bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Expression Profiles and Clinical Significance of PKM2 and Notch1 in Colorectal Cancer
Authors: Wang Jia , Sun Meijuan , Du Wenlong , Guo Yuanxian , Pan Jiebin , Kou Bangguo , Jiang Yongjie , Bian Pan , Li Bingtai , Yin Lanning 
Published: September 2021

Abstract
Background Studies have shown that pyruvate kinase M2 (PKM2) and Notch1 are highly expressed in colorectal cancer (CRC) tissues and have a certain relationship with disease occurrence and development. The expression levels of PKM2 and Notch1 are also related to the effect of chemotherapy and radiotherapy, which seriously influence the prognosis of CRC patients. Thus, both PKM2 and Notch1 have been identified as key targets of CRC treatment and research. However, correlations between PKM2 and Notch1 have not yet been established. Methods Immunohistochemical analysis was conducted to detect the expression of PKM2 and Notch1 in CRC tissues. The mRNA and protein expression levels of PKM2 and Notch1 in CRC cell lines were detected by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) and western blot analysis, respectively. Compound 3K and tangeretin (TGN) were used to inhibit the expression of PKM2 and Notch1, respectively. The proliferation and migration of cancer cells in each group were detected with the CCK-8 and wound healing assays. Results The Immunohistochemical analysis showed that PKM2 and Notch1 were highly expressed in CRC and related to tumor stage and lymph node metastasis. The qRTPCR and western blot results showed that PKM2 and Notch1 were notably upregulated in CRC cells both at the mRNA and protein levels. PKM2 and Notch1 form a positive feedback loop to promote the occurrence and development of CRC, and inhibition of PKM2 and Notch1 has a synergistic effect on the proliferative and invasive capabilities of CRC cells. Conclusion The combination of the PKM2 inhibitor compound 3K and the Notch1 inhibitor TGN presents a novel and effective strategy for treatment of CRC.
Evaluation of Musculoskeletal Medicine Knowledge Among Physicians and Physical Therapists in Saudi Arabia: A Cross-Sectional Study
Authors: Alrwaily Muhammad , Alanazi Fahad 
Published: September 2021

Abstract
Background: Musculoskeletal (MSK) conditions are rapidly rising in Saudi Arabia and considered the 3rd reason for hospital visits across the country. Despite their prevalence, the adequacy of knowledge in MSK medicine has not been assessed. The purpose of this study is to assess MSK medicine knowledge amongst healthcare providers (orthopedists, primary care physicians, and physical therapists) and medical and physical therapy students and interns.Method: In this cross-sectional study, a web-based 25-question MSK test was given to licensed physical therapists and physicians; as well as final year physical therapy and medical students and interns in Saudi Arabia. One-way analysis of variance was used to determine MSK test scores differences amongst orthopedists, primary care physicians, and physical therapists; and amongst medical and physical therapy students and interns.Results: A total of 680 participants were included (response rate is 86.7%.) The overall MSK test score was 48.2%; and the passing rate was 14%. There was a significant score difference amongst orthopedists (88.8%), primary care physicians (53.6%), and physical therapists (46.7%); F(2,431) = 38.1, p < .001). There was significant score difference amongst physical therapy students (45.3%), physical therapy interns (42.6%), medical students (52.3%) and medical interns (67.4%); F(3,242) = 10.7, p < .001).Conclusion: Except for orthopedists, the MSK medicine knowledge appears inadequate amongst healthcare providers, medical and physical therapy students and interns in Saudi Arabia. To improve knowledge in MSK medicine, increasing contents of MSK medicine in undergraduate education and postgraduate training is necessary.
Development and Validation of Prognostic Nomograms for Patients with Parotid Gland Adenocarcinoma Not Otherwise Specified: A SEER Analysis From 2004 To 2016
Authors: Wang Zi-Meng , Xiang Zuo-Lin 
Published: September 2021

Abstract
Background

Parotid gland adenocarcinoma not otherwise specified (PANOS) is a rare malignancy, and the characteristics and prognosis of this disease remain unclear. This study aims to characterize PANOS and establish prognostic prediction models for patients with PANOS.
Methods

Cases from 2004–2016 were retrieved from the Surveillance, Epidemiology, and End Results Program database (SEER database). Univariate and multivariate Cox regression analyses, Gray's test and propensity score matching (PSM) were conducted to analyze demographics, treatments, and survival outcomes .
Results

The 446 patients ( 289 men) selected for analysis had a median age of 66 (19–95) years, and 307 patients were diagnosed with stage III/IV disease. The median survival of all patients was 66 months, with a 51.8% 5-year overall survival (OS) rate. Surgical treatment clearly improved survival time (p < 0.001). In the subgroup analysis, radiotherapy showed survival benefits in patients with advanced-stage disease (III/IV) (p < 0.001). Multivariate Cox regression analyses revealed that age, T stage, N stage, M stage and surgery were independent prognostic indicators for OS;T stage, N stage, M stage and surgery were independent risk factors for cancer-specific survival(CSS).In addition, age was independently associated with noncancer-related death. Two nomograms were established based on the results of the multivariate analysis, which was validated by the concordance index (C-index) (0.747 and 0.780 for OS and CSS, respectively) and the area under the time-dependent receiver operating characteristic(ROC) curve(0.756, 0.764 and 0.819 regarding for nomograms predicting 3-, 5- and 10- year OS, respectively and 0.794, 0.789 and 0.806 for CSS, respectively).
Conclusions

Our study clearly presents the clinicopathological characteristics and survival analysis of patients with PANOS. In addition, our constructed nomogram prediction models may assist physicians in evaluating the individualized prognosis and deciding on treatment for patients.
Short-Term Results of Percutaneous Closure of Patent Foramen Ovale Guided by Transoesophageal Echocardiography in Patients with Cryptogenic Stroke: A Retrospective Study
Authors: Guo Yilong , Shi Zhensu , Zheng Yin , Wang Xiaoqi , Chen Zelun , Shu Yue , Zhou Dexing 
Published: September 2021

Abstract
Background

Patent foramen ovale (PFO) is a risk factor for cryptogenic stroke (CS), and interventional therapy for PFO can reduce the recurrence rate of CS. However, interventional therapies are primarily guided by X-ray imaging, and regular postsurgical follow-up with transthoracic ultrasound foaming test (UFT) is rarely performed. Thus, this study aimed to assess the short-term (1 year) results of PFO occlusion guided by transoesophageal echocardiography (TEE) and the results of regular UFTs.
Methods

Clinical records, echocardiographic data, and UFT results of 27 patients who underwent interventional therapy for PFO and CS were retrospectively analysed. The patients were grouped according to their preoperative UFT results: group A (n = 4), small volume of right-to-left shunts; group B (n = 8), moderate volume of right-to-left shunts; and group C (n = 15), large volume of right-to-left shunts. All patients were treated using an Amplatzer occluder under TEE guidance. UFT follow-up was conducted regularly until 1 year post-surgery.
Results

No significant differences in preoperative clinical data, echocardiographic data, or operative time were noted between the groups (P > 0.05). The length of the PFO and the diameter of the occluder differed between the groups as follows: group A = group B < group C (p < 0.05). One year postoperatively, there was no stroke recurrence. Two patients in group C developed atrial arrhythmia, which improved after 3 months of antiarrhythmic treatment. The positive UFT rate gradually decreased postoperatively, and 50% of patients still had a positive UFT 11.75 months after surgery. The positive UFT rate 1 year postoperatively differed between the groups as follows: group A = group B < group C (p = 0.010). A preoperative large-volume shunt was negatively associated with a negative UFT rate 1 year postoperatively (b=-2.118, RR = 0.120, p = 0.002).
Conclusion

In patients with PFO and CS, interventional therapy guided by TEE led to excellent short-term (1 year) outcomes. The positive UFT rate gradually decreased within 1 year of surgery. Preoperatively, a large volume of right-to-left shunts and large occluders were two risk factors for positive UFT results after surgery. Further studies are required to clarify the relationship between positive UTF results postoperatively and stroke recurrence.
Non-invasive Myocardial Work Index Contributes to Early Identification of Impaired Left Ventricular Myocardial Function in Uremic Patients With Preserved Left Ventricular Ejection Fraction
Authors: Zhu Huizhen , Li Yanan , Cui Cunying , Huang Danqing , Liu Yuanyuan , Liu Ruijie , Zhao Qingqing , Wang Ying , Liu Lin 
Published: September 2021

Abstract
BackgroundCardiac damage is the leading cause of death in uremic patients. This study aimed to evaluate the application of non-invasive myocardial work index (NIMWI) by echocardiography in assessing the left ventricular (LV) systolic function in uremic patients.MethodsTwenty-six uremic patients and twenty-seven age- and sex-matched healthy volunteers were enrolled in the study. Except for the conventional echocardiographic parameters, the LV myocardial work (MW) parameters including GWI (myocardial global work index), GCW (global constructive work), GWW (global wasted work), and GWE (global work efficiency) were calculated in study participants. Differences in MW parameters between the uremic and normal groups were compared by independent-sample t-test. Receiver operating characteristic (ROC) curves were constructed for MW parameters to detect abnormal LV systolic function in uremic patients.ResultsCompared with the normal group, GWW was significantly increased and GWE decreased in the uremic group (P< 0.05). Area under the curve (AUC) for GWE by the ROC analysis was 0.966. The best threshold, sensitivity and specificity values of GWE to detect abnormality of LV systolic function in uremic patients were 92.5%, 0.89 and 0.96 respectively. Conclusions﻿NIMWI may be applied to assess the global MW of uremic patients. The presence of reduced GWE can help identify impaired left ventricular myocardial function in uremic patients with preserved LV ejection fraction with a high sensitivity and specificity.
Landscape and tree community effects on the infestation of an endemic fungal pathogen in riparian forests were mediated by leaf traits
Authors: Wang Binli , Tian Chengming , Liang Yingmei 
Published: September 2021

Abstract
Background

Plant pathogens are regarded as crucial agents shaping the dynamics of natural forest communities. Marssonina leaf spot of poplar is induced by an endemic pathogenic fungus Drepanopeziza populi, causing increased damage to riparian poplar stands in recent years. However, such endemic fungal diseases have received little attention at the landscape scale, despite the key role of landscape heterogeneity in the development and spread of emerging forest diseases. Moreover, most studies have insufficiently captured multiple ecological factors driving the infestation of an endemic pathogen acting at the landscape, community, and individual scales.
Methods

We measured pathogen load, disease prevalence, and disease severity of Marssonina leaf spot in poplars in riparian forests. We explored the direct and indirect effects of multiple ecological factors on pathogen infestation using a path analysis. Specifically, we first assessed the effects of landscape and community factors on leaf traits including leaf area, specific leaf area (SLA) and leaf dry matter content (LDMC), and then examined the role of these factors in shaping disease dynamics.
Results

Path analysis showed that landscape features had no direct impact on leaf traits and pathogen infestation, but directly affected tree community composition. Landscapes with higher forest cover resulted in higher host density and tree diversity. Host density was the most important factor of pathogen load, with higher host density resulting in more symptomatic leaves. Tree diversity had direct effects on disease prevalence, with poplars growing in mixed forest stands far less affected by pathogens than in pure stands. Moreover, disease prevalence was positively related to pathogen load. Tree diversity strongly reduced SLA, but increased LDMC. Higher SLA was found to increase pathogen load and disease severity, but higher LDMC was found to reduce both of them.
Conclusions

Our results show that the effects of landscape and tree community on Marssonina leaf spot disease are mediated by leaf traits. Disentangling the effects of biotic and abiotic factors affecting pathogen infestation contributes to reduce the overall impact of this disease, which can provide policy makers with sustainable management of endemic plant diseases in natural forests.
Probability of Transition of Normal Esophageal Mucosa and Precancerous Lesion to the Esophageal Cancer
Authors: Chen Zhiyu , YU Yong , YANG Xue , WANG Jing-Xuan , Wei Wen-Qiang , Qiao You-Lin , YANG Chun-Xia , DAI Li 
Published: September 2021

Abstract
Background: To estimate the transition probabilities of esophageal cancer（EC） and its precancerous lesions by Markov model, which could provide important information for EC screening about choosing reasonable screening and follow-up intervals.Methods: The transition probabilities among pathological stages were estimated by establishing Markov models for the natural history of EC and repeatedly adjusting and calibrating Markov models by comparing the modeled incidence and distributions of pathological stages (alone or combined) with observed data in real-world condition. Results: In one year, the probabilities were 0.024, 0.05, 0.12 for people from health state progressing to mild dysplasia (mD), mild dysplasia (mD) to moderate dysplasia (MD), and moderate dysplasia (MD) to severe dysplasia/carcinoma in situ (SD/CIS), respectively. The age-specific transition probabilities were 0.08~0.18 for severe dysplasia/carcinoma in situ (SD/CIS) progressing to intramucosal carcinoma(IC), 0.4~0.87 for intramucosal carcinoma (IC) to submucosal carcinoma (T1N0M0) (SC), and 0.2~0.85 for submucosal carcinoma (T1N0M0) (SC) to invasive carcinoma (INC). The progression probabilities increased with age and the severity of the disease. Based on the estimated transition probabilities, we predicted the incidence of EC and distributions of its pathological stages. Comparisons between modeled results with observed data confirmed the validation of our transition probabilities.Conclusions: An esophageal cancer transition model in high-risk areas of China has been established with validity. It could be a point of reference for further economic evaluation and policy formulation of esophageal cancer screening.
Characterization of Scotopic and Mesopic Rod Signaling Pathways in Dogs Using the On-Off Electroretinogram
Authors: Pasmanter Nate , Petersen-Jones Simon M 
Published: September 2021

Abstract
Background: The On-Off, or long flash, full field electroretinogram (ERG) separates retinal responses to flash onset and offset. Depending on degree of dark-adaptation and stimulus strength the On and Off ERG can be shaped by rod and cone photoreceptors and postreceptoral cells, including ON and OFF bipolar cells. Interspecies differences have been shown, with predominantly positive Off-response in humans and other primates and a negative Off-response in rodents and dogs. However, the rod signaling pathways that contribute to these differential responses have not been characterized. In this study, we designed a long flash protocol in the dog that varied in background luminance and stimulus strength allowing for some rod components to be present to better characterize how rod pathways vary from scotopic to mesopic conditions.Results: With low background light the rod a-wave remains while the b-wave is significantly reduced resulting in a predominantly negative waveform in mesopic conditions. Through modeling and subtraction of the rod-driven response, we show that rod bipolar cells saturate with dimmer backgrounds than rod photoreceptors, resulting in rod hyperpolarization contributing to a large underlying negativity with mesopic backgrounds. Conclusions: Reduction in rod bipolar cell responses in mesopic conditions prior to suppression of rod photoreceptor responses may reflect the changes in signaling pathway of rod-driven responses needed to extend the range of lighting conditions over which the retina functions.
Analysis of Free Vibration of Hydraulic Opposing Cylinder Controlled by Servo Valve
Authors: Yuan Xiaoming , Wang Weiqi , Zhu Xuan , Du Bing , Zhang Lijie 
Published: September 2021

Abstract
The fluid transmission medium has large compressibility and low rigidity, and its physical properties are extremely sensitive to state parameters such as flow, pressure and temperature. Therefore, compared with the mechanical transmission system, the natural frequency of the fluid transmission system is relatively low and has time-varying characteristics. After a wide frequency range changing of the load frequency and long-term operation, the excitation frequency of the fluid transmission system is more likely to approach its natural frequency and causes resonance, which seriously affects the normal operation of the system. Therefore, taking the hydraulic opposing cylinder controlled by servo valve as the research object, based on the analytical relationship between the dynamic bulk modulus and the equivalent stiffness of oil, the vibration dynamics models and equations of the system is established by using the lumped parameter method. Through the free vibration analysis, the natural frequencies and main vibration modes of the system are determined and the sensitivity changes of the natural frequencies to the design parameters are revealed. The maximum error between the theoretical modal frequency and the experimental one is 3.77%, which verifies the correctness of the dynamic model of the system. This research can provide a theoretical reference for the optimization of the dynamic performance of the hydraulic transmission system.
The Role of TM6SF2 in Non-Alcoholic Fatty Liver Disease: From Mechanisms To Therapeutic Strategy
Authors: Li Zuyin , Wu Gang , Qiu Chen , Zhou Zhijie , Wang Yupeng , Song Guohe , Xiao Chao , Zhang Xin , Deng Guilong , Wang Ruitao , Yang Yulong , Wang Xiaoliang 
Published: September 2021

Abstract
Background and aims

: Lack of effective pharmacotherapies for nonalcoholic fatty liver disease (NAFLD) is mainly attributed to an insufficient research on its pathogenesis. In this paper, we investigated the role of TM6SF2 on fatty acid metabolism in the background of fatty liver, and proposed the possible therapeutic strategies of NAFLD caused by TM6SF2 deficiency.
Methods

Liver samples collected from both NAFLD mouse models and human subjects, and RNA-seq data retrieved from GEO database were used to evaluate the expression of TM6SF2 in NAFLD. Knockdown of TM6SF2 was performed for clarifying the mechanistic basis of hepatic lipid accumulation in NAFLD. After confirming that TM6SF2 deficiency would cause an abnormality in fatty acid metabolism, MK-4074 administration served as the therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency.
Results

Hepatic TM6SF2 levels are elevated in both NAFLD patients and mouse NAFLD models. In vivo and in vitro experiments confirmed that TM6SF2 knockdown increases intracellular lipid deposition due to dysregulated fatty acid metabolism in the context of TM6SF2 deficiency, being characterized by enhanced fatty acid uptake and synthesis, accompanied by impaired fatty acid oxidation. Moreover, MK-4074 treatment could reverse the NAFLD phenotypes caused by TM6SF2 deficiency.
Conclusions

TM6SF2 deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.
Dickkopf-1 is a Prognostic Biomarker and Correlated With Immune Infiltrates in Head and Neck Squamous Cell Carcinoma
Authors: Zhao Chaofen , Liu Lina , He Qianyong , Li Yuanyuan , Jiang Jieqing , Chen Yue , Li Xiaomei , Tang Yaxue , Li Yuxin , Zhou Dingan , Jin Feng 
Published: September 2021

Abstract
Background: Head and neck squamous cell carcinoma(HNSCC) has a high level of immune infiltration, and immunotherapy generates new hope to patients with head and neck tumors. It is currently one of the most promising treatments for HNSCC. Previous studies have shown that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, is related to the prognosis of a variety of tumors. DKK1 is a key mediator of immune activation and is highly associated with tumor progress and tumor microenvironment. However, the association between DKK1 expression and the prognosis of HNSCC and tumor infiltrating lymphocytes is still unknown.Objective: We aim to test the relationship between DKK1 and HNSCC prognosis and tumor infiltrating lymphocytes.Methods:We explored the DKK1 expression differences in multiple tumor tissues and normal tissues via examing TIMER, Oncomine, and UALCAN databases. Then, we searched the Kaplan-Meier database to assess the correlation between DKK1 mRNA levels and clinical outcomes. Subsequently, the TIMER platform and TISIDB website were selected to evaluate the correlation between DKK1 and the level of tumor immune cell infiltration. We used cBioPortal and UCSC Xena database to further explore the reasons for the aberrant expression of DKK1 in tumorigenesis.Results: We found that DKK1 level was significantly elevated in HNSCC tissues compared with normal tissues. The expression of DKK1 is related to the tumor stage, tumor grade, histology, lymph node metastasis and worse clinical prognosis of HNSCC. In addition, DKK1 is negatively correlated with different tumor-infiltrating immune cells in HNSCC. Moreover, DKK1 is closely related to the genetic markers of a variety of immune cells. Also, the prognosis of HNSCC is worse based on the high DKK1 expression of immune cells. Copy number variation (CNV) and DNA methylation may be the cause of abnormal up-regulation of DKK1 in HNSCC.Conclusion: DKK1 can be used as a biomarker for predicting the prognosis and immune infiltration of HNSCC. These results provide us with important clues to better understand the role of DKK1 in the immunotherapy of head and neck tumors from the perspective of bioinformatics.This study provides a theoretical basis for clinical research on the treatment of head and neck squamous cell carcinoma with the DKK1 gene as a target. It may play a major role in advancing the immunotherapy of head and neck squamous cell carcinoma and enhance the therapeutic effect.