bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Diagnostic Potential of SHOX2 and RASSF1A DNA Methylation in Early Lung Adenocarcinoma
Authors: Gao Hong , Yang Jun , He Lu , Wang Wei , Liu Yanhong , Hu Yue , Ge Meiling , Ding Jie , Ye Qing 
Published: June 2022

ObjectiveMethylation of the promoters of SHOX2 and RASSF1A are potentially informative biomarkers for the diagnosis of early lung adenocarcinoma (LUAD). Abnormal methylation of SHOX2 and RASSF1A promoters may promote the occurrence and facilitate the progression of LUAD.Materials and MethodsWe selected 54 patients with early LUAD and 31 patients with benign lung nodules as a NJDT cohort and evaluated their DNA methylation and mRNA sequencing levels. The DNA methylation sequencing, mRNA sequencing, and clinical data for patients with LUAD were obtained from The Cancer Genome Atlas, and served as a TCGA cohort. We evaluated the diagnostic potential of a SHOX2 and RASSF1A combined promoter methylation assay for detection of early LUAD in the NJDT cohort. Then we explored the promoter methylation levels of SHOX2 and RASSF1A and their gene expression between normal and tumor samples at different stages in both cohorts. Pathways enriched between tumor and normal samples of methylation-positive patients in the NJDT cohort were analyzed.ResultsIn the NJDT cohort, the sensitivity of the combined promoter methylation assay on tumor samples was 74.07%, the sensitivity on paired tumor and paracancerous samples was 77.78%, and the specificities in both contexts were 100%. The combined promoter methylation-positive patients had clinicopathologic features including older age, larger tumors, deeper invasion, and higher Ki-67 expression. In both cohorts, SHOX2 expression increased and RASSF1A expression decreased in tumor samples. The promoter methylation level of SHOX2 and RASSF1A was significantly higher in tumor samples at stage I-II than that in normal samples. The promoter methylation levels of these two genes were both negative associated with their expression in early tumor samples. In the NJDT cohort, methylation-positive patients of both individual SHOX2 and RASSF1A assays exhibited upregulation of folate acid metabolism and nucleotide metabolism in tumor samples. The SHOX2 methylation-positive and RASSF1A methylation-positive patients showed the downregulation of pathways related to cell proliferation and apoptosis and pathways involved in DNA repair, cell growth and cell adhesion, respectively.ConclusionThe combined promoter methylation assay for SHOX2 and RASSF1A can be used for screening and diagnosis of early LUAD, with good sensitivity and specificity. The promoter methylation levels of SHOX2 and RASSF1A were associated with their abnormal mRNA expression, and affected DNA instability, cell proliferation, apoptosis and tumor microenvironment in patients with LUAD.
Analysis of KRAS, NRAS, and BRAF Mutations, Microsatellite Instability, and Relevant Prognosis Effects in Patients With Early Colorectal Cancer: A Cohort Study in East Asia
Authors: Li Yang , Xiao Jun , Zhang Tiancheng , Zheng Yanying , Jin Hailin 
Published: June 2022

BackgroundEarly colorectal cancer (ECRC) refers to any size of colorectal cancer (CRC) whose depth of invasion is limited to the mucosa and submucosa. About 10% of patients with ECRC die from cancer after surgery. KRAS, NRAS, and BRAF mutations and microsatellite instability (MSI) are considered diagnostic and prognostic markers in CRC. However, their characteristics in ECRC and whether postoperative chemotherapy based on them will benefit ECRC patients or not remain unknown.Patients and MethodsPatients with ECRC and 298 patients with advanced colorectal cancer (ACRC) were collected in our hospital from January 2013 to December 2015. The Amplification Refractory Mutation System (ARMS)-PCR was used to perform the KRAS, NRAS, and BRAF mutant tests.ResultsIn ECRC patients, 43 cases of KRAS mutation were found, accounting for 69.35%. Interestingly, among KRAS mutations, there were 10 KRAS multi-site mutation patients (16.13% in 62 ECRC patients). Moreover, the NRAS mutation rate was 3.23% but no BRAF mutation was found and only 1 case of MSI-High was detected. KRAS mutation was only related to the depth of tumor invasion whereas KRAS multi-site mutations were related to mucus components and tumor size. As far as NRAS is concerned, mutations were associated with elevated CEA, mucus components, and the depth of tumor invasion. Notably, compared with 2.35% KRAS multi-site mutation in ACRC, the rate of KRAS multi-site mutation in ECRC was much higher. Furthermore, Cox regression analysis revealed that KRAS mutation could be an independent prognostic factor of ECRC in patients who have undergone endoscopic resection or surgery.ConclusionPatients with ECRC might benefit from KRAS mutation testing but not from postoperative chemotherapy.
Towards an Improved Pathological Node Classification for Prognostic Stratification of Patients With Oral Cavity Squamous Cell Carcinoma: Results From a Nationwide Registry Study
Authors: Kang Chung-Jan , Wen Yu-Wen , Lee Shu-Ru , Ng Shu-Hang , Tsai Chi-Ying , Lee Li-Yu , Chu Ying-Hsia , Lin Chien-Yu , Fan Kang-Hsing , Wang Hung-Ming , Hsieh Chia-Hsun , Yeh Chih-Hua , Lin Chih-Hung , Tsao Chung-Kan , Fang Tuan-Jen , Huang Shiang-Fu , Lee Li-Ang , Fang Ku-Hao , Wang Yu-Chien , Lin Wan-Ni , Hsin Li-Jen , Yen Tzu-Chen , Cheng Nai-Ming , Liao Chun-Ta 
Published: June 2022

BackgroundTo assess the prognostic significance of different nodal parameters [i.e., number of pathologically positive nodes, log odds of positive lymph nodes, lymph node ratio (LNR), and extra-nodal extension (ENE)] in Taiwanese patients with oral cavity squamous cell carcinoma (OCSCC), and to devise an optimized pN classification system for predicting survival in OCSCC.MethodsA total of 4287 Taiwanese patients with first primary OCSCC and nodal metastases were enrolled. Cox proportional hazards regression analysis with the spline method was applied to identify the optimal cut-off values for LNR, log odds of positive lymph nodes, and number of pathologically positive nodes.ResultsOn multivariable analysis, we identified a LNR ≥0.078/0.079, the presence of at least three pathologically positive nodes, and ENE as independent prognosticators for 5-year disease-specific survival (DSS) and overall survival (OS) rates. We therefore devised a four-point prognostic scoring system according to the presence or absence of each variable. The 5-year DSS and OS rates of patients with scores of 0−3 were 70%/62%/50%/36% (p &lt;0.0001) and 61%/52%/40%25%, respectively (p &lt;0.0001). On analyzing the AJCC 2017 pN classification, patients with pN3a displayed better survival rates than those with pN2 disease. The 5-year DSS and OS rates of patients with pN1/pN2/pN3a/pN3b disease were 72%/60%/67%/43% (p &lt;0.0001) and 63%/51%/67%/33%, respectively (p &lt;0.0001).ConclusionsThree nodal parameters (i.e., a LNR ≥0.078/0.079, the presence of at least three pathologically positive nodes, and ENE) assessed in combination provided a better prognostic stratification than the traditional AJCC pN classification.
Ginkgolide B Protects Against Ischemic Stroke via Targeting AMPK/PINK1
Authors: Cao Yile , Yang Lei , Cheng Hong 
Published: June 2022

Introduction: Ginkgolide B (GB), which is an active constituent derived from Ginkgo biloba leaves, has been reported to ameliorate Alzheimer’s disease (AD), ischemic stroke, as well as other neurodegenerative diseases due to its viable immunosuppressive and anti-inflammatory functions. However, it has yet to be proven whether GB inhibits neuronal apoptosis in ischemic stroke.Methods: In the present research, the inhibition function of GB on neuronal apoptosis and its underpinning process(s) after cerebral ischemia were studied through transient middle cerebral artery occlusion (t-MCAO) in an in vivo rat model as well as in cultured SH-SY5Y cells subjected to oxygen and glucose deprivation (OGD)/reoxygenation in vitro. The neurological score was calculated and Nissl and TUNEL staining were performed to evaluate the stroke outcome, neuronal loss, and neuronal apoptosis. Subsequently, the western blot was utilized to detect Bcl2 and p-AMPK/AMPK expression.Results: Compared to t-MCAO rats, rats receiving GB treatment showed a significant reduction of neuronal loss and apoptosis and improved neurological behavior at 72 h after MCAO. GB treatment also upregulated the expression of Bcl2 and p-AMPK. In vitro, GB suppressed the apoptosis in OGD/reoxygenation-challenged neuronal SH-SY5Y cells through AMPK activation.Conclusions: Our observations suggest that GB enhanced AMPK activation in neural cells, reducing neuronal apoptosis, thus eventually preventing ischemic stroke.
Comparisons of High Intensity Interval Training and Continuous Training on Metabolomic Alteration and Cardiac Function in Male Adolescent Rats
Authors: Zheng Molin , Liu Chuanan , Lv Yuanyuan , Mi Jing , Qiu Dan , He Lingxiao , Zhao Li 
Published: June 2022

Background: Comparisons between high intensity interval training (HIIT) and continuous training (CT) regarding improvements of adolescents’ cardiac function are scarce and the preferred intensity for cardiac improvement with restricted myocardial damage remains unknown. This study conducted a 4-weeks training in male adolescent rats under moderate (MI) or high intensity (HI) HIIT and CT programs, aiming to discover and compare exercise-induced myocardial adaptations towards these two training methods.Methods: 39 male adolescent Sprague-Dawley rats (aged 4 weeks) were randomly assigned to high intensity HIIT (HI-HIIT, n = 8), moderate intensity HIIT (MI-HIIT, n = 8), high intensity CT (HI-CT, n = 8), moderate intensity CT (MI-CT, n = 8) and sedentary control (SC, n = 7) groups. Rats in training groups were trained for 4 weeks and echocardiography was performed at baseline and after the final training. Serum creatine kinase myocardial band (CK-MB), cardiac troponin T (cTn-T) and untargeted metabolomics analysis were measured from blood samples collected 24 h after the final training.Results: HIIT groups had greater cardiac output improvement than CT groups while no significant difference was found between the HI-HIIT and the MI-HIIT groups. HI-CT group showed higher serum CK-MB and cTn-T levels compared to MI-HIIT, MI-CT and control groups. Untargeted metabolomics analysis identified eleven HI-HIIT-related metabolites, five MI-HIIT-related metabolites and two HICT-related metabolites. The majority of the identified metabolites were phospholipid-related. Phosphatidylglyceride 18 level was significantly different between the HI-CT and MI-CT groups, and was negatively associated with cTn-T in CT groups.Conclusion: HIIT and CT improve cardiac function of adolescent rats while the HIIT demonstrates better improvement and less myocardial damage. High and moderate training intensities in HIIT exert similar cardiac benefits. HI-CT induced myocardial damage might be associated with serum phospholipids.
Modulation of Gap Junction Coupling Within the Islet of Langerhans During the Development of Type 1 Diabetes
Authors: Farnsworth Nikki L. , Piscopio Robert A. , Schleicher Wolfgang E. , Ramirez David G. , Miranda Jose G. , Benninger Richard K. P. 
Published: June 2022

In type 1 diabetes (T1D), islet dysfunction occurs prior to diabetes onset. Pro-inflammatory cytokines can disrupt insulin secretion and Ca2+ homeostasis. Connexin36 (Cx36) gap junctions electrically couple β-cells to coordinate glucose-stimulated Ca2+ and insulin secretion. Cx36 gap junction coupling can also protect against cytokine-induced apoptosis. Our goal was to determine how islet gap junction coupling and Ca2+ dynamics are altered in mouse models of T1D prior to diabetes. Glucose tolerance was assessed in NOD and immunodeficient NOD-RAG1KO mice at 6–12 weeks age. Glucose-stimulated insulin secretion, Ca2+ dynamics, and gap junction coupling were measured in islets isolated at each age. Gap junction coupling was also measured in islets from mice that underwent transfer of diabetogenic splenocytes and from chromograninA knockout NOD mice. Cell death was measured in islets isolated from wild-type, Cx36 knockout or Cx36 over-expression mice, each treated with a cocktail of pro-inflammatory cytokines and KATP or SERCA activators/inhibitors. NOD mice over-expressing Cx36 were also monitored for diabetes development, and islets assessed for insulitis and apoptosis. NOD and NOD-RAG1KO controls showed similar glucose tolerance at all ages. Ca2+ dynamics and gap junction coupling were disrupted in islets of NOD mice at 9 weeks, compared to controls. Transfer of diabetogenic splenocytes also decreased gap junction coupling. Islets from chromograninA knockout mice displayed normal coupling. Overexpression of Cx36 protected islets from cytokine-induced apoptosis. A knockout of Cx36 amplified cytokine-induced apoptosis, which was reversed by KATP activation or SERCA activation. Cx36 overexpression in NOD mice delayed diabetes development compared to NOD controls. However, apoptosis and insulitis were not improved. Decreases in islet gap junction coupling occur prior to T1D onset. Such decreases alter islet susceptibility to apoptosis due to altered Ca2+. Future studies will determine if increasing Cx36 gap junction coupling in combination with restoring Ca2+ homeostasis protects against islet decline in T1D.
The Healthy Body Image Intervention and Reduction in Eating Disorder Symptomatology and Muscle Building Supplement Use in High School Students: A Study of Mediating Factors
Authors: Svantorp-Tveiten Kethe Marie Engen , Ivarsson Andreas , Torstveit Monica Klungland , Sundgot-Borgen Christine , Mathisen Therese Fostervold , Bratland-Sanda Solfrid , Rosenvinge Jan Harald , Friborg Oddgeir , Pettersen Gunn , Sundgot-Borgen Jorunn 
Published: June 2022

BackgroundMediation analysis is important to test the theoretical framework underpinning an intervention. We therefore aimed to investigate if the healthy body image (HBI) intervention’s effect on eating disorder (ED) symptomatology and use of muscle building supplements was mediated by the change in risk and protective factors for ED development and muscle building supplement use.MethodsThis study used data from the HBI intervention: a cluster randomized controlled universal intervention aiming to promote positive body image and embodiment and reduce the risk for ED development including 30 schools in Norway. A total of 1,713 (37% boys) participants were included in the analyses. Conditional latent growth curve analyses were performed to test for indirect effects on ED symptomatology and weekly frequency of protein and creatine supplement use measured at the 12-month follow-up via change in the proposed mediators.ResultsIn girls, the reduction in ED symptomatology was mediated by positive changes in protective factors (self-esteem and body image flexibility) and reductions in risk factor scores (perceived media pressure and thin appearance internalization). Comparable changes in protective and risk factors among boys played no mediating role.ConclusionInterventions aiming to reduce the risk of ED development in girls may benefit from aiming to enhance self-esteem and body image flexibility and reduce perceived media pressure and thin appearance internalization. Future studies should investigate the casual relationship between muscle building supplement use and risk and protective factors for ED development in both girls and boys.
Specific and Non-specific Factors of Animal-Assisted Interventions Considered in Research: A Systematic Review
Authors: Wagner Cora , Grob Carmina , Hediger Karin 
Published: June 2022

Research on animal-assisted interventions (AAIs) has increased massively in the last few years. But it is still not clear how AAIs work and how important the animal is in such interventions. The aim of this systematic review was to compile the existing state of knowledge about the working mechanisms of AAIs. We searched 12 major electronic databases for previous AAI studies with active control groups. Of 2001 records identified, we included 172 studies in the systematic review. We extracted previously published hypotheses about working mechanisms and factors that have been implicitly considered specific or non-specific in AAI research by categorizing control conditions using content analysis. We analyzed the categories using descriptive statistics. We found that 84% of the included studies mentioned a hypothesis of working mechanisms, but 16% did not define specific hypotheses. By analyzing their control conditions, we found that in most controlled studies, the animal or the interaction with the animal was implicitly considered as a specific factor for the effects of the AAI. Non-specific factors such as therapeutic aspects, social interactions, or novelty have also been controlled for. We conclude that AAI research still cannot answer the question of how and why AAIs work. To address this important research gap, we suggest using component studies with innovative control conditions and results from placebo research to address both the specific and non-specific, contextual factors of AAIs to disentangle its mechanisms.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=158103, identifier: CRD42020158103.
Job Crafting and Nurses' Presenteeism: The Effects of Job Embeddedness and Job Irreplaceability
Authors: Liu Taotao , Wang Wei , Shan Geyan , Zhang Yijie , Liu Jie , Li Yongxin 
Published: June 2022

BackgroundPresenteeism is defined as the behavior of people who insist on attending work despite complaints of ill health that should prompt rest and absence from work. Due to the heavy workloads and irreplaceable duties of the nursing service, nurses are a typical representative group suffering from presenteeism. Although more scholars have recently begun focusing on presenteeism, an abundant number of studies have tended to focus on presenteeism's external objective factors. There is, thus, a lack of studies based on variables related to the intra-individual initiative. This study aimed to address this gap by exploring the relationship between job crafting and nurses' presenteeism from the perspective of the individual internal initiative. Furthermore, this study also aimed to examine job embeddedness' mediating effect and job irreplaceability's moderating effect on presenteeism.MethodsA total of 900 nurses from a 3A-graded hospital in Henan Province were invited to participate in the online study in October, November, and December 2021, respectively. Participants were asked to complete Self-report scales on job crafting, job embeddedness, job irreplaceability, and presenteeism at three time points above. Job crafting was measured at Time 1, job embeddedness and job irreplaceability were measured at Time 2, and presenteeism was measured at Time 3.ResultsPresenteeism was significantly associated with differences in participants' age and tenure. Job crafting was significantly positively associated with job embeddedness, and job embeddedness was significantly negatively correlated with presenteeism. Job embeddedness mediated the relationship between job crafting and presenteeism. Job irreplaceability moderated the relationship between job embeddedness and presenteeism.ConclusionsThis study explored job crafting's influence mechanism on nurses' presenteeism, which is beneficial to providing effective suggestions for managing and preventing the incidence of nurses' presenteeism. Future research should consider expanding the sampling area and enriching the occupational fields of included participants to conduct a more in-depth discussion on the relationship between job crafting and nurses' presenteeism.
The Value of Negative-Pressure Wound Therapy and Flap Surgery in Hidradenitis Suppurativa – A Single Center Analysis of Different Treatment Options
Authors: Stumpfe M. C. , Horch R. E. , Arkudas A. , Cai A. , Müller-Seubert W. , Hauck T. , Ludolph I. 
Published: June 2022

BackgroundHidradenitis suppurativa is manifested by painful abscesses and scarring of sweat glands. Axillary, inguinal and genital regions are mostly affected. Multiple options exist in the treatment of hidradenitis suppurativa. The aim of this retrospective, mono-center cohort study was to analyze the outcome of different treatment methods after radical excision of hidradenitis suppurativa.MethodsWe retrospectively evaluated the treatment strategy and recurrence rate of hidradenitis suppurativa. We included all eligible patients of legal age between February 2003 and October 2021, with the diagnosis of Hidradenitis suppurativa and the necessity for surgical treatment. All patients with surgical treatment and direct wound closure by suture were excluded. Bacterial load and flora were analyzed for primary and secondary reconstruction in combination with negative-pressure wound therapy. Patient data were analyzed for recurrence rate and remission time according to different reconstructive techniques.ResultsIn 44 affected anatomical sites (n = 23 patients) we treated 15 patients with negative-pressure wound therapy. Bacterial load and flora were lower in the last wound swab of patients with multi-surgical procedures (22 localizations) compared to the first wound swab independent of the use of negative-pressure wound therapy.Wound closure, independent of a direct and multi-stage procedure was achieved by local fasciocutaneous flaps (n = 12), secondary intention healing (n = 7), secondary intention healing with buried chip skin grafts (n = 10), or split-thickness skin grafts (n = 15). Radical excision combined with split-thickness skin grafts showed the lowest recurrence rate in the follow-up (16%; n = 4).ConclusionRadical excision of hidradenitis suppurativa as gold standard for surgical treatment combined with negative-pressure wound therapy as multi-stage procedures ultimately reduced bacterial load and flora in our study. The use of split-thickness skin grafts showed the lowest recurrence rate.
The Role of Magnetic Resonance Imaging in the Planning of Surgical Treatment of Deep Pelvic Endometriosis
Authors: Manti Francesco , Battaglia Caterina , Bruno Iennarella , Ammendola Michele , Navarra Giuseppe , Currò Giuseppe , Laganà Domenico 
Published: June 2022

BackgroundTo prospectively evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) for the planning of surgical treatment of deep pelvic endometriosis.Materials and MethodsFrom January 2020 to December 2021, we evaluated 72 patients with symptoms characteristic of endometriosis to plan appropriate surgical treatment. Sensitivity (Se), specificity (Sp), positive and negative predictive values (VPP/VPN), and the accuracy of MRI for the detection of deep pelvic endometriosis were calculated.ResultsSeventy-two patients (mean age, 35.5 years; range, 20–46 years) suspected of having pelvic endometriosis were recruited. Pelvic endometriosis was confirmed at pathologic examination in 56 (77.7%) of 72 patients. A total of 22 (39.3%) of 56 patients were subjected to video laparoscopy (VLS), and 16 (72.2%) of 22 were treated by surgery. Se, Sp, VPP, and VPN in intestinal endometriosis diagnosis were, respectively, 100%, 93.3%, 100%, and 87.5%, and diagnostic accuracy was 95.4%. MRI Se in ureteral endometriosis diagnosis was 50%, Sp 100%, VPP 100%, VPN 78%, and diagnostic accuracy 82%. MRI Se in endometrioma diagnosis was 92.3%, Sp 100%, VPP 100%, VPN 90%, and diagnostic accuracy 95.4%. MRI Se in rectum-vaginal septum (SRV) endometriosis diagnosis was 80%, Sp 100%, VPP 100% VPN 85.7%, and diagnostic accuracy 91%. The MRI Se in the diagnosis of endometriosis involving ULS was 100%, Sp 92.8%, VPP 89%, VPN 100%, and diagnostic accuracy 95.4%. Complete concordance results in a 100% accuracy for all calculated values in diagnosing bladder endometriosis localizations.ConclusionMR imaging demonstrates high accuracy in detecting deep pelvic endometriosis in specific locations. It allows the localization of deep pelvic lesions with highly fibrotic components that are hardly recognizable with other imaging methods and not visible with VLS.