bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated profiling identifies CACNG3 as a prognostic biomarker for patients with glioma
Authors: Shan Enfang , Cao Yi-nan , Zhang Yang , Chen Wen , Ren Xurui , Zhu Shanjie , Xi Xueru , Mu Shuai , Ma Mian , Zhi Tongle , Li Xianwen 
Published: September 2023

AbstractGliomas are the most common malignant primary brain tumors in adults with poor prognoses. The purpose of this study is to explore CACNG3 as a prognostic factor that is closely related to the progression and survival outcome of gliomas and to provide a potential new molecular target for the diagnosis and treatment of glioma patients. CACNG3 expression and related clinical data were collected from three major databases of The Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO). The CGGA dataset was used as a training set, and TCGA and GEO datasets obtained from the GEO database were used for validation. CACNG3 was expressed at low levels in the tumor group, and the overall survival (OS) in patients with low CACNG3 expression is shorter. Furthermore, CACNG3 expression was negatively associated with glioma grades, which was confirmed in the IHC results of clinical samples. The expression level of CACNG3 in the IDH1 wide-type group, 1p/19q non-codel group, and mesenchymal subtype group was significantly reduced, and the results showed that CACNG3 could serve as a biomarker for the mesenchymal molecular subtype. In addition, the univariate and multivariate analysis verified the prognostic value of CACNG3 in predicting the OS of gliomas of all grades. The results of functional annotation and pathway enrichment analysis of differently expressed genes(DEGs), showed that CACNG3 might affect the development of glioma by interfering with synaptic transmission. Moreover, temozolomide (TMZ), commonly used in the treatment of glioma, increased CACNG3 expression in a dose and time-dependent manner. Therefore, CACNG3 plays a vital role in the occurrence and development of gliomas and can serve as a potential biomarker for targeted therapy and further investigation in the future.
Increased TCP11 gene expression can inhibit the proliferation, migration and promote apoptosis of cervical cancer cells
Authors: Wang Fang , Song Shuyan , Guo Bingxuan , Li Yangyang , Wang Huijuan , Fu Shaowei , Wang Luyue , Zhe Xiangyi , Li Hongtao , Li Dongmei , Shao Renfu , Pan Zemin 
Published: September 2023

Abstract
Background
Cervical cancer is a common gynecological malignancy. Gene microarray found that TCP11 gene was highly expressed in cervical cancer. However, the effect of TCP11 gene on the proliferation, apoptosis and migration of cervical cancer cells and its underlying molecular mechanisms are unclear.

Methods
GEPIA database, tissue microarray, western blot and qRT-PCR were used to analyze the expression of TCP11 gene in cervical cancer tissues and cells and its relationship with patients’ survival rate. The cell cycle and apoptosis were detected by flow cytometry, and the expressions of cell cycle and apoptosis related molecules and EMT-related molecules were detected by Western blot and qRT-PCR.

Results
The results showed that TCP11 gene was highly expressed in cervical cancer tissues and cells compared with normal cervical tissues and cells, and its expression was positively correlated with patients’ survival rate. The results of proliferation and migration assays showed that TCP11 overexpression inhibited the proliferation and migration of HeLa and SiHa cells. The results showed that TCP11 overexpression blocked the cell cycle of HeLa and SiHa cells, decreased the expression of CDK1 and Cyclin B1, and increased the apoptosis and the expression of caspase-3, cleaved-caspase-3 and cleaved-PARP. TCP11 overexpression increased the protein and mRNA expression of EMT-related molecules ZO-1 and E-cadherin. Conversely, TCP11 knockdown promoted the proliferation of HeLa and SiHa cells and the migration of HeLa cells.

Conclusions
TCP11 overexpression significantly inhibited the occurrence and development of cervical cancer cells, it may be a potentially beneficial biomarker for cervical cancer.
German mammography screening program: program sensitivity between 2010 and 2016 estimated based on German health claims data
Authors: Heinze Franziska , Czwikla Jonas , Heinig Miriam , Langner Ingo , Haug Ulrike 
Published: September 2023

Abstract
Background
Program sensitivity is a key quality indicator for mammography screening programs (MSP). Estimating program sensitivity usually requires a linkage of screening and cancer registry data. For the German MSP, such data linkage-based estimates have only been reported for two out of 16 federal states. We aimed to explore the potential of estimating program sensitivity for the German MSP based on information available in health claims data.

Methods
We used data from the second-largest statutory health insurance fund in Germany, BARMER (~ 9 million members all over Germany). We included women aged 50 to 69 years with a non-initial screening mammography between 2010 and 2016 and followed them up for two years. We estimated the rate of screen-detected and interval cancers as well as program sensitivity.

Results
Per year, we included 212,400 to 303,667 women (mean age: 60–61 years). Overall, 1,992,287 non-initial MSP screening examinations conducted in these women between 2010 and 2016 were considered for the analyses. Age-standardized program sensitivity ranged between 69.9% [95% CI: 67.3–72.0%] and 71.7% [95% CI: 69.5-73.9%] during the study period. Per 1,000 non-initial screening examinations, the rate of screen-detected breast cancer ranged between 4.6 and 5.3, and the rate of interval breast cancer rates ranged between 0.6 and 0.8 for the first and between 1.3 and 1.4 for the second year after screening.

Conclusions
Our results were plausible and consistent with quality indicators estimated for the German MSP based on data linkage and thus support the value of German health claims data in this regard. The quality indicators estimated in our study are in line with levels expected according to European Guidelines.
Causal associations between gut microbiota and urological tumors: a two-sample mendelian randomization study
Authors: Mingdong Wang , Xiang Gao , Yongjun Quan , Mingshuai Wang , Hao Ping 
Published: September 2023

Abstract
Background
Dysbiosis of gut microbiota has been linked to numerous diseases, including cancer. The unique role of gut microbiota in urological tumors is gaining prominence. However, it is still controversial whether the dysbiosis of gut microbiota should be one of the etiological factors of bladder cancer (BCa), prostate cancer (PCa) or kidney cancer (KCa).

Materials and methods
The microbiome genome-wide association study (GWAS) from the MiBioGen consortium (18,340 samples of 24 population-based cohorts) was utilized as the exposure data. Additionally, outcomes data (951 BCa cases and 307,092 controls; 1,631 KCa cases and 238,678 controls; 79,148 PCa cases and 61,106 controls) were extracted from the GWAS of the FinnGen and PRACTICAL consortia. To detect the potential causative bacterial traits for BCa, PCa, and KCa, a two-sample Mendelian randomization (MR) analysis was performed, employing the inverse-variance weighted or Wald ratio method. Sensitivity analyses were subsequently conducted to explore the robustness of the primary results. Finally, the reverse MR analysis was undertaken to mitigate the reverse causation.

Results
This study suggested that Bifidobacterium (p = 0.030), Actinobacteria (p = 0.037 for phylum, 0.041 for class), and Ruminococcustorques group (p = 0.018), exhibited an association with an increased risk of BCa using either the inverse-variance weighted or Wald ratio method. By utilizing the Wald ratio method, Allisonella (p = 0.004, p = 0.038) was associated with a decreased risk of BCa and PCa, respectively. Furthermore, Ruminococcustorques group (p = 0.028) and Erysipelatoclostridium (p = 0.048) were causally linked to an elevated risk of KCa.

Conclusions
This MR study supports that genetically predicted gut microbiota is causally related to BCa, PCa and KCa. Additionally, distinct bacterial traits are identified in relation to each tumor type.
Painted playgrounds for preschoolers’ physical activity and fundamental motor skill improvement: a randomized controlled pilot trial of effectiveness
Authors: Webster E. Kipling , Kepper Maura M. , Saha Sanjoy , Beyl Robbie A. , Kracht Chelsea L. , Romain Jessica St. , Staiano Amanda E. 
Published: September 2023

Abstract
Background
Preschool children are not meeting recommended levels of physical activity (PA) nor are they proficient in fundamental motor skills (FMS), which are the foundation for PA. As such, interventions are needed to increase PA and FMS in young children. This trial examined the effects of an environmental (“painted playgrounds”) and capacity-building (written toolkit) intervention on child FMS, PA, and sedentary behavior at early childhood education (ECE) centers and examined feasibility.

Methods
In a randomized controlled trial, four ECE centers were randomly assigned to an intervention group or wait-list control. For intervention centers, stencils were spray painted adjacent to playgrounds and teachers were provided material for using stencils for FMS practice. Follow-up assessments were conducted six to eight weeks after baseline. Time spent in PA and sedentary behavior was assessed via accelerometry and FMS were evaluated using the Test of Gross Motor Development (TGMD-3) at baseline and follow-up. A repeated measures linear model was performed to test the effects of the painted playgrounds on the primary outcomes of interest. Feasibility was measured by stencil engagement via direct observation and satisfaction surveys.

Results
A total of 51 preschoolers completed baseline assessments (4.3±0.6 years; 43.1% male). There were no significant changes in PA or sedentary behavior (all confidence intervals contain 0) between control and intervention groups. Intervention children significantly improved ball skill, locomotor, and overall TGMD-3 percentile scores at follow-up (all (all confidence intervals contain 0), which was not observed in control group. However, there was no significant change in FMS between the control and intervention groups (confidence intervals contain 0). For stencil use, boys and girls interacted with different stencils during their free play. Directors and teachers reported children incorporated academic concepts and initiated games, and teachers prompted more PA opportunities on the playground.

Conclusions
This intervention did not show statistically significant changes in children’s PA, FMS, or sedentary behavior compared to a control group; however, small FMS improvements for the intervention group were found from baseline to follow-up. Further work should examine intervention fidelity as well as inexpensive supplies, teacher training, or other strategies to increase preschool children’s PA and improve FMS at ECE centers.
Safe use of the ketogenic diet in an infant with microcephaly, epilepsy, and diabetes syndrome: a case report
Authors: Zegarra Walter A. , Gallentine William B. , Ruzhnikov Maura R. , McAndrews Catherine A. , Gloyn Anna L. , Addala Ananta 
Published: September 2023

Abstract
Background
Microcephaly, epilepsy, and diabetes syndrome (MEDS) is a rare syndromic form of monogenic diabetes caused by bi-allelic loss of function mutations in IER3IP1. In vitro studies have shown that loss of IER31P leads to apoptosis in both neurons and pancreatic β-cells. Simultaneous management of seizures and diabetes is challenging in patients with MEDS. We present the challenges and successes in the use of ketogenic diet in an infant with insulinopenic diabetes.

Case presentation
Our term female proband presented at 2 months of age with new onset multifocal seizures followed by the onset of infantile spasms (IS) at 4 months of age. An epilepsy gene panel identified bi-allelic variants, c.239T > G (p.Leu80*) and c.2T > A (initiator codon), in IER3IP1 that were subsequently shown to be inherited in trans. Following initiation of steroid therapy for IS, the patient developed clinically apparent insulin requiring diabetes. Her epilepsy was ultimately refractory to multiple antiseizure medications, thus the ketogenic diet (KD) was initiated. We were able to successfully titrate to a therapeutic KD ratio of 3:1 and maintain a ketotic state without diabetic ketoacidosis (DKA). With intercurrent illnesses, however, the patient had rapid decompensation and mild DKA due to delays in treatment, and for this reason, KD was discontinued after 5 months.

Conclusions
We report two novel IER31P1 mutations in a patient with MEDS and the successful management of the cooccurring conditions of IS and insulinopenic diabetes with the KD. Our experience underscores the importance of careful monitoring during KD as our patient had DKA more easily when on the KD.
A cross-sectional study on resilience, anxiety, depression, and psychoactive substance use among heterosexual and sexual minority adolescents in Nigeria
Authors: Ibigbami Olanrewaju Ibikunle , Oginni Olakunle Ayokunmi , Bradley Cory , Lusher Joanne , Sam-Agudu Nadia Adjoa , Folayan Morenike Oluwatoyin 
Published: September 2023

AbstractBackgroundMental health-related problems predispose alcohol and other psychoactive substances use as coping strategies. We assessed associations between resilience and anxiety symptoms, depressive symptoms, problematic alcohol, and multiple psychoactive substance use among sexual minority and heterosexual adolescents in Nigeria.MethodsThis was a secondary analysis of a subset of data generated through an online cross-sectional study conducted between 16thand 31stof October 2020. Data extracted for adolescents in Nigeria age 13–19 years were: dependent variables (alcohol use using the CAGE test, multiple psychoactive substance use, depressive symptoms using the Patient Health Questionnaire-9, and anxiety symptoms using the Generalized Anxiety Disorder-7 measure); independent variables (resilience using the Connor-Davidson resilience scale and sexual identity), and confounding factors (age and sex). Associations between dependent and independent variables were determined using multivariable logistic regression analyses after controlling for confounders.ResultsOf the 1419 adolescent participants, 593 (42%) were sexual minority individuals, 533 (37.6%) had high depressive symptoms, 381 (26.8%) had high anxiety symptoms, 177 (12.5%) had problematic alcohol use and 389 (27.4%) used multiple psychoactive substances. Resilience was significantly associated with lower odds of anxiety (AOR:0.96, 95% CI: 0.94–0.97,p < 0.001) and depressive (AOR:0.94, 95% CI: 0.92–0.96,p < 0.001) symptoms, problematic alcohol use (AOR:0.97, 95% CI: 0.95–0.99,p = 0.002), and multiple psychoactive substance use (AOR:0.95, 95% CI: 0.93–0.96,p < 0.001). Sexual minority adolescents had significantly higher odds of anxiety (AOR:4.14, 95% CI: 3.16–5.40,p < 0.001) and depressive symptoms (AOR:4.79; 95% CI: 3.73–6.15,p < 0.001), problematic alcohol use (AOR:2.48, 95% CI: 1.76–3.49,p < 0.001), and multiple psychoactive substance use (AOR:5.69, 95% CI: 4.34–7.47,p < 0.001).ConclusionSexual minority adolescents and adolescents with low resilience have a higher need for interventions to reduce the risk of anxiety, depression, and the use of alcohol and other psychoactive substances.
The causal relationship between thyroid function, autoimune thyroid dysfunction and lung cancer: a mendelian randomization study
Authors: Wang Xinhui , Liu Xue , Li Yuchen , Tang Mulin , Meng Xue , Chai Yuwei , Zhang Li , Zhang Haiqing 
Published: September 2023

Abstract
Background
The role of thyroid hormones in cancers has been discussed in observational studies; however, the causal relationship between them remains controversial.

Methods
The SNPs associated with hypothyroidism and hyperthyroidism were selected from a FinnGen biobank of 342,499 (190,879 females and 151,620 males) Finnish adult subjects. Data from the Thyroidomics Consortium on 72,167 individuals were used to assess genetically determined thyroid-stimulating hormone (TSH) and free thyroxine (FT4). Lung cancer, lung adenocarcinoma and squamous cell lung cancer GWAS data from the International Lung Cancer Consortium(ILCCO). Six different Mendelian randomization (MR) Methods, including Inverse variance weighted (IVW), MR-Egger, Simple mode, MR-Pleiotropy Residual Sum and Outlier methods (MR-PRESSO), Weighted mode and Weighted median were used to Two-Sample MR analysis. IVW was used as the primary estimate. Sensitivity analyses were examined via four aspects (Cochran’s Q-test, MR Egger intercept analysis, Funnel plot and Leave-one-out sensitivity test).

Results
The OR of hypothyroidism on lung cancer was 0.918 (95% CI, 0.859–0.982; p = 0.013) in MR analysis with IVW method. No evidence for effects of hyperthyroidism, TSH and FT4 on lung cancer risk was found via six MR methods. Meanwhile, there was no evidence for effects of lung cancer on hypothyroidism through six MR methods. Lung adenocarcinoma and squamous cell lung carcinoma were further analyzed on the basis of lung cancer. The OR of hypothyroidism on lung adenocarcinoma was 0.893(95% CI, 0.813–0.981; p = 0.019), the OR of hypothyroidism on squamous cell lung cancer was 0.888(95%CI,0.797–0.990, p = 0.032) in MR analysis with IVW method.

Conclusion
In summary, hypothyroidism genetically had a protective causal association with lung cancer. Furthermore, hypothyroidism had protective effects both on lung adenocarcinoma and squamous cell lung cancer. Further work is needed to elucidate the potential mechanisms.
Neoadjuvant chemotherapy weakens the prognostic value of the pathological tumor burden score for colorectal cancer liver metastases
Authors: Liao Leen , Sun Hui , He Jiahua , Liu Yujun , Pan Zhizhong , Wu Xiaojun , Fan Wenhua , Peng Jianhong , Li Cong 
Published: September 2023

Abstract
Background
The pathological tumor burden score (TBS) has been proven to be a better risk stratification tool for liver metastasis of colorectal cancer than the traditional clinical risk score (CRS). The aim of this study was to evaluate the prognostic value of the pathological tumor burden score in patients with or without neoadjuvant chemotherapy (NAC).

Methods
A total of 348 patients with colorectal liver metastases (CRLM) who underwent curative hepatic resection were retrospectively enrolled from September 1999 to December 2016. Univariable and multivariable Cox regression analyses were conducted to identify the independent predictors of prognosis. Kaplan–Meier curves and log-rank tests were used to determine whether TBS has enough discriminatory ability under certain grouping.

Results
Patients who received NAC had a higher median TBS than patients who did not receive NAC (4.07 vs. 2.69, P < 0.001). Among patients who did not receive NAC, those with TBS > 3 showed a significantly worse 3-year RFS (41.1% vs. 63.6%, P < 0.001) and 3-year OS rate (73.3% vs. 84.1%, P = 0.003) than those with TBS ≤ 3. Among the patients who received NAC, those with TBS ≤ 3 or TBS > 3 showed comparable 3-year RFS (33.3% vs. 26.4%, P = 0.400) and 3-year OS rates (76.5% vs. 58.2%, P = 0.064) to those who did not. Regardless of the regimen and response to NAC, there was no significant difference about 3-year RFS and 3-year OS rates between the TBS ≤ 3 and TBS > 3 groups.

Conclusion
Pathological TBS can be applied to predict the RFS and OS of patients suffering from CRLM who did not receive NAC. However, pathological TBS might not be regard as prognosis in patients who did receive NAC.
“I didn’t know it was going to be like this.”: unprepared for end-of-Life care, the experiences of care aides care in long-term care
Authors: Booi Laura , Sixsmith Judith , Chaudhury Habib , O’connor Deborah , Surr Claire , Young Melanie , Sixsmith Andrew 
Published: September 2023

Abstract
Background
Care aides provide up to 70–90% of the direct care for residents in long-term care (LTC) and thus hold great potential in improving residents’ quality of life and end-of-life (EoL) care experiences. Although the scope and necessity of the care aide role is predicted to increase in the future, there is a lack of understanding around their perceptions and experiences of delivering EoL care in LTC settings. The aim of this study was to gain an understanding of the perspectives, experiences, and working conditions of care aides delivering end-of-life care in LTC in a rural setting, within a high-income country.

Methods
Data were collected over ten months of fieldwork at one long-term care home in western Canada; semi-structured interviews (70 h) with 31 care aides; and observation (170 h). Data were analysed using Reflexive Thematic Analysis.

Results
Two themes were identified: (i) the emotional toll that delivering this care takes on the care aids and; (ii) the need for healing and support among this workforce. Findings show that the vast majority of care aides reported feeling unprepared for the delivery of the complex care work required for good EoL care. Findings indicate that there are no adequate resources available for care aides’ to support the mental and emotional aspects of their role in the delivery of EoL care in LTC. Participants shared unique stories of their own self-care traditions to support their grief, processing and emotional healing.

Conclusions
To facilitate the health and well-being of this essential workforce internationally, care aides need to have appropriate training and preparation for the complex care work required for good EoL care. It is essential that mechanisms in LTC become mandatory to support care aides’ mental health and emotional well-being in this role. Implications for practice highlight the need for greater care and attention played on the part of the educational settings during their selection and acceptance process to train care aides to ensure they have previous experience and societal awareness of what care in LTC settings entails, especially regarding EoL experiences.