bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations in the GNAS Gene Prevent the Cell Invasion by Activating the MEG3/Wnt/β-catenin Axia in Growth Hormone-secreting Pituitary Adenoma
Authors: Tang Chao , Zhong Chunyu , Zhu Junhao , Yuan Feng , Yang Jin , Cai Xiangming , Xu Yong , Ma Chiyuan 
Published: April 2022

Abstract
Approximately 30–40% of growth hormone-secreting pituitary adenoma (GHPA) harbor somatic mutations in the GNAS (α subunit of the stimulatory G protein) gene. However, the latent functional role of the mutations and relative molecular mechanism in GHPA remain unknown. The GNAS gene mutations were detected in GHPAs using a standard PCR-sequencing procedure. The mutation-associated MEG3 expression was measured by RT-qPCR. MEG3 was manipulated in GH3 cells using a lentiviral expression system. Alterations in mRNA profiles in the MEG3-overexpressed cells were analyzed by RNA-seq. The cell invasion ability was measured using a Transwell assay, and the EMT-associated proteins were quantified by immunofluorescence and western blot. Finally, a tumor cell xenograft mouse model was applied to verify the effect of MEG3 on tumor growth and invasiveness. The percentage of invasive tumors was significantly declined in GNAS-mutated GHPA tumors with the GNAS mutations compared to those tumors with the wild-type of GNAS. Consistently, the GH3 cell invasion capacity was decreased by expressing the mutant GNAS. MEG3 is uniquely expressed at high levels in GHPA harboring the mutated GNAS gene. Accordingly, the upregulation of MEG3 resulted in inhibiting cell invasion; and vice versa, the downregulation of MEG3 led to enhancing cell invasion. Mechanistically, the high level of MEG3 in mutated GNAS cells prevented the cell invasion via inactivation of the Wnt/β-catenin signaling pathway, which was further validated in vivo. The GNAS mutations inhibit the invasiveness of GHPA cells via inactivation of the MEG3/Wnt/β-catenin signaling pathway.
Secreted Phosphoprotein 1 (SPP1) Promotes Angiogenesis of Glioblastoma Through Up-regulating PSMA Expression Via Transcription Factor HIF-1α
Authors: Gao Yang , Tu Wenjing , Zheng Hui , Li Liangdong , Zhou Changshuai , Feng Mingtao , Chen Lei , Li Deheng , Chen Xin , Hao Bin , Cao Yiqun 
Published: April 2022

Abstract
Background: Glioblastoma multiforme (GBM) is a highly vascular-rich and devastatingly aggressive type of malignant brain tumors, thus anti-angiogenesis therapy plays an essential role in the treatment of GBM. Our previous study had showed that the prostate-specific membrane antigen (PSMA) promoted angiogenesis of GBM through interacting with Integrin β4 (ITGB4) and regulating NF-kB signaling pathway. This study aims to explore the upstream molecular mechanism of GBM regulating the expression of PSMA and promoting angiogenesis process.Methods: Human cytokine antibody array and bioinformatics were used to explore potential cytokines involved in regulating PSMA expression. Recombinant protein was applied and western blot, qRT-PCR were assessed to verify that the contributing cytokine was SPP1. Potential transcription factor mediating the expression of PSMA was sifted through PROMO and JASPAR website. ChIP assay and dual luciferase were used to confirm that the transcription factor HIF-1α could regulate PSMA expression. Cellular migration and tube formation ability were assessed by scratch assay and tube formation assay in human umbilical vein endothelial cells (HUVECs). ELISA was conducted to evaluate the variation of SPP1 in the serum of GBM patients pre- and post-surgery. Expression levels, prognosis and receiver operation characteristic (ROC) curve of SPP1 were determined by bioinformatics to evaluate its clinical value. Results: We demonstrated that cytokine SPP1 secreted from GBM could regulate the expression of PSMA in HUVEC. The mechanistic study revealed that SPP1 regulated the expression of PSMA through transcription factor HIF1α. Recombinant protein SPP1 could promote migration and tube formation ability of HUVEC, which could be blocked by knockdown of HIF1α. SPP1 was abundantly expressed in the GBM, and the high expression of SPP1 is associated with poor prognosis. Furthermore, SPP1 had a high value of clinical diagnosis with considerable sensitivity and specificity. Conclusions: In this study, we identified that upstream cytokine SPP1 secreted from GBM could upregulate PSMA expression in endothelial cells via transcription factor HIF1α, which constructs a positive chain in angiogenesis and provides promising candidates for targeted therapy of GBM.
Effects of early palatoplasty on procedural related blood loss and fistula formation in patients with unilateral complete cleft lip and palate: A randomized controlled trial study
Authors: Gharehgheshlaghi Lida Jabbari , Yazdani Yalda , Segherlou Zahra Hasanpour , Fakhim Shahin Abdollahi , Nouri-Vaskeh Masoud 
Published: April 2022

Abstract
Background: Different timelines are preferred for repair surgeries in patients with unilateral complete cleft lip and palate (UCLP). The aim of this study was to evaluate the effects of early palatoplasty on procedural related blood loss (anemia) and fistula formation in patients with UCLP. Methods: This randomized controlled trial conducted on patients candidate for UCLP repair. Patients in control group underwent cheiloplasty, closure of nasal floor, caudal septum dislocation repair, and primary rhinoplasty in first surgery at age of 28 days-4 months. In second surgery, patients in control group underwent two flap palatoplasty with vomerian flap and intravelar veloplasty, soft palate repair and also myringotomy at age of 9-12 month. In case group, infants underwent cleft lip and nose repair (like control group), hard palate repair in first surgery and then in second surgery, patients underwent soft palate repair with intravelarveloplasty. Results: Fifteen patients were included in each group. Two patients in primary surgery in the case group and two patients in secondary surgery in the control group were developed to oronasal fistula after palatoplasty (P= 0.432). The mean hemoglobin levels in the case and control groups at the primary surgery were 10.32±0.68 and 10.31±0.49 g/dL, respectively (P= 0.968) and at the secondary surgery were 11.29±0.54 and 11.37±0.40 g/dL, respectively (P= 0.666). Conclusion: There were no perioperative hemorrhagic events and need to blood transfusion in both groups. Early palatoplasty may as safe as conventional technique in patients with UCLP.Trial registration number: IRCT20180802040678N5
Endoscopic Management for Difficult Biliary Cases in the era of Laparoscopic Surgery
Authors: Lesmana Cosmas Rinaldi Adithya , Paramitha Maria Satya , Pratiwi Yulia Estu , Lesmana Laurentius Adrianto 
Published: April 2022

Abstract
Background: Biliary disorders are still the most challenging cases in the field of gastroenterology, as comprehensive clinical evaluation and treatment considerations are still necessary. In the era of laparoscopic procedure, there are a lot of innovations on non-surgical management approaches, such as endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS). Since there is no clear consensus yet in managing complicated biliary disorders, this study is aimed to see the impact of endoscopic management for difficult biliary cases. Methods: A cohort-retrospective endoscopy database study was conducted at a tertiary-referral private hospital in Jakarta, Indonesia, between January and December 2020. Difficult biliary cases defined as biliary case which required at least one of the following conditions: multi-management approach, biliary obstruction with cholangitis or biliary sepsis, difficult CBD stone, recurrent CBD stone, or advanced progressive malignant biliary obstruction. Results: Sixty-one subjects in this retrospective database study were suitable as difficult biliary cases. The proportions of malignant and non-malignant etiologies were similar (44.3% versus 55.7%, respectively). In this study, 68.8% of all subjects underwent standard therapeutic ERCP procedure, while 16.4% of the subjects underwent combination of therapeutic ERCP and EUS in one session based on the complexity of the case; and 8.2% of the subjects underwent therapeutic ERCP with additional single operator cholangioscopy procedure. One subject underwent rendezvous ERCP procedure through percutaneous approach. Around 4.9% of the subjects underwent EUS-biliary drainage procedure. The technical success rate of all procedures was 100%. Re-intervention ERCP was performed in 6 subjects (9.8%). No significant association was observed between all mortality outcomes and baseline characteristics of the patients. There were also no significant associations between re-intervention procedures, as well as post-procedural pain or acute pancreatitis, with mortality outcomes. Conclusion: Difficult biliary cases require a good clinical approach algorithm to decide which procedure comes first based on comprehensive evaluation consists of patient’s factor, expertise, cost, and the risk of complications.
Case series of colonic pseudolipomatosis: Could the scope be the cause?
Authors: Baccouche Charfeddine , Abdelaali Imen , Ayari Myriam , Dhaoui Amen , Doggui Mohamed Hedi , Jomni Mohamed Taieb 
Published: April 2022

Abstract
Background: Colic pseudolipomatosis is a rare and benign condition of which many endoscopists and pathologists are unaware. Several pathogenic mechanisms have been postulated. For a better understanding and recognition of this uncommon lesion with particular attention to its etiology, we report and discuss a series of patients in whom colonic pseudolipomatosis was found during routine colonoscopy and occurring in an epidemic pattern.Methods: This was an observational cross-sectional study reporting a form of unprecedented colitis, colonic pseudolipomatosis, observed in a series of patients at our endoscopy center during a 3−month period in late 2021 (October - December). We collected demographic/clinical data, endoscopic and histological findings from all included patients. For statistical analysis, we used the simple method of ratio to provide percentagesResults: In total, eight patients were included. Their median age was 59,5 years with a male/female sex ratio of 0.6. During endoscopy, flat or slightly elevated whitish−yellow plaques extending from a few millimeters to several centimeters, were found in the colonic mucosa of all patients at variable sites. In three patients, a whitish foamy fluid appeared under our observation rapidly followed by the formation of whitish plaques when water was irrigated. Histological specimens showed in all cases, numerous optically empty vacuoles of variable size in the lamina propria. After confronting histological findings to endoscopic features, the diagnosis of pseudolipomatosis was made in all cases. The disinfectant we use contains hydrogen peroxide and peracetic acid. We found that our disinfectant machine had a technical malfunctioning in the rinse cycle of endoscope channels during this period. No further cases were observed after we serviced the machine. No patient subsequently suffered morbidity or mortality.Conclusion: Pseudolipomatosis seems to be an endoscopy induced lesion rather than a true pathological entity. The detection of such lesions should incite to a careful check of the disinfection process, thus, minimizing patients’ exposure to residual disinfecting agents in the endoscope and avoid further unnecessary investigations.
Renal protective effect of Cinnamon ethanolic extract against induced renal damage by carbon tetrachloride administration in rats
Authors: Marie Ohoud , Elfakhrany Amany Tawfik , Dessouki Amina A. , Omar Mohamed S. 
Published: April 2022

Abstract
One of the most dangerous environmental contaminants is carbon tetrachloride (CCl4) that induces oxidative stress damage in various pathophysiological situations. It's critical to find a potent antioxidant that can reverse CCl4-induced kidney damage. Therefore, the aim of this study was to investigate the efficacy of cinnamon ethanolic extract (CE) to modulate the kidney damage induced by CCl4. The CCl4 was given intraperitoneally twice a week for four weeks as a positive kidney toxic agent at a dose of 0.5 mL/kg. Compared to normal group, CCl4 increased significantly MDA level and decreased significantly both SOD and GSH levels whereas, CE significantly decreased MDA level and increased both SOD as well as GSH levels relative to CCl4 group. CCl4 also led to increase in tumor necrosis factor alpha (TNF-α), beta-2 microglobulin (β2-MG) and kidney injury molecule-1(KIM-1) which indicated the nephrotoxicity induced by CCl4. Based on its strong antioxidant activity and its phenolic and terpenoid contents, CE significantly decreased oxidative damage and pro-inflammatory markers compared to CCl4 treated group.
The effect of perioperative intravenous lidocaine infusion on postoperative sleep of elderly patients with colorectal cancer
Authors: Deng Liqin , Wang Xiaomei , Wu Yanan , Wang Lu , Qiu Yuxue , Hou Haitao 
Published: April 2022

Abstract
Background: Postoperative sleep disturbance (POSD) in patients with colorectal cancer is a key factor affecting their rapid postoperative recovery. Studies have confirmed that perioperative use of opioids can disturb postoperative sleep, and perioperative oligoopioids or no opioid in elderly patients can promote postoperative recovery. To reduce the use of opioids, this study was to investigate the effect of perioperative intravenous lidocaine analgesia on the postoperative sleep of elderly patients undergoing laparoscopic radical resection for colorectal cancer. Methods 63 patients aged 65-80 years with body mass index (BMI) values of 20-30 kg/m2 and American society of anesthesiologists (ASA) grades of II-III, who underwent elective laparoscopic radical resection for colorectal cancer, were selected. The patients were divided into the lidocaine group (group L, n = 32) and the control group (group C, n = 31) by using a random number table. Patients in both groups received total intravenous anesthesia. In group L, a dose of 1.5 mg/kg of lidocaine was injected intravenously during induction of anesthesia, and lidocaine (1.0 mg·kg-1·h-1) was injected intravenously during surgery and for 24 hours after surgery. In Group C, the same volume of normal saline was injected, and intravenous patient-controlled analgesia (Sufentanil 1.5-1.8 μg/kg) was given after surgery. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep function 1 d before surgery, 1 d, 2 d, and 3 d after surgery. The incidence of postoperative sleep disturbance (POSD) at 1 d, 2 d and 3 d after surgery was calculated. The pain intensity of the two groups at different time points after surgery was evaluated. The intraoperative consumption of opioids and propofol and the incidence of postoperative complications and lidocaine adverse reactions in 2 groups were recorded. Results Compared with group C, sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance, daytime dysfunction scores, and total PSQI score was improved significantly in group L at 1 d, 2 d, and 3 d after surgery (P <0.05). Compared with group C, the incidence of POSD in group L was lower, and the difference was statistically significant (P <0.05). There was no significant difference in postoperative pain intensity between the two groups (P > 0.05) Compared with group C, the consumption of opioids and propofol in group L decreased significantly (P <0.05). There was no statistically significant difference in the incidence of postoperative complications. No patient in group L had side effects of lidocaine. Conclusions For elderly patients undergoing laparoscopic radical resection of colorectal cancer, perioperative intravenous lidocaine infusion can improve the early postoperative sleep quality, reduce the incidence of postoperative sleep disturbance, and promote the recovery of postoperative sleep function.
Investigating the 'Techno-eco-efficiency' Performance of Pump Impellers: Metal 3D Printing vs CNC Machining
Authors: Jayawardane Heshan , Davies Ian J. , Gamage J. R. , John Michele , Biswas Wahidul K. 
Published: April 2022

Abstract
The economic, environmental, and social impacts caused by the extensive resource consumption and harmful emissions from the metal manufacturing industry should be lowered through innovative sustainable manufacturing strategies. This study aims to investigate the techno-eco-efficiency performance of metal additive manufactured (AM) parts in comparison with metal subtractive manufactured (SM) parts to determine the technical, economic, and environmental performance as a decision support tool for selecting the most techno-eco-efficient manufacturing method. In this study, a novel metal extrusion AM technology has been used to create a centrifugal semi-open pump impeller in 316L stainless steel material. The technical feasibility of the impellers has been determined by evaluating the geometry, build material, mechanics, morphology, and functional performance of the impellers. The eco-efficiency performance of technically feasible impellers was evaluated through environmental life cycle assessment, life cycle costing, and portfolio analysis. The findings reveal that AM impeller’s higher normalised costs (43.8%) have been offset by its lower normalised environmental impacts (54.6%) compared to the SM impeller. The centrifugal semi-open pump impellers made by the novel metal AM technology are technically feasible, cost-effective, and environmentally friendly compared to their SM counterparts.
Pharmacokinetic booster simulation of ritonavir improves the benefits of lopinavir for virtual patients with COVID-19
Authors: Nakamaru Yuta , Maeda Tomoji , Matsuda Yoshikazu , Sako Ken-ichi 
Published: April 2022

Abstract
The coronavirus disease 2019 (COVID-19) pandemic and its persistence have created a need for effective treatments. Patients with COVID-19 have been treated with a combinatorial therapy comprising lopinavir and ritonavir (LPV/r), which is used to treat human immunodeficiency virus infection. However, the results of an open-label randomized controlled trial led to the removal of this modality from the list of recommended agents in the Japanese COVID-19 Treatment Guide. We believe that an insufficient dose of LPV/r caused the lack of therapeutic effect. Therefore, based on previous models, we quantitatively evaluated whether adequate amounts of the pharmacokinetic booster LPV/r could modulate LPV clearance. Our results showed that the strategy of increasing the dose of LPV/r improved the safety and efficacy of the treatment. Thus, owing to the fact that it increased the LPV concentration, the pharmacokinetic booster LPV/r may serve as a potential therapeutic for COVID-19.
Effect of lactate levels on the carbon dioxide pressure discrepancies between transcutaneous and arterial measurements among hypercapnic patients receiving noninvasive ventilation
Authors: Kaya Aslıhan Gürün , Öz Miraç , Özpınar Şeyda Nur , Erol Serhat , Çiftçi Fatma , Çiledağ Aydın , Kaya Akın 
Published: April 2022

Abstract
Purpose
Partial carbon dioxide pressure (PaCO2) is widely used to evaluate alveolar ventilation. Transcutaneous CO2 (TcCO2) monitoring has been developed as a noninvasive alternative to ABG. Studies demonstrated an association between hypoperfusion and increased tissue CO2. The research question of this study is if there is any relation between lactate level and TcCO2-PaCO2 among hypercapnic patients receiving noninvasive ventilation (NIV).
Methods
In this prospective study, simultaneously measured TcCO2 and PaCO2 values of hypercapnic patients receiving NIV were recorded. Each paired measurement was categorized into two groups; normal lactate (< 2 mmol/L) and increased lactate (≥ 2 mmol/L).
Results
A total of 116 paired TcCO2 and PaCO2 measurements of 29 patients were recorded in the study. Bland Altman analysis showed the mean bias between the TcCO2 and PaCO2 and %95 limits of agreement (LOA) in total measurements (1.75 mmHg %95 LOA − 3.67 to 7.17); in the normal lactate group (0.66 mmHg 95% LOA − 1.71 to 3.03); and in the increase lactate group (5.17 mmHg 95% LOA − 1.63 to 11.97). A positive correlation of lactate level and with the difference between TcCO2 and PaCO2 (r = 0.789, p < 0.001) and a negative correlation between mean blood pressure and the difference between TcCO2 and PaCO2 (r= -0.540, p = 0.001). Multiple regression analysis results showed lactate level was independently associated with increased differences between TcCO2 and PaCO2 (Beta = 0.875, p < 0.001)
Conclusion
Transcutaneous CO2 monitoring may not be reliable in patients with increased lactate levels. TcCO2 levels should be checked by ABG analysis in these patients.
Effects of hypophosphatemia and low serum parathyroid hormone on protein-energy wasting
Authors: Li Qian , Yuan Dongbo , Da Jingjing , Yu Jiali , Yuan Jing , Hu Shanshan , Wu Libo , Yang Xia , Zha Yan 
Published: April 2022

Abstract
Objective
To explore the effect of low serum phosphorus and parathyroid hormone (PTH) levels on protein-energy wasting (PEW) in patients on maintenance hemodialysis (MHD) and provide a new method of nutritional monitoring and intervention in patients on MHD.
Methods
Four hundred end-stage renal disease (ESRD) patients on MHD for at least 3 months were selected from 17 dialysis units. Logistic regression analysis was used to analyze the relationship between serum phosphorus and PTH levels and PEW risk. Receiver operating characteristic (ROC) analysis was used to compare the predictive value of these two indices for PEW. We used the survival curve to analyze the effects of low serum phosphorus and PTH levels on mortality.
Results
In the unadjusted model, The PEW risk in group Q1 was 16.4 times higher than that in group Q4. Compared with group Q4 of PTH, the PEW risk in groups Q1 and Q2 of PTH was 2.817 times higher and 2.087 times higher, respectively, after adjusting. However, serum phosphorus and PTH levels were associated with PEW risk. PEW risk in the serum phosphorus Q1 group was 7.305 times higher than that in the Q4 group, and PEW risk in the PTH Q1 group was 2.75 times higher than that in the Q4 group. ROC analysis showed that the areas under the curve of serum phosphorus and PTH predicting PEW in MHD patients were 0.862 and 0.695, respectively, while the cut-off values of ROC curve were 1.36 mmol/L and 212.5 ng/L, respectively. The survival rate was significantly lower in patients with serum phosphorus ≤ 1.36 mmol/L of ≤ 212.5 ng/L.
Conclusion
Low serum phosphorus and PTH levels increased the incidence of PEW and death and seriously affected the prognosis of patients on hemodialysis. Therefore, The nutritional status of patients on MHD can be monitored and evaluated by integrating serum phosphorus, PTH, albumin, and body mass index.