rosalba , Vicario Nunzio , Simčič Saša , Pozo Devoto Victorio Martin , Stokin Gorazd B. , Wiche Gerhard , Jorgačevski Jernej , Zorec Robert , Potokar Maja 
Published: January 2024

Abstract
Background
The expression of aquaporin 4 (AQP4) and intermediate filament (IF) proteins is altered in malignant glioblastoma (GBM), yet the expression of the major IF-based cytolinker, plectin (PLEC), and its contribution to GBM migration and invasiveness, are unknown. Here, we assessed the contribution of plectin in affecting the distribution of plasmalemmal AQP4 aggregates, migratory properties, and regulation of cell volume in astrocytes.

Methods
In human GBM, the expression of glial fibrillary acidic protein (GFAP), AQP4 and PLEC transcripts was analyzed using publicly available datasets, and the colocalization of PLEC with AQP4 and with GFAP was determined by immunohistochemistry. We performed experiments on wild-type and plectin-deficient primary and immortalized mouse astrocytes, human astrocytes and permanent cell lines (U-251 MG and T98G) derived from a human malignant GBM. The expression of plectin isoforms in mouse astrocytes was assessed by quantitative real-time PCR. Transfection, immunolabeling and confocal microscopy were used to assess plectin-induced alterations in the distribution of the cytoskeleton, the influence of plectin and its isoforms on the abundance and size of plasmalemmal AQP4 aggregates, and the presence of plectin at the plasma membrane. The release of plectin from cells was measured by ELISA. The migration and dynamics of cell volume regulation of immortalized astrocytes were assessed by the wound-healing assay and calcein labeling, respectively.

Results
A positive correlation was found between plectin and AQP4 at the level of gene expression and protein localization in tumorous brain samples. Deficiency of plectin led to a decrease in the abundance and size of plasmalemmal AQP4 aggregates and altered distribution and bundling of the cytoskeleton. Astrocytes predominantly expressed P1c, P1e, and P1g plectin isoforms. The predominant plectin isoform associated with plasmalemmal AQP4 aggregates was P1c, which also affected the mobility of astrocytes most prominently. In the absence of plectin, the collective migration of astrocytes was impaired and the dynamics of cytoplasmic volume changes in peripheral cell regions decreased. Plectin’s abundance on the plasma membrane surface and its release from cells were increased in the GBM cell lines.

Conclusions
Plectin affects cellular properties that contribute to the pathology of GBM. The observed increase in both cell surface and released plectin levels represents a potential biomarker and therapeutic target in the diagnostics and treatment of GBMs.
Tobacco-derived and tobacco-free nicotine cause differential inflammatory cell influx and MMP-9 in mouse lung
Authors: Lamb Thomas , Kaur Gagandeep , Rahman Irfan 
Published: January 2024

Abstract
Background
Electronic nicotine delivery systems (ENDS) or electronic cigarettes (e-cigarettes) aerosolize an e-liquid composed of propylene glycol (PG) and vegetable glycerin (VG) as humectants, flavoring chemicals, and nicotine. Nicotine naturally occurs in two isomers R- and S-nicotine, with tobacco-derived nicotine (TDN) composed of S-nicotine, and tobacco-free/synthetic nicotine (TFN) composed of a racemic mixture of R- and S-nicotine. Currently, there is limited knowledge of the potential differences in the toxicity of TFN versus TDN. We hypothesized that exposure of TFN and TDN salts to C57BL/6J mice would result in a differential response in lung inflammation and protease/ antiprotease imbalance.

Methods
Five-week-old male and female C57BL/6J mice were exposed to air, PG/VG, PG/VG with TFN salts (TFN), or PG/VG with TDN salts (TDN) by nose-only exposure. Lung inflammatory cell counts, cytokine/chemokine levels, and matrix metalloproteinase (MMP) protein abundance and activity levels were determined by flow cytometry, ELISA, immunoblotting, and gel zymography, respectively.

Results
Exposure to the humectants (PG/VG) alone increased cytokine levels- IL-6, KC, and MCP-1 in the BALF and KC levels in lung homogenate of exposed mice. While no change was observed in the cytokine levels in lung homogenate of TDN aerosol exposed mice, exposure to TFN aerosols resulted in an increase in KC levels in the lungs of these mice compared to air controls. Interestingly, exposure to TDN aerosols increased MMP-9 protein abundance in the lungs of female mice, while exposure to TFN aerosol showed no change. The metabolism of nicotine or the clearance of cotinine for TFN exposure may differ from that for TDN.

Conclusion
Exposure to humectants, PG/VG alone, induces an inflammatory response in C57BL/6J mice. TFN and TDN salts show distinct changes in inflammatory responses and lung proteases on acute exposures. These data suggest variable toxicological profiles of the two forms of nicotine in vivo. Future work is thus warranted to delineate the harmful effects of synthetic/natural nicotine with humectants to determine the potential toxicological risks for users.
Re-exploration of prognosis in type B thymomas: establishment of a predictive nomogram model
Authors: Zhao Ke , Liu Lei , Zhou Xiaoyun , Wang Guige , Zhang Jiaqi , Gao Xuehan , Yang Libing , Rao Ke , Guo Chao , Zhang Ye , Huang Cheng , Liu Hongsheng , Li Shanqing , Chen Yeye 
Published: January 2024

Abstract
Objective
To explore the risk factors for disease progression after initial treatment of type B thymomas using a predictive nomogram model.

Methods
A single-center retrospective study of patients with type B thymoma was performed. The Cox proportional hazard model was used for univariate and multivariate analyses. Variables with statistical and clinical significance in the multivariate Cox regression were integrated into a nomogram to establish a predictive model for disease progression.

Results
A total of 353 cases with type B thymoma were retrieved between January 2012 and December 2021. The median follow-up was 58 months (range: 1–128 months). The 10-year progression-free survival (PFS) was 91.8%. The final nomogram model included R0 resection status and Masaoka stage, with a concordance index of 0.880. Non-R0 resection and advanced Masaoka stage were negative prognostic factors for disease progression (p < 0.001). No benefits of postoperative radiotherapy (PORT) were observed in patients with advanced stage and non-R0 resection (p = 0.114 and 0.284, respectively).

Conclusion
The best treatment strategy for type B thymoma is the detection and achievement of R0 resection as early as possible. Long-term follow-up is necessary, especially for patients with advanced Masaoka stage and who have not achieved R0 resection. No prognostic benefits were observed for PORT.
Detecting prokaryote-specific gene and other bacterial signatures in thrombi from patients with acute ischemic stroke
Authors: Wang Xiaoke , Gao Jie , Chen Yantong , Zhang Xiaohao , Dai Zhengze , Dai Qiliang , Peng Mengna , Xiao Lulu , Jia Xuerong , Cai Haodi , Mou Tao , Li Xiang , Xu Gelin 
Published: January 2024

Abstract
Background and purpose
Microbial infection has been associated with thrombogenesis. This study aimed to detect bacterium-specific genes and other signatures in thrombi from patients with acute ischemic stroke and to relate these signatures to clinical characteristics.

Methods
Blood samples were collected before thrombectomy procedures, and thrombus samples were obtained during the procedure. Identification and classification of bacteria in the samples were accomplished using 16 S rRNA gene sequencing. Bacterium-specific structures were observed with transmission electron microscopy. Bacterium-specific biomarkers were detected through immunohistochemical staining.

Results
16 S rRNA gene was detected in 32.1% of the thrombus samples from 81 patients. Bacillus (0.04% vs. 0.00046%, p = 0.003), Parabacteroides (0.20% vs. 0.09%, p = 0.029), Prevotella (1.57% vs. 0.38%, p = 0.010), Streptococcus (1.53% vs. 0.29%, p = 0.001), Romboutsia (0.18% vs. 0.0070%, p = 0.029), Corynebacterium (1.61% vs. 1.26%, p = 0.026) and Roseburia (0.53% vs. 0.05%, p = 0.005) exhibited significantly higher abundance in thrombi compared to arterial blood. Bacteria-like structures were observed in 22 (27.1%), while whole bacteria-like structures were observed in 7 (8.6%) thrombi under transmission electron microscopy. Immunohistochemical staining detected bacterium-specific monocyte/macrophage markers in 51 (63.0%) out of 81 thrombi. Logistic regression analysis indicated that alcohol consumption was associated with a higher bacteria burden in thrombi (odds ratio = 3.19; 95% CI, 1.10–9.27; p = 0.033).

Conclusion
Bacterial signatures usually found in the oral cavity and digestive tract were detected in thrombi from patients with ischemic stroke. This suggests a potential involvement of bacterial infection in the development of thrombosis. Long-term alcohol consumption may potentially enhance this possibility.
Interference of pseudorabies virus infection on functions of porcine granulosa cells via apoptosis modulated by MAPK signaling pathways
Authors: Deng Lingcong , Min Wenpeng , Guo Songyangnian , Deng Jiping , Wu Xiaosong , Tong Dewen , Yuan Anwen , Yang Qing 
Published: January 2024

Abstract
Background
Pseudorabies virus (PRV) is one of the major viral pathogens leading to reproductive disorders in swine. However, little is known about the effects of PRV infection on porcine reproductive system. Ovarian granulosa cells are somatic cells surrounding oocytes in ovary and required for folliculogenesis. The present study aimed to investigate the interference of PRV on functions of porcine ovarian granulosa cells in vitro.

Methods
Primary granulosa cells were isolated from porcine ovaries. To investigate the PRV infectivity, transmission electron microscopy (TEM) was used to check the presence of viral particles, and the expression of viral gE gene was detected by quantitative real-time PCR (qPCR) in PRV-inoculated cells. After PRV infection, cell viability was detected by MTS assay, Ki67 for proliferative status was determined by immunofluorescence assay (IFA), cell cycle and apoptosis were detected by flow cytometry, and progesterone (P4) and estradiol (E2) were determined by radioimmunoassay. The checkpoint genes of cell cycle and apoptosis-related proteins were studied by qPCR and western blotting.

Results
Virus particles were observed in the nucleus and cytoplasm of PRV-infected granulosa cells by TEM imaging, and the expression of viral gE gene increased in a time-dependent manner post infection. PRV infection inhibited cell viability and blocked cell cycle at S phase in porcine granulosa cells, accompanied by decreases in expression of Ki67 protein and checkpoint genes related to S phase. Radioimmunoassay revealed decreased levels in P4 and E2, and the expressions of key steroidogenic enzymes were also down-regulated post PRV-infection. In addition, PRV induced apoptosis with an increase in Bax expression and activation of caspase 9, and the phosphorylation of JNK, ERK and p38 MAPKs were significantly up-regulated in porcine ovarian granulosa cells post PRV infection.

Conclusions
The data indicate that PRV causes infection on porcine ovarian granulosa cells and interferes the cell functions through apoptosis, and the MAPK signaling pathway is involved in the viral pathogenesis.
Cone beam CT-based adaptive intensity modulated proton therapy assessment using automated planning for head-and-neck cancer
Authors: Xu Yihang , Jin William , Butkus Michael , De Ornelas Mariluz , Cyriac Jonathan , Studenski Matthew T. , Padgett Kyle , Simpson Garrett , Samuels Stuart , Samuels Michael , Dogan Nesrin 
Published: January 2024

Abstract
Background
To assess the feasibility of CBCT-based adaptive intensity modulated proton therapy (IMPT) using automated planning for treatment of head and neck (HN) cancers.

Methods
Twenty HN cancer patients who received radiotherapy and had pretreatment CBCTs were included in this study. Initial IMPT plans were created using automated planning software for all patients. Synthetic CTs (sCT) were then created by deforming the planning CT (pCT) to the pretreatment CBCTs. To assess dose calculation accuracy on sCTs, repeat CTs (rCTs) were deformed to the pretreatment CBCT obtained on the same day to create deformed rCT (rCTdef), serving as gold standard. The dose recalculated on sCT and on rCTdef were compared by using Gamma analysis. The accuracy of DIR generated contours was also assessed. To explore the potential benefits of adaptive IMPT, two sets of plans were created for each patient, a non-adapted IMPT plan and an adapted IMPT plan calculated on weekly sCT images. The weekly doses for non-adaptive and adaptive IMPT plans were accumulated on the pCT, and the accumulated dosimetric parameters of two sets were compared.

Results
Gamma analysis of the dose recalculated on sCT and rCTdef resulted in a passing rate of 97.9% ± 1.7% using 3 mm/3% criteria. With the physician-corrected contours on the sCT, the dose deviation range of using sCT to estimate mean dose for the most organ at risk (OARs) can be reduced to (− 2.37%, 2.19%) as compared to rCTdef, while for V95 of primary or secondary CTVs, the deviation can be controlled within (− 1.09%, 0.29%). Comparison of the accumulated doses from the adaptive planning against the non-adaptive plans reduced mean dose to constrictors (− 1.42 Gy ± 2.79 Gy) and larynx (− 2.58 Gy ± 3.09 Gy). The reductions result in statistically significant reductions in the normal tissue complication probability (NTCP) of larynx edema by 7.52% ± 13.59%. 4.5% of primary CTVs, 4.1% of secondary CTVs, and 26.8% tertiary CTVs didn’t meet the V95 > 95% constraint on non-adapted IMPT plans. All adaptive plans were able to meet the coverage constraint.

Conclusion
sCTs can be a useful tool for accurate proton dose calculation. Adaptive IMPT resulted in better CTV coverage, OAR sparing and lower NTCP for some OARs as compared with non-adaptive IMPT.
The correlation between tumor radiological features and spread through air spaces in peripheral stage IA lung adenocarcinoma: a propensity score-matched analysis
Authors: Jia Chao , Jiang Hai-Cheng , Liu Cong , Wang Yu-Feng , Zhao Hong-Ying , Wang Qiang , Xue Xiu-Qing , Li Xiao-Feng 
Published: January 2024

Abstract
Background
The consolidation tumor ratio (CTR) is a predictor of invasiveness in peripheral T1N0M0 lung adenocarcinoma. However, its association with spread through air spaces (STAS) remains largely unexplored. We aimed to explore the correlation between the CTR of primary tumors and STAS in peripheral T1N0M0 lung adenocarcinoma.

Methods
We collected data from patients who underwent surgery for malignant lung neoplasms between January and November 2022. Univariate and multivariate analyses following propensity-score matching with sex, age, BMI, were performed to identify the independent risk factors for STAS. The incidence of STAS was compared based on pulmonary nodule type. A smooth fitting curve between CTR and STAS was produced by the generalized additive model (GAM) and a multiple regression model was established using CTR and STAS to determine the dose-response relationship and calculate the odds ratio (OR) and 95% confidence interval (CI).

Results
17 (14.5%) were diagnosed with STAS. The univariate analysis demonstrated that the history of the diabetes, size of solid components, spiculation, pleural indentation, pulmonary nodule type, consolidation/tumor ratio of the primary tumor were statistically significant between the STAS-positive and STAS-negative groups following propensity-score matching(p = 0.047, 0.049, 0.030, 0.006, 0.026, and < 0.001, respectively), and multivariate analysis showed that the pleural indentation was independent risk factors for STAS (with p-value and 95% CI of 0.043, (8.543–68.222)). Moreover, the incidence of STAS in the partially solid nodule was significantly different from that in the solid nodule and ground-glass nodule (Pearson Chi-Square = 7.49, p = 0.024). Finally, the smooth fitting curve showed that CTR tended to be linearly associated with STAS by GAM, and the multivariate regression model based on CTR showed an OR value of 1.24 and a p-value of 0.015.

Conclusions
In peripheral stage IA lung adenocarcinoma, the risk of STAS was increased with the solid component of the primary tumor. The pleural indentation of the primary tumor could be used as a predictor in evaluating the risk of the STAS.
Distinguishing sterile inflammation from graft infection
Authors: Mitsuishi Atsuyuki , Miura Yujiro , Arakawa Yu , Noguchi Tatsuya 
Published: January 2024

AbstractWe describe the case of a 68-year-old man who underwent ascending aortic replacement and thoracic endovascular aortic repair. Four years later, the patient developed neck pain on the right side and chest computed tomography showed expansion of fluid in the mediastinum which had extended to the neck. Echocardiography revealed advanced severity of aortic regurgitation and decreased ejection fraction. Given the progression of aortic regurgitation, decreased cardiac function, and rapidly expanding fluid accumulation causing neck pain, reoperation was indicated. All microbiological test including polymerase chain reaction were negative indicating absence of any infection. The patient is being followed-up without antibiotics and CT has not shown peri-graft fluid 2 years postoperatively. Since infection cannot be excluded completely, it is important to assess the condition with selective medium, extended culture periods, genetic testing, and consultations with microbiology laboratories when normal culture tests for general bacteria, and fungi are negative which can help avoid drug-resistant bacteria count, elevated medical costs, and drug side effects due to the improper use of antibiotics through proper diagnosis.
A study of rural populations’ knowledge, attitude, and practice about brucellosis: a descriptive, cross-sectional, multicenter study
Authors: Montaseri Zahra , Mohebi Zahra , Masoumi Rahil , Dehghan Azizallah , Bijani Mostafa 
Published: January 2024

Abstract
Objective
Brucellosis is a highly contagious disease which is transmitted from animals to humans. One of the populations at high risk of infection is those living in rural areas. The present study was conducted to investigate rural populations’ knowledge, attitude, and practice about brucellosis in Iran. The study used a descriptive, cross-sectional design to assess 300 individuals who were living in rural areas. The subjects were selected using convenience sampling from six villages located in the south of Iran. The data gathered were analyzed using Analysis of variance (ANOVA), and Pearson correlation coefficient in SPSS version 23.

Results
From the 300 individuals who were enrolled in this study, 189 were male and 111 were female. The mean age of the participants was 48.27 ± 4.28 years. The mean scores of the study population’s knowledge, attitude, and practice about brucellosis were found to be low. A significant direct correlation was found between the subjects’ knowledge, attitude, and practice regarding brucellosis.
Diet patterns and cognitive performance in a UK Female Twin Registry (TwinsUK)
Authors: McEvoy Claire T. , Jennings Amy , Steves Claire J. , Macgregor Alexander , Spector Tim , Cassidy Aedin 
Published: January 2024

Abstract
Background
Plant-based diets may provide protection against cognitive decline and Alzheimer’s disease, but observational data have not been consistent. Previous studies include early life confounding from socioeconomic conditions and genetics that are known to influence both cognitive performance and diet behaviour. This study investigated associations between Mediterranean (MED) diet and MIND diets and cognitive performance accounting for shared genotype and early-life environmental exposures in female twins.

Methods
Diet scores were examined in 509 female twins enrolled in TwinsUK study. The Cambridge Neuropsychological Test Automated Battery was used to assess cognition at baseline and 10 years later (in n = 275). A co-twin case–control study for discordant monozygotic (MZ) twins examined effects of diet on cognitive performance independent of genetic factors. Differences in relative abundance of taxa at 10-year follow-up were explored in subsamples.

Results
Each 1-point increase in MIND or MED diet score was associated with 1.75 (95% CI: − 2.96, − 0.54, p = 0.005 and q = 0.11) and 1.67 (95% CI: − 2.71, − 0.65, p = 0.002 and q = 0.02) fewer respective errors in paired-associates learning. Within each MZ pair, the twin with the high diet score had better preservation in spatial span especially for MED diet (p = 0.02). There were no differences between diet scores and 10-year change in the other cognitive tests. MIND diet adherence was associated with higher relative abundance of Ruminococcaceae UCG-010 (0.30% (95% CI 0.17, 0.62), q = 0.05) which was also associated with less decline in global cognition over 10 years (0.22 (95% CI 0.06, 0.39), p = 0.01).

Conclusions
MIND or MED diets could help to preserve some cognitive abilities in midlife, particularly episodic and visuospatial working memory. Effects may be mediated by high dietary fibre content and increased abundance of short-chain fatty acid producing gut bacteria. Longer follow-up with repeated measures of cognition will determine whether diet can influence changes in cognition occurring in older age.