bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting CLDN6 in germ cell tumors by an antibody-drug-conjugate and studying therapy resistance of yolk-sac tumors to identify and screen specific therapeutic options
Authors: Skowron Margaretha A. , Kotthoff Mara , Bremmer Felix , Ruhnke Katja , Parmaksiz Fatma , Richter Annika , Küffer Stefan , Reuter-Jessen Kirsten , Pauls Stella , Stefanski Anja , Ströbel Philipp , Stühler Kai , Nettersheim Daniel 
Published: March 2023

Abstract
Background
Being the standard-of-care for four decades, cisplatin-based chemotherapy is highly efficient in treating germ cell tumors (GCT). However, often refractory patients present with a remaining (resistant) yolk-sac tumor (YST(-R)) component, resulting in poor prognosis due to lack of novel treatment options besides chemotherapy and surgery. The aim of this study was to identify novel targets for the treatment of YST by deciphering the molecular mechanisms of therapy resistance. Additionally, we screened the cytotoxic efficacy of a novel antibody-drug-conjugate targeting CLDN6 (CLDN6-ADC), as well as pharmacological inhibitors to target specifically YST.

Methods
Protein and mRNA levels of putative targets were measured by flow cytometry, immunohistochemical stainings, mass spectrometry of formalin-fixed paraffin-embedded tissues, phospho-kinase arrays, or qRT-PCR. Cell viability, apoptosis and cell cycle assays of GCT and non-cancerous cells were performed using XTT cell viability assays or Annexin V / propidium iodide flow cytometry, respectively. Druggable genomic alterations of YST(-R) tissues were identified by the TrueSight Oncology 500 assay.

Results
We demonstrated that treatment with a CLDN6-ADC enhanced apoptosis induction specifically in CLDN6+ GCT cells in comparison with non-cancerous controls. In a cell line-dependent manner, either an accumulation in the G2 / M cell cycle phase or a mitotic catastrophe was observed. Based on mutational and proteome profiling, this study identified drugs targeting the FGF, VGF, PDGF, mTOR, CHEK1, AURKA, or PARP signaling pathways as promising approaches to target YST. Further, we identified factors relevant for MAPK signaling, translational initiation and RNA binding, extracellular matrix-related processes as well as oxidative stress and immune response to be involved in therapy resistance.

Conclusions
In summary, this study offers a novel CLDN6-ADC to target GCT. Additionally, this study presents novel pharmacological inhibitors blocking FGF, VGF, PDGF, mTOR, CHEK1, AURKA, or PARP signaling for the treatment of (refractory) YST patients. Finally, this study shed light on the mechanisms of therapy resistance in YST.
The DNA demethylation-regulated SFRP2 dictates the progression of endometriosis via activation of the Wnt/β-catenin signaling pathway
Authors: Yang Mei , Li Lin , Huang Xiaojie , Xing Hui , Hong Li , Jiang Chunfan 
Published: March 2023

Abstract
Background
Endometriosis cause decreases in life quality and pelvic pain in reproductive-age women. Methylation abnormalities played a functional role in the progression of endometriosis, this study aimed to explore the mechanisms mediated by abnormal methylation in the development of EMS.

Materials and methods
Next-generation sequencing dataset and methylation profiling dataset were used to screen out the key gene SFRP2. Western bolt, Real-time PCR, Aza-2?deoxycytidine treatment, luciferase reporter assay, Methylation-specific PCR , Bisulfite sequencing PCR and lentivirus infection were carried out to detect the methylation status and signaling pathway with the primary epithelial cells. Transwell assay and wound scratch assay were implemented to observe the differences of migration ability with the intervening with the expression of SFRP2.

Results
To define the role of the DNA methylation-regulated genes in the pathogenesis of EMS, we performed both DNA methylomic and expression analyses of ectopic endometrium and ectopic endometrium epithelial cells(EEECs) and found that SFRP2 is demethylated/upregulated in ectopic endometrium and EEECs. The expression of lentivirus carrying SFRP2 cDNA up-regulates the activity of Wnt signaling and the protein expression of ?-catenin in EEECs. SFRP2 impact on the invasion and migration of ectopic endometrium by modulating the activities of the Wnt/?-catenin signaling pathway. The invasion and migration ability of EEECs were significantly strengthened after demethylation treatment including 5-Aza and the knockdown of DNMT1.

Conclusion
In summary, the increased SFRP2 expression-induced Wnt/?-catenin signaling due to the demethylation of the SFRP2 promoter plays an important role in the pathogenesis of EMS, suggesting that SFRP2 might be a therapeutic target for EMS treatment.
Pinpointing the precise stimulation targets for brain rehabilitation in early-stage Parkinson’s disease
Authors: Lu Hanna , Li Jing , Zhang Li , Meng Lin , Ning Yuping , Jiang Tianzi 
Published: March 2023

Abstract
Background
Transcranial magnetic stimulation (TMS) is increasingly used as a promising non-pharmacological treatment for Parkinson’s disease (PD). Scalp-to-cortex distance (SCD), as a key technical parameter of TMS, plays a critical role in determining the locations of treatment targets and corresponding dosage. Due to the discrepancies in TMS protocols, the optimal targets and head models have yet to be established in PD patients.

Objective
To investigate the SCDs of the most popular used targets in left dorsolateral prefrontal cortex (DLPFC) and quantify its impact on the TMS-induced electric fields (E-fields) in early-stage PD patients.

Methods
Structural magnetic resonance imaging scans from PD patients (n = 47) and normal controls (n = 36) were drawn from the NEUROCON and Tao Wu datasets. SCD of left DLPFC was measured by Euclidean Distance in TMS Navigation system. The intensity and focality of SCD-dependent E-fields were examined and quantified using Finite Element Method.

Results
Early-stage PD patients showed an increased SCDs, higher variances in the SCDs and SCD-dependent E-fields across the seven targets of left DLPFC than normal controls. The stimulation targets located on gyral crown had more focal and homogeneous E-fields. The SCD of left DLPFC had a better performance in differentiating early-stage PD patients than global cognition and other brain measures.

Conclusion
SCD and SCD-dependent E-fields could determine the optimal TMS treatment targets and may also be used as a novel marker to differentiate early-stage PD patients. Our findings have important implications for developing optimal TMS protocols and personalized dosimetry in real-world clinical practice.
Alleviating the adverse effects of salinity stress on Salicornia persica using sodium nitroprusside and potassium nitrate
Authors: Moghaddam Abbasali , Larijani Hamid Reza , Oveysi Meysam , Moghaddam Hamid Reza Tohidi , Nasri Mohammad 
Published: March 2023

AbstractBackgroundGlasswort (Salicornia persica) is identified as a halophyte plant, which is one of the most tolerant plants to salt conditions. The seed oil of the plant contains about 33% oil. In the present study, the effects of sodium nitroprusside (SNP; 0, 0.1, 0.2, and 0.4 mM) and potassium nitrate (KNO3; 0, 0.5, and 1%) were evaluated on several characteristics of glasswort under salinity stress (0, 10, 20, and 40 dS/m).Resultsmorphological features, phenological traits, and yield parameters such as plant height, number of days to flowering, seed oil, biological yield, and seed yield significantly decreased in response to severe salt stress. However, the plants needed an optimal salinity concentration (20 dS/m NaCl) to obtain high amounts of seed oil and seed yield. The results also showed that a high level of salinity (40 dS/m NaCl) caused a decrease in plant oil and yield. In addition, by increasing the exogenous application of SNP and KNO3, the seed oil and seed yield increased.ConclusionsThe application of SNP and KNO3were effective in protectingS. persicaplants from the deleterious effects of severe salt stress (40 dS/m NaCl), thereby restoring the activity of antioxidant enzymes, increasing the proline content, and maintaining cell membrane stability. It seems that both factors, i.e. SNP and KNO3, can be applied as mitigators of salt stress in plants.
Ethnic differences in the lifestyle behaviors and premature coronary artery disease: a multi-center study
Authors: Babahajiani Media , Zarepur Ehsan , Khosravi Alireza , Mohammadifard Noushin , Noohi Feridoun , Alikhasi Hasan , Nasirian Shima , Moezi Bady Seyed Ali , Janjani Parisa , Solati Kamal , Lotfizadeh Masoud , Ghaffari Samad , Javanmardi Elmira , Salari Arsalan , Gholipour Mahboobeh , Dehghani Mostafa , Cheraghi Mostafa , Assareh Ahmadreza , Haybar Habib , Namayandeh Seyedeh Mahdieh , Madadi Reza , Kojuri Javad , Mansourian Marjan , Sarrafzadegan Nizal 
Published: March 2023

Abstract
Background
Diverse ethnic groups that exist in Iran may differ regarding the risk factors such as hypertension, hyperlipidemia, dyslipidemia, diabetes mellitus, and family history of non-communicable disease. Premature Coronary Artery Disease (PCAD) is more endemic in Iran than before. This study sought to assess the association between ethnicity and lifestyle behaviors in eight major Iranian ethnic groups with PCAD.

Methods
In this study, 2863 patients aged ≤ 70 for women and ≤ 60 for men who underwent coronary angiography were recruited in a multi-center framework. All the patients’ demographic, laboratory, clinical, and risk factor data were retrieved. Eight large ethnicities in Iran, including the Farses, the Kurds, the Turks, the Gilaks, the Arabs, the Lors, the Qashqai, and the Bakhtiari were evaluated for PCAD. Different lifestyle components and having PCAD were compared among the ethnical groups using multivariable modeling.

Results
The mean age of the 2863 patients participated was 55.66 ± 7.70 years. The Fars ethnicity with 1654 people, was the most subject in this study. Family history of more than three chronic diseases (1279 (44.7%) was the most common risk factor. The Turk ethnic group had the highest prevalence of ≥ 3 simultaneous lifestyle-related risk factors (24.3%), and the Bakhtiari ethnic group had the highest prevalence of no lifestyle-related risk factors (20.9%). Adjusted models showed that having all three abnormal lifestyle components increased the risk of PCAD (OR = 2.28, 95% CI: 1.04–1.06). The Arabs had the most chance of getting PCAD among other ethnicities (OR = 2.26, 95%CI: 1.40–3.65). While, the Kurds with a healthy lifestyle showed the lowest chance of getting PCAD (OR = 1.96, 95%CI: 1.05–3.67)).

Conclusions
This study found there was heterogeneity in having PACD and a diverse distribution in its well-known traditional lifestyle-related risk factors among major Iranian ethnic groups.
Prolonged length of stay and its associated factors at adult emergency department in amhara region comprehensive specialized hospitals, northwest Ethiopia
Authors: Belayneh Asnake Gashaw , Temachu Yemataw Zewdu , Messelu Mengistu Abebe , Gebrie Mignote Hailu 
Published: March 2023

Abstract
Background
Prolonged length of stay at the emergency department interferes with the main goal of emergency care and results in adverse patient outcomes like nosocomial infection, dissatisfaction, morbidity, and mortality. Despite this, little is known about the length of stay and the factors that influence it in Ethiopia’s emergency department.

Methods
An institution-based cross-sectional study was conducted on 495 patients admitted at Amhara region comprehensive specialized hospitals emergency department from May 14 to June 15/2022. A systematic random sampling was employed to select study participants. A pretested structured interview-based questionnaire was used to collect data by using Kobo toolbox software. SPSS version 25 was used for data analysis. Bi-variable logistic regression analysis was carried out to select variables with P-value < 0.25. The significance of association was interpreted using an Adjusted Odds Ratio with a 95% confidence interval. Variables with P-value < 0.05 in the multivariable logistic regression analysis were inferred to be significantly associated with length of stay.

Result
Out of 512 enrolled participants, 495 were participated with a response rate of 96.7%. The prevalence of prolonged length of stay in the adult emergency department was 46.5% (95%CI: 42.1, 51.1). Lack of insurance (AOR: 2.11; 95% CI: 1.22, 3.65), non-communicative presentation (AOR: 1.98; 95% CI: 1.07, 3.68), delayed consultation (AOR: 9.5; 95% CI: 5.00, 18.03), overcrowding (AOR: 4.98; 95% CI: 2.13, 11.68), and shift change experience (AOR: 3.67; 95% CI: 1.30, 10.37) were significantly associated with prolonged length of stay.

Conclusion
The result of this study is found to be high based on Ethiopian target emergency department patient length of stay. Lack of insurance, presentation without communication, delayed consultation, overcrowding, and shift change experience were significant factors for prolonged emergency department length of stay. Therefore, interventions like expansion of organizational setup are needed to decrease the length of stay to an acceptable level.
Recruitment to a trial of antipsychotic reduction: impact of an acceptability study
Authors: Ramsay Georgina , Haime Zoë , Crellin Nadia E , Stansfeld Jacki L , Priebe Stefan , Long Maria , Moncrieff Joanna 
Published: March 2023

Abstract
Objectives
Pre-trial acceptability studies may boost recruitment, especially in trials comparing distinctly different interventions. We evaluated the impact of an acceptability study on recruitment to a randomised trial of antipsychotic reduction versus maintenance treatment and explored demographic and clinical predictors of subsequent enrolment.

Methods
Participants with a diagnosis of a schizophrenia spectrum disorder who were taking antipsychotic medication were interviewed about their views of taking part in a future trial.

Results
In a sample of 210 participants, 151 (71.9%) expressed an interest in taking part in the future trial, 16 (7.6%) said they might be interested, and 43 (20.5%) said they were not. Altruistic reasons were most commonly given for wanting to take part, and concern about randomisation for not wanting to. Ultimately 57 people enrolled in the trial (27.1% of the original sample). Eighty-five people who initially expressed an interest did not enrol due to declining or not being eligible (for clinical reasons). Women and people from a white ethnic background were more likely to enrol in the trial, but no illness or treatment-related characteristics were associated with enrolment.

Conclusion
An acceptability study can be a useful tool for recruitment to challenging trials, but it may over-estimate recruitment.
External validation of the American prediction model for incident type 2 diabetes in the Iranian population
Authors: Asgari Samaneh , Khalili Davood , Azizi Fereidoun , Hadaegh Farzad 
Published: March 2023

Abstract
Background
The primary aim of the present study was to validate the REasons for Geographic and Racial Differences in Stroke (REGARDS) model for incident Type 2 diabetes (T2DM) in Iran.

Methods
Present study was a prospective cohort study on 1835 population aged ≥ 45 years from Tehran lipids and glucose study (TLGS).The predictors of REGARDS model based on Bayesian hierarchical techniques included age, sex, race, body mass index, systolic and diastolic blood pressures, triglycerides, high-density lipoprotein cholesterol, and fasting plasma glucose. For external validation, the area under the curve (AUC), sensitivity, specificity, Youden’s index, and positive and negative predictive values (PPV and NPV) were assessed.

Results
During the 10-year follow-up 15.3% experienced T2DM. The model showed acceptable discrimination (AUC (95%CI): 0.79 (0.76–0.82)), and good calibration. Based on the highest Youden’s index the suggested cut-point for the REGARDS probability would be ≥ 13% which yielded a sensitivity of 77.2%, specificity 66.8%, NPV 94.2%, and PPV 29.6%.

Conclusions
Our findings do support that the REGARDS model is a valid tool for incident T2DM in the Iranian population. Moreover, the probability value higher than the 13% cut-off point is stated to be significant for identifying those with incident T2DM.
Effect of including a dietary supplement of raisins, a food rich in polyphenols, on cognitive function in healthy older adults; a study protocol for a randomized clinical trial
Authors: Rodrigo-Gonzalo María J. , Recio-Rodríguez José I. , Méndez-Sánchez Roberto , Pablos-Hernández María C. , González-Ramírez Alfonso , González-Sánchez Jesús , Fermoso-Palmero María J. , Puente-González Ana S. , Sánchez-Sánchez María C. , Barbero-Iglesias Fausto J. , Rihuete-Galve María I. , González-Manzano Susana 
Published: March 2023

Abstract
Background
Polyphenols have been shown to be effective against many chronic diseases, including neurodegenerative diseases. Specifically, the consumption of raisins, being a food rich in polyphenols, has been attributed with neuroprotective benefits. Therefore, our main objective is to evaluate the effect of including 50 g of raisins in the diet daily for 6 months, on the improvement of cognitive performance, cardiovascular risk factors and markers of inflammation in a population of older adults without cognitive impairment.

Methods
Design and intervention: This study will be a randomized controlled clinical trial of two parallel groups. Each subject included in the study will be randomly assigned to one of two study groups: control group (no supplement), intervention group (50 g of raisins daily during 6 months).
Study population: The participants will be selected by consecutive sampling in the Primary Care consultations of urban health centers in Salamanca and Zamora (Spain), taking into account the selection criteria.
Study variables: Two visits will be made, baseline and at 6 months. Cognitive performance will be evaluated (Mini-Mental State Examination test, Rey Auditory Verbal Learning Test, verbal fluency and montreal cognitive assessment (Moca)). It will also be analyzed the level of physical activity, quality of life, activities of daily living, energy and nutritional composition of the diet, body composition, blood pressure, heart rate, markers of inflammation and other laboratory tests of clinical relevance (glycaemia, total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides). In addition, sociodemographic data, personal and family history, medication use and alcohol and tobacco consumption will be collected.

Discussion
In this project, it is intended to contribute to minimize the problems derived from cognitive deterioration in older people.

Trial registration
ClincalTrials.gov Identifier: NCT04966455 Registration date: July 1, 2021.
The distribution characteristics of global blaOXA-carrying Klebsiella pneumoniae
Authors: Meng Lingning , Liu Ziyao , Liu Chang , Li Chuchu , Shen Han , Cao Xiaoli 
Published: March 2023

Abstract
Objective
To analyze the distribution of blaOXA among global Klebsiella pneumoniae and the characteristics of blaOXA-carrying K. pneumoniae.

Materials and Methods
The genomes of global K. pneumoniae were downloaded from NCBI by Aspera software. After quality check, the distribution of blaOXA among the qualified genomes was investigated by annotation with the resistant determinant database. The phylogenetic tree was constructed for the blaOXA variants based on the single nucleotide polymorphism (SNP) to explore the evolutionary relationship between these variants. The MLST (multi-locus sequence type) website and blastn tools were utilized to determine the sequence types (STs) of these blaOXA-carrying strains. and sample resource, isolation country, date and host were extracted by perl program for analyzing the characteristics of these strains.

Results
A total of 12,356 K. pneumoniae genomes were downloaded and 11,429 ones were qualified. Among them, 4386 strains were found to carry 5610 blaOXA variants which belonged to 27 varieties of blaOXAs, blaOXA-1 (n = 2891, 51.5%) and blaOXA-9 (n = 969, 17.3%) were the most prevalent blaOXA variants, followed by blaOXA-48 (n = 800, 14.3%) and blaOXA-232 (n = 480, 8.6%). The phylogenetic tree displayed 8 clades, three of them were composed of carbapenem-hydrolyzing oxacillinase (CHO). Totally, 300 distinct STs were identified among 4386 strains with ST11 (n = 477, 10.9%) being the most predominant one followed by ST258 (n = 410, 9.4%). Homo sapiens (2696/4386, 61.5%) was the main host for blaOXA-carrying K. pneumoniae isolates. The blaOXA-9-carrying K. pneumoniae strains were mostly found in the United States and blaOXA-48-carrying K. pneumoniae strains were mainly distributed in Europe and Asia.

Conclusion
Among the global K. pneumoniae, numerous blaOXA variants were identified with blaOXA-1, blaOXA-9, blaOXA-48 and blaOXA-232 being the most prevalent ones, indicating that blaOXA rapidly evolved under the selective pressure of antimicrobial agents. ST11 and ST258 were the main clones for blaOXA-carrying K. pneumoniae.
Intraoperative hemodialysis during open-heart surgery in patients with severe chronic kidney disease: a retrospective cohort study
Authors: Inoue Takahiro , Kuji Hiroshi , Nagaoka Kanako , Akanuma Takafumi , Fukuda Junko , Matsui Hiroki , Tanabe Hiroaki , Ohara Mamiko , Suzuki Tomo 
Published: March 2023

Abstract
Background
Acute kidney injury and chronic kidney disease (CKD) after cardiac surgery are associated with poor renal prognosis and increased mortality. The impact of intraoperative hemodialysis (IHD) on postoperative renal function remains unknown. We aimed to evaluate the utility of IHD during open-heart surgery in patients with severe non-dialysis-dependent chronic kidney disease (CKD-NDD) and its association with clinical outcomes.

Methods
This was a single-center retrospective cohort study that employed IHD during non-emergency open-heart surgery in patients with CKD stage G4 or G5. Patients who underwent emergent surgery, chronic dialysis, and/or kidney transplantation were excluded. We retrospectively compared the clinical characteristics and outcomes between patients from the IHD and non-IHD groups. The primary outcomes were 90-day mortality and postoperative initiation of renal replacement therapy (RRT).

Results
Twenty-eight patients were categorized into the IHD group and 33 into the non-IHD group. When comparing the IHD and non-IHD groups, men accounted for 60.7 vs. 50.3% of patients, the mean patient age was 74.5 (standard deviation [SD] 7.0) vs. 72.9 (SD 9.4) years (p = 0.744), and the proportion of patients with CKD G4 was 67.9 vs. 84.9% (p = 0.138). Regarding clinical outcomes, no significant differences were observed in the 90-day mortality (7.1 vs. 3.0%; p = 0.482) and 30-day RRT (17.9 vs. 30.3%; p = 0.373) rates between the groups. Among the patients with CKD G4, the IHD group had significantly lower 30-day RRT rates than the non-IHD group (0 vs. 25.0%; p = 0.032). RRT initiation was less likely for patients with CKD G4 (odds ratio 0.07, 95% confidence interval [CI] 0.01–0.37; p = 0.002); however, IHD did not significantly decrease the incidence of poor clinical outcomes (odds ratio 0.20, 95% CI 0.04–1.07; p = 0.061).

Conclusions
IHD during open-heart surgery in patients with CKD-NDD did not improve their clinical outcomes with regards to postoperative dialysis. However, for patients with CKD G4, IHD may be useful for postoperative cardiac management.