bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geographical variations of cancer incidence in Guadeloupe, French West Indies
Authors: Bhakkan-Mambir Bernard , Deloumeaux Jacqueline , Luce Danièle 
Published: July 2022

Abstract
Background
Geographical disparities in cancer incidence are observed at different scales and may highlight areas of high risk that need special attention to improve health policies. In Guadeloupe, a French archipelago in the Caribbean, environmental and socioeconomic factors are potential factors associated with cancer incidence. Our objective was to describe geographical variations of cancer incidence in Guadeloupe at a small-area level, in order to identify potential clusters.

Methods
We conducted spatial analyses for the 18 most frequent cancer sites, using data collected by the population-based cancer registry of Guadeloupe over the period 2008–2017. For each cancer sites, we used the Besag, York and Mollié model to estimate smoothed standardized incidence ratios (SIRs) at a sub-municipality level. In addition, we performed ascendant hierarchical clustering of these smoothed SIRs to describe the relationship between the different cancer sites and to identify geographical clusters.

Results
We observed geographical disparities with a spatial pattern that varied across cancer sites. Clustering of the smoothed SIRs showed aggregations between breast cancer and multiple myeloma, thyroid and stomach cancer, cervical and head and neck cancers, lung and rectal cancers, ovarian and endometrial cancers. Cluster analysis also identified six geographical clusters. Features of these clusters suggest alcohol consumption, exposure to pesticides, pollution generated by open landfills, and ethnicity as possible explanatory factors.

Discussion/conclusion
Our study provided for the first time an extensive description of geographical disparities in cancer incidence in Guadeloupe, in a region where socioeconomic and environmental issues are major concerns. Although the identification of underlying factors was out of the scope of the present study, we highlighted areas of special interest and put forward some hypotheses that warrant to be further investigated in more in-depth analyses.
Prognostic impact of stromal periostin expression in upper urinary tract urothelial carcinoma
Authors: Miyai Kosuke , Kawamura Kazuki , Ito Keiichi , Matsukuma Susumu , Tsuda Hitoshi 
Published: July 2022

Abstract
Background
Periostin is an extracellular matrix protein that has been known to be implicated in fibrillogenesis and cell migration, including cancer metastasis. Periostin overexpression in cancer cells and/or intervening stroma is usually related to tumor progression and poor patient outcomes in various human cancers; however, its role in urothelial carcinoma, especially upper urinary tract urothelial carcinomas (UTUCs), remains inconclusive.

Methods
Samples from 126 consecutive cases of invasive UTUC (69 renal pelvic cancers and 57 ureteral cancers) were histologically reviewed and analyzed for periostin expression using immunohistochemistry. The intensities of immunoreactivity and the fraction of positive cancer cells and stroma (i.e., epithelial and stromal expression, respectively) were classified into four categories each (intensity, 0–3; fraction, 0–25% = 1; 26–50% = 2; 51–75% = 3; and > 75% = 4). The overall score was determined by multiplying both scores, and overall scores ≥ 6 were considered to indicate high periostin expression.

Results
Among 126 UTUCs, 55 (44%; 27 renal pelvic and 28 ureteral cancers) showed high stromal periostin expression. None of the cases were considered to have high epithelial periostin expression. High stromal periostin expression was associated with non-papillary gross findings, higher pathological T category, lymphovascular invasion, concomitant carcinoma in situ, subtype histology, lymph node metastasis, positive surgical margins, high tumor budding, and high tumor-associated immune cell status. Multivariate analysis revealed that high stromal periostin expression was an independent predictor of overall survival (p = 0.00072, hazard ratio = 3.62), and lymphovascular invasion and high stromal periostin expression were independent predictors of cancer-specific survival (p = 0.032 and 0.020, hazard ratio = 2.61 and 3.07, respectively).

Conclusions
Stromal periostin expression was often observed in invasive UTUCs with adverse clinicopathological factors and may be a useful predictor of patient outcomes.
TTK Protein Kinase promotes temozolomide resistance through inducing autophagy in glioblastoma
Authors: Yu Jian , Gao Ge , Wei Xiangpin , Wang Yang 
Published: July 2022

Abstract
Background
Temozolomide (TMZ) resistance remains the main therapy challenge in patients with glioblastoma multiforme (GBM). TTK Protein Kinase (TTK) contributes to the radioresistance and chemoresistance in many malignancies. However, the role of TTK in the TMZ resistance of GBM cells remains unknown.

Methods
The expression of TTK was measured by western blot. The proliferation of GBM cells was assessed through MTT assay and clonogenic assay. Cell apoptosis was evaluated using western blot. LC3B puncta were detected using immunohistochemistry staining. The mouse xenograft model was used to investigate the role of TTK in vivo.

Results
Knockdown of TTK increased the sensitivity of GBM cells to TMZ treatment, while overexpression of TTK induced TMZ resistance. Two specific TTK inhibitors, BAY-1217389 and CFI-402257, significantly inhibited GBM cell proliferation and improved the growth-suppressive effect of TMZ. In addition, the knockdown of TTK decreased the autophagy levels of GBM cells. Inhibition of TTK using specific inhibitors could also suppress the autophagy process. Blocking autophagy using chloroquine (CQ) abolished the TMZ resistance function of TTK in GBM cells and in the mouse model.

Conclusions
We demonstrated that TTK promotes the TMZ resistance of GBM cells by inducing autophagy in vitro and in vivo. The use of a TTK inhibitor in combination with TMZ might help to overcome TMZ resistance and improve therapy efficiency in GBM.
Assessing the accuracy of multiparametric MRI to predict clinically significant prostate cancer in biopsy naïve men across racial/ethnic groups
Authors: Meza Julio , Babajide Rilwan , Saoud Ragheed , Sweis Jamila , Abelleira Josephine , Helenowski Irene , Jovanovic Borko , Eggener Scott , Miller Frank H. , Horowitz Jeanne M. , Casalino David D. , Murphy Adam B. 
Published: July 2022

AbstractIntroductionThe Prostate Imaging Reporting and Data System (PIRADS) has shown promise in improving the detection of Gleason grade group (GG) 2–5 prostate cancer (PCa) and reducing the detection of indolent GG1 PCa. However, data on the performance of PIRADS in Black and Hispanic men is sparse. We evaluated the accuracy of PIRADS scores in detecting GG2-5 PCa in White, Black, and Hispanic men.MethodsWe performed a multicenter retrospective review of biopsy-naïve Black (n = 108), White (n = 108), and Hispanic (n = 64) men who underwent prostate biopsy (PB) following multiparametric MRI. Sensitivity and specificity of PIRADS for GG2-5 PCa were calculated. Race-stratified binary logistic regression models for GG2-5 PCa using standard clinical variables and PIRADS were used to calculate area under the receiver operating characteristics curves (AUC).ResultsRates of GG2-5 PCa were statistically similar between Blacks, Whites, and Hispanics (52.8% vs 42.6% vs 37.5% respectively,p = 0.12). Sensitivity was lower in Hispanic men compared to White men (87.5% vs 97.8% respectively,p = 0.01). Specificity was similar in Black versus White men (21.6% vs 27.4%,p = 0.32) and White versus Hispanic men (27.4% vs 17.5%,p = 0.14).The AUCs of the PIRADS added to standard clinical data (age, PSA and suspicious prostate exam) were similar when comparing Black versus White men (0.75 vs 0.73,p = 0.79) and White versus Hispanic men (0.73 vs 0.59,p = 0.11). The AUCs for the Base model and PIRADS model alone were statistically similar when comparing Black versus White men and White versus Hispanic men.ConclusionsThe accuracy of the PIRADS and clinical data for detecting GG2-5 PCa seems statistically similar across race. However, there is concern that PIRADS 2.0 has lower sensitivity in Hispanic men compared to White men. Prospective validation studies are needed.
Oral health professionals screening for undiagnosed type-2 diabetes and prediabetes: the iDENTify study
Authors: Mariño Rodrigo , Priede Andre , King Michelle , Adams Geoffrey G. , Sicari Maria , Morgan Mike 
Published: July 2022

Abstract
Background
As part of an evaluation of an oral healthcare practice-based model that identifies patients with prediabetes or type-2 diabetes, this study reports on the proportion of patients identified with clinically confirmed type-2 diabetes (T2D)/prediabetes and barriers of implementation of the model.

Methodology
Urban and rural oral healthcare practices were invited to participate. Participating practices invited eligible patients to participate in the screening program using the Australian Type-2 Diabetes Risk Assessment Tool (AUSDRISK). Participants were categorised as low, intermediate, or high-risk for prediabetes/T2D. Patients in the intermediate or high-risk category were referred to their General Medical Practitioner (GP) for further investigation.

Results
Fifty-one oral healthcare practices and 76 Oral Health Professionals (OHP) participated (60 Dentists, 8 Dental Hygienists, 8 Oral Health Therapists). 797 patients were screened; 102 were low-risk; 331 intermediate-risk; and 364 high-risk for T2D. Of the 695 participants in the intermediate or high-risk groups, 386 (55.5%) were referred to their GP for T2D assessment. Of them, 96 (25.0%) results were returned to OHPs. Of the returned results, six were (6.3%) diagnosed with pre-T2D.

Conclusion
Patients found to have undiagnosed T2D/prediabetes (6.3%) were within the expected range reported in the literature. Findings indicate that identifying individuals at an elevated risk of having or developing T2D is effective, feasible and could be incorporated into oral healthcare settings. However, this integration may require additional OHPs training and education to ensure that patients at elevated risk of T2D are referred for further assessment.
The mediating role of life satisfaction in the relationship between depression, anxiety, stress and burnout among Portuguese nurses during COVID-19 pandemic
Authors: Martins Vera , Serrão Carla , Teixeira Andreia , Castro Luísa , Duarte Ivone 
Published: July 2022

AbstractBackgroundThe COVID-19 pandemic had a large consequence on healthcare systems, increasing the risks of psychological issues in health professionals. Nurses, in particular, have been exposed to multiple psychosocial stressors and struggled with intensive work, insufficiency of resources and uncertainty in the face of an unknown disease. Life satisfaction might protect nurses from the consequences of chronic stress. The aim of this study was to explore the mediating role of satisfaction with life in the relationship between depression, stress, anxiety and burnout (personal, work-related, and client-related).MethodsA cross-sectional, descriptive, correlational study design was performed, using an online questionnaire distributed via social networks. A total of 379 nurses completed the survey, comprising standardized measures of satisfaction with life, resilience (Resilience Scale), depression, anxiety, stress (Depression Anxiety Stress Scales), and burnout (Copenhagen Burnout Inventory Scale). A hierarchical regression model was estimated for each burnout dimension.ResultsParticipants showed high levels of work, personal and client-related burnout, 57.3%, 57%, and 35.1%, respectively. More than 70% of the respondents had a normal level of depressive symptoms, 66.8% presented normal level of anxiety and 33.5% of the respondents reported mild, moderate, severe or extremely severe symptoms of stress. The results revealed that life satisfaction partially mediated the association between stress and personal burnout, depression and work-related burnout, and the association between anxiety and client-related burnout in nurses.ConclusionsThe COVID-19 pandemic brought added difficulties for nurses’ work conditions, whereby it became necessary to develop adaptative measures that reduce stressors in work environment and promote nurses’ life satisfaction.
Work schedule characteristics associated with sleep disturbance among healthcare professionals in Europe and South Korea: a report from two cross-sectional surveys
Authors: Min Ari , Hong Hye Chong 
Published: July 2022

Abstract
Background
Healthcare professionals worldwide are prone to sleep disturbance. Such sleep disturbance is associated with lower patient safety and quality of care. Therefore, this study aimed to identify the prevalence of sleep disturbance and determine the effect of work schedule characteristics on sleep disturbance among healthcare professionals in Europe and South Korea.

Methods
We used the sixth European Working Conditions Survey and the fifth Korean Working Conditions Survey for analyses. The study included 2285 healthcare professionals aged 18–65 years. Work schedule characteristics included shift work, night work, working hours per week, long work hours (i.e., more than 10 hours per shift), quick return to work, having to come to work on short notice, and changes in work schedules. A multiple logistic regression analysis was performed.

Results
The overall prevalence of sleep disturbance was 37.7%. The multivariate logistic regression model indicated that long work hours, quick return to, having to come to work on short notice, and changes in work schedules were significant factors associated with sleep disturbance among healthcare professionals.

Conclusion
The findings revealed that several work schedule-related factors were associated with sleep disturbances in healthcare professionals in Europe and Korea. Institutions and policymakers should implement strategies and policies to reduce the unpredictability of work schedules to ensure an adequate rest period between shifts and to reduce sleep disturbances.
An integrative perspective on interorganizational multilevel healthcare networks: a systematic literature review
Authors: van der Weert Galina , Burzynska Katarzyna , Knoben Joris 
Published: July 2022

Abstract
Background
Interorganizational networks in healthcare do not always attain their goals. Existing models outline the factors that could explain poor network performance: governance; structure; and the alignment of professional, organizational and network levels. However, these models are very generic and assume a functional approach. We investigate available empirical knowledge on how network structure and governance relate to each other and to network performance in a multilevel context, to get deeper insight, supported with empirics, of why networks (fail to) achieve their goals.

Method
A systematic literature review based on a search of Web of Science, Business Source Complete and PubMed was executed in May 2021 and repeated in January 2022. Full papers were included if they were written in English and reported empirical data in a healthcare interorganizational setting. Included papers were coded for the topics of governance, structure, performance and multilevel networks. Papers from the scientific fields of management, administration and healthcare were compared. Document citation and bibliographic coupling networks were visualized using Vosviewer, and network measures were calculated with UCINET.

Results
Overall, 184 papers were included in the review, most of which were from healthcare journals. Research in healthcare journals is primarily interested in the quality of care, while research in management and administration journals tend to focus on efficiency and financial aspects. Cross-citation is limited across different fields. Networks with a brokered form of governance are the most prevalent. Network performance is mostly measured at the community level. Only a few studies employed a multilevel perspective, and interaction effects were not usually measured between levels.

Conclusions
Research on healthcare networks is fragmented across different scientific fields. The current review revealed a range of positive, negative and mixed effects and points to the need for more empirical research to identify the underlying reasons for these outcomes. Hardly any empirical research is available on the effects of different network structures and governance modes on healthcare network performance at different levels. We find a need for more empirical research to study healthcare networks at multiple levels while acknowledging hybrid governance models that may apply across different levels.
DNA methylation subtypes guiding prognostic assessment and linking to responses the DNA methyltransferase inhibitor SGI-110 in urothelial carcinoma
Authors: Li Juan , Liang Yuan , Fan Jian , Xu Chunru , Guan Bao , Zhang Jianye , Guo Bin , Shi Yue , Wang Ping , Tan Yezhen , Zhang Qi , Yuan Changwei , Wu Yucai , Zhou Liqun , Ci Weimin , Li Xuesong 
Published: July 2022

Abstract
Background
At present, the extent and clinical relevance of epigenetic differences between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) remain largely unknown. Here, we conducted a study to describe the global DNA methylation landscape of UTUC and UCB and to address the prognostic value of DNA methylation subtype and responses to the DNA methyltransferase inhibitor SGI-110 in urothelial carcinoma (UC).

Methods
Using whole-genome bisulfite sequencing (n = 49 samples), we analyzed epigenomic features and profiles of UTUC (n = 36) and UCB (n = 9). Next, we characterized potential links between DNA methylation, gene expression (n = 9 samples), and clinical outcomes. Then, we integrated an independent UTUC cohort (Fujii et al., n = 86) and UCB cohort (TCGA, n = 411) to validate the prognostic significance. Furthermore, we performed an integrative analysis of genome-wide DNA methylation and gene expression in two UC cell lines following transient DNA methyltransferase inhibitor SGI-110 treatment to identify potential epigenetic driver events that contribute to drug efficacy.

Results
We showed that UTUC and UCB have very similar DNA methylation profiles. Unsupervised DNA methylation classification identified two epi-clusters, Methy-High and Methy-Low, associated with distinct muscle-invasive statuses and patient outcomes. Methy-High samples were hypermethylated, immune-infiltrated, and enriched for exhausted T cells, with poor clinical outcome. SGI-110 inhibited the migration and invasion of Methy-High UC cell lines (UMUC-3 and T24) by upregulating multiple antitumor immune pathways.

Conclusions
DNA methylation subtypes pave the way for predicting patient prognosis in UC. Our results provide mechanistic rationale for evaluating SGI-110 in treating UC patients in the clinic.
Optimization of the production process for the anticancer lead compound illudin M: process development in stirred tank bioreactors
Authors: Chaverra-Muñoz Lillibeth , Hüttel Stephan 
Published: July 2022

Abstract
Background
The fungal natural products illudin S and M have been investigated as precursors for the development of semisynthetic anticancer agents such as Irofulven (illudin S derivative) which is currently in phase II clinical trials. Recently, illudin M derivatives have shown improved in vitro selectivity towards cancer cells encouraging further investigation. This requires a stable supply of the precursor which is produced by Basidiomycota of the genus Omphalotus. We have recently reported a robust shake flask process for the production of gram quantities of illudin M from Omphalotus nidiformis aiming to transfer that process into stirred tank bioreactors, which can be used in a commercial production set-up. However, process transfer across different systems is not straightforward and particularly challenging when the producer is morphologically complex. There are only a few reports that address the development of bioprocesses for the production of compounds from Basidiomycota as these organisms have not been extensively studied because of their complex life cycles and often are difficult to cultivate under laboratory conditions.

Results
The recently developed shake flask process delivering stable titers of ~ 940 mg L−1 of illudin M was investigated using off-gas analysis to identify critical parameters which facilitated the transfer from shaken into stirred tank bioreactors. Comparable titers to the shake flask process were achieved in 2 L stirred tank bioreactors (1.5 L working volume) by controlling growth of biomass with a carefully timed pH-shift combined with an improved precursor-feeding strategy. A scale-up experiment in a 15 L bioreactor (10 L working volume), resembling the process at 1.5 L resulted in 523 mg L−1 and is the starting point for optimization of the identified parameters at that scale.

Conclusion
By identifying and controlling key process parameters, the production process for illudin M was transferred from shake flasks into 2 L stirred tank bioreactors reaching a comparable titer (> 900 mg L−1), which is significantly higher than any previously reported. The insights obtained from 10 L scale pave the way towards further scale-up studies that will enable a sustainable supply of illudin M to support preclinical and clinical development programs.
Mutual regulation between N6-methyladenosine (m6A) modification and circular RNAs in cancer: impacts on therapeutic resistance
Authors: Lin Hong , Wang Yuxi , Wang Pinghan , Long Fangyi , Wang Ting 
Published: July 2022

AbstractThe resistance of tumor cells to therapy severely impairs the efficacy of treatment, leading to recurrence and metastasis of various cancers. Clarifying the underlying mechanisms of therapeutic resistance may provide new strategies for overcoming cancer resistance. N6-methyladenosine (m6A) is the most prevalent RNA modification in eukaryotes, and is involved in the regulation of RNA splicing, translation, transport, degradation, stability and processing, thus affecting several physiological processes and cancer progression. As a novel type of multifunctional non-coding RNAs (ncRNAs), circular RNAs (circRNAs) have been demonstrated to play vital roles in anticancer therapy. Currently, accumulating studies have revealed the mutual regulation of m6A modification and circRNAs, and their interaction can further influence the sensitivity of cancer treatment. In this review, we mainly summarized the recent advances of m6A modification and circRNAs in the modulation of cancer therapeutic resistance, as well as their interplay and potential mechanisms, providing promising insights and future directions in reversal of therapeutic resistance in cancer.
High glucose and palmitic acid induces neuronal senescence by NRSF/REST elevation and the subsequent mTOR-related autophagy suppression
Authors: Xue Wen-Jiao , He Cheng-Feng , Zhou Ren-Yuan , Xu Xiao-Die , Xiang Lv-Xuan , Wang Jian-Tao , Wang Xin-Ru , Zhou Hou-Guang , Guo Jing-Chun 
Published: July 2022

AbstractCell senescence is a basic aging mechanism. Previous studies have found that the cellular senescence in adipose tissue and other tissues, such as the pancreas, muscle and liver, is associated with the pathogenesis and progression of type 2 diabetes; however, strong evidence of whether diabetes directly causes neuronal senescence in the brain is still lacking. In this study, we constructed a high glucose and palmitic acid (HGP) environment on PC12 neuronal cells and primary mouse cortical neurons to simulate diabetes. Our results showed that after HGP exposure, neurons exhibited obvious senescence-like phenotypes, including increased NRSF/REST level, mTOR activation and cell autophagy suppression. Downregulation of NRSF/REST could remarkably alleviate p16, p21 and γH2A.X upregulations induced by HGP treatment, and enhance mTOR-autophagy of neurons. Our results suggested that the diabetic condition could directly induce neuronal senescence, which is mediated by the upregulation of NRSF/REST and subsequent reduction of mTOR-autophagy.