Miracle-dz/UniFAR-FTUs huggingface dataset:
Smad4-deficient T cells promote colitis-associated colon cancer via an IFN-γ-dependent suppression of 15-hydroxyprostaglandin dehydrogenase

Immune cells and the cytokines they produce are important mediators of the transition from colitis to colon cancer, but the mechanisms mediating this disease progression are poorly understood. Interferon gamma (IFN-γ) is known to contribute to the pathogenesis of colitis through immune modulatory mechanisms, and through direct effects on endothelial and epithelial homeostasis. Here we explore whether IFN-γ influences tumor progression by expanding the effector memory T cells (TEM) population and restricting the expression of tumor suppressors in a preclinical model of spontaneous colitis-associated colorectal cancer (CAC). We show that IFN-γ expression is significantly increased both in the T cells and the colonic mucosal epithelia of mice with a T cell-restricted deletion of the TGF-β intermediate, SMAD4 (Smad4TKO). The increase of IFN-γ expression correlates with the onset of spontaneous CAC in Smad4TKO mice by 6 months of age. This phenotype is greatly ameliorated by the introduction of a germline deletion of IFN-γ in Smad4TKO mice (Smad4TKO/IFN-γKO, DKO). DKO mice had a significantly reduced incidence and progression of CAC, and a decrease in the number of mucosal CD4+ TEM cells, when compared to those of Smad4TKO mice. Similarly, the colon epithelia of DKO mice exhibited a non-oncogenic signature with a decrease in the expression of iNOS and p-STAT1, and a restoration of the tumor suppressor gene, 15-hydroxyprostaglandin dehydrogenase (15-PGDH). In vitro, treatment of human colon cancer cells with IFN-γ decreased the expression of 15-PGDH. Our data suggest that Smad4-deficient T cells promote CAC through mechanisms that include an IFN-γ-dependent suppression of the tumor suppressor 15-PGDH.
Signaling pathways activated by sea bass gonadotropin-inhibitory hormone peptides in COS-7 cells transfected with their cognate receptor

Results of previous studies provided evidence for the existence of a functional gonadotropin-inhibitory hormone (GnIH) system in the European sea bass, Dicentrarchus labrax, which exerted an inhibitory action on the brain-pituitary-gonadal axis of this species. Herein, we further elucidated the intracellular signaling pathways mediating in sea bass GnIH actions and the potential interactions with sea bass kisspeptin (Kiss) signaling. Although GnIH1 and GnIH2 had no effect on basal CRE-luc activity, they significantly decreased forskolin-elicited CRE-luc activity in COS-7 cells transfected with their cognate receptor GnIHR. Moreover, an evident increase in SRE-luc activity was noticed when COS-7 cells expressing GnIHR were challenged with both GnIH peptides, and this stimulatory action was significantly reduced by two inhibitors of the PKC pathway. Notably, GnIH2 antagonized Kiss2-evoked CRE-luc activity in COS-7 cells expressing GnIHR and Kiss2 receptor (Kiss2R). However, GnIH peptides did not alter NFAT-RE-luc activity and ERK phosphorylation levels. These data indicate that sea bass GnIHR signals can be transduced through the PKA and PKC pathways, and GnIH can interfere with kisspeptin actions by reducing its signaling. Our results provide additional evidence for the understanding of signaling pathways activated by GnIH peptides in teleosts, and represent a starting point for the study of interactions with multiple neuroendocrine factors on cell signaling.
Machine learning: A non-invasive prediction method for gastric cancer based on a survey of lifestyle behaviors

Gastric cancer remains an enormous threat to human health. It is extremely significant to make a clear diagnosis and timely treatment of gastrointestinal tumors. The traditional diagnosis method (endoscope, surgery, and pathological tissue extraction) of gastric cancer is usually invasive, expensive, and time-consuming. The machine learning method is fast and low-cost, which breaks through the limitations of the traditional methods as we can apply the machine learning method to diagnose gastric cancer. This work aims to construct a cheap, non-invasive, rapid, and high-precision gastric cancer diagnostic model using personal behavioral lifestyles and non-invasive characteristics. A retrospective study was implemented on 3,630 participants. The developed models (extreme gradient boosting, decision tree, random forest, and logistic regression) were evaluated by cross-validation and the generalization ability in our test set. We found that the model developed using fingerprints based on the extreme gradient boosting (XGBoost) algorithm produced better results compared with the other models. The overall accuracy of which test set was 85.7%, AUC was 89.6%, sensitivity 78.7%, specificity 76.9%, and positive predictive values 73.8%, verifying that the proposed model has significant medical value and good application prospects.
Morinda officinalis oligosaccharides mitigate chronic mild stress-induced inflammation and depression-like behaviour by deactivating the MyD88/PI3K pathway via E2F2

Morinda officinalis oligosaccharides (MOs) are natural herbal extracts that have been shown to exert antidepressant effects. However, the mechanism of this effect remains unclear. Here, we explored the mechanism by which MOs improved experimental depression. Using a chronic mild stress (CMS) murine model, we examined whether MOs could protect against depressive-like behaviour. Lipopolysaccharide (LPS)- and ATP-treated BV2 cells were used to examine the potential mechanism by which MOs mediate the inflammatory response. We found that MOs prevented the CMS-induced reduction in the sucrose preference ratio in the sucrose preference test (SPT) and shortened the immobility durations in both the tail suspension test (TST) and forced swim test (FST). We also noticed that MOs suppressed inflammatory effects by deactivating the MyD88/PI3K pathway via E2F2 in CMS mice or LPS- and ATP-stimulated BV2 cells. Furthermore, overexpression of E2F2 blunted the beneficial effects of MOs in vitro. Collectively, these data showed that MOs exerted antidepressant effects in CMS mice by targeting E2F2-mediated MyD88/PI3K signalling pathway.
Prognostic significance of combined score of fibrinogen and neutrophil-lymphocyte ratio for functional outcome in patients with aneurysmal subarachnoid hemorrhage

Objective To explore the relationship between fibrinogen and neutrophil to lymphocyte ratio (F-NLR) score and functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Method A retrospective study was conducted that involved all consecutive patients with aSAH admitted to our institution from March 2018 to October 2021. Factors, such as demographics, comorbidities, clinical characteristics, neuroradiological data, and laboratory parameters, were collected from institutional databases. All patients achieved neurological assessment using the modified Rankin Scale (mRS) score 3 months after discharge to clarify the functional outcomes. The results were classified as favorable (mRS score 0–2) and unfavorable (mRS score 3–6). Univariate and multivariable analyses were performed to identify the relevant factors between inflammatory markers and functional outcomes after aSAH. Subsequently, a receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predicting performance of variables. A propensity score match (PSM) was performed to correct imbalances in patients' baseline characteristics. Results Finally, 256 patients with aSAH were included in the study cohort. A total of 94 (36.7%) patients had an unfavorable outcome. F-NLR scores were 0 [interquartile range (IQR) 0–1] and 1 (IQR 1–2) in patients with favorable and unfavorable outcomes, respectively (p < 0.001). After adjustment, the F-NLR score on admission remained significantly associated with unfavorable outcomes in patients with aSAH. In the multivariable analysis, the F-NLR score was regarded as an independent risk factor of unfavorable outcomes [odds ratio (OR) 3.113, 95% CI 1.755–5.523, p < 0.001]. In ROC analysis, the optimal cutoff value of the F-NLR score was 0.5 points. Two cohorts (n = 86 in each group) obtained from PSM with low F-NLR scores (0 points) and high F-NLR scores (1–2 points) were used for analysis. A significantly higher unfavorable functional outcome rate was observed in patients with high F-NLR scores (33.7 vs. 9.3%, p < 0.001). The area under the curve (AUC) values of F-NLR scores before and after PSM were 0.767 and 0.712, respectively. Conclusion Fibrinogen and neutrophil to lymphocyte ratio score was an independent risk parameter associated with unfavorable functional outcomes at 3 months after aSAH. A higher F-NLR score predicts the occurrence of poor functional outcomes.
Inequity in the Distribution of Non-Communicable Disease Multimorbidity in Adults in South Africa: An Analysis of Prevalence and Patterns

Objectives: The present study examined the prevalence and patterns of non-communicable disease multimorbidity by wealth quintile among adults in South Africa. Methods: The South African National Income Dynamics Study Wave 5 was conducted in 2017 to examine the livelihoods of individuals and households. We analysed data in people aged 15 years and older (N = 27,042), including self-reported diagnosis of diabetes, stroke, heart disease and anthropometric measurements. Logistic regression and latent class analysis were used to analyse factors associated with multimorbidity and common disease patterns. Results: Multimorbidity was present in 2.7% of participants. Multimorbidity was associated with increasing age, belonging to the wealthiest quintile group, increasing body mass index and being a current smoker. Having secondary education was protective against multimorbidity. Three disease classes of multimorbidity were identified: Diabetes and Hypertension; Heart Disease and Hypertension; and Stroke and Hypertension. Conclusion: Urgent reforms are required to improve health systems responsiveness to mitigate inequity in multimorbidity patterns in the adult population of South Africa as a result of income inequality.
Lysosomal-associated transmembrane protein 5 deficiency exacerbates cerebral ischemia/reperfusion injury

Lysosomal-associated transmembrane protein 5 (LAPTM5) has been demonstrated to be involved in regulating immunity, inflammation, cell death, and autophagy in the pathophysiological processes of many diseases. However, the function of LAPTM5 in cerebral ischemia-reperfusion (I/R) injury has not yet been reported. In this study, we found that LAPTM5 expression was dramatically decreased during cerebral I/R injury both in vivo and in vitro. LAPTM5 knockout (KO) mice were compared with a control, and they showed a larger infarct size and more serious neurological dysfunction after transient middle cerebral artery occlusion (tMCAO) treatment. In addition, inflammatory response and apoptosis were exacerbated in these processes. Furthermore, gain- and loss-of-function investigations in an in vitro model revealed that neuronal inflammation and apoptosis were aggravated by LAPTM5 knockdown but mitigated by its overexpression. Mechanistically, combined RNA sequencing and experimental verification showed that the apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase (JNK)/p38 pathway was mainly involved in the detrimental effects of LAPTM5 deficiency following I/R injury. Specifically, LAPTM5 directly interacts with ASK1, leading to decreased ASK1 N-terminal dimerization and the subsequent reduced activation of downstream JNK/p38 signaling. In conclusion, LAPTM5 was demonstrated to be a novel modulator in the pathophysiology of brain I/R injury, and targeting LAPTM5 may be feasible as a stroke treatment.
Seroprevalence and associated risk factors for foot and mouth disease virus seropositivity in cattle in selected districts of Gamo zone, Southern Ethiopia

Background Foot and mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals, which hampers livestock production and productivity in Ethiopia. This cross-sectional study was conducted from January to December 2021 to estimate the seroprevalence of FMD in cattle and to assess farmers' knowledge about the disease in selected districts of the Gamo zone. Three districts and two kebeles (smallest administrative division) from each district were purposively sampled using a simple random sampling technique to select individual animals from each kebeles. A total of 384 sera samples were collected, and concurrently, 100 farmers were interviewed. The samples were tested for antibodies against nonstructural proteins of the FMD virus using a 3ABC enzyme-linked immunosorbent assay (ELISA). Univariable and multivariable logistic regressions were used to analyze FMD-associated risk factors. Result The questionnaire survey result revealed that among the interviewed farmers, 66% of farmers had knowledge about the disease, and 28% of farmers reported having a case of FMD in at least one cattle in their farm in the previous 6 months. The overall seroprevalence of FMD in cattle was 26.8%. The multivariable logistic regression revealed that age, breed, and agroecology had a significant association with seropositivity. Higher seroprevalence (64.57%) was observed in lowland, followed by midland (9.30%) and highland (5.88%). Study animals from lowland areas were 9.26 times more likely to be seropositive (OR = 9.26, CI = 2.22–38.62) for FMD than highland animals. Also, adult animals were 9.01 times (OR = 9.01, CI = 3.18–25.53) more likely to be seropositive for the disease than young animals. The multivariable logistic regression revealed that crossbreeds have an 84.7% (OR = 0.153, CI = 0.028–0.82) lower likelihood to be seropositive to FMD than local breeds. Conclusion This study result confirms that FMD is highly prevalent in the study area, and farmers' knowledge regarding disease transmission and vaccine availability is minimal. Hence the regional concerned bodies should implement FMD vaccination campaigns and create awareness for smallholder farmers regarding the disease transmission, FMD vaccine schedule, and vaccination importance.
RNA sequencing profiling of mRNAs, long noncoding RNAs, and circular RNAs in Trigeminal Ganglion following Temporomandibular Joint inflammation

Patients with temporomandibular joint disorders (TMD) have high levels of inflammatory pain-related disability, which seriously affects their physical and mental health. However, an effective treatment is yet to be developed. Both circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) contribute to regulating pain conduction. In our current study, we report the expression profiles of circRNAs, lncRNAs, and mRNAs in the trigeminal ganglion (TG) associated with complete Freund’s adjuvant (CFA)-induced TMD inflammation pain. The collected TGs from the experimental (CFA) and control (saline) groups were processed for deep RNA sequencing. Overall, 1078,909,068 clean reads were obtained. A total of 15,657 novel lncRNAs were identified, where 281 lncRNAs were differentially expressed on CFA3D and 350 lncRNAs were differentially expressed on CFA6D. In addition, a total of 55,441 mRNAs and 27,805 circRNAs were identified, where 3,914 mRNAs and 91 circRNAs were found differentially expressed, between the CFA3D and saline groups, while 4,232 mRNAs and 98 DE circRNAs were differentially expressed between the CFA6D and saline groups. Based on functional analyses, we found that the most significant enriched biological processes of the upregulated mRNAs were involved in the immunity, neuron projection, inflammatory response, MAPK signaling pathway, Ras signaling pathway, chemokine signaling pathway, and inflammatory response in TG. Further analyses of Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway suggest the involvement of dysregulated genes in the pain occurrence mechanism. Our findings provide a resource for expression patterns of gene transcripts in regions related to pain. These results suggest that apoptosis and neuroinflammation are important pathogenic mechanisms underlying TMD pain. Some of the reported differentially expressed genes might be considered promising therapeutic targets. The current research study revealed the expression profiles of circRNAs, lncRNAs, and mRNAs during TMD inflammation pain and sheds light on the roles of circRNAs and lncRNAs underlying the pain pathway in the trigeminal system of TMD inflammation pain.
Predicting prolonged postoperative length of stay risk in patients undergoing lumbar fusion surgery: Development and assessment of a novel predictive nomogram

Objective The purpose of this study was to develop and internally validate a prediction nomogram model in patients undergoing lumbar fusion surgery. Methods A total of 310 patients undergoing lumbar fusion surgery were reviewed, and the median and quartile interval were used to describe postoperative length of stay (PLOS). Patients with PLOS > P75 were defined as prolonged PLOS. The least absolute shrinkage and selection operator (LASSO) regression was used to filter variables for building the prolonged PLOS risk model. Multivariable logistic regression analysis was applied to build a predictive model using the variables selected in the LASSO regression model. The area under the ROC curve (AUC) of the predicting model was calculated and significant test was performed. The Kappa consistency test between the predictive model and the actual diagnosis was performed. Discrimination, calibration, and the clinical usefulness of the predicting model were assessed using the C-index, calibration plot, and decision curve analysis. Internal validation was assessed using the bootstrapping validation. Results According to the interquartile range of PLOS in a total of 310 patients, the PLOS of 235 patients was ≤P75 (7 days) (normal PLOS), and the PLOS of 75 patients was > P75 (prolonged PLOS). The LASSO selected predictors that were used to build the prediction nomogram included BMI, diabetes, hypertension, duration of surgery, duration of anesthesia, anesthesia type, intraoperative blood loss, sufentanil for postoperative analgesia, and postoperative complication. The model displayed good discrimination with an AUC value of 0.807 (95% CI: 0.758–0.849, P < 0.001), a Kappa value of 0.5186 (cutoff value, 0.2445, P < 0.001), and good calibration. A high C-index value of 0.776 could still be reached in the interval validation. Decision curve analysis showed that the prolonged PLOS nomogram was clinically useful when intervention was decided at the prolonged PLOS possibility threshold of 3%. Conclusions This study developed a novel nomogram with a relatively good accuracy to help clinicians access the risk of prolonged PLOS in lumbar fusion surgery patients. By an estimate of individual risk, surgeons and anesthesiologists may shorten PLOS and accelerate postoperative recovery of lumbar fusion surgery through more accurate individualized treatment.
A dimensional approach to affective disorder: The relations between Scl-90 subdimensions and QEEG parameters

Objectives QEEG reflects neuronal activity directly rather than using indirect parameters, such as blood deoxygenation and glucose utilization, as in fMRI and PET. The correlation between QEEG spectral power density and Symptom Check List-90-R may help identify biomarkers pertaining to brain function, associated with affective disorder symptoms. This study aims at determining whether there is a relation between QEEG spectral power density and Symptom Check List-90-R symptom scores in affective disorders. Methods This study evaluates 363 patients who were referred for the initial application and diagnosed with affective disorders according to DSM-V, with QEEG and Scl-90-R. Spectral power density was calculated for the 18 electrodes representing brain regions. Results Somatization scores were found to be correlated with Pz and O1 theta, O1 and O2 high beta. Whereas FP1 delta activities were correlated with anxiety, F3, F4, and Pz theta were correlated with obsession scores. Interpersonal sensitivity scores were found to be correlated with F4 delta, P3, T5, P4, T6 alpha and T5, and T6 theta activities. While depression scores were correlated with P3 and T4 delta, as well as T4 theta, there was a correlation between anger and F4, as well as T4 alpha and F8 high beta activities. Paranoia scores are correlated with FP1, F7, T6 and F8 theta, T5 and F8 delta, and O2 high beta activities. Conclusions According to our results, anxiety, obsession, interpersonal sensitivity, depression, anger, and paranoia are related to some spectral powers of QEEG. Delta-beta coupling seems to be a neural biomarker for affective dysregulation.
Heterotypic neutrophil-in-tumor structure: A novel pathological feature first discovered in the tissues of OPSCC

Objective To reveal a novel pathological feature: heterotypic neutrophil-in-tumor structure (hNiT) first discovered in patients with oropharyngeal squamous cell carcinoma (OPSCC), to analyze the prognostic role of hNiT in OPSCC patients and to explore the role of p16 in the formation of hNiT structures. Methods Clinically, 197 patients were enrolled. Clinicopathological information was extracted and analyzed. All pathologic sections made from primary tumors were re-evaluated by immunohistochemistry and immunostaining. In vitro, we cocultured OPSCC cell line SCC-15 with neutrophils to form hNiT structures, which were then subject to fluorescence staining. By RNAi and overexpression techniques, we investigated the role of CDKN2A in the formation of hNiTs. We validated the two techniques by qPCR and Western Blot. Results The hNiT as a novel pathological feature was first discovered in the tissues of OPSCC. The FNiT was significantly associated with tumor stage, disease stage, p16 and tumor grade. A total of 119 patients died of the disease, and the 5-year disease-specific survival (DSS) rate was 36%. The median survival time was 52.6 months. In patients with an FNiT<0.5%, the 5-year DSS rate was 40%; in patients with an FNiT>=0.5%, the 5-year DSS was 28%, and the difference was significant (p=0.001). Cox model analysis showed that FNiT along with disease stage, p16 and tumor grade was an independent prognostic factor for DSS. Immunostaining results of p16 expression showed hNiT formation was negatively correlated to p16 in OPSCC as well as in the hNiT formation assays in vitro indicated by fluorescent staining. Function assays of CDKN2A implied that reduce CDKN2A promoted the formation of hNiT while elevated CDKN2A impeded the hNiT formation. Conclusion The hNiT as a novel pathological feature is associated with the adverse prognosis of OPSCC patients with p16 inhibiting the formation of hNiT structures.