bluuebunny/crossref_metadata_2025_split huggingface dataset:
The oncogenic axis YAP/MYC/EZH2 impairs PTEN tumor suppression activity enhancing lung tumorigenicity
Authors: Blandino Giovanni , Sardo Federica Lo , Turco Chiara , Messina Beatrice , Sacconi Andrea , Auciello Francesca Romana , Pulito Claudio , Strano Sabrina , Lev Sima 
Published: October 2024

Abstract

The tumor suppressor PTEN (phosphatase and tensin homolog deleted in chromosome 10) is genetically deleted or downregulated in many cancer types. Loss of PTEN protein expression is frequently found in lung cancer while genetic alterations are less abundant. PTEN expression is regulated at multiple genetic and epigenetic levels and even partial reduction of its expression increases cancer occurrence. We show that YAP and TAZ cooperate with EZH2, and MYC to transcriptionally repress onco-suppressor genes, including PTEN, in Non-small cell lung cancer (NSCLC) cells. YAP/TAZ-EZH2-MYC transcriptional regulators form a nuclear complex that represses PTEN transcription, while their combinatorial targeting restores PTEN expression, attenuates NSCLC cell growth, and prevents compensatory responses induced by single treatments. Datasets analysis of NSCLC patients revealed that PTEN expression is negatively correlated to YAP/TAZ, EZH2 and MYC and that low expression of PTEN is predictive of poor prognosis, especially at earlier stages of the disease. These findings highlight the repressive role of the YAP/TAZ-EZH2-MYC axis on tumor suppressor genes and offer a potential therapeutic strategy for lung cancer patients with low PTEN levels.
P63 Expression in Primary Mediastinal Lymphomas
Authors: Houcine Yoldez , Mnif Omar , Yaiche Rahma , Jabr Dorra , Ayadi Aida 
Published: October 2024

Abstract

p63 protein is frequently used as an immunohistochemical marker in the pathologic diagnosis of non-hematological solid tumors. In malignant lymphoproliferative disorders, Primary mediastinal large B-cell lymphoma (PMLBCL) and classic Hodgkin lymphoma (CHL) represent two major types of mature B-cell lymphoma of the mediastinum. They have morphological and phenotypic overlap features, making this differential diagnosis challenging.
This study aims to evaluate the diagnostic utility of p63 immunohistochemistry (IHC) in distinguishing these entities.
In this single-center retrospective cohort study, we analyzed p63 expression using a tissue microarray approach in 44 cases of PMLBCL, 15 CHL cases and 7 Grey Zone Lymphoma (GZL). Diagnoses were made by experienced pathologists familiar with the nuances of lymphoma diagnosis, alongside clinical, morphological and immunohistochemical information. P63 expression was correlated with clinicopathological features.
P63 nuclear expression was found in 26/44 (59%) cases of PMLCBL, followed by only 4/7 cases of GZL and 1/15 cases CHL.
For PMLBCL, p63 demonstrated a sensitivity of 59%, specificity of 77%, a positive predictive value (PPV) of 83%, and a negative predictive value (NPV) of 49.7%.
Survival analysis revealed no significant differences in metastasis-free survival based on p63 expression across PMLBCL, CHL, and GZL.
These findings demonstrates that p63 has potential diagnostic value in differentiating PMLBCL from CHL and may be used as a potential tool in diagnosis of thoracic lymphoma. However, It has no prognostic value.
Explore the key genes and prognosis related to mitochondrial permeability transition driving necrosis gene in kidney renal clear cell carcinoma
Authors: Wang Yikai , Lv Dingyang , Zhang Wei , Shuang Weibing 
Published: October 2024

Abstract

Background: Mitochondrial permeability transition (MPT) driven necrosis may play a key role in the proliferation, death and spread of kidney renal clear cell carcinoma (KIRC). However, few studies have investigated key genes of MPT driven necrosis-related genes (MPTDNRGs) and KIRC using bioinformatics methods. Consequently, this study aims to create a precise prognostic tool for forecasting patient outcomes of KIRC patients.
Methods: First, differentially expressed genes (DEGs) were acquired from KIRC and control samples in TCGA-KIRC dataset, as well as between high and low MPTDNRGs scores groups. Then, candidate MPTDNRGs were acquired by overlapping both DEGs. Next, key MPTDNRGs were obtained by Cox regression analysis. Subsequently, risk model and nomogram were constructed, along with enrichment analysis, immune analysis, and regulatory network were completed. Finally, the expression of key MPTDNRGs was validated clinically using reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Results: Three key MPTDNRGs, namely IL2RA, CD7, and CXCL13, were obtained to construct the risk model. The ROC analysis results showed that the AUC for 1 year, 3 years, and 5 years were 0.658, 0.614, and 0.625, respectively, indicating that the risk model has good effectiveness. Besides, risk score and age are independent prognostic factors. Next, we constructed a nomogram with a decent potential for clinical utility over risk score and age alone. Among the high-risk group, there was a significant concentration of pathways related to immune functions, particularly systemic lupus erythematosus, while the low-risk group was largely enriched in pathways associated with metabolic processes, such as butanoate metabolism. A sum of 25 immune cells exhibited significant differences from different risk groups, and high-risk group patients revealed significantly higher TIDE score, which indicated a higher likelihood of tumor immune escape in high risk group. Moreover, ceRNA network showed complex interaction pairs such as CXCL13-hsa-miR-670-5p-AL121985.1, IL2RA-hsa-miR-6088-AL513497.1, and in total 25 TFs were predicted for key MPTDNRGs.
Conclusion: In this study, three key genes (IL2RA, CD7 and CXCL13) were integrated into a newly constructed prognostic model for KIRC, which offers clinicians a novel framework for more accurately forecasting patient outcomes and also presents a fresh target and approach for the management of KIRC.
Machine learning identified the application of Disulfidoptosis-Related Ferroptosis Genes Guinness in Lung Adenocarcinoma
Authors: liu Zichen , Yan Rongdi , Pang Xuemeng , Luo Yingxu , Zheng Xin 
Published: October 2024

Abstract

Disulfidoptosis, a recently recognized form of Regulated Cell Death (RCD), is known to play a crucial role in the development and progression of lung adenocarcinoma (LUAD). This study employed correlation analysis to identify 21 ferroptosis-related genes associated with disulfidoptosis, subsequently utilizing these genes to distinguish between two distinct groups characterized by contrasting prognostic and immune cell infiltration features. A risk model consisting of 17 DFG-related genes (SOD1, AKT1S1, TMPRSS11E, EPHX3, CPS1, PAK1, PSMB1, CDH17, NLRP2, HSD17B14, MRPL16, LACTB2, DEDD2, MCEMP1, LCAL1, VSTM2L, FLNC) was constructed through univariate Cox analysis and Lasso regression analysis. Within the TCGA cohort, the prognostic significance of these risk features was established as independent factors. Furthermore, a nomogram was developed to predict individual overall survival rates at 1, 3, and 5 years; with an AUC value of 0.833 for the first year, indicating its marked clinical utility. Conversely, high-scoring attributed encompass tumors in advanced stages and lower levels of cell differentiation. Furthermore, our observations suggested that patients in the high-risk group may potentially derive benefits from the administration of drugs such as 5-Fluorouracil.In conclusion, DFG holds potential for assessing patient prognosis, immune characteristics, and treatment outcomes. The findings of this study offer novel insights for clinical application and immune-based therapies.
Blood flow velocity analysis in cerebral perforating arteries on 7T 2D phase contrast MRI with an open-source software tool (SELMA)
Authors: Pham S. D.T. , Chatziantoniou C. , Vliet J. T. , Tuijl R. J. , Bulk M. , Ronen I. , Ladd M. E. , Kraff O. , de Rochefort L. , Villringer A. , Pine K. , Siero J.C.W. , Costagli M. , Tosetti M. , Biessels G.J. , Zwanenburg J.J.M. 
Published: October 2024

Abstract

Blood flow velocity in the cerebral perforating arteries can be quantified in a two-dimensional plane with phase contrast magnetic imaging (2D PC-MRI). The velocity pulsatility index (PI) can inform on the stiffness of these perforating arteries, which is related to several cerebrovascular diseases. Currently, there is no open-source analysis tool for 2D PC-MRI data from these small vessels, impeding the usage of these measurements. In this study we present the Small vessEL MArker (SELMA) analysis software as a novel, user-friendly, open-source tool for velocity analysis in cerebral perforating arteries. The implementation of the analysis algorithm in SELMA was validated against previously published data with a Bland-Altman analysis. The inter-rater reliability of SELMA was assessed on PC-MRI data of sixty participants from three MRI vendors between eight different sites. The mean velocity (vmean) and velocity PI of SELMA was very similar to the original results (vmean: mean difference ± standard deviation: 0.1 ± 0.8 cm/s; velocity PI: mean difference ± standard deviation: 0.01 ± 0.1) despite the slightly higher number of detected vessels in SELMA (Ndetected: mean difference ± standard deviation: 4 ± 9 vessels), which can be explained by the vessel selection paradigm of SELMA. The Dice Similarity Coefficient of drawn regions of interest between two operators using SELMA was 0.91 (range 0.69–0.95) and the overall intra-class coefficient for Ndetected, vmean, and velocity PI were 0.92, 0.84, and 0.85, respectively. The differences in the outcome measures was higher between sites than vendors, indicating the challenges in harmonizing the 2D PC-MRI sequence even across sites with the same vendor. We show that SELMA is a consistent and user-friendly analysis tool for small cerebral vessels.
Impact of shear wave elastography and attenuation imaging for predicting life-threatening event in patients with metabolic dysfunction-associated steatotic liver disease
Authors: Fujiwara Yudai , Kuroda Hidekatsu , Abe Tamami , Nagasawa Tomoaki , Nakaya Ippeki , Ito Asami , Watanabe Takuya , Yusa Kenji , Sato Hiroki , Suzuki Akiko , Endo Kei , Yoshida Yuichi , Oikawa Takayoshi , Kakisaka Keisuke , Sawara Kei , Tada Toshifumi , Miyasaka Akio , Oguri Takuma , Kamiyama Naohisa , Matsumoto Takayuki 
Published: October 2024

Abstract

We aimed to elucidate the value of ultrasound-based biomarkers for predicting the major life-threatening events in metabolic dysfunction-associated steatotic liver disease (MASLD). We established a prospective cohort of 279 patients who underwent two-dimensional shear wave elastography (2D-SWE), ultrasound-guided attenuation parameter (UGAP). An area under the curve analysis was performed to determine the cutoff values of liver stiffness measurements (LSM) by 2D-SWE and attenuation coefficient (AC) by UGAP for a moderate fibrosis and a moderate steatosis. We then classified the cohort into Groups A (low LSM and low AC), B (low LSM and high AC), C (high LSM and high AC), and D (high LSM and low AC). We compared the incidence of events between the groups, and estimated the hazard ratios (HRs) with 95% confidence intervals (CIs). The LSM and AC cut off values were 8.37 kPa and 0.62 dB/cm/MHz, respectively. The cumulative incidence rate in Groups A, B, C, and D were 11.2%, 12.2%, 29.5%, and 31.0%/5years, respectively (p < 0.05). LSM (HRs = 1.20, 95%CIs: 1.09–1.32, p < 0.01), and AC (HRs = 1.62, 95%CIs: 1.04–2.51, p = 0.03) were associated with life-threatening events. A combination of 2D-SWE and UGAP may help identify patients with MASLD at high risk for subsequent life-threatening events.
Liver Enzymes in End Stage Renal Disease Patients Diabetic and Non- Diabetic. Does it Differ than General Population?
Authors: Abdel-Atty-Gadallah Abdel-Nasser , Bahnasy Abdallah Abdel-Aziz , Milad Sahar , Toulan Safwa Othman 
Published: October 2024

Abstract

Background: End-stage renal disease (ESRD) often necessitates hemodialysis and is frequently caused by diabetes mellitus (DM). Liver enzyme levels are vital for assessing liver function but are complex to interpret in ESRD patients due to uremia, dialysis, and comorbidities. The effect of DM on liver enzymes in ESRD patients remains unclear. This study aims to evaluate liver enzyme levels in ESRD patients on hemodialysis and determine the impact of ESRD per se on liver enzymes and of ESRD with diabetes mellitus on liver enzymes levels.
Methods: This cross-sectional study was conducted on 140 participants, divided into ESRD (70 patients) and control (70 healthy individuals) groups. The ESRD group was further classified into diabetic (n=14) and non-diabetic (n=56) subgroups. Laboratory parameters including liver enzymes, serum albumin, bilirubin, urea, creatinine, sodium, potassium, coagulation parameters, hematological indices, and glycemic control were collected.
Results: ESRD group exhibited significantly higher AST (P=0.012) and ALP (P<0.001) levels, and lower serum albumin (P<0.001) compared to controls. No significant differences in ALT and total bilirubin were observed. Diabetic ESRD patients had significantly higher AST (P=0.017), ALT (P=0.003), serum albumin (P=0.034), and ALP (P=0.013) levels compared to non-diabetic ESRD patients. The urea reduction ratio and kt/v were significantly lower in diabetic ESRD patients (P=0.005 and P=0.039, respectively).
Conclusion: ESRD patients, particularly those with diabetes, have significantly altered liver enzyme profiles than general population. These results may change our view to liver enzymes levels in ESRD patients particulary ESRD patients with diabetes in routine monthly follow up and in other occasions.
Effect of genetically proxied use of PDE5 inhibitors on risk of CHD: A drug target Mendelian Randomization study
Authors: Zhang Hongchen , Dong Zhenhua , Hao Wei , Cao Guohua , Dong Qi , Chen Yiyang , Li Shihui , Chen Lanlan , Fan Zhongqi , Lv Guoyue 
Published: October 2024

Abstract

Background and aim
There have been previous and recent studies generating conflicting findings on effect of phosphodiesterase 5 (PDE5) inhibitors with CHD, Diabetes, breast cancer and prostatic cancer. Since we intended to use naturally occurring variation in genes encoding PDE5 to investigate association between genetically proxied PDE5 inhibitors and them.
Method
We used drug target mendelian randomization as main analytical method. 60,801 cases and 123,504 controls from 48 GWAS studies, mainly European ancestry (77%) for CHD were included. Inverse-variance weighted (IVW) random-effects model was employed as the primary analysis method to estimate the causal effect. And several robust methods were also used to detect the causal association as sensitive analysis. What’s more, colocalization analysis was also applied to verify the association.
Result
We observed strong evidence for the causal effect of genetically proxied PDE5 inhibitors on decreased CHD risk (IVW method, OR 1.22, 95% confidence interval (95%CI) 1.14-1.29, p-value=7.16E-07). Colocalization analysis also proved the association (H4=99.99%). Besides, we found weak association between genetically proxied inhibition of PDE5 and lower risk of breast cancer as well as prostatic cancer. At last, we found no evidence for effect of PDE5 inhibitors on risk of Diabetes.
Conclusion
We performed a drug target mendelian randomization supporting that use of PDE5 inhibitors is associated with lower risk of CHD. Though in 1990s studies found frustrating effect of PDE5 inhibitors on curing CHD, future RCT studies can focus on protective effect of PDE5 inhibitors on CHD. Our result may enlighten clinical use of PDE5 inhibitors.
Effect of Balanced Energy Protein Supplementation, Azithromycin and Micronutrients During Pregnancy on Birth Outcomes- A Four arm Assessor Blinded Open-label Randomized Controlled Trial
Authors: Jehan Fyezah , Pasha Aneela , Muhammad Ameer , Balouch Benazir , Shafiq Yasir , Nisar Muhammad Imran , Rizvi Arjumand , Shahid Shahira 
Published: October 2024

Abstract

Maternal undernutrition predicts poor birth outcomes. We performed a community-based, open-label, assessor-blinded, randomized controlled trial in Pakistan. Pregnant women (PW) with ultrasound-confirmed gestational age (GA) 8–18·9 weeks, were assigned (1:1:1:1) to one of four groups: control, BEP alone (10·5 g protein, 400 kcal per sachet, two sachets daily), BEP plus AZ (two doses of 2 g orally at weeks 20 and 28), or BEP plus choline (450 mg orally daily) and nicotinamide (100 mg orally daily). All arms received standard-of-care. Interventions began at enrollment and continued until birth. The primary outcome for the modified intention-to-treat analysis included infants born alive with anthropometric measurements taken within 72 hours of birth (n = 1678). The unadjusted difference in birth weight between BEP plus AZ arm compared to the controls was 104g; 95% CI: 20 to 188 (p = 0.008) and BEP plus choline/nicotinamide was 58g; 95% CI: -26, 142 (p = 0.07). Early neonatal mortality (NND) was 14.0 (95% CI: 5.2, 30.3; p = 0.04) in the BEP plus AZ arm, and 21.3 (95% CI:9.8, 40.1; p = 0.17) in BEP plus choline/ nicotinamide arm, as compared to 31.7 (95% CI: 16.9, 53.6) per 1000 live births in controls. The synergistic use of BEP with AZ, or with choline/nicotinamide in PW could improve birth outcomes. This trial is registered with ClinicalTrials.gov Identifier: NCT04012177.
Investigating the behavioral and antioxidative effects of ethanolic extract from Schumanniophyton magnificum (K. Schum) in ketamine-induced mice.
Authors: Asowata-Ayodele Abiola , Olusola Ayomide , Olatuyi lekan , afolabi felix , Olatunji Babawale , salemcity aanuoluwapo 
Published: October 2024

Abstract

This work presents an investigation on the behavioral and antioxidative effects of ethanolic extract from Schumanniophyton magnificum (K. Schum) in mice. Psychosis has several detrimental effects on health, as a result, a therapeutic strategy for managing psychosis is crucial to maintaining the global community’s health because when mental illness comes up in the human brain it’s reflected through different display of behavior like slow reasoning ability, depression, memory loss and isolating of oneself from others. However, it is not known whether Schumanniophyton magnificum leaves could cure or prevent psychosis because no study has ever cover the aspect of this plant nor any ethnobotanical study done on its activity in managing psychosis, thisfurther emphasizes the urgency for innovative treatment approaches. The plant was administered through oral route to group of ketamine induced mice at a dosages of 100, 200 and 400 mg/kg; compared with controls group of mice for 14 days. The behavioral assessment was demonstrated using the Open Field Test for assessing the ketamine-induced hyperlocomotion, Y-Maze test was used for assessing the behavior, learning and memory (cognition) and novel object recognition test to evaluate the willingness of the mice to explore new environment or object in animal models of the central nervous disorders. Thereafter, some biochemical assay were conducted. This research shows that after 14 days of administration, the animals were sacrificed and antioxidant bioassay was carried out on the brain. Schumanniophyton magnificum treatment significantly (P < 0.05) reduced hyper-locomotion induced by ketamine, which is a predictor of positive symptoms. Schumanniophyton magnificum treatment (100 and 400 mg/kg) significantly enhanced spatial memory formation preventing cognitive deficits by ketamine. Schumanniophyton magnificum treatments significantly increased the SOD & CAT activities, as well as decreased MDA levels, this is suggesting that the antipsychotic-like action of Schumanniophyton magnificummaybe through inhibition of oxidative crises induced by ketamine. This study could potentially pave new way for cost-effective interventions that address both the health and socioeconomic burdens associated with psychosis.
The Nexus Between Changes in CEO Successor’s Attributes and Firm Performance: Evidence from Emerging Countries
Authors: Hazem Sama Mohamed , Ali Assoc. Prof. Dr. Heba Ahmed Abass , Abou-Elkheir Prof. Dr. Ehab Kamel 
Published: October 2024

Abstract

This paper aims to comprehensively analyze the impact of Chief Executive Officer (CEO) succession on the firm’s post-succession performance, specifically through investigating the direction of changes in CEO successor attributes compared to the predecessor CEO. The paper uses a sample of 1,729 firms in twenty-six emerging countries from 2000 to 2019. The sample yields 9,498 firm-year observations embracing 913 CEO successions. Using fixed effect (FE) regression, the findings conclude that hiring an insider CEO successor significantly decreases the negative impact of CEO succession on the firm’s asset utilization. However, hiring a CEO successor of the same gender, younger, less experienced, or with smaller social networks significantly amplifies the negative impact of CEO succession on the firm’s asset utilization. Moreover, the direction of change in CEO education and busyness has revealed mixed results on the firm’s asset utilization. In addition, hiring an insider, of the same gender, more experienced, with a larger social network and less busy CEO successor significantly decreases the negative impact of CEO succession on the firm’s liquidity. Finally, hiring an outsider, a different gender, younger, less educated, less experienced, with a larger social network or busier CEO successor significantly amplifies the negative impact of CEO succession on the firm’s liquidity.
JEL: C12, C23, G41, O16
Saguna Rice Technology Adoption in Maharashtra: Benefits, Challenges, and Pathways to Sustainable Agriculture
Authors: Wadghane Rahul , Sonawaney Vandana , Gotise Piyush , Bhandarkar Pankaj 
Published: October 2024

Abstract

This study investigates the adoption of Saguna Rice Technology (SRT) by 27 farmers across Maharashtra, India. This research highlights the challenges and potential benefits of SRT, with a focus on the technical, economic, and institutional factors influencing adoption. Utilizing purposive and snowball sampling, data were collected through five-minute telephone interviews and face-to-face discussions. Thematic analysis using NVivo software revealed that while SRT offers economic benefits such as a 30–40% reduction in production costs and improved soil fertility, challenges such as weed management and the need for specialized equipment hinder widespread adoption. Farmers suggest solutions, including the timely use of herbicides, enhanced availability of SRT-specific tools, and targeted training for effective implementation. This study provides valuable insights for policymakers and stakeholders aiming to promote sustainable agricultural practices in Maharashtra.