bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from KDM6A Loss Recruits Tumor-Associated Neutrophils and Promotes Neutrophil Extracellular Trap Formation in Pancreatic Cancer
Authors: Yang Jing , Jin Lin , Kim Hong Sun , Tian Feng , Yi Zhujun , Bedi Karan , Ljungman Mats , Pasca di Magliano Marina , Crawford Howard , Shi Jiaqi
Published: March 2023

Abstract
Lysine (K)-specific demethylase 6A (KDM6A) is a frequently mutated tumor suppressor gene in pancreatic ductal adenocarcinoma (PDAC). However, the impact of KDM6A loss on the PDAC tumor immune microenvironment is not known. This study used a genetically engineered, pancreas-specific Kdm6a knockout (KO) PDAC mouse model and human PDAC tissue samples to demonstrate that KDM6A loss correlates with increased tumor-associated neutrophils and neutrophil extracellular traps (NET) formation, which are known to contribute to PDAC progression. Genome-wide bromouridine sequencing analysis to evaluate nascent RNA synthesis showed that the expression of many chemotactic cytokines, especially CXC motif chemokine ligand 1 (CXCL1), was upregulated in KDM6A KO PDAC cells. KDM6A-deficient PDAC cells secreted higher levels of CXCL1 protein, which in turn recruited neutrophils. Furthermore, in a syngeneic orthotopic mouse model, treatment with a CXCL1 neutralizing antibody blocked the chemotactic and NET-promoting properties of KDM6A-deficient PDAC cells and suppressed tumor growth, confirming CXCL1 as a key mediator of chemotaxis and PDAC growth driven by KDM6A loss. These findings shed light on how KDM6A regulates the tumor immune microenvironment and PDAC progression and suggests that the CXCL1–CXCR2 axis may be a candidate target in PDAC with KDM6A loss.
Significance:
KDM6A loss in pancreatic cancer cells alters the immune microenvironment by increasing CXCL1 secretion and neutrophil recruitment, providing a rationale for targeting the CXCL1–CXCR2 signaling axis in tumors with low KDM6A.
Data from SMAD4 Loss Induces c-MYC–Mediated NLE1 Upregulation to Support Protein Biosynthesis, Colorectal Cancer Growth, and Metastasis
Authors: Loevenich Leon P. , Tschurtschenthaler Markus , Rokavec Matjaz , Silva Miguel G. , Jesinghaus Moritz , Kirchner Thomas , Klauschen Frederick , Saur Dieter , Neumann Jens , Hermeking Heiko , Jung Peter
Published: March 2023

Abstract
Growth and metastasis of colorectal cancer is closely connected to the biosynthetic capacity of tumor cells, and colorectal cancer stem cells that reside at the top of the intratumoral hierarchy are especially dependent on this feature. By performing disease modeling on patient-derived tumor organoids, we found that elevated expression of the ribosome biogenesis factor NLE1 occurs upon SMAD4 loss in TGFβ1-exposed colorectal cancer organoids. TGFβ signaling-mediated downregulation of NLE1 was prevented by ectopic expression of c-MYC, which occupied an E-box–containing region within the NLE1 promoter. Elevated levels of NLE1 were found in colorectal cancer cohorts compared with normal tissues and in colorectal cancer subtypes characterized by Wnt/MYC and intestinal stem cell gene expression. In colorectal cancer cells and organoids, NLE1 was limiting for de novo protein biosynthesis. Upon NLE1 ablation, colorectal cancer cell lines activated p38/MAPK signaling, accumulated p62- and LC3-positive structures indicative of impaired autophagy, and displayed more reactive oxygen species. Phenotypically, knockout of NLE1 inhibit.ed proliferation, migration and invasion, clonogenicity, and anchorage-independent growth. NLE1 loss also increased the fraction of apoptotic tumor cells, and deletion of TP53 further sensitized NLE1-deficient colorectal cancer cells to apoptosis. In an endoscopy-guided orthotopic mouse transplantation model, ablation of NLE1 impaired tumor growth in the colon and reduced primary tumor-derived liver metastasis. In patients with colorectal cancer, NLE1 mRNA levels predicted overall and relapse-free survival. Taken together, these data reveal a critical role of NLE1 in colorectal cancer growth and progression and suggest that NLE1 represents a potential therapeutic target in colorectal cancer patients.
Significance:
NLE1 limits de novo protein biosynthesis and the tumorigenic potential of advanced colorectal cancer cells, suggesting NLE1 could be targeted to improve the treatment of metastatic colorectal cancer.
Supplementary Table 1 from Methylation Markers for CCNA1 and C13ORF18 Are Strongly Associated with High-Grade Cervical Intraepithelial Neoplasia and Cervical Cancer in Cervical Scrapings
Authors: Yang Nan , Eijsink Jasper J.H. , Lendvai Ágnes , Volders Haukeline H. , Klip Harry , Buikema Henk J. , van Hemel Bettien M. , Schuuring Ed , van der Zee Ate G.J. , Wisman G. Bea A.
Published: March 2023

Supplementary Table 1 from Methylation Markers for CCNA1 and C13ORF18 Are Strongly Associated with High-Grade Cervical Intraepithelial Neoplasia and Cervical Cancer in Cervical Scrapings
Data Supplement from Gene–Environment Interaction Involving Recently Identified Colorectal Cancer Susceptibility Loci
Authors: Kantor Elizabeth D. , Hutter Carolyn M. , Minnier Jessica , Berndt Sonja I. , Brenner Hermann , Caan Bette J. , Campbell Peter T. , Carlson Christopher S. , Casey Graham , Chan Andrew T. , Chang-Claude Jenny , Chanock Stephen J. , Cotterchio Michelle , Du Mengmeng , Duggan David , Fuchs Charles S. , Giovannucci Edward L. , Gong Jian , Harrison Tabitha A. , Hayes Richard B. , Henderson Brian E. , Hoffmeister Michael , Hopper John L. , Jenkins Mark A. , Jiao Shuo , Kolonel Laurence N. , Le Marchand Loic , Lemire Mathieu , Ma Jing , Newcomb Polly A. , Ochs-Balcom Heather M. , Pflugeisen Bethann M. , Potter John D. , Rudolph Anja , Schoen Robert E. , Seminara Daniela , Slattery Martha L. , Stelling Deanna L. , Thomas Fridtjof , Thornquist Mark , Ulrich Cornelia M. , Warnick Greg S. , Zanke Brent W. , Peters Ulrike , Hsu Li , White Emily
Published: March 2023

Supplemental Table 3. Environmental Factors and colorectal cancer: associations by study design
Supplementary Tables 1-4 from Validity and Reliability of the Munsell Soil Color Charts for Assessing Human Skin Color
Authors: Reeder Anthony I. , Iosua Ella , Gray Andrew R. , Hammond Vanessa A.
Published: March 2023

Supplementary Tables 1-4. â€¢ Table S1. Spectrophotometer readings for the MunsellÂ® 2.5YR hue chart by value and chroma. Table S2. Spectrophotometer readings for the MunsellÂ® 5YR hue chart by value and chroma. Table S3. Spectrophotometer readings for the MunsellÂ® 7.5YR hue chart by value and chroma. Table S4. Spectrophotometer readings for the MunsellÂ® 10YR hue chart by value and chroma.
Supplementary Table 3 from Genetic Variants in XRCC2: New Insights Into Colorectal Cancer Tumorigenesis
Authors: Curtin Karen , Lin Wei-Yu , George Rina , Katory Mark , Shorto Jennifer , Cannon-Albright Lisa A. , Smith Gillian , Bishop D. Timothy , Cox Angela , Camp Nicola J.
Published: March 2023

Supplementary Table 3 from Genetic Variants in XRCC2: New Insights Into Colorectal Cancer Tumorigenesis
Supplementary Table 2 from Gender Disparities in the Tumor Genetics and Clinical Outcome of Multiple Myeloma
Authors: Boyd Kevin D. , Ross Fiona M. , Chiecchio Laura , Dagrada GianPaolo , Konn Zoe J. , Tapper William J. , Walker Brian A. , Wardell Christopher P. , Gregory Walter M. , Szubert Alex J. , Davies Faith E. , Morgan Gareth J.
Published: March 2023

Supplementary Table 2 from Gender Disparities in the Tumor Genetics and Clinical Outcome of Multiple Myeloma
Supplementary Tables 1-4 from Expression and Cytoplasmic Localization of SAM68 Is a Significant and Independent Prognostic Marker for Renal Cell Carcinoma
Authors: Zhang Zhiling , Li Jun , Zheng Haiqing , Yu Chunping , Chen Jin , Liu Zhuowei , Li Manzhi , Zeng Musheng , Zhou Fangjian , Song Libing
Published: March 2023

Supplementary Tables 1-4 from Expression and Cytoplasmic Localization of SAM68 Is a Significant and Independent Prognostic Marker for Renal Cell Carcinoma
Supplementary Tables 1-9 from Generalizability and Epidemiologic Characterization of Eleven Colorectal Cancer GWAS Hits in Multiple Populations
Authors: He Jing , Wilkens Lynne R. , Stram Daniel O. , Kolonel Laurence N. , Henderson Brian E. , Wu Anna H. , Le Marchand Loic , Haiman Christopher A.
Published: March 2023

Supplementary Tables 1-9 from Generalizability and Epidemiologic Characterization of Eleven Colorectal Cancer GWAS Hits in Multiple Populations
Data from Polymorphisms in the TOX3/LOC643714 Locus and Risk of Breast Cancer in African-American Women
Authors: Ruiz-Narváez Edward A. , Rosenberg Lynn , Cozier Yvette C. , Cupples L. Adrienne , Adams-Campbell Lucile L. , Palmer Julie R.
Published: March 2023

Abstract
Background: The rs3803662 single nucleotide polymorphism (SNP) in the TOX3/LOC643714 region was identified as a breast cancer susceptibility genetic variant in recent genome-wide association studies of women of European ancestry and has been replicated in other populations of European ancestry. The position of the causal variant tagged by the rs3803662 marker is still unknown. In fact, because the rs3803662 polymorphism is located between the TOX3 and the LOC643714 loci, it is unclear which gene is the one causally related to the risk of breast cancer. Because linkage disequilibrium blocks are smaller in populations of African ancestry, fine-mapping in African ancestry samples might be an effective approach to narrowing the position of the causal variant(s) in the TOX3/LOC643714 locus.

Methods: We evaluated a total of 60 tagging SNPs throughout the TOX3/LOC643714 region in a nested case-control study of breast cancer within the Black Women's Health Study, which included 906 cases and 1,111 controls.

Results: No significant association was found for the rs3803662 SNP. However, four other SNPs (rs3104746, rs3112562, rs3104793, and rs8046994), all of them located in the LOC643714 gene, were associated with risk of breast cancer. The strongest association was observed for rs3104746: each copy of the A-rs3104746 allele was associated with a 23% higher risk of breast cancer (odds ratios, 1.23; 95% confidence intervals, 1.05-1.44; P = 0.009).

Conclusions: Our results confirm the association observed in genome-wide association studies of European ancestry populations.

Impact: The results narrow the locus to a smaller linkage disequilibrium block in the LOC643714 gene. Cancer Epidemiol Biomarkers Prev; 19(5); 1320–7. ©2010 AACR.
Data from Novel Changes in Glycosylation of Serum Apo-J in Patients with Hepatocellular Carcinoma
Authors: Comunale Mary Ann , Wang Mengjun , Rodemich-Betesh Lucy , Hafner Julie , Lamontagne Anne , Klein Andrew , Marrero Jorge , Di Bisceglie Adrian M. , Gish Robert , Block Timothy , Mehta Anand
Published: March 2023

Abstract
Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the occurrence of HCC has more than doubled in the United States in the past decade. Early detection is considered key to reducing the mortality of HCC.

Methods: Using two-dimensional gel electrophoresis and high-performance liquid chromatography we have analyzed the glycosylation of Apo-J from healthy controls, patients with liver cirrhosis, or those with HCC.

Results: Apo-J in the serum from patients with HCC had decreased levels of (β-1,4) triantennary N-linked glycan compared with the healthy controls or patients with liver cirrhosis. We analyzed this change in an independent cohort of 76 patients with HCC, 32 with cirrhosis, and 43 infected with hepatitis C virus using the Datura stramonium lectin (DSL), which binds to (β-1,4) triantennary N-linked glycan. The level of DSL-reactive Apo-J allowed us to differentiate HCC from cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.852. When Apo-J was combined with other serum biomarkers such as α-fetoprotein (AFP) and fucosylated kininogen by using a multivariate logistic regression model, the AUROC increased to 0.944, a value much greater than that observed with AFP alone (AUROC of 0.765).

Conclusions: The glycosylation of Apo-J is a useful marker when used alone or in combination with outer makers for the early detection of HCC.

Impact: The potential use of a combination of AFP, DSL-reactive Apo-J, and fucosylated kininogen as a biomarker of HCC would have great value in the management of patients with liver disease. Cancer Epidemiol Biomarkers Prev; 20(6); 1222–9. ©2011 AACR.
Data from Relationship of Extreme Chromosomal Instability with Long-term Survival in a Retrospective Analysis of Primary Breast Cancer
Authors: Roylance Rebecca , Endesfelder David , Gorman Patricia , Burrell Rebecca A. , Sander Jil , Tomlinson Ian , Hanby Andrew M. , Speirs Valerie , Richardson Andrea L. , Birkbak Nicolai J. , Eklund Aron C. , Downward Julian , Kschischo Maik , Szallasi Zoltan , Swanton Charles
Published: March 2023

Abstract
Background: Chromosomal instability (CIN) is thought to be associated with poor prognosis in solid tumors; however, evidence from preclinical and mouse tumor models suggest that CIN may paradoxically enhance or impair cancer cell fitness. Breast cancer prognostic expression signature sets, which reflect tumor CIN status, efficiently delineate outcome in estrogen receptor ER-positive breast cancer in contrast to ER-negative breast cancer, suggesting that the relationship of CIN with prognosis differs in these two breast cancer subtypes.

Methods: Direct assessment of CIN requires single-cell analysis methods, such as centromeric FISH, aimed at determining the variation around the modal number of two or more chromosomes within individual tumor nuclei. Here, we document the frequency of tumor CIN by dual centromeric FISH analysis in a retrospective primary breast cancer cohort of 246 patients with survival outcome.

Results: There was increased CIN and clonal heterogeneity in ER-negative compared with ER-positive breast cancer. Consistent with a negative impact of CIN on cellular fitness, extreme CIN in ER-negative breast cancer was an independent variable associated with improved long-term survival in multivariate analysis. In contrast, a linear relationship of increasing CIN with poorer prognosis in ER-positive breast cancer was observed, using three independent measures of CIN.

Conclusions: The paradoxical relationship between extreme CIN and cancer outcome in the ER-negative cohorts may explain why prognostic expression signatures, reflecting tumor CIN status, fail to predict outcome in this subgroup.

Impact: Assessment of tumor CIN status may support risk stratification in ER-negative breast cancer and requires prospective validation. Cancer Epidemiol Biomarkers Prev; 20(10); 2183–94. ©2011 AACR.
Data from Feasibility of Identifying Pancreatic Cancer Based on Serum Metabolomics
Authors: Bathe Oliver F. , Shaykhutdinov Rustem , Kopciuk Karen , Weljie Aalim M. , McKay Andrew , Sutherland Francis R. , Dixon Elijah , Dunse Nicole , Sotiropoulos Dina , Vogel Hans J.
Published: March 2023

Abstract
Background: We postulated that the abundance of various metabolites in blood would facilitate the diagnosis of pancreatic and biliary lesions, which could potentially prevent unnecessary surgery.

Methods: Serum samples from patients with benign hepatobiliary disease (n = 43) and from patients with pancreatic cancer (n = 56) were examined by 1H NMR spectroscopy to quantify 58 unique metabolites. Data were analyzed by “targeted profiling” followed by supervised pattern recognition and orthogonal partial least-squares discriminant analysis (O-PLS-DA) of the most significant metabolites, which enables comparison of the whole sample spectrum between groups.

Results: The metabolomic profile of patients with pancreatic cancer was significantly different from that of patients with benign disease (AUROC, area under the ROC curve, = 0.8372). Overt diabetes mellitus (DM) was identified as a possible confounding factor in the pancreatic cancer group. Thus, diabetics were excluded from further analysis. In this more homogeneous pancreatic cancer group, compared with benign cases, serum concentrations of glutamate and glucose were most elevated on multivariate analysis. In benign cases, creatine and glutamine were most abundant. To examine the usefulness of this test, a comparison was made to age- and gender-matched controls with benign lesions that mimic cancer, controlling also for presence of jaundice and diabetes (n = 14 per group). The metabolic profile in patients with pancreatic cancer remained distinguishable from patients with benign pancreatic lesions (AUROC = 0.8308).

Conclusions: The serum metabolomic profile may be useful for distinguishing benign from malignant pancreatic lesions.

Impact: Further studies will be required to study the effects of jaundice and diabetes. A more comprehensive metabolomic profile will be evaluated using mass spectrometry. Cancer Epidemiol Biomarkers Prev; 20(1); 140–7. ©2010 AACR.
Data from Shorter Leukocyte Telomere Length Is Independently Associated with Poor Survival in Patients with Bladder Cancer
Authors: Russo Alessia , Modica Federica , Guarrera Simonetta , Fiorito Giovanni , Pardini Barbara , Viberti Clara , Allione Alessandra , Critelli Rossana , Bosio Andrea , Casetta Giovanni , Cucchiarale Giuseppina , Destefanis Paolo , Gontero Paolo , Rolle Luigi , Zitella Andrea , Fontana Dario , Frea Bruno , Vineis Paolo , Sacerdote Carlotta , Matullo Giuseppe
Published: March 2023

Abstract
Background: Shorter telomere length (TL) has been reported to be associated with increased risk of early death in elder individuals. Telomere shortening has been also related to chromosomal instability, which may possibly contribute to the development of several types of digestive or urogenital system cancers and smoking-related tumors. Therefore, we investigated the impact of TL on bladder cancer survival.

Methods: TL was measured in leukocyte DNA from whole peripheral blood using quantitative real-time PCR in 463 patients with bladder cancer from a total 726 cases who were followed for up to 18 years.

Results: Patients with muscle-invasive tumor/any grade had shorter telomere than patients with non–muscle-invasive tumor/high-grade and with non–muscle-invasive tumor/non–high-grade (TL reference 0.7 ± 0.2; vs. respectively, 0.8 ± 0.2, P = 3.4 × 10−2 and 0.8 ± 0.2, P = 3.6 × 10−2). Moreover, patients in the lowest quartiles of TL were associated with decreased survival after diagnosis (log-rank test, P = 3.9 × 10−4). A Cox regression adjusted by age, cancer aggressiveness, Bacillus Calmette-Guérin, radical cystectomy, radiotherapy, and chemotherapy showed an independent effect of TL on bladder cancer survival (HR, 3.9; 95% confidence interval, 1.7–9.1; P = 1.2 × 10−3).

Conclusions: Our results suggest that leukocyte TL is only partly related to tumor aggressiveness and that shorter telomeres act as independent prognostic predictor of survival in patients with bladder cancer. TL information may allow to better select therapeutic approaches in patients with the same stage and grade.

Impact: Blood leukocyte TL levels could provide an additional noninvasive prognostic marker to better predict survival and personalize therapies in patients with bladder cancer. Cancer Epidemiol Biomarkers Prev; 23(11); 2439–46. ©2014 AACR.
Data from Use of Multiple Imputation to Correct for Bias in Lung Cancer Incidence Trends by Histologic Subtype
Authors: Yu Mandi , Feuer Eric J. , Cronin Kathleen A. , Caporaso Neil E.
Published: March 2023

Abstract
Background: Over the past several decades, advances in lung cancer research and practice have led to refinements of histologic diagnosis of lung cancer. The differential use and subsequent alterations of nonspecific morphology codes, however, may have caused artifactual fluctuations in the incidence rates for histologic subtypes, thus biasing temporal trends.

Methods: We developed a multiple imputation (MI) method to correct lung cancer incidence for nonspecific histology using data from the Surveillance, Epidemiology, and End Results Program during 1975 to 2010.

Results: For adenocarcinoma in men and squamous in both genders, the change to an increasing trend around 2005, after more than 10 years of decreasing incidence, is apparently an artifact of the changes in histopathology practice and coding system. After imputation, the rates remained decreasing for adenocarcinoma and squamous in men, and became constant for squamous in women.

Conclusions: As molecular features of distinct histologies are increasingly identified by new technologies, accurate histologic distinctions are becoming increasingly relevant to more effective “targeted” therapies, and therefore, are important to track in patients. However, without incorporating the coding changes, the incidence trends estimated for histologic subtypes could be misleading.

Impact: The MI approach provides a valuable tool for bridging the different histology definitions, thus permitting meaningful inferences about the long-term trends of lung cancer by histologic subtype. Cancer Epidemiol Biomarkers Prev; 23(8); 1546–58. ©2014 AACR.
Data from Prostate Cancer Detected by Methylated Gene Markers in Histopathologically Cancer-Negative Tissues from Men with Subsequent Positive Biopsies
Authors: Troyer Dean A. , Lucia M. Scott , de Bruïne Adriann P. , Mendez-Meza Rosario , Baldewijns Marcella M. , Dunscomb Nancy , Van Engeland Manon , McAskill Theresa , Bierau Katja , Louwagie Joost , Bigley Joseph W.
Published: March 2023

Abstract
The goal of this retrospective, multicenter study was to evaluate the ability of a newly developed refinement of a quantitative methylation-specific PCR assay to detect prostate cancer in histopathologically negative biopsy samples collected from men who were later positively diagnosed during a follow-up biopsy procedure. Biomarkers tested in the assay included the much-studied glutathione-S-transferase P1 gene and others reported to be frequently methylated in prostate cancer. Core biopsy tissue from subjects with serial negative biopsies served as a negative control to assess assay specificity. As a positive control, biopsy core tissue from patients histopathologically diagnosed with prostate cancer was used to gauge true marker sensitivity in known cancer-containing specimens. Testing was completed in 971 archived paraffin-embedded tissue blocks from 264 men screened for prostate cancer. More samples were initially tested, but due to the advanced age of the paraffinized tissue, DNA quality for quantitative methylation-specific PCR analysis was insufficient in 34% of the available blocks. The glutathione-S-transferase P1 gene has been confirmed as a powerful indicator of the presence of prostate cancer cells. A sensitivity of 52% was observed in the “potentially false-negative first biopsies,” with a corresponding specificity of 85% and the sensitivity in biopsy tissue cores containing histopathologically confirmed prostate cancer was 95%. An even higher sensitivity can be reached with RAR-2β (84%) and APC (72%), with respective specificities of 48% and 50%. Gene methylation was detected in initial, negative biopsy tissue in men who were later diagnosed with prostate cancer. Testing for methylation in histopathologically negative biopsies could improve the early detection of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2717–22)
Data from Breast Cancer Incidence Rates in U.S. Women Are No Longer Declining
Authors: DeSantis Carol , Howlader Nadia , Cronin Kathleen A. , Jemal Ahmedin
Published: March 2023

Abstract
Background: Several publications reported breast cancer incidence rates continued to decrease among white women, following the decline of about 7% from 2002 to 2003. However, none of these reports exclusively examined the trend after 2003. In this paper, we examined breast cancer incidence rates among non-Hispanic (NH) white women from 2003 to 2007 to determine whether the decrease in breast cancer incidence rates indeed persisted through 2007. In addition, we present breast cancer incidence trends for NH black and Hispanic women and postmenopausal hormone use for all three racial/ethnic groups.

Methods: Breast cancer incidence rates were calculated by race/ethnicity, age and ER status using data from the Surveillance, Epidemiology, and End Results (SEER) 12 registries for 2000 to 2007. Prevalence of postmenopausal hormone use was calculated using National Health Interview Survey data from 2000, 2005, and 2008.

Results: From 2003 to 2007, overall breast cancer incidence rates did not change significantly among NH white women in any age group. However, rates increased (2.7% per year) for ER+ breast cancers in ages 40 to 49, and decreased for ER− breast cancers in ages 40 to 49 and 60 to 69. Similarly, overall breast cancer incidence rates did not change significantly for black and Hispanic women. Hormone use continued to decrease from 2005 to 2008 in all groups, although the decreases were smaller compared to those from 2000 to 2005.

Conclusions: The sharp decline in breast cancer incidence rates that occurred from 2002 to 2003 among NH white women did not continue through 2007.

Impact: Further studies are needed to better understand the recent breast cancer trends. Cancer Epidemiol Biomarkers Prev; 20(5); 733–9. ©2011 AACR.
Data from Prospective Study of HPV16 Viral Load and Risk of In Situ and Invasive Squamous Cervical Cancer
Authors: Sundström Karin , Ploner Alexander , Dahlström Lisen Arnheim , Palmgren Juni , Dillner Joakim , Adami Hans-Olov , Ylitalo Nathalie , Sparén Pär
Published: March 2023

Abstract
Background: A strong association has been shown between high viral DNA load (VL) of human papillomavirus (HPV) type 16 and risk for cervical cancer in situ (CIS). However, little data is available for the significance of VL in invasive squamous cell carcinoma (SCC).

Methods: In 2 nested case–control studies among women participating in cervical screening, with a cytologically normal first smear, we collected 5,665 smears from 621 women with CIS, 457 with SCC, and individually matched controls. All smears were tested for HPV, and VLs of HPV16 positive smears were quantified using real time-PCR. The median follow-up until diagnosis of CIS or SCC was 6.1 to 7.7 years.

Results: Low VL's were common among both CIS and SCC case women, until 1 to 2 years before diagnosis when a surge in VL occurred. The relative risk (RR) associated with low viral load of HPV16 was around 10 for CIS, and 10 to 20 for SCC throughout 10 years before diagnosis, compared with HPV16-negative women. For women with medium to high VL, the risk for CIS was greatly increased from 5 years before diagnosis [RR, 19; 95% confidence interval (CI), 7–48]. In SCC, a high VL conferred an increased risk, but only from 3 years before diagnosis [RR, 60; 95% CI, 6–580].

Conclusions: We show differing risk functions associated with HPV16 viral load in CIS and SCC, respectively. We further show that viral loads were unexpectedly low early in the SCC disease process.

Impact: HPV16 viral load appears highly complex which may limit its use in cervical screening. Cancer Epidemiol Biomarkers Prev; 22(1); 150–8. ©2012 AACR.
Data from History of Comorbidities and Survival of Ovarian Cancer Patients, Results from the Ovarian Cancer Association Consortium
Authors: Minlikeeva Albina N. , Freudenheim Jo L. , Eng Kevin H. , Cannioto Rikki A. , Friel Grace , Szender J. Brian , Segal Brahm , Odunsi Kunle , Mayor Paul , Diergaarde Brenda , Zsiros Emese , Kelemen Linda E. , Köbel Martin , Steed Helen , deFazio Anna , Jordan Susan J. , Fasching Peter A. , Beckmann Matthias W. , Risch Harvey A. , Rossing Mary Anne , Doherty Jennifer A. , Chang-Claude Jenny , Goodman Marc T. , Dörk Thilo , Edwards Robert , Modugno Francesmary , Ness Roberta B. , Matsuo Keitaro , Mizuno Mika , Karlan Beth Y. , Goode Ellen L. , Kjær Susanne K. , Høgdall Estrid , Schildkraut Joellen M. , Terry Kathryn L. , Cramer Daniel W. , Bandera Elisa V. , Paddock Lisa E. , Kiemeney Lambertus A. , Massuger Leon F.A.G. , Sutphen Rebecca , Anton-Culver Hoda , Ziogas Argyrios , Menon Usha , Gayther Simon A. , Ramus Susan J. , Gentry-Maharaj Aleksandra , Pearce Celeste L. , Wu Anna H. , Kupryjanczyk Jolanta , Jensen Allan , Webb Penelope M. , Moysich Kirsten B.
Published: March 2023

Abstract
Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients.

Methods: Among patients diagnosed with invasive ovarian carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival. Using Cox proportional hazards regression models adjusted for age at diagnosis, stage of disease, histology, and study site, we estimated pooled HRs and 95% confidence intervals to assess associations between each comorbidity and ovarian cancer outcomes.

Results: None of the comorbidities were associated with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced).

Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic diseases were not associated with ovarian cancer overall or progression-free survival.

Impact: These previously diagnosed chronic diseases do not appear to affect ovarian cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(9); 1470–3. ©2017 AACR.
Data from Genome-wide Gene–Asbestos Exposure Interaction Association Study Identifies a Common Susceptibility Variant on 22q13.31 Associated with Lung Cancer Risk
Authors: Liu Chen-yu , Stücker Isabelle , Chen Chu , Goodman Gary , McHugh Michelle K. , D'Amelio Anthony M. , Etzel Carol J. , Li Su , Lin Xihong , Christiani David C.
Published: March 2023

Abstract
Background: Occupational asbestos exposure has been found to increase lung cancer risk in epidemiologic studies.

Methods: We conducted an asbestos exposure–gene interaction analyses among several Caucasian populations who were current or ex-smokers. The discovery phase included 833 Caucasian cases and 739 Caucasian controls, and used a genome-wide association study (GWAS) to identify single-nucleotide polymorphisms (SNP) with gene–asbestos interaction effects. The top ranked SNPs from the discovery phase were replicated within the International Lung and Cancer Consortium (ILCCO). First, in silico replication was conducted in those groups that had GWAS and asbestos exposure data, including 1,548 cases and 1,527 controls. This step was followed by de novo genotyping to replicate the results from the in silico replication, and included 1,539 cases and 1,761 controls. Multiple logistic regression was used to assess the SNP–asbestos exposure interaction effects on lung cancer risk.

Results: We observed significantly increased lung cancer risk among MIRLET7BHG (MIRLET7B host gene located at 22q13.31) polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325 heterozygous and homozygous variant allele(s) carriers (P < 5 × 10−7 by likelihood ratio test; df = 1). Among the heterozygous and homozygous variant allele(s) carriers of polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325, each unit increase in the natural log-transformed asbestos exposure score was associated with age-, sex-, smoking status, and center-adjusted ORs of 1.34 [95% confidence interval (CI), 1.18–1.51], 1.24 (95% CI, 1.14–1.35), 1.28 (95% CI, 1.17–1.40), and 1.26 (95% CI, 1.15–1.38), respectively, for lung cancer risk.

Conclusion: Our findings suggest that MIRLET7BHG polymorphisms may be important predictive markers for asbestos exposure–related lung cancer.

Impact: To our knowledge, our study is the first report using a systematic genome-wide analysis in combination with detailed asbestos exposure data and replication to evaluate asbestos-associated lung cancer risk. Cancer Epidemiol Biomarkers Prev; 24(10); 1564–73. ©2015 AACR.
Supplementary Figure 2 from Adjuvant therapy with oncolytic adenovirus Delta-24-RGDOX after intratumoral adoptive T-cell therapy promotes antigen spread to sustain systemic antitumor immunity
Authors: Jiang Hong , Shin Dong Ho , Yi Yanhua , Fan Xuejun , Gumin Joy , He Jiasen , Gillard Andrew G. , Lang Frederick F. , Gomez-Manzano Candelaria , Fueyo Juan
Published: March 2023

Expression of TCRs in CD8+ T cells from pmel-1 (A, gp100-Tet+) or OT-I (B, OVA-Tet+) transgenic mice. Splenocytes from the mice were stained with tetramers binding with TCR specific for gp100 (pmel-1) or OVA (OT-I), and antibody against CD8. Stained cells were analyzed with flow cytometry. The numbers in upright corner of the dot plots indicate the frequency (% of splenocytes) of gp100-targeting (A) or OVA-targeting (B) in CD8+ T cells.
Cervicalgias
Authors: Teixeira Manoel Jacobsen , Barros Filho Tarcísio de , Yeng Lin Tchia , Hamani Clement , Teixeira William Gemio Jacobsen
Published: March 2023

A cervicalgia pode ser decorrente de condições sistêmicas, ou de anormalidades viscerais, músculo-esqueléticas ou neurológicas envolvendo a região cervical. Muitas vezes, entretanto, os exames laboratoriais, eletrofisiológicos e de imagem não identificam precisamente sua origem. Além disto muitas anormalidades, especialmente evidenciadas nos exames de imagem, não são relacionadas às condições álgicas. A região cervical apresenta intensa mobilidade o que condiciona fadiga e degeneração de estruturas regionais ricamente inervadas. A cervicalgia músculo-esquelética pode ser aguda, auto-limitada, ou crônica e, freqüentemente, é associada à dor em outras regiões. O diagnóstico clínico mais que os exames complementares são de grande importância no diagnóstico das razões da ocorrência das cervicalgias.
Insuficiência renal aguda induzida pelo contraste em pacientes submetidos à cineangiocoronariografia – análise dos métodos de prevenção*
Authors: Soeiro Alexandre de Matos , Carlos Alexandre Stievano , Felício Carlos Henrique Chirnev , Luz Daniel Petkevicius , Borda Aldunate Johnny Leandro Conduta , Cabral Richard Halti
Published: March 2023

A insuficiência renal aguda induzida por contraste (IRAIC) é considerada, atualmente, uma importante causa de disfunção renal em pacientes hospitalizados submetidos à cinecoronarioangiografia (CAG). Este achado adquire maior importância quando se verifica que a IRAIC é responsável por um aumento significativo dos índices de morbidade e mortalidade hospitalar. Com o objetivo de evidenciar as principais formas de prevenção e tratamento da IRAIC, realizou-se uma revisão bibliográfica ampla, utilizando as principais bases de dados internacionais. A adoção de medidas de prevenção da instalação da IRAIC como, autilização de N-acetil-cisteína ou do fenoldopam antes da injeção do contraste, foi o método que melhor repercutiu na sobrevida dos pacientes estudados, principalmente naqueles que são diabéticos ou que apresentam algum prejuízo da função renal.
Effects of Three Different Tillage Patterns on Ground and Below-Ground Dwelling Insect Assemblage
Authors: Feng Lichao , Liang Aizhen , Gao Qiang , Wu Donghui
Published: March 2023

Tillage could significantly change the biodiversity in farmlands. As a prominent component of farmland ecology, crops play a key role in regulating biological communities. To explore the effects of tillage patterns and planting modes, including high-disturbance tillage practices and
different plant compositions, on the abundance of soil insects, we tested the responses of soil insects to no-tillage (NT), ridge tillage (RT), and fall plow (FP) treatments with different planting modes. The results illustrated that planting modes significantly changed the distributions of
ground-dwelling insect species and disturbed interactions on the farmland. Soil-dwelling insect assemblages were mainly influenced by tillage patterns, which reflected that soil physicochemical properties, especially pH, had the highest contribution to the determination of community composition.
The no-tillage system supported the highest predator species richness and lower herbivore richness with higher abundance. In the no-tillage system, most of the insects on the farmland have established relationships, forming a relatively high degree of connection between different insects.
The network was more specialized and nested in the field with fall ploughing. In conclusion, the effects of tillage patterns and planting modes on insect assemblage can be divided into two spatial dimensions: the success of soil-ground insect maintenance determined by plants and below-ground
depended on tillage.
Seasonality of Upper-Ocean Vertical Eddy Buoyancy Flux in the Kuroshio Extension
Authors: Zhang Xiangyu , Jing Zhao , Yang Peiran
Published: March 2023

Oceanic mesoscale and submesoscale eddies produce a pronounced vertical buoyancy flux, playing an important role in ocean restratification. This study used a 1-km ocean simulation to investigate the seasonality of the vertical eddy buoyancy flux (VEBF) in the Kuroshio Extension as well as its underlying dynamics. The simulated VEBF in the upper 200 m over the Kuroshio Extension has a pronounced seasonal cycle. The winter VEBF peaks in the mixed layer, whereas the summer VEBF has a much smaller magnitude but a more complicated vertical structure with a narrow peak in the shallow mixed layer and a broader and stronger peak in the seasonal thermocline. The baroclinic instability (BCI), frontogenesis, and turbulent thermal wind (TTW) balance all contribute to the VEBF seasonal cycle. In winter, large surface heat loss and intense winds destroy stratification and enhance turbulent vertical mixing in the upper ocean. These phenomena intensify VEBF by promoting its components induced by the frontogenesis and TTW balance and by triggering mixed layer instability (MLI). In summer, strong stratification associated with suppressed turbulent vertical mixing weakens the contributions of the frontogenesis and TTW balance to VEBF and shifts the dominant BCI type from the MLI to the surface Charney- and Philips-like types with greatly reduced growth rate compared with that of MLI in winter. The shallow peak of the VEBF in summer is mainly attributed to the TTW balance, whereas the BCI and frontogenesis account primarily for its deep peak.
B-LBConA: a medical entity disambiguation model based on Bio-LinkBERT and context-aware mechanism
Authors: Yang Siyu , Zhang Peiliang , Che Chao , Zhong Zhaoqian
Published: March 2023

Background

The main task of medical entity disambiguation is to link mentions, such as diseases, drugs, or complications, to standard entities in the target knowledge base. To our knowledge, models based on Bidirectional Encoder Representations from Transformers (BERT) have achieved good results in this task. Unfortunately, these models only consider text in the current document, fail to capture dependencies with other documents, and lack sufficient mining of hidden information in contextual texts.

Results

We propose B-LBConA, which is based on Bio-LinkBERT and context-aware mechanism. Specifically, B-LBConA first utilizes Bio-LinkBERT, which is capable of learning cross-document dependencies, to obtain embedding representations of mentions and candidate entities. Then, cross-attention is used to capture the interaction information of mention-to-entity and entity-to-mention. Finally, B-LBConA incorporates disambiguation clues about the relevance between the mention context and candidate entities via the context-aware mechanism.

Conclusions

Experiment results on three publicly available datasets, NCBI, ADR and ShARe/CLEF, show that B-LBConA achieves a signifcantly more accurate performance compared with existing models.
Decision-makers’ experiences with rapid evidence summaries to support real-time evidence informed decision-making in crises: a mixed methods study
Authors: Khalid Ahmad Firas , Grimshaw Jeremy M. , Parakh Nandana D. , Charide Rana , Rab Faiza , Sohani Salim
Published: March 2023

Background

There is a clear need for research evidence to drive policymaking and emergency responses so that lives are saved and resources are not wasted. The need for evidence support for health and humanitarian crisis is even more pertinent because of the time and practical constraints that decision-makers in these settings face. To improve the use of research evidence in policy and practice, it is important to provide evidence resources tailored to the target audience. This study aims to gain real-world insights from decision-makers about how they use evidence summaries to inform real-time decision-making in crisis-settings, and to use our findings to improve the format of evidence summaries.

Methods

This study used an explanatory sequential mixed method study design. First, we used a survey to identify the views and experiences of those who were directly involved in crisis response in different contexts, and who may or may not have used evidence summaries. Second, we used the insights generated from the survey to help inform qualitative interviews with decision-makers in crisis-settings to derive an in-depth understanding of how they use evidence summaries and their desired format for evidence summaries.

Results

We interviewed 26 decision-makers working in health and humanitarian emergencies. The study identified challenges decision-makers face when trying to find and use research evidence in crises, including insufficient time and increased burden of responsibilities during crises, limited access to reliable internet connection, large volume of data not translated into user friendly summaries, and little information available on preparedness and response measures. Decision-makers preferred the following components in evidence summaries: title, target audience, presentation of key findings in an actionable checklist or infographic format, implementation considerations, assessment of the quality of evidence presented, citation and hyperlink to the full review, funding sources, language of full review, and other sources of information on the topic. Our study developed an evidence summary template with accompanying training material to inform real-time decision-making in crisis-settings.

Conclusions

Our study provided a deeper understanding of the preferences of decision-makers working in health and humanitarian emergencies about the format of evidence summaries to enable real-time evidence informed decision-making.
Psychological Capital and Job Search: A Systematic Literature Review and Agenda for Future Research
Authors: Fernández-Valera María-Magdalena
Published: March 2023

Purpose: There is consistent evidence that a positive mindset could foster the job search process. Psychological capital, defined as a tendency to hold cognitions and positive appraisals of one's ability, could highlight the importance of individual cognitive appraisal in the job search process. Nevertheless, psychological capital's impact on job seekers is still unclear. Methods: The purpose of the present study was to explore the role of psychological capital in the job search process. The author conducted a systematic review following the PRISMA-P guidelines. This systematic review sought answers to three questions: 1) What theories are applied to explain the relationship between psychological capital and the job search process? 2) How is the association between psychological capital and the job search process? 3) Did the psychological capital interventions positively influence the job search process? The review focused on quantitative studies carried out between 2007 and 2021 on job seekers. Finally, 11 studies fit the inclusion criteria. Results: Overall, the literature review supports the significant association between psychological capital and the job search process. On the one hand, the studies analyzed have shown the resonance of psychological capital on the job search outcomes and job seekers' well-being. On the other hand, the results showed insufficient evidence to make any firm conclusions concerning psychological capital interventions' effects on the job search process improvement. Conclusion: It is concluded that psychological capital may be a valuable advantage for helping job seekers engage in their job search process. The results presented in this study could have important implications for job seekers and public and private employment agencies. Even so, it is necessary to continue contributing to its development. Particularly, there is still considerable scope for improvement in the study of psychological capital and the job search process in terms of the study design we apply, the variables we study and their measure, and the theoretical background we use to explain the previous relationship.
Padrões de Lineamentos e Controle Estrutural, Tectônico e Neotectônico no Relevo da Região de Pancas (Espírito Santo, Sudeste do Brasil)
Authors: Luna da Silva Marcos Cesar , Bricalli Luiza Leonardi
Published: March 2023

Esta pesquisa tem como objetivo principal investigar o controle litoestrutural, tectônico e neotectônico no relevo da região de Pancas (Espírito Santo, Sudeste do Brasil). A metodologia foi organizada em análises de gabinete e de campo. Em gabinete foram gerados mapas de lineamentos e de trends estruturais, a partir da técnica de extração manual, utilizando ferramentas de edição do software ArcGIS 10.3.1™ (ESRI, 2012), sobre um Modelo Digital de Elevação (MDE) com diferentes iluminações artificiais (escala 1:110.000) e geradas rosetas de orientação. Os mapas geológicos e geomorfológicos foram organizados/elaborados com o ArcGIS, a partir do Sistema de Informações Geográficas (SIG) e as bases cartográficas foram configuradas no sistema de projeção UTM e DATUM SIRGAS 2000, zona 24S, posteriormente analisados e comparados com os dados das orientações dos lineamentos decalcados, com a orientação das falhas de afloramentos estudados e com a literatura existente. Os resultados apresentaram orientações NW-SE/NNW-SSE e NE-SW/NNE-SSW, com a predominância das orientações NNW-SSE e NW-SE identificadas na análise dos lineamentos e dos trends estruturais, semelhantes com as orientações das falhas geológicas e das falhas neotectônicas presentes na área estudada, refletindo a estruturação regional da área, apresentando as mesmas orientações da Faixa Colatina. As orientações secundárias do Orógeno Araçuaí (NE-SW), a identificação de feições morfotectônicas, a presença de diferenças topográficas abruptas (perfis topográficos), a identificação de regiões tectônicas (mapa de superfície de bases) e de blocos tectônicos (perfil em varredura) demonstram o controle tectônico no relevo da região de Pancas-ES, atingindo o objetivo desta pesquisa.