bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor quiescence: elevating SOX2 in diverse tumor cell types downregulates a broad spectrum of the cell cycle machinery and inhibits tumor growth
Authors: Metz Ethan P. , Wuebben Erin L. , Wilder Phillip J. , Cox Jesse L. , Datta Kaustubh , Coulter Donald , Rizzino Angie 
Published: October 2020

Abstract
Background
Quiescent tumor cells pose a major clinical challenge due to their ability to resist conventional chemotherapies and to drive tumor recurrence. Understanding the molecular mechanisms that promote quiescence of tumor cells could help identify therapies to eliminate these cells. Significantly, recent studies have determined that the function of SOX2 in cancer cells is highly dose dependent. Specifically, SOX2 levels in tumor cells are optimized to promote tumor growth: knocking down or elevating SOX2 inhibits proliferation. Furthermore, recent studies have shown that quiescent tumor cells express higher levels of SOX2 compared to adjacent proliferating cells. Currently, the mechanisms through which elevated levels of SOX2 restrict tumor cell proliferation have not been characterized.

Methods
To understand how elevated levels of SOX2 restrict the proliferation of tumor cells, we engineered diverse types of tumor cells for inducible overexpression of SOX2. Using these cells, we examined the effects of elevating SOX2 on their proliferation, both in vitro and in vivo. In addition, we examined how elevating SOX2 influences their expression of cyclins, cyclin-dependent kinases (CDKs), and p27Kip1.

Results
Elevating SOX2 in diverse tumor cell types led to growth inhibition in vitro. Significantly, elevating SOX2 in vivo in pancreatic ductal adenocarcinoma, medulloblastoma, and prostate cancer cells induced a reversible state of tumor growth arrest. In all three tumor types, elevation of SOX2 in vivo quickly halted tumor growth. Remarkably, tumor growth resumed rapidly when SOX2 returned to endogenous levels. We also determined that elevation of SOX2 in six tumor cell lines decreased the levels of cyclins and CDKs that control each phase of the cell cycle, while upregulating p27Kip1.

Conclusions
Our findings indicate that elevating SOX2 above endogenous levels in a diverse set of tumor cell types leads to growth inhibition both in vitro and in vivo. Moreover, our findings indicate that SOX2 can function as a master regulator by controlling the expression of a broad spectrum of cell cycle machinery. Importantly, our SOX2-inducible tumor studies provide a novel model system for investigating the molecular mechanisms by which elevated levels of SOX2 restrict cell proliferation and tumor growth.
Simple calculation using anatomical features on pre-treatment verification CT for bladder volume estimation during radiation therapy for rectal cancer
Authors: Kim Nalee , Yoon Hong In , Kim Jin Sung , Koom Woong Sub , Chang Jee Suk , Chung Yoonsun 
Published: October 2020

Abstract
Background
Despite detailed instruction for full bladder, patients are unable to maintain consistent bladder filling during a 5-week pelvic radiation therapy (RT) course. We investigated the best bladder volume estimation procedure for verifying consistent bladder volume.

Methods
We reviewed 462 patients who underwent pelvic RT. Biofeedback using a bladder scanner was conducted before simulation and during treatment. Exact bladder volume was calculated by bladder inner wall contour based on CT images (Vctsim). Bladder volume was estimated either by bladder scanner (Vscan) or anatomical features from the presacral promontory to the bladder base and dome in the sagittal plane of CT (Vratio). The feasibility of Vratio was validated using daily megavoltage or kV cone-beam CT before treatment.

Results
Mean Vctsim was 335.6 ± 147.5 cc. Despite a positive correlation between Vctsim and Vscan (R2 = 0.278) and between Vctsim and Vratio (R2 = 0.424), Vratio yielded more consistent results than Vscan, with a mean percentage error of 26.3 (SD 19.6, p < 0.001). The correlation between Vratio and Vctsim was stronger than that between Vscan and Vctsim (Z-score: − 7.782, p < 0.001). An accuracy of Vratio was consistent in megavoltage or kV cone-beam CT during treatment. In a representative case, we can dichotomize for clinical scenarios with or without bowel displacement, using a ratio of 0.8 resulting in significant changes in bowel volume exposed to low radiation doses.

Conclusions
Bladder volume estimation using personalized anatomical features based on pre-treatment verification CT images was useful and more accurate than physician-dependent bladder scanners.

Trial registration
Retrospectively registered.
Profiles of autophagy-related genes in esophageal adenocarcinoma
Authors: Zhu Lei , Dong Lin , Feng Minghao , Yang Fugui , Jiang Wenhao , Huang Zhiyuan , Liu Fabing , Wang Lingwei , Wang Guangxue , Li Qinchuan 
Published: October 2020

Abstract
Background
Several studies have demonstrated autophagy was involved in the process of esophageal adenocarcinoma (EAC). The aim of this study was to explore autophagy-related genes (ARGs) correlated with overall survival (OS) in EAC patients.

Methods
Expressions of ARGs in EAC and normal samples were downloaded from TCGA database. GO and KEGG enrichment analyses were used to investigate the ARGs bioinformatics functions. Univariate and multivariate cox regressions were performed to identify prognostic ARGs and the independent risk factors. ROC curve was established to evaluate the feasibility to predict the prognosis. Finally, the correlations between ARGs and clinical features were further explored. In addition, significantly different ARGs were verified in EAC specimens and normal esophageal mucosal tissues.

Results
Thirty significantly different ARGs were selected from EAC and normal tissues. Functional enrichments showed these ARGs were mainly related apoptosis. Multivariate cox regression analyses demonstrated eight ARGs were significantly associated with OS. Among these eight genes, BECN1 (HR = 0.321, P = 0.046), DAPK1 (HR = 0.636, P = 0.025) and CAPN1 (HR = 0.395, P = 0.004) played protective roles in survival. Gender (HR = 0.225, P = 0.032), stage (HR = 5.841, P = 0.008) and risk score (HR = 1.131, P < 0.001) were independent prognostic risk factors. ROC curves showed better efficacy to predict survival using the risk score. Additionally, we found BECN1, DAPK1, VAMP7 and SIRT1 genes were correlated significantly with survival status, gender, primary tumor and tumor stage (all P < 0.05). The experimental results confirmed the BIRC5 was overexpressed and the ITPR1, PRKN were downregulated in the EAC tissues compared with the normal esophageal mucosal tissues (all P < 0.05).

Conclusion
Our findings suggested that autophagy was involved in the process of EAC. Several ARGs probably could serve as diagnostic and prognostic biomarkers and may help facilitate therapeutic targets in EAC patients.
Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions
Authors: Akahane Toshiaki , Kanomata Naoki , Harada Oi , Yamashita Tetsumasa , Kurebayashi Junichi , Tanimoto Akihide , Moriya Takuya 
Published: October 2020

Abstract
Background
Next-generation sequencing (NGS) has shown that recurrent/metastatic breast cancer lesions may have additional genetic changes compared with the primary tumor. These additional changes may be related to tumor progression and/or drug resistance. However, breast cancer-targeted NGS is not still widely used in clinical practice to compare the genomic profiles of primary breast cancer and recurrent/metastatic lesions.

Methods
Triplet samples of genomic DNA were extracted from each patient’s normal breast tissue, primary breast cancer, and recurrent/metastatic lesion(s). A DNA library was constructed using the QIAseq Human Breast Cancer Panel (93 genes, Qiagen) and then sequenced using MiSeq (Illumina). The Qiagen web portal was utilized for data analysis.

Results
Successful results for three or four samples (normal breast tissue, primary tumor, and at least one metastatic/recurrent lesion) were obtained for 11 of 35 breast cancer patients with recurrence/metastases (36 samples). We detected shared somatic mutations in all but one patient, who had a germline mutation in TP53. Additional mutations that were detected in recurrent/metastatic lesions compared with primary tumor were in genes including TP53 (three patients) and one case each of ATR, BLM, CBFB, EP300, ERBB2, MUC16, PBRM1, and PIK3CA. Actionable mutations and/or copy number variations (CNVs) were detected in 73% (8/11) of recurrent/metastatic breast cancer lesions.

Conclusions
The QIAseq Human Breast Cancer Panel assay showed that recurrent/metastatic breast cancers sometimes acquired additional mutations and CNV. Such additional genomic changes could provide therapeutic target.
Carbon ion radiotherapy as definitive treatment in non-metastasized pancreatic cancer: study protocol of the prospective phase II PACK-study
Authors: Liermann Jakob , Naumann Patrick , Hommertgen Adriane , Pohl Moritz , Kieser Meinhard , Debus Juergen , Herfarth Klaus 
Published: October 2020

Abstract
Background
Radiotherapy is known to improve local tumor control in locally advanced pancreatic cancer (LAPC), although there is a lack of convincing data on a potential overall survival benefit of chemoradiotherapy over chemotherapy alone. To improve efficacy of radiotherapy, new approaches need to be evolved. Carbon ion radiotherapy is supposed to be more effective than photon radiotherapy due to a higher relative biological effectiveness (RBE) and due to a steep dose-gradient making dose delivery highly conformal.

Methods
The present Phase II PACK-study investigates carbon ion radiotherapy as definitive treatment in LAPC as well as in locally recurrent pancreatic cancer. A total irradiation dose of 48 Gy (RBE) will be delivered in twelve fractions. Concurrent chemotherapy is accepted, if indicated. The primary endpoint is the overall survival rate after 12 months. Secondary endpoints are progression free survival, safety, quality of life and impact on tumor markers CA 19–9 and CEA. A total of twenty-five patients are planned for recruitment over 2 years.

Discussion
Recently, Japanese researches could show promising results in a Phase I/II-study evaluating chemoradiotherapy of carbon ion radiotherapy and gemcitabine in LAPC. The present prospective PACK-study investigates the efficacy of carbon ion radiotherapy in pancreatic cancer at Heidelberg Ion Beam Therapy Center (HIT) in Germany.

Trial registration
The trial is registered at ClinicalTrials.gov: NCT04194268 (Retrospectively registered on December, 11th 2019).
Clinical outcomes of chemotherapy in patients with undifferentiated carcinoma of the pancreas: a retrospective multicenter cohort study
Authors: Imaoka Hiroshi , Ikeda Masafumi , Maehara Kosuke , Umemoto Kumiko , Ozaka Masato , Kobayashi Satoshi , Terashima Takeshi , Inoue Hiroto , Sakaguchi Chihiro , Tsuji Kunihiro , Shioji Kazuhiko , Okamura Keiya , Kawamoto Yasuyuki , Suzuki Rei , Shirakawa Hirofumi , Nagano Hiroaki , Ueno Makoto , Morizane Chigusa , Furuse Junji 
Published: October 2020

Abstract
Background
Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer. Although UC has been considered a highly aggressive malignancy, no clinical studies have addressed the efficacy of chemotherapy for unresectable UC. Therefore, we conducted multicenter retrospective study to investigate the efficacy of chemotherapy in patients with UC of the pancreas.

Methods
This multicenter retrospective cohort study was conducted at 17 institutions in Japan between January 2007 and December 2017. A total of 50 patients treated with chemotherapy were analyzed.

Results
The median overall survival (OS) in UC patients treated with chemotherapy was 4.08 months. The details of first-line chemotherapy were as follows: gemcitabine (n = 24), S-1 (n = 12), gemcitabine plus nab-paclitaxel (n = 6), and other treatment (n = 8). The median progression-free survival (PFS) was 1.61 months in the gemcitabine group, 2.96 months in the S-1 group, and 4.60 months in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel significantly improved PFS compared with gemcitabine (p = 0.014). The objective response rate (ORR) was 4.2% in the gemcitabine group, 0.0% in the S-1 group, and 33.3% in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel also showed a significantly higher ORR compared with both gemcitabine and S-1 (gemcitabine plus nab-paclitaxel vs. gemcitabine: p = 0.033; gemcitabine plus nab-paclitaxel vs. S-1: p = 0.034). A paclitaxel-containing first-line regimen significantly improved OS compared with a non-paclitaxel-containing regimen (6.94 months vs. 3.75 months, respectively; p = 0.041). After adjustment, use of a paclitaxel-containing regimen in any line was still an independent predictor of OS (hazard ratio for OS, 0.221; 95% confidence interval, 0.076–0.647; p = 0.006) in multiple imputation by chained equation.

Conclusions
The results of the present study indicate that a paclitaxel-containing regimen would offer relatively longer survival, and it is considered a reasonable option for treating patients with unresectable UC.
Nanophthalmos patient with a THR518MET mutation in MYRF, a case report
Authors: Hagedorn Joshua , Avdic Armin , Schnieders Michael J. , Roos Benjamin R. , Kwon Young H. , Drack Arlene V. , Boese Erin A. , Fingert John H. 
Published: October 2020

Abstract
Background
Nanophthalmos has a significant genetic background and disease-causing mutations have been recently been reported in the myelin regulatory factor (MYRF) gene. We report clinical features in a patient with nanophthalmos and a Thr518Met MYRF mutation.

Case presentation
A three-year-old male was discovered to have nanophthalmos after first presenting to the emergency department for a frontal headache, eye pain, emesis, and lethargy. Imaging studies (CT and MRI) were negative except for increased posterior fossa cerebrospinal fluid. Subsequent examinations revealed nanophthalmos (short axial eye lengths 18.1 mm OD and 18.3 mm OS), microcornea, and a large crystalline lens. Peripheral chorioretinal pigment abnormalities were also observed. He experienced episodes of marked ocular hypertension (53 mmHg OD and 60 mmHg) likely due to intermittent angle closure precipitated by nanophthalmos. The ocular hypertension was responsive to topical medicines. Genetic analysis of known nanophthalmos genes MFRP and TMEM98 were negative, while a novel mutation, Thr518Met was detected in MYRF. The Thr518Met mutation was absent from 362 matched normal controls and was extremely rare in a large population database, allele frequency of 0.000024. The Thr518Met mutation altered a highly conserved amino acid in the MYRF protein and three of four algorithms suggested that this mutation is likely pathogenic. Finally, molecular modeling showed that the Thr518Met mutation is damaging to MYRF structure. Together these data suggest that the Thr518Met mutation causes nanophthalmos.

Conclusions
Nanophthalmos may present at an early age with features of angle closure glaucoma and a Thr518Met mutation in MYRF was detected in a patient with nanophthalmos. Prevalence data, homology data, mutation analysis data, and protein modeling data suggest that this variant is pathogenic and may expand the phenotypic range of syndromic nanophthalmos caused by MYRF mutations to include central nervous system abnormalities (increased posterior fossa cerebrospinal fluid).
Are comparisons of mental disorders between Chinese and German students possible? An examination of measurement invariance for the PHQ-15, PHQ-9 and GAD-7
Authors: Zhou Yan , Xu Jing , Rief Winfried 
Published: October 2020

Abstract
Background
The Patient Health Questionnaire (PHQ) is one of the most commonly used instruments to assess mental disorders. However, research on its cross-cultural measurement invariance is not yet sufficient. This study examined the measurement invariance of the Chinese and German versions of the PHQ’s somatic symptom severity scale (PHQ-15), depressive symptom severity scale (PHQ-9) and seven-item Generalized Anxiety Disorder (GAD-7) scale as a prerequisite for their use in cross-cultural comparisons.

Methods
We used online data collected from groups of Chinese students in China (n = 413) and German students in Germany (n = 416). Separate measurement models for each group were examined using confirmatory factor analysis and measurement invariance testing was conducted to test the cross-cultural equivalence.

Results
Findings demonstrated that the PHQ-9 and GAD-7 had partial scalar measurement invariance, but the cross-cultural measurement invariance of the PHQ-15 could not be confirmed. Comparisons of latent means did not indicate differences in the levels of depression and anxiety symptoms between Chinese and German samples.

Conclusion
The PHQ-9 and GAD-7 can be used in cross-cultural comparison of prevalence, but the intercultural use of PHQ-15 is more problematic. Findings are discussed from intercultural and methodological perspectives.
Examining the application of behaviour change theories in the context of infectious disease outbreaks and emergency response: a review of reviews
Authors: Weston Dale , Ip Athena , Amlôt Richard 
Published: October 2020

Abstract
Background
Behavioural science can play a critical role in combatting the effects of an infectious disease outbreak or public health emergency, such as the COVID-19 pandemic. The current paper presents a synthesis of review literature discussing the application of behaviour change theories within an infectious disease and emergency response context, with a view to informing infectious disease modelling, research and public health practice.

Methods
A scoping review procedure was adopted for the searches. Searches were run on PubMed, PsychInfo and Medline with search terms covering four major categories: behaviour, emergency response (e.g., infectious disease, preparedness, mass emergency), theoretical models, and reviews. Three further top-up reviews was also conducted using Google Scholar. Papers were included if they presented a review of theoretical models as applied to understanding preventative health behaviours in the context of emergency preparedness and response, and/or infectious disease outbreaks.

Results
Thirteen papers were included in the final synthesis. Across the reviews, several theories of behaviour change were identified as more commonly cited within this context, specifically, Health Belief Model, Theory of Planned Behaviour, and Protection Motivation Theory, with support (although not universal) for their effectiveness in this context. Furthermore, the application of these theories in previous primary research within this context was found to be patchy, and so further work is required to systematically incorporate and test behaviour change models within public health emergency research and interventions.

Conclusion
Overall, this review identifies a range of more commonly applied theories with broad support for their use within an infectious disease and emergency response context. The Discussion section details several key recommendations to help researchers, practitioners, and infectious disease modellers to incorporate these theories into their work. Specifically, researchers and practitioners should base future research and practice on a systematic application of theories, beginning with those reported herein. Furthermore, infectious disease modellers should consult the theories reported herein to ensure that the full range of relevant constructs (cognitive, emotional and social) are incorporated into their models. In all cases, consultation with behavioural scientists throughout these processes is strongly recommended to ensure the appropriate application of theory.
Severe food insecurity associated with mortality among lower-income Canadian adults approaching eligibility for public pensions: a population cohort study
Authors: Men Fei , Tarasuk Valerie 
Published: October 2020

AbstractBackgroundThe prevalence of food insecurity among adults over 65 in Canada is less than half of that among adults approaching 65, possibly due in part to the public pension universally disbursed from the age of 65. Given research associating food insecurity with higher risk of premature mortality, our objective was to determine the likelihood that food-insecure adults with incomes below the national median would live past 65 to collect the public pension.MethodsWe linked respondents of the Canadian Community Health Survey 2005–15 to the death records from the Canadian Vital Statistics Database 2005–17. We assessed household food insecurity status through a validated 18-item questionnaire for 50,780 adults aged 52–64 at interview and with household income below the national median. We traced their vital status up to the age of 65. We fitted Cox proportional hazard models to compare hazard of all-cause mortality before 65 by food insecurity status while adjusting for individual demographic attributes, baseline health, and household socioeconomic characteristics. We also stratified the sample by income and analyzed the subsamples with income above and below the Low Income Measure separately.ResultsMarginal, moderate, and severe food insecurity were experienced by 4.1, 7.3, and 4.5% of the sampled adults, respectively. The crude mortality rate was 49 per 10,000 person-years for food-secure adults and 86, 98, and 150 per 10,000 person-years for their marginally, moderately, and severely food-insecure counterparts, respectively. For the full sample and low-income subsample, respectively, severe food insecurity was associated with 1.24 (95% CI: 1.06, 1.45) and 1.28 (95% CI: 1.07, 1.52) times higher hazard of dying before 65 relative to food security. No association was found between food insecurity and mortality in the higher-income subsample.ConclusionsSeverely food-insecure adults approaching retirement age were more likely to die before collecting public pensions that might attenuate their food insecurity. Policymakers need to acknowledge the challenges to food security and health faced by working-age adults and provide them with adequate assistance to ensure healthy ageing into retirement.