bluuebunny/crossref_metadata_2025_split huggingface dataset:
A potential link between AQP3 and SLC14A1 gene expression level and clinical parameters of maintenance hemodialysis patients
Authors: Zwiech Rafał , Bruzda-Zwiech Agnieszka , Balcerczak Ewa , Szczepańska Joanna , Krygier Adrian , Małachowska Beata , Michałek Dominika , Szmajda-Krygier Dagmara 
Published: August 2022

Abstract
Background
The transport of water and urea through the erythrocyte membrane is facilitated by aquaporins such as aquaglyceroporin (AQP3), and type B urea transporters (UT-B). As they may play an important role in osmotic balance of maintenance hemodialysis (HD) patients, the aim of the present study was to determine whether any relationship exists between the expression of their genes and the biochemical / clinical parameters in HD patients.

Methods
AQP3 and UT-B (SLC14A1) gene expression was evaluated using RT-qPCR analysis in 76 HD patients and 35 participants with no kidney failure.

Results
The HD group demonstrated significantly higher median expression of AQP3 and UT-B (Z = 2.16; P = 0.03 and Z = 8.82; p < 0.0001, respectively) than controls. AQP3 negatively correlated with pre-dialysis urea serum concentration (R = -0.22; P = 0.049) and sodium gradient (R = -0.31; P = 0.04); however, no significant UT-B correlations were observed. Regarding the cause of end-stage kidney disease, AQP3 expression positively correlated with erythropoietin dosages in the chronic glomerulonephritis (GN) subgroup (R = 0.6; P = 0.003), but negatively in the diabetic nephropathy subgroup (R = -0.59; P = 0.004). UT-B positively correlated with inter-dialytic weight gain% in the GN subgroup (R = 0.47; P = 0.03).

Conclusion
Maintenance hemodialysis seems significantly modify AQP3 and UT-B expression but their link to clinical and biochemical parameters needs further large-scale evaluation.
Preoperative prediction of intrahepatic cholangiocarcinoma lymph node metastasis by means of machine learning: a multicenter study in China
Authors: Huang Tingfeng , Liu Hongzhi , Lin Zhaowang , Kong Jie , Lin Kongying , Lin Zhipeng , Chen Yifan , Lin Qizhu , Zhou Weiping , Li Jingdong , Li Jiang-Tao , Zeng Yongyi 
Published: August 2022

Abstract
Background
Hepatectomy is currently the most effective modality for the treatment of intrahepatic cholangiocarcinoma (ICC). The status of the lymph nodes directly affects the choice of surgical method and the formulation of postoperative treatment plans. Therefore, a preoperative judgment of lymph node status is of great significance for patients diagnosed with this condition. Previous prediction models mostly adopted logistic regression modeling, and few relevant studies applied random forests in the prediction of ICC lymph node metastasis (LNM).

Methods
A total of 149 ICC patients who met clinical conditions were enrolled in the training group. Taking into account preoperative clinical data and imaging features, 21 indicators were included for analysis and modeling. Logistic regression was used to filter variables through multivariate analysis, and random forest regression was used to rank the importance of these variables through the use of algorithms. The model’s prediction accuracy was assessed by the concordance index (C-index) and calibration curve and validated with external data.

Result
Multivariate analysis shows that Carcinoembryonic antigen (CEA), Carbohydrate antigen19-9 (CA19-9), and lymphadenopathy on imaging are independent risk factors for lymph node metastasis. The random forest algorithm identifies the top four risk factors as CEA, CA19-9, and lymphadenopathy on imaging and Aspartate Transaminase (AST). The predictive power of random forest is significantly better than the nomogram established by logistic regression in both the validation group and the training group (Area Under Curve reached 0.758 in the validation group).

Conclusions
We constructed a random forest model for predicting lymph node metastasis that, compared with the traditional nomogram, has higher prediction accuracy and simultaneously plays an auxiliary role in imaging examinations.
Notch signaling mutations increase intra-tumor chemokine expression and predict response to immunotherapy in colorectal cancer
Authors: Wang Fei , Huang Chuan , Long Jie , Zhao Zhi-Bin , Ma Hai-Qing , Yao Xue-Qing , Li Liang , Lian Zhe-Xiong 
Published: August 2022

Abstract
Background
The Notch signaling mutation is associated with enhanced anti-tumor immune response in colorectal cancer (CRC). In this study, we aim to investigate the underlying mechanism and the predictive potential of Notch signaling mutation for responding to immunotherapy in CRC.

Methods
We analyzed the immune response associated genes in CRC with Notch signaling mutation concomitant with or without microsatellite instability (MSI) using TCGA dataset and investigated the mutation profiles of the Notch signaling pathway using cBioPortal. The Notch signaling scores and immune cell infiltration scores in different groups were calculated. We applied the Kaplan–Meier method for survival analysis in CRC patients who underwent immunotherapy, and the log-rank test to determine the statistically significant differences in survival. Notch1-knock-down cell line was constructed to detect the pathway and gene variations.

Results
We found that Notch signaling pathway mutation was associated with activated immune response, especially in those with MSI. Such association is useful for predicting a prolonged overall survival of CRC patients who underwent immune checkpoint inhibitor treatment. The mutation resulted in the functional loss of Notch signaling and may modulate the tumor immune microenvironment by increasing the expression of chemokines that are important for recruiting immune cells.

Conclusions
The Notch signaling mutation can modulate the chemotaxis of immune cells by upregulating the chemokine levels of the tumor immune microenvironment, and CRC patients with Notch signaling pathway mutation have better overall survival after immune checkpoint inhibitor treatment.
Comparison of hyperreflective foci in macular edema secondary to multiple etiologies with spectral-domain optical coherence tomography: An observational study
Authors: Zhu Ruilin , Xiao Shiyu , Zhang Wenbo , Li Jun , Yang Menglu , Zhang Yadi , Gu Xiaopeng , Yang Liu 
Published: August 2022

Abstract
Background
Hyperreflective foci (HRF) features in macular edema associated with different etiologies may indicate the disease pathogenesis and help to choose proper treatment. The goal of this study is to investigate the retinal microstructural features of macular edema (ME) secondary to multiple etiologies with spectral-domain optical coherence tomography (SD-OCT) and analyze the origin of HRF in ME.

Methods
This was a retrospective study. SD-OCT images were reviewed to investigate macular microstructural features such as the number and distribution of HRF and hard exudates and the internal reflectivity of the cysts. The differences in microstructural features between groups and the correlations between the number of HRF and other parameters were analyzed.

Results
A total of 101 eyes with ME from 86 diabetic (diabetic macular edema, DME) patients, 51 eyes from 51 patients with ME secondary to branch retinal vein occlusion (branch retinal vein occlusion-macular edema, BRVO-ME), 59 eyes from 58 central retinal vein occlusion (central retinal vein occlusion-macular edema, CRVO-ME) patients, and 26 eyes from 22 uveitis (uveitic macular edema, UME) patients were included in this study. The number of HRF, the frequency of hard exudates and the enhanced internal reflectivity of the cysts were significantly different among the groups. The number of HRF in the DME group was significantly higher than that in the other groups (all P < 0.05). The frequency of hard exudates and enhanced internal reflectivity of the cysts in the DME group were significantly higher than ME secondary to other etiologies (all P < 0.001). Within the DME group, the number of HRF in the patients with hard exudates was significantly higher than that in the patients without hard exudates (P < 0.001).

Conclusion
HRF detected with SD-OCT were more frequent in DME patients than in BRVO-ME, CRVO-ME, or UME patients. The occurrence of HRF was correlated with the frequency of hard exudates. HRF may result from the deposition of macromolecular exudates in the retina, which is speculated to be a precursor of hard exudates.
Prognostic significance of immunoscore related markers in bladder cancer
Authors: Ariafar Ali , Sanati Alireza , Ahmadvand Simin , Shekarkhar Golsa , Safaei Akbar , Shayan Zahra , Faghih Zahra 
Published: August 2022

Abstract
Background
The significance of total and specific subpopulations of tumor-infiltrating lymphocytes (TILs) in cancer is now well-documented. In the present study, we investigated the relevance of CD3+, CD8 +, CD45RO +, and FOXP3 + TILs to the prognosis and survival of patients with bladder cancer and the disease's clinical-pathological parameters.

Methods
Infiltration of each subset was immunohistochemically evaluated in both stromal and intratumoral regions of tumor tissues from 85 patients with urothelial cell carcinoma of the bladder, with known survival.

Results
Our results indicated that intratumoral CD45RO+ lymphocytes were significantly higher in high-grade tumors than in low-grade ones (P = 0.028). The frequencies of intratumoral CD3+ (P = 0.002), CD8 + (P = 0.008), intratumoral (P = 0.002), and stromal (P = 0.017) CD45RO+ lymphocytes were also higher in patients with muscular invasion than those without invasion. The frequencies of intratumoral CD3+ (P = 0.043), CD8+ (P = 0.003), CD45RO+ (P = 0.023), and total CD45RO+ (P = 0.015), showed variation in patients with different T-stage, as well; mostly increased in T2 versus Ta and T1. Comparing patients in different stages revealed an increase in the frequencies of total CD3+ (P = 0.011), intratumoral CD3+ (P = 0.006), total CD8+ (P = 0.012), intratumoral CD8+ (P = 0.009) and stromal CD8+ (P = 0.034), as well as total and stromal CD45RO+ lymphocytes (P = 0.01 and P = 0.034, respectively) in stage II comparing to stage I, while the frequencies of stromal CD3+ (P = 0.077) and CD8+ (P = 0.053) cells tended to be decreased in stage III compared to stage II.

Conclusions
We collectively observed that the frequency of immune cells, especially CD45RO+, CD3+, and CD8+ lymphocytes, were significantly higher in early-progressed tumors. This observation could be explained by continuous and prolonged stimulation of immune cells with tumor antigens during tumor progression or an increase in the recruiting factors, especially in the early stages, to eliminate tumor cells. However, with tumor progression to the late stages, the inhibitory microenvironment provided by tumor cells suppresses or changes the functionality of the effector and memory immune cells to help tumor growth. However, more functional studies with larger sample sizes are needed to reveal the real status of the immune system in patients with bladder cancer.
Psychological safety between pediatric residents and nurses and the impact of an interdisciplinary simulation curriculum
Authors: Haviland Courtney , Green Janet , Dzara Kristina , Hardiman Wendy O. , Petrusa Emil R. , Park Yoon Soo , Frey-Vogel Ariel S. 
Published: August 2022

Abstract
Background
Effective teamwork in interdisciplinary healthcare teams is necessary for patient safety. Psychological safety is a key component of effective teamwork. The baseline psychological safety on pediatric inpatient healthcare teams is unknown. The purpose of this study is to determine the baseline psychological safety between pediatric nurses and residents and examine the impact of an interdisciplinary nighttime simulation curriculum.

Methods
A convergent, multistage mixed methods approach was used. An interprofessional simulation curriculum was implemented fall 2020 to spring 2021. Qualitative focus group data and quantitative survey data on team psychological safety were collected and compared, both pre- and post-intervention and across nurses and residents. Thematic analysis of the qualitative data was conducted, and themes integrated with survey findings.

Results
Data were collected from 30 nurses and 37 residents pre-intervention and 32 and 38 post-intervention, respectively. Residents and nurses negatively rated psychological safety (pre-intervention mean = 3.40 [SD = 0.72]; post-intervention mean = 3.35 [SD = 0.81]). At both times psychological safety was rated significantly lower for residents (pre-intervention mean = 3.11 [SD = 0.76], post-intervention mean = 2.98 [SD = 0.84]) than nurses (pre-intervention mean = 3.76 [SD = 0.45], post-intervention mean = 3.79 [SD = 0.50]), all P < .001. Qualitative analysis identified six integrated themes: (1) influence of existing relationships on future interactions, (2) unsatisfactory manner and frequency of communication, (3) unsatisfactory resolution of disagreements (4) overwhelming resident workload impairs collaboration, (5) interpersonal disrespect disrupts teamwork, and (6) interprofessional simulation was useful but not sufficient for culture improvement.

Conclusion
Resident-nurse team psychological safety ratings were not positive. While interprofessional simulation curriculum shows promise, additional efforts are needed to improve psychological safety among residents and nurses.
Evaluation of an individual anamnesis tool for teaching risk-oriented prevention – a pilot study in undergraduate dental students
Authors: Schmalz Gerhard , Lange Jacqueline , Krause Felix , Haak Rainer , Lethaus Bernd , Zimmerer Rüdiger , Ziebolz Dirk 
Published: August 2022

Abstract
Background
A comprehensive medical history is needed to establish and ensure a high standard in dental care; however, it is challenging to draw clinical consequences on the variety of potential diseases and medications, especially for dental students. Aim of this observational study was to investigate, whether undergraduate dental students using an analog anamnesis tool for risk classification would be more confident and have more knowledge in risk classification than other students in the same year of study.

Methods
A cohort of 48 fifth year dental students was included and allocated into two groups based on their curriculum-related division (group A: n = 25, group B: n = 23). Group A received a teaching event and provision of an analog anamnesis tool for risk classification; group B received neither a teaching event nor the anamnesis tool. At baseline and after two weeks (follow-up), questionnaires regarding self-perceived confidence with risk classification, questions on different disease, medications and lifestyle factors and a task with 15 medical histories of prepared patient cases were applied. The data was statistically analyzed using Mann–Whitney or Wilcoxon test.

Results
In group comparison of the differences between baseline and follow-up regarding self-perceived confidence, significantly higher improvement was noted in group A compared to group B for all questions (p < 0.05). With regard to knowledge, the group comparison revealed that the differences in all of the four tasks were significantly higher in group A compared to group B (pi ≤ 0.01). Thereby, the different tasks in group A differed between baseline and follow-up as follows: Risk of complications: 49.04 ± 13.59 vs. 67.96 ± 17.22, p < 0.01, Risk of oral diseases: 48.77 ± 13.57 vs. 63.44 ± 16.78, p = 0.01, Indication of antibiotic prophylaxis: 75.70 ± 13.45 vs. 87.97 ± 10.37, p < 0.01 and the Medical history task on 15 patient cases: 58.45 ± 4.74 vs. 71.47 ± 9.54, p < 0.01.

Conclusion
The applied analog anamnesis tool supported an increase in students´ confidence with issues related to at-risk patients alongside with their knowledge in risk classification. The applied anamnesis tool can be recommended for improving teaching of risk management for undergraduate dental students.
Barriers and facilitators to scaling up Healthy Choices, a motivational interviewing intervention for youth living with HIV
Authors: MacDonell Karen , Dinaj-Koci Veronica , Koken Juline , Naar Sylvie 
Published: August 2022

Abstract
Background
This study included Community Health Workers and their supervisors from HIV clinical care teams who participated in the Healthy Choices intervention program. Healthy Choices is a Motivational Interviewing-based intervention aimed at improving medication adherence and reducing alcohol use for adolescents and emerging adults ages 16—24 living with HIV. In this study, the intervention was “scaled up” for delivery by local HIV care providers in real-world clinic settings.

Methods
Providers (N = 21) completed semi-structured interviews (N = 29) about their experiences with intervention scale-up. Rigorous thematic analyses were conducted within discussions of barriers and facilitators of intervention implementation.

Results
Three dominant thematic areas emerged from the data: (1) perceptions of the Healthy Choices intervention, (2) engaging high risk YLH in in-person behavior interventions, and (3) perspectives on implementation of the intervention using local staff. Results offer insights into implementation of MI-based interventions for adolescents and emerging adults in clinic settings using local clinical staff instead of dedicated research staff.

Conclusions
Overall, scaled-up intervention programs for youth are challenged to maintain scientific rigor, provide rigorous training and supports, and offer an attractive and engaging program.
Pyrotinib combined with apatinib for targeting metastatic non-small cell lung cancer with HER2 alterations: a prospective, open-label, single-arm phase 2 study (PATHER2)
Authors: Yang Guangjian , Xu Haiyan , Yang Yaning , Zhang Shuyang , Xu Fei , Hao Xuezhi , Li Junling , Xing Puyuan , Hu Xingsheng , Liu Yutao , Wang Lin , Lin Lin , Wang Zhijie , Duan Jianchun , Wang Jie , Wang Yan 
Published: August 2022

Abstract
Background
Although targeted agents have been gradually applied in the treatment of HER2-mutated non-small cell lung cancer (NSCLC) in recent years, patients’ therapeutic demands are far from being met. PATHER2 was the first phase 2 trial to explore the efficacy and safety of the HER2-targeted tyrosine kinase inhibitor (TKI) pyrotinib plus the antiangiogenic agent apatinib in previously treated HER2-altered metastatic NSCLC patients.

Methods
HER2-mutated or HER2-amplified metastatic NSCLC patients who had failed at least first-line chemotherapy or HER2-targeted TKIs received oral pyrotinib 400 mg plus apatinib 250 mg once daily until disease progression, intolerable toxicity, or death. The primary endpoint was the investigator-assessed objective response rate (ORR).

Results
Between March 2019 and December 2020, 33 patients were enrolled; 13 (39.4%) presented brain metastases, and 16 (48.5%) had received at least two lines of prior chemotherapy or HER2-targeted TKIs. As of September 20, 2021, the median follow-up duration was 11.3 (range, 3.5–26.0) months. The investigator-assessed ORR was 51.5% (17/33; 95% CI, 33.5 to 69.2%), and the disease control rate was 93.9% (31/33; 95% CI, 79.8 to 99.3%). The median duration of response, progression-free survival, and overall survival were 6.0 (95% CI, 4.4 to 8.6) months, 6.9 (95% CI, 5.8 to 8.5) months, and 14.8 (95% CI, 10.4 to 23.8) months, respectively. The most frequent grade ≥ 3 treatment-related adverse events included diarrhea (3.0%) and hypertension (9.1%). No treatment-related deaths were reported.

Conclusions
Pyrotinib plus apatinib demonstrated promising antitumor activity and a manageable safety profile in HER2-mutated or HER2-amplified metastatic NSCLC patients.

Trial registration
Chinese Clinical Trial Registry Identifier: ChiCTR1900021684.
Impact of the interaction between the polymorphisms and hypermethylation of the CD36 gene on a new biomarker of type 2 diabetes mellitus: circulating soluble CD36 (sCD36) in Senegalese females
Authors: Touré Maïmouna , Samb Abdoulaye , Sène Mbaye , Thiam Souleymane , Mané Cheikh A. B. , Sow Abdou K. , Ba-Diop Awa , Kane Modou O. , Sarr Mamadou , Ba Abdoulaye , Gueye Lamine 
Published: August 2022

Abstract
Background
Several predisposing factors for diabetes mellitus have been identified, including cluster determinant 36 (CD36) receptor expression. We aimed to determine the effects of CD36 gene polymorphisms and hypermethylation on the plasma CD36 protein levels in type 2 diabetes.

Materials and methods
We conducted a cross-sectional study involving 100 females (lean healthy control subjects and subjects with type 2 diabetes). This study was conducted at the Human Physiology Laboratory at the Dakar Faculty of Medicine in Senegal. Circulating sCD36 levels and DNA methyltransferase 3a levels were determined by enzyme-linked immunosorbent assay. The other biological parameters were evaluated in a biochemical laboratory. CD36 gene polymorphisms and methylation were explored by real-time polymerase chain reaction and methylation-specific polymerase chain reaction, respectively.

Results
sCD36 was negatively correlated with HDL-cholesterol levels (r =  − 0.52 p = 0.0001) and triglyceride levels (r =  − 0.36 p = 0.01) in control subjects. However, in the type 2 diabetes group, sCD36 levels were positively correlated with total cholesterol levels (r = 0.28 p = 0.04). For rs3211867, control subjects harboring the CC genotypes had significantly higher sCD36 levels than control subjects harboring the AA/AC genotype (p = 0.02); in the type 2 diabetes group, the sCD36 level was not significantly lower in subjects harboring the AA/AC genotype than in subjects harboring the CC genotype (p = 0.27). CD36 gene methylation reduced the sCD36 level in the control subjects compared to control subjects without CD36 gene methylation (p = 0.03). This difference was not significant in the type 2 diabetes group comparing subjects with diabetes with CD36 gene methylation to subjects with diabetes without CD36 gene methylation (p = 0.09). We noted a nonsignificant increase in sCD36 levels in subjects with diabetes with CD36 gene methylation compared to control subjects with CD36 gene methylation (p = 0.27). A combination of the CD36 polymorphism effect and the CD36 methylation effect did not significantly reduce sCD36 levels in subjects with type 2 diabetes.

Conclusion
CD36 gene polymorphisms and CD36 gene methylation separately reduce sCD36 levels. Their impacts are compensated for in subjects with type 2 diabetes by an increase in sCD36 levels, the mechanism of which needs to be elucidated.