bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANK2 as a novel predictive biomarker for immune checkpoint inhibitors and its correlation with antitumor immunity in lung adenocarcinoma
Authors: Zhang Wengang , Shang Xiaoling , Liu Ni , Ma Xinchun , Yang Rui , Xia Handai , Zhang Yuqing , Zheng Qi , Wang Xiuwen , Liu Yanguo 
Published: December 2022

Abstract
Background
Immune checkpoint inhibitors (ICIs) have been shown to significantly improve the survival of patients with advanced lung adenocarcinoma (LUAD). However, only limited proportion of patients could benefit from ICIs. Novel biomarkers with strong predictability are needed for clinicians to maximize the efficacy of ICIs. Our study aimed to identify potential biomarkers predicting ICIs efficacy in LUAD.

Methods
The Cancer Genome Atlas (TCGA) PanCancer Atlas studies in cBioportal were used to evaluate the mutation frequency of ANK2 across multiple cancers. Clinical and mutational data for LUAD from ICIs-treated cohorts (Hellmann et al. and Rizvi et al.) were collected to explore the correlation between ANK2 mutation and clinical outcomes. In addition, the relationship between ANK2 expression and clinical outcomes was analyzed using LUAD data from TCGA and Gene Expression Omnibus. Furthermore, the impact of ANK2 mutation and expression on the tumor immune microenvironment of LUAD was analyzed using TCGA and TISIDB databases.

Results
Patients with ANK2 mutation benefited more from ICIs. In ICIs-treated cohort, prolonged progression-free survival (PFS) (median PFS: NR (not reached) vs. 5.42 months, HR (hazard ratio) 0.31, 95% CI 0.18–0.54; P = 0.0037), improved complete response rate (17.65% vs. 1.85%, P = 0.0402), and improved objective response rate (64.71% vs. 24.07%, P = 0.0033) were observed in LUAD patients with ANK2 mutation compared to their wild-type counterparts. Regarding ANK2 expression, it was observed that ANK2 expression was decreased in LUAD (P < 0.05) and a higher level of ANK2 expression was associated with longer overall survival (HR 0.69, 95% CI 0.52–0.92; P = 0.012) in TCGA LUAD cohort. Moreover, ANK2 mutation or higher ANK2 expression correlated with enhanced antitumor immunity and “hot” tumor microenvironment in LUAD, which could be potential mechanisms that ANK2 mutation facilitated ICIs therapy and patients with higher ANK2 expression survived longer.

Conclusion
Our findings suggest that ANK2 mutation or increased ANK2 expression may serve as a favorable biomarker for the efficacy of ICIs in patients with LUAD.
The predictive association between radiological findings and lung cancer development in patients exposed to sulfur mustard gas: 4 decades follow up of 719 victims
Authors: Kavousi Shahin , Akbarialiabad Hossein , Mehrabani Davood , Mohamadian Alireza , Ghahramani Aria , Shirkhoda Ali , Jalli Reza 
Published: December 2022

Abstract
Background
Respiratory diseases are the leading cause of morbidity and mortality in the survivors exposed to Sulfur Mustard (SM). The late abnormalities can be present as chronic bronchitis, tracheobronchial stenosis, asthma, bronchiectasis, airway narrowing, lung fibrosis, and lung cancers. This study aims to investigate the association between radiological findings and lung cancer development in patients exposed to sulfur mustard gas.

Methods
We entered 719 victims exposed to SM during the Iran–Iraq war into our follow-up study in a consensus manner. They were periodically followed with Chest HRCT scans from 2001 to an interval of 2014–2019. The mean year interval between exposure and the last follow-up was 38 years. For confirming the lung cancer in those with evidence of malignancy in their imaging, fine needle aspiration/biopsy and/or surgical intervention were done.

Results
Among 719 patients, 57% were free from any pathologic findings in their HRCT scan. Among the subjects who had the abnormal radiologic findings, Air Trapping (AT), Lung Fibrosis (LF), Bronchiectasis (B), and the evidence of lung cancer were found in 265 (36.9%), 207 (28.8%), 151 (21.0%), and 42 (5.8%), respectively. Adenocarcinoma (38.1%) was the most common type of cancer. The right lung was involved more than the left one regarding LF, B, and cancer (p value < 0.05). Considering the laterality, a significant correlation was found between the side of LF and B and the tumor side. Furthermore, it was shown that the lung lobes with LF were statistically correlated to tumor-involved lobes. The relative risk of AT and B existence for tumor development was 11.73 [4.87–28.26] and 10.14 [5.12–20.090], respectively. The most predictive finding was LF which caused the risk of developing tumor 17.75 [7.35–42.86] times higher in the patient with this pathology. By each increment of the number of LF and B, the risk of developing tumors increased by 51% and 76%, respectively.

Conclusion
In survivors exposed to Sulfur Mustard, those with bronchiectasis and lung fibrosis have a significantly higher risk of developing lung cancers, so a close follow-up of these victims is recommended.
Trial registration This study was confirmed by the institutional review board and ethics committee at Shiraz University of Medical Sciences (SUMS) with the ethical code IR.SUMS.MED.REC.1399.637.
Evaluation of the quality and accuracy of breast cancer knowledge among persian language websites
Authors: Alipour Sadaf , Nikooei Shekoofeh , Hosseinpour Reza , Yavari Barhaghtalab Mohammad Javad 
Published: December 2022

AbstractIntroductionThe internet has become a powerful worldwide information source that revolutionized access to knowledge, especially in the fields of health and medicine (health knowledge). Therefore, providing high-quality, accurate, reliable, and relevant information on dependable websites is a possible way of providing the patient with needed information and, thus, achieving the benefits of informed patients regarding outcomes. This study aimed to evaluate the quality and accuracy of breast cancer knowledge among Persian language websites.MethodsTwo search engines were searched in the Persian language about breast cancer. The first 30 websites were selected for further evaluation based on the completeness, correctness, transparency, and accessibility of health knowledge. The DISCERN instrument was used to assess the quality of the Persian language websites on this issue.ResultsAmong the 30 websites, about 23% of websites provide completely correct information and about 30% provide mostly correct information. Sixty percent of the websites provided author information, and 46% of them had a healthcare professional or expert as the author. Sixty percent of the websites stated the creation date on the pages, while 40% of them did not provide any health knowledge. Scores on accessibility were always easy for most of the websites. Based on the quality rating system of DISCERN, about 60% of the websites were presented as very poor.ConclusionWebsite rankings enable healthcare professionals to identify and signpost patients to reliable up-to-date websites to ensure that patients receive high-quality knowledge. This review has provided evidence of inadequate and inaccurate health knowledge about breast cancer on the Persian language websites. This issue requires further investigation to understand the barriers and solutions available to provide reliable information about breast cancer and how this information affects the patient's outcomes.Trial registrationThe project was found to be in accordance with the ethical principles and the national norms and standards for conducting research in Iran with the approval ID and date of IR.TUMS.IKHC.REC.1399.379 and 2021–01-01 respectively, and is registered with research project number 49890 in the Vice Chancellor for Research and Technology Development of Tehran University of Medical Sciences, Tehran, Iran.URL:https://ethics.research.ac.ir/EthicsProposalViewEn.php?id=170978.
Early emergence of sexual dimorphism in offspring leukocyte telomere length was associated with maternal and children’s glucose metabolism—a longitudinal study
Authors: Wong Kwun Kiu , Cheng Feifei , Lim Cadmon K. P. , Tam Claudia H. T. , Tutino Greg , Yuen Lai Yuk , Wang Chi Chiu , Hou Yong , Chan Michael H. M. , Ho Chung Shun , Joglekar Mugdha V. , Hardikar Anandwardhan A. , Jenkins Alicia J. , Metzger Boyd E. , Lowe William L. , Tam Wing Hung , Ma Ronald C. W. 
Published: December 2022

Abstract
Background
Leukocyte telomere length (LTL) is suggested to be a biomarker of biological age and reported to be associated with metabolic diseases such as type 2 diabetes. Glucose metabolic traits including glucose and insulin levels have been reported to be associated with LTL in adulthood. However, there is relatively little research focusing on children’s LTL and the association with prenatal exposures. This study investigates the relationship between maternal and offspring glucose metabolism with offspring LTL in early life.

Methods
This study included 882 mother-child pairs from the HAPO Hong Kong Field Centre, with children evaluated at age 7.0 ± 0.4 (mean ± SD) years. Glucose metabolic traits including maternal post-load glucose during pregnancy, children’s glucose and insulin levels, and their derived indices at follow-up were measured or calculated. Offspring LTL was assessed using real-time polymerase chain reaction.

Results
Sex- and age-adjusted children’s LTL was found to be associated with children’s HOMA-IR (β=−0.046 ± 0.016, p=0.005). Interestingly, both children’s and maternal post-load glucose levels were positively associated with children’s LTL. However, negative associations were observed between children’s LTL and children’s OGTT insulin levels. In addition, the LTL in females was more strongly associated with pancreatic beta-cell function whilst LTL in males was more strongly associated with OGTT glucose levels.

Conclusions
Our findings suggest a close association between maternal and offspring glucose metabolic traits with early life LTL, with the offspring sex as an important modifier of the disparate relationships in insulin production and response.
Modulation of histone H3K4 dimethylation by spermidine ameliorates motor neuron survival and neuropathology in a mouse model of ALS
Authors: Choi Seung-Hye , Yousefian-Jazi Ali , Hyeon Seung Jae , Nguyen Phuong Thi Thanh , Chu Jiyeon , Kim Sojung , Kim Suhyun , Ryu Hannah L. , Kowall Neil W. , Ryu Hoon , Lee Junghee 
Published: December 2022

Abstract
Background
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive paralysis due to motor neuron degeneration. It has been proposed that epigenetic modification and transcriptional dysregulation may contribute to motor neuron death. In this study, we investigate the basis for therapeutic approaches to target lysine-specific histone demethylase 1 (LSD1) and elucidate the mechanistic role of LSD1-histone H3K4 signaling pathway in ALS pathogenesis.

Methods
In order to examine the role of spermidine (SD), we administered SD to an animal model of ALS (G93A) and performed neuropathological analysis, body weight, and survival evaluation.

Results
Herein, we found that LSD1 activity is increased while levels of H3K4me2, a substrate of LSD1, is decreased in cellular and animal models of ALS. SD administration modulated the LSD1 activity and restored H3K4me2 levels in ChAT-positive motor neurons in the lumbar spinal cord of ALS mice. SD prevented cellular damage by improving the number and size of motor neurons in ALS mice. SD administration also reduced GFAP-positive astrogliogenesis in the white and gray matter of the lumbar spinal cord, improving the neuropathology of ALS mice. Moreover, SD administration improved the rotarod performance and gait analysis of ALS mice. Finally, SD administration delayed disease onset and prolonged the lifespan of ALS (G93A) transgenic mice.

Conclusion
Together, modulating epigenetic targets such as LSD1 by small compounds may be a useful therapeutic strategy for treating ALS.
The impact of a family web-based nutrition intervention to increase fruit, vegetable, and dairy intakes: a single-blinded randomized family clustered intervention
Authors: Drapeau Vicky , Harvey Andrée-Anne , Jacob Raphaëlle , Provencher Véronique , Panahi Shirin 
Published: December 2022

Abstract
Background
The importance of adopting healthy eating habits at a young age to prevent obesity and chronic diseases justifies the need for effective interventions.

Objective
This study evaluated the impact of a family web-based nutrition intervention on vegetable and fruit (V/F) and dairy product (DP) consumption, nutrient intakes, diet quality and BMI or BMI z-scores.

Methods
Forty-three families with children aged 8–16 years were randomized to either the family web-based intervention, or web-based general nutrition guidelines (control) over 8 weeks. Nutritional variables were assessed with three-day dietary records while anthropometry (body weight and height) was assessed with standardized measures at baseline (PRE), immediately after the intervention (POST 1) and 3–6 months after the intervention (POST 2). Linear mixed models for repeated measures were used to assess the main effects and their interactions followed by post hoc tests.

Results
The intervention had an effect on DP, total sugar, potassium, magnesium, and calcium in children (Group x Time, P = 0.02 to 0.03) and on DP, V/F juice, carbohydrates, total sugar, saturated fat, protein and calcium in parents (Group x Time, P = 0.01 to 0.03). Post hoc tests revealed children in the intervention group increased their DP intakes immediately after the intervention (POST1) but decreased at follow-up (POST2). No effect of the intervention on V/F, diet quality or BMI was observed.

Conclusion
Compared to general nutrition guidelines, this family web-based nutrition intervention had a modest effect on nutrient intakes, but beneficial effect on DP intakes in the short term.

Trial registration
ClinicalTrials.gov, NCT03798808, Registered 10 january 2019 - Retrospectively registered.
Waiting times in healthcare: equal treatment for equal need?
Authors: García-Corchero Juan David , Jiménez-Rubio Dolores 
Published: December 2022

Abstract
Background
In many universal health systems, waiting times act as a non-monetary rationing mechanism, one that should be based on clinical need rather than the ability to pay. However, there is growing evidence that among patients with similar levels of need, waiting times often differ according to socioeconomic status. The mechanisms underlying inequality in access remain unclear.

Methods
Using data for Spain, we study whether waiting times for primary and specialist care depend on patients’ socioeconomic status (SES). Additionally, we make use of the continuous nature of our data to explore whether the SES-related differences in waiting times found for specialist consultations vary among different points of the waiting time distribution.

Results
Our results reveal the presence of a SES gradient in waiting times for specialist services explained on the basis of education, employment status and income. In addition, for primary care, we found evidence of a slightly more moderate SES gradient mostly based on employment status. Furthermore, although quantile regression estimates indicated the presence of a SES gradient within the distribution of waiting times for specialist visits, the SES differences attenuated in the context of longer waiting times in the public sector but did not disappear.

Conclusion
Our findings suggest the principle of equal treatment for equal need, assumed to be inherent to national health systems such as the Spanish system, is not applied in practice. Determining the mechanism(s) underlying this selective barrier to healthcare is of crucial importance for policymakers, especially in the current COVID-19 health and economic crises, which could exacerbate these inequalities as increasing numbers of treatments are having to be postponed.
The impact of sulfur mustard on quality of life and mental health in Kurdish survivors in Sweden, thirty years after exposure
Authors: Moradi Faraidoun , Moradi Fazil , Li Ying , Olin Anna-Carin , Daka Bledar 
Published: December 2022

Abstract
Background
The Iraqi state used chemical warfare agents (CWAs) like sulfur mustard (SM) in al-Anfal genocide in the present-day Kurdistan Region of Iraq. In addition to somatic injuries, exposure to CWAs causes biopsychosocial complications. We investigated the long-term impact of SM exposure on quality of life (QoL) and depression severity in Kurdish survivors resettled in Sweden.

Methods
This is a case-control study, where subjects exposed to SM (n = 18, mean age 51.3 years, 50% women) and sex- and age-matched nonexposed subjects (n = 30, mean age 48.7 years, 47% women) of Kurdish residents in Sweden. Data were collected through in-person interviews based on the RAND 36-item Short Form Health Survey to assess QoL and the Montgomery-Åsberg Depression Rating Scale-self assessment (MADRS-S) to investigate the presence and the gravity of depressive symptoms.

Results
The SM-exposed group had a significantly lower QoL than the nonexposed group (p < 0.001). Also, the overall mean MADRS-S scores among the SM-exposed group, corresponding to moderate depression, were higher than the scores of the nonexposed (22 points (p) vs. 9 p, p < .001). Overall, the participants within the exposed group reported worse mental than physical well-being 36p and 32p, respectively. Within the SM-exposed group, there was no gendered-related difference neither in terms of depression severity nor for QoL, but the groups were small.

Conclusion
Individuals exposed to SM had worse QoL and a higher level of depressive severity compared with nonexposed individuals three decades after exposure, indicating the importance of increased clinician knowledge, guidelines, and an approach to assess and respond to the exposed groups’ biopsychosocial needs. These findings indicate that those exposed to SM might need early identification of mental illnesses and more support to promote QoL.
Anatomical type analysis of right interlobar artery based on chest thin-slice CT scan and three-dimensional reconstruction
Authors: Wang Long-fei , Zhao Lei , Lv Chang-sheng , Xu Qing-tao , Wang Rong 
Published: December 2022

Abstract
Purpose
To analyse and summarize branching pattern types of the interlobar portion of right pulmonary arteries (RPA) through chest thin-slice CT scans and three-dimensional reconstruction.

Methods
A total of 179 patients (58 males and 121 females, with an average age of 53.9 years) at the Thoracic Surgery Department of Ningbo First Hospital were retrospectively included from December 2020 to December 2021. All patients completed preoperative thin-slice CT scans and three-dimensional reconstructions of the chest. The clinical data and branching patterns were collected. Data were analysed using SPSS 21.0.

Results
The branching pattern types of the interlobar portion of RPA were divided into 4 types according to the order and number of branches: Type I (145/179, 81.0%), Asc. A2, MA, A6; Type II (28/179, 15.6%), Asc. A2 deletion, MA, A6; Type III (5/179, 2.8%), Asc. A2, A6, MA; and Type IV (1/179, 0.6%), MA, Asc. A2, A6. Type I was the most common pattern. Furthermore, according to the number of branches of MA and A6, this pattern can be subdivided into 15 subcategories.

Conclusion
Chest thin-slice CT scans and 3D reconstructions can provide surgeons with accurate lung anatomy, which helps surgeons perform preoperative planning and complete surgery successfully.
Nauclea officinalis: A Chinese medicinal herb with phytochemical, biological, and pharmacological effects
Authors: Liu Bin , Geng Qi , Cao Zhiwen , Li Li , Lu Peipei , Lin Lin , Yan Lan , Lu Cheng 
Published: December 2022

AbstractNauclea officinalis (N. officinalis), a medicinal plant of the genus Nauclea in the family Rubiaceae, is used in the treatment of fever, pneumonia, pharyngolaryngitis, and enteritis in China. Extracts of N. officinalis include alkaloids, phenolic acids, pentacyclic triterpenoids, and flavonoids, which exert all kinds of pharmacological effects, for instance anti-inflammatory, anti-tumor, antibacterial, and antiviral and therefore show good effectiveness. To gain a comprehensive and deep understanding, the medicinal chemistry and chemical biology of N. officinalis are summarized in this review to provide a theoretical basis. The pharmacological effects were reviewed to provide evidence or insights into potential opportunities for further studies and medicinal exploitation of N. officinalis.
Ring finger protein 126 promotes breast cancer metastasis and serves as a potential target to improve the therapeutic sensitivity of ATR inhibitors
Authors: Pan You , Yang Yuchao , Huang Rong , Yang Huawei , Huang Qinghua , Ji Yinan , Dai Jingxing , Qiao Kun , Tang Wei , Xie Longgui , Yin Ming , Ouyang Jun , Ning Shipeng , Su Danke 
Published: December 2022

Abstract
Background/aims
This study explores the relationship between the E3 ubiquitin ligase Ring finger protein 126 (RNF126) and early breast cancer metastasis and tests the hypothesis that RNF126 determines the efficacy of inhibitors targeting Ataxia telangiectasia mutated and Rad3-related kinase (ATR).

Methods
Various metastasis-related genes were identified by univariable Cox proportional hazards regression analysis based on the GSE11121 dataset. The RNF126-related network modules were identified by WGCNA, whereas cell viability, invasion, and migration assays were performed to evaluate the biological characteristics of breast cancer cells with or without RNF126 knockdown. MTT, immunoblotting, immunofluorescence, and DNA fiber assays were conducted to determine the efficiency of ATR inhibitor in cells with or without RNF126 knockdown.

Results
RNF126 was associated with early breast cancer metastasis. RNF126 promoted breast cancer cell proliferation, growth, migration, and invasion. ATR inhibitors were more effective at killing breast cancer cells with intact RNF126 due to replication stress compared with the corresponding cells with RNF126 knockdown. Cyclin-dependent kinase 2 (CDK2) was involved in regulating replication stress in breast cancer cells with intact RNF126.

Conclusion
A high level of expression of RNF126 in early breast cancer patients without lymph node metastases may indicate a high-risk type of metastatic disease, possibly due to RNF126, which may increase breast cancer cell proliferation and invasion. RNF126-expressing breast cancer cells exhibit CDK2-mediated replication stress that makes them potential targets for ATR inhibitors.