bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of acute and long-term exercise on leptin levels in depressed outpatients
Authors: Heinen Darlene , Heissel Andreas , Heinzel Stephan , Fydrich Thomas , Ströhle Andreas , Rapp Michael , Vogel Heike 
Published: February 2023

Abstract
Background: Depression is a leading cause of disability worldwide and a significant contributor to the global burden of disease. Altered leptin levels are known to be associated with depressive symptoms, however discrepancies in the results of increased or decreased levels exist. Due to various limitations associated with commonly used antidepressant drugs, alternatives such as exercise therapy are gaining more importance. Therefore, the current study investigates whether depressed patients have higher leptin levels compared to healthy controls and if exercise is efficient to reduce these levels.
Methods: Leptin levels of 105 participants with major depressive disorder (MDD; 45.7% female, age mean ± SEM: 39.1 ± 1.0) and 34 healthy controls (HC; 61.8% female, age mean ± SEM: 36.0 ± 2.0) were measured before and after a bicycle ergometer test. Additionally, the MDD group was separated into three groups: two endurance exercise intervention groups (EX) differing in their intensities, and a waiting list control group (WL). Leptin levels were measured pre and post a 12-week exercise intervention or the waiting period.
Results: Baseline data showed no significant differences in leptin levels between the MDD and HC groups. As expected, correlation analyses displayed significant relations between leptin levels and body weight (HC: r = 0.474, p = 0.005; MDD: r = 0.198, p = 0.043) and even more with body fat content (HC: r = 0.755, p < 0.001; MDD: r = 0.675, p < 0.001). The acute effect of the bicycle ergometer test and the 12-week training intervention showed no significant changes in circulating leptin levels.
Conclusion: Leptin levels were not altered in patients with major depression compared to healthy controls and exercise, both the acute response and after 12 weeks of endurance training, had no effect on the change in leptin levels.
Crosstalk between KDEL receptor and EGF receptor mediates cell proliferation and migration via STAT3 signaling
Authors: Jia Jie , Yue Xihua , Jing Shuaiyang , Zhu Lianhui , Tan Chuanting , Du Yulei , Gao Jingkai , Tang Shuocheng , Lee Intaek , Qian Yi 
Published: February 2023

Abstract
Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that hosts complex signaling events and plays diverse roles in a variety of cellular processes. Secreted ER chaperones are capable of activating EGFR and its downstream transcription factor, STAT3. However, the molecular mechanism of these ER proteins triggering EGFR signaling is largely unknown. In this study, we identify KDEL receptor (KDELR) as a cell surface receptor for secreted ER chaperones and a co-receptor for EGFR. Prior to ligand addition, KDELR spontaneously oligomerizes and constantly undergoes recycling near the plasma membrane. Upon ligand binding, the interactions of KDELR with itself and with EGFR increase rapidly, leading to augmented internalization of KDELR and tyrosine phosphorylation in the C-terminus of EGFR. STAT3, which binds the phosphorylated tyrosine motif on EGFR, is subsequently activated by EGFR and induces transcription of genes relevant to cell proliferation and migration. Taken together, our results suggest that secreted ER chaperones bind surface-expressed KDELR and transactivates EGFR-STAT3 signaling pathway.
Prevalence and Determinants of Cognitive Dysfunction among Patients with Diabetes in Eastern Saudi Arabia
Authors: Lone Ayoob , Pathath Abdul Wahab 
Published: February 2023

Abstract
Background: Cognitive dysfunction is recognized as a major diabetes comorbidity and complication that affects an individual's well-being. Recent studies demonstrated that diabetic patients have a higher incidence of cognitive dysfunction. As a result, new diabetes management guidelines recommend screening for cognitive impairments in older diabetics.
Objectives: This study aims to explore the prevalence and potential risk of cognitive dysfunction in diabetic patients.
Method: This cross-sectional study was conducted from June to November, 2022 where 257 patients with diabetes were selected byconvenient sample technique. Cognitive dysfunction was measured by using Mini-mental state examination (MMSE). Sociodemographic, diabetes related and clinical factors were analyzed as cofactors of cognitive dysfunction.
Result: The findings of the study revealed that 38.9% of participants had cognitive dysfunction while 12.1% had severe cognitive dysfunction. The domain of delayed recall was the most affected, while language/praxis was least affected domain of MMSE. Duration of diabetes was inversely associated with cognitive dysfunction. Results of logistic regression analysis revealed low level of education (OR = 4.95; p =.043) and more duration of diabetes (OR = 6.08; p =.010) were independently associated with severe cognitive impairment.
Conclusion: Diabetes patients in their middle and advanced years are particularly vulnerable to cognitive decline. Therefore, healthcare professionals and family physicians should focus more on detecting cognitive decline in the early stages of diabetes mellitus.
STE20-Type Kinases MST3 and MST4 Act Non-Redundantly to Promote the Progression of Hepatocellular Carcinoma
Authors: Caputo Mara , Xia Ying , Anand Sumit Kumar , Cansby Emmelie , Andersson Emma , Marschall Hanns-Ulrich , Königsrainer Alfred , Peter Andreas , Mahlapuu Margit 
Published: February 2023

Abstract
Aims
Hepatocellular carcinoma (HCC) is one of the most fatal and fastest-growing malignancies. Recently, non-alcoholic steatohepatitis (NASH), characterized by liver steatosis, inflammation, cell injury (hepatocyte ballooning), and different stages of fibrosis, has emerged as a major catalyst for HCC. Because the STE20-type kinases MST3 and MST4 have been described as critical molecular regulators of NASH pathophysiology, we here focused on determining the relevance of these proteins in human HCC.
Methods
The clinical importance of MST3 and MST4 in HCC was assessed in publicly available datasets and by qRT-PCR analysis of a validation cohort recruited at the University Hospital of Tübingen (n = 48 for HCC patients and n = 214 for control subjects). The functional significance of MST3 and MST4 was examined in HepG2 and Hep3B cells transfected with MST3, MST4, or MST3/4 small interfering RNA. Potential downstream pathways were investigated by co-immunoprecipitation and Western blotting.
Results
By analyzing public datasets and in-house cohorts, we found that hepatic MST3 and MST4 expression was positively correlated with the incidence and severity of HCC. We also found that the silencing of both MST3 and MST4, but also either of them individually, markedly suppressed the tumorigenesis of human HCC cells including attenuated proliferation, migration, invasion, and epithelial-mesenchymal transition. Mechanistic investigations revealed lower activation of STAT3 signaling in MST3/MST4-deficient hepatocytes, and identified GOLGA2 and STRIPAK complex as the binding partners of both MST3 and MST4 in HCC cells.
Conclusions
These findings reveal that MST3 and MST4 play a critical role in promoting the progression of HCC and suggest that targeting these kinases may provide a novel strategy for the treatment of liver cancer.
Multiple epithelioid angiosarcoma of stomach and small intestine with multiple lymph node metastases: A case report
Authors: Yu Junhua , Cao Lulu , Qian Jun 
Published: February 2023

Abstract
Background
Angiosarcoma is a mesenchymal soft tissue sarcoma with a tendency for vascular endothelial differentiation. It is highly malignant with a poor prognosis but has a low incidence. Epithelioid angiosarcoma of the gastrointestinal tract is rare, and simultaneous multiple lesions of the stomach and small intestine are even rarer. It is easy to be misdiagnosed clinically. We report on a case of preoperative misdiagnosis of gastric cancer and postoperative diagnosis of epithelioid angiosarcoma with multiple lymph node metastases.
Case presentation
A 75-year-old patient who was admitted to the hospital because of fatigue, melena and dysuria for > 1 mo. Gastroscopy revealed gastric fundus ulcer and the biopsy revealed poorly differentiated adenocarcinoma of the fundus. We performed a radical gastrectomy for gastric cancer during which multiple ulcers were found in the jejunum and resected. Postoperative pathology showed multiple epithelioid angiosarcoma in the stomach and small intestine with lymph node metastases. The patient did not receive further treatment and died 2 mo after the surgery.
Conclusions
Gastrointestinal epithelioid angiosarcoma is one of the differential diagnoses of gastrointestinal adenocarcinoma and surgery is the main treatment. The lymph nodes are one of the main sites of metastasis.
Low protein expression of LZTR1 in hepatocellular carcinoma triggers tumorigenesis via activating the RAS/RAF/MEK/ERK signaling
Authors: Ye Ganghui , Xia Jingyi , Zhu Chenlu , Gu Chaoyu , Li Xinming , Ye Meng , Jin Xiaofeng 
Published: February 2023

Abstract

LZTR1 is a substrate specific adaptor for E3 ligase involved in ubiquitination and degradation of RAS GTPases, which inhibits the RAS/RAF/MEK/ERK signaling to suppress tumor progression. However, it’s still unknown whether LZTR1 destabilizes RAS GTPases to suppress HCC progression by inhibiting such signaling pathway. Lenvatinib is the first-line drug for the treatment of advanced HCC, which has faced serious problem of drug resistance. To explore the roles of LZTR1 in HCC progression and the potential mechanisms of lenvatinib resistance, techniques such as bioinformatics analysis, immunohistochemical staining, RT-qPCR, western blot, cell functional experiments, small interfering RNA transfection and cycloheximide chase assay were applied in our study. Among these, bioinformatics analysis and immunohistochemical staining results indicated that LZTR1 protein was aberrantly low expressed in HCC tissues and low protein expression of LZTR1 was associated with poor prognosis of HCC patients. In vitro experiments confirmed that LZTR1 knockdown promoted HCC cell proliferation and migration, and western blot and cycloheximide chase assay further demonstrated that LZTR1 induced KRAS ubiquitination and degradation, thereby inhibiting the RAS/RAF/MEK/ERK signaling. In lenvatinib resistance inducible experiment, upregulation of LZTR1 protein as well as downregulation of KRAS protein were detected in HCC cells exposed to gradient concentrations of lenvatinib for 48 h. Transwell assay found that both LZTR1 knockdown and KRAS knockdown can induce lenvatinib resistance in HCC cells. In conclusion, our study revealed that LZTR1 knockdown promoted HCC cell proliferation/migration and induced lenvatinib resistance via activating the RAS/RAF/MEK/ERK signaling, which may provide new ideas and hope for the precision therapy of HCC.
A preoperative prediction model for sentinel lymph node status using artificial intelligence on mammographic images and clinicopathological variables in patients with clinically node-negative breast cancer
Authors: Rejmer Cornelia , Dihge Looket , Bendahl Pär-Ola , Förnvik Daniel , Dustler Magnus , Rydén Lisa 
Published: February 2023

Abstract
Background:
Cancer detection systems using artificial intelligence (AI) are a rapidly growing research area, in breast cancer. Sentinel lymph node biopsy (SLNB) is the recommended surgical axillary staging method in patients with clinically node-negative breast cancer, although approximately 75–80% have a negative sentinel lymph node (N0) status in the final pathology report. Previous prediction models for N0 status included variables only available postoperatively, thus defeating their purpose. Therefore, we aimed to investigate whether two AI systems, Transpara (Screenpoint Medical) and Laboratory for Individualized Breast Radiodensity Assessment (LIBRA), on mammographic images can be used to improve a previous prediction model for N0 status using only preoperatively available variables. To our knowledge, this is the first preoperative prediction model for N0 status combining AI detection on mammographic images with clinicopathological variables.
Methods:
This retrospective cohort study included 755 women with primary breast cancer treated at Lund University Hospital between 2009 and 2012. Mammographic images were analyzed using Transpara and LIBRA. Preoperative clinicopathological and radiological variables were used in a multivariable logistic regression analysis to predict N0 status with multiple imputation. The area under the receiver operating curve (AUC) was used to assess model performance and a nomogram was developed. The agreement between preoperative radiological and postoperative pathological tumor size was assessed using correlation.
Results:
We proposed a preoperative prediction model for N0 status using AI detection on mammographic images and clinicopathological variables, with an AUC of 0.695 (confidence interval: 0.653–0.736). Applying the model, SLNB could be putatively omitted in 23.8% of patients if a false-negative rate of 10% was accepted. The mean difference between radiologic and pathologic tumor size was 0.4 mm and the corresponding Pearson correlation coefficient 0.62.
Conclusion:
To our knowledge, the prediction model proposed in this manuscript is the first preoperative prediction model for N0 status using AI on mammographic images and routine preoperative patients and tumor characteristics. The correlation between tumor size measurements suggests that radiologic tumor size can replace pathologic size as a predictor of N0 status. Applying this model may enable safe omission of SLNB in 23.8% of patients.
The burden of critical illness among adults in a Swedish region – a population-based point-prevalence study
Authors: Schell Carl Otto , Wellhagen Andreas , Lipcsey Miklós , Kurland Lisa , Bjurling-Sjöberg Petronella , Lundborg Cecilia Stålsby , Castegren Markus , Baker Tim 
Published: February 2023

Abstract
Background: Patients with critical illness have a high risk of mortality. Key decision-making in the health system affecting the outcomes of critically ill patients requires epidemiological evidence, but the burden of critical illness is largely unknown. This study aimed to estimate the prevalence of critical illness in a Swedish region. Secondary objectives were to estimate the proportion of hospital inpatients who are critically ill and to describe the in-hospital location of critically ill patients.
Methods: A prospective, multi-center, population-based, point-prevalence study on specific days in 2017-2018. All adult (>18 years) in-patients, regardless of admitting specially, in all acute hospitals in Sörmland, and the patients from Sörmland who had been referred to university hospitals, were included. Patients in the operating theatres, with a psychiatric cause of admission, women in active labor and moribund patients were excluded. All participants were examined by trained data collectors. Critical illness was defined as “a state of ill health with vital organ dysfunction, a high risk of imminent death if care is not provided and a potential for reversibility”. The presence of one or more severely deranged vital signs was used to classify critical illness. The prevalence of critical illness was calculated as the number of critically ill patients divided by the number of adults in the region.
Results: A total of 1269 patients were included in the study. Median age was 74 years and 50% of patients were female. Critical illness was present in 133 patients, resulting in an adult population prevalence of critical illness per 100,000 people of 19.4 (95% CI 16.4-23.0). The proportion of patients in hospital who were critically ill was 10.5% (95% CI 8.8%-12.3%). Among the critically ill, 125 (95% CI 94.0% (88.4%-97.0%)) were cared for in general wards.
Conclusions: The prevalence of critical illness was higher than previous, indirect estimates. One in ten hospitalized patients were critically ill, the large majority of which were cared for in general wards. This suggests a hidden burden of critical illness of potential public health, health system and hospital management significance.
Comprehensive Genome-Wide Identification and Transcript Profiling of GLK transcription factors in Castanea mollissima
Authors: Yang Yong , Wang Xuan , Liu Jing , Wang Meng , Li Jingshi , Wang Dongsheng , Zhang Jingzheng , Zhang Haie 
Published: February 2023

Abstract
Transcription factors Golden2-like (GLKs), belonging to GARP superfamily, are involved in chloroplast development in many plant species. However, it remains unclear whether GLKs contributes to chloroplast development in Chinese chestnut. In this study, 343 GLKs genes from other plant species were blasted in the Chinese chestnut genome, of which 37 genes were identified. An unrooted ML phylogenetic tree was constructed based on the CmGLKs amino acid sequences to evaluate the evolutional relationship of CmGLKs in the Chinese chestnut. The 37 CmGLKs were clustered into six clades and were widely distributed in 11 chromosomes of the Chinese chestnut genome. Three pairs of segmental duplications and one duplication occurred during the evolution of CmGLKs. CmGLK17 was involved in both tandem duplication and segmental duplication. Comparative syntenic analysis of the Chinese chestnut with Arabidopsis thaliana and maize indicated that GLKs share extensive sequence homology among the C3 plants but not between C3 and C4 plants. Motifs 1 and 2, encoding DNA-binding domain, are the most conserved domain in all the 37 CmGLKs. A total of 24 light-responsive elements were identified in CmGLKs, of which 53.85% were in CmGLK13. Box 4 was found in all CmGLKs. Results further showed that CmGLK33, CmGLK34, and CmGLK35 could play key roles in regulating chloroplast development. A total of 37 GLK genes were identified in the chestnut genome and were conducted to reveal the molecular characteristics and evolution of the GLKs family, which provides new insight into the biological functions of GLKs in chestnut photosynthesis.
The Evaluation of Anti-biofilm Agents Efficacy Against Plankton Microorganisms And Biofilm Formation
Authors: Ulyanov Vladimir Yu. , Pichkhidze Sergey Ya. , Shpinyak Sergey P. , Opredelentseva Svetlana V. , Puchinyan Daniil M. 
Published: February 2023

Abstract
We evaluated the impact of prototype agents effective against plankton and sessile cultures of 65 microorganism clinical strains with bacterioscopic and bacteriological research methods. It has been established that the developed prototypes of thin-film coatings containing the physical mixture of bound Ca10(PO4)6(OH)2+CuO; С6H9NO 5 wt%+СuO with CuO concentration of 9-10 wt% at an exposure time of 60 and 120 minutes have the greatest antimicrobial effect on plankton cultures. CuO concentration of 9-10 wt% within the physical mixture of bound Ca10(PO4)6(OH)2+CuO; С6H9NO 5 wt%+СuO causes a decrease in the mass of biofilms preformed by microorganism clinical strains at an exposure time of 24 hours, thereby exerting an antimicrobial effect on them.
Bilateral comparison VSL-NPL on primary gas standards for the siloxane content in biomethane
Authors: Veen Adriaan M H van der , de Krom Iris , Ziel Ruben , Nieuwenkamp Gerard , Culleton Lucy P , Worton David R , Allden John 
Published: February 2023

Abstract
Siloxanes are silicon-containing volatile organic compounds that occur in air, biogas and biomethane. Their presence in biogas and biomethane may give rise to silica deposits in gas transmission and distribution infrastructure, as well as in end-user appliances. The silicon concentration in biomethane is therefore regulated, and implementing these regulations requires reliable measurement methods and appropriate certified reference materials (CRMs) to calibrate analytical instruments. In this work, the primary measurement standards of two national metrology institutes are compared to assess their equivalence by means of gas chromatography analysis. The comparison addressed hexamethyldisiloxane (L2), octamethyltrisiloxane (L3), hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) in methane gas mixtures. Two mixtures were exchanged, one with siloxane amount fractions at the ppb-level as specified in the European specification EN 16723, and a second on ppm-level. The latter CRMs can be dynamically diluted or directly used to process concentrated biomethane samples.
The results at both levels demonstrate equivalence in the preparation and analysis of the addressed siloxanes in methane.
Shaking table tests of large cross-sectional multi-crack tunnel linings
Authors: You Dongmei , Gao Feng 
Published: February 2023

To study the dynamic response law of large-section cracked lining structures under seismic waves, comparative tests of large-scale shaker tunnel models of non-destructive lining structure (model 1), a crack in the vault of the lining structure (model 2), and two parallel cracks in the vault of the lining structure (model 3) were carried out by applying 0.1-1.0 g progressively increasing the peak acceleration of the input waves. This paper visually showed the distribution of cracks in three groups of the lining structures. In addition, the acceleration response of the lining and surrounding rock, dynamic soil pressure, the dynamic strain on the inner and outer surfaces of the lining, and dynamic internal force variation were obtained, and the seismic performance of three groups of lining structures was discussed. The results showed that the seismic weak positions of model 1 were the arch shoulder and the arch foot, the seismic weak positions of model 2 were the arch shoulder, the arch foot, the initial damage area, and the inverted arch, and the seismic weak positions of model 3 were the positions of the arch foot, the cracks of the vault, the inverted arch, and the arch wall. The soil pressure values at the vault of three groups of models were model 2 > model 1 > model 3 in turn. The surrounding rock amplified the input seismic waves. With the gradual increase of the peak acceleration, the seismic energy was gradually consumed due to plastic damage to the lining structure or the loosening and destruction of the overlying soil, resulting in the acceleration amplification coefficient value of the surrounding rock in the upper part of the lining structure showing a changing trend of first increasing and then decreasing. When the peak acceleration was 0.2 g, the crack propagation phenomenon occurs in the initial crack position of model 2 and model 3. When the peak acceleration was 0.4 g, the cracking phenomenon occurs at the right arch foot of model 1. The above phenomenon confirmed the conclusion that cracks can weaken the seismic performance of the structure. When the peak acceleration was 0.8 g, the peak values of the amplification coefficient of the lining at the inverted arch and near the filled soil surface were about 1.2 and 1.6 respectively. The research results can provide a reference for the seismic performance evaluation of cracked tunnels.