bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary Communication: Glycated Hemoglobin, Diabetes, and Incident Colorectal Cancer in Men and Women: A Prospective Analysis from the European Prospective Investigation into Cancer–Norfolk Study
Authors: Khaw Kay-Tee , Wareham Nicholas , Bingham Sheila , Luben Robert , Welch Ailsa , Day Nicholas 
Published: June 2022

Abstract
Background: Increasing evidence suggests that abnormal glucose metabolism may be associated with increased risk of colorectal cancer. Methods: We examined the relationship between known diabetes and glycated hemoglobin (HbA1c) concentrations measured in 1995 to 1997 and subsequent incident colorectal cancer after 6 years follow-up in 9,605 men and women ages 45 to 79 years in the European Prospective Investigation into Cancer–Norfolk Study. Results: Among individuals not known to have cancer at the baseline survey, there were 67 incident colorectal cancers. HbA1c concentration appeared continuously related to incident colorectal cancer risk, with lowest rates observed in those with HbA1c below 5%. Known diabetes was also associated with incident colorectal cancer, with relative risk (RR) 3.18 and 95% confidence interval (CI) 1.36-7.40 (P &lt; 0.01) adjusting for age and sex and RR 2.78 and 95% CI 1.10-7.00 (P = 0.03) adjusting for age, sex, body mass index, and smoking compared with those without known diabetes. The RR (95% CI) of incident colorectal cancer per 1% absolute increase in HbA1c was 1.34 (1.12-1.59; P &lt; 0.001). HbA1c concentrations appeared to explain the increased colorectal cancer risk associated with diabetes in multivariate models. Conclusions: Known diabetes was associated with ∼3-fold risk of colorectal cancer in this analysis; this increased risk was largely explained by HbA1c concentrations, which appears continuously related to colorectal cancer risk across the population distribution.
Cell Proliferation and Apoptotic Indices Predict Adenoma Regression in a Placebo-Controlled Trial of Celecoxib in Familial Adenomatous Polyposis Patients
Authors: Sinicrope Frank A. , Half Elizabeth , Morris Jeffrey S. , Lynch Patrick M. , Morrow Jason D. , Levin Bernard , Hawk Ernest T. , Cohen Deborah S. , Ayers Gregory D. , Stephens L. Clifton ,   Familial Adenomatous Polyposis Study Group
Published: June 2022

Abstract
Background: Celecoxib was shown to regress colorectal adenomas in familial adenomatous polyposis (FAP) patients relative to placebo. To address the mechanism of polyp regression, we determined whether celecoxib can modulate cell proliferation, apoptosis, and prostaglandin E2 (PGE2) levels in colorectal epithelia from FAP trial participants and whether such alterations correlate with observed reductions in polyp number. Materials and Methods: Colorectal mucosal biopsies were obtained at baseline and on last day of celecoxib (100 or 400 mg twice daily) or placebo administration (6 months). Residual paraffin-embedded adenomas and normal mucosa from the same patients (n = 17) or normal tissue alone (n = 15) were analyzed. Immunoperoxidase staining for Ki-67 was performed and apoptotic cells were identified by their morphology. Ki-67 and apoptotic labeling indices and their ratios were calculated in superficials (s) and nonsuperficial (ns) regions of adenomas and normal mucosa, and baseline to 6-month differences were calculated. PGE2 levels were analyzed by mass spectroscopy (normal, n = 64; adenoma, n = 56). Biomarkers were analyzed by treatment arm and correlated with previously determined mean percentage reductions in colorectal polyp number. Results: In adenomas, a reduction in the superficial proliferative activity i.e., Ki-67s labeling index, accompanied polyp regression (r = −0.76, P = 0.006). An increase in the apoptotic ratio [i.e., superficial apoptotic index (AIs)/nonsuperficial apoptotic index (AIns)] was found to correlate with reduced polyp counts in that higher apoptotic ratios correlated with better response to celecoxib (r = 0.71, P = 0.004). Furthermore, the AIs/Ki-67s ratio (r = 0.58, P = 0.026) accompanied polyp regression. In normal mucosa, a trend toward increased AIs (r = 0.33, P = 0.053) and polyp regression was found. PGE2 levels did not significantly correlate with polyp regression. Changes in biomarker levels (baseline to 6 months) were correlated in adenomas and normal mucosa (AIs, r = 0.29, P = 0.024; AIns, r = 0.34, P = 0.009; PGE2, r = 0.50, P = 0.059) within individual patients. Conclusion: Suppression of cell proliferation and an increased apoptotic ratio, as well as the ratio of apoptosis to cell proliferation, accompany polyp regression in a chemoprevention trial in FAP patients. These findings suggest potential mechanisms for the efficacy of celecoxib and warrant further study of these biomarkers as intermediate endpoints in FAP patients.
Variation in Estradiol, Estradiol Precursors, and Estrogen-related Products in Nipple Aspirate Fluid from Normal Premenopausal Women
Authors: Chatterton Robert T. , Geiger Angela S. , Khan Seema A. , Helenowski Irene B. , Jovanovic Borko D. , Gann Peter H. 
Published: June 2022

Abstract
The purpose of the study was to measure the concentrations of estradiol, its primary precursors, and factors with which it interacts in the breast, and determine their sources of variation. Nipple aspirate fluid (NAF) was collected from premenopausal women during the mid-luteal phase of the menstrual cycle. The fluid was diluted and unconjugated steroids were extracted. Estradiol was further purified by a solvent partition into aqueous NaOH. Androgens were measured in the non-phenolic fraction. Water-soluble, conjugated steroids and proteins were measured in the aqueous residue. All analytes were measured by immunoassays. Permutation methods were used to determine the correlations over multiple periods of time. The average concentration of estradiol in NAF was 435 pmol/L after purification but was many times higher when assayed without purification. Estrone and dehydroepiandrosterone (DHEA) sulfates were present in 3.7 and 75 μmol/L concentrations, respectively, while unconjugated androstenedione and DHEA were present in nanomole per liter concentrations. Lack of the steroid sulfates in NAF in 19% of subjects had no effect on NAF estradiol levels but was associated with a 77% lower concentration of unconjugated DHEA. Progesterone was present in concentrations that were 3- to 4-fold higher than normal serum concentrations (mean: 291 nmol/L). Cathepsin D, epidermal growth factor, and interleukin 6 had average values of 3.4 μg/mL, 424 ng/mL, and 1.7 ng/mL, respectively. Correlations between breasts were between 0.57 and 0.84 for the several analytes; correlations over time ranged from 0.64 and 0.93 with estrone sulfate highest in both categories. The lower correlation between breasts than within breasts indicates that local factors play an important role in determining the levels of many of these analytes in the breast. The high stability of the concentrations of several analytes over time indicates that fluctuations in environmental factors have little immediate effect on levels in the breast, and portends their utility as surrogate breast cancer risk markers.
Cancer Prevention Services and Physician Consensus in Primary Care Group Practices
Authors: Love Richard R. , Baumann Linda C. , Brown Roger L. , Fontana Susan A. , Clark Caroline C. , Sanner Louis A. , Davis James E. 
Published: June 2022

Abstract
Background: We conducted a randomized clinical trial of interventions to achieve physician consensus, practice changes, and patient activation designed to help primary care group practices enhance the delivery of cancer prevention and screening services. Methods: In each of 42 primary care practices in 1991 to 1994, we studied approximately 60 patients per physician who were between the ages 53 and 64. Data sources included patient and physician questionnaires, medical record audits of consenting patients for evidence of 11 cancer prevention services during the previous 3 years, and telephone interviews with key practice personnel. Results: None of the interventions was associated with significant changes in frequency of services or procedures received or provided. Increased frequencies of services overall and of specific activities were associated with HMO membership or insurance coverage for six screening procedures. Patient reports of clinic staff recommendations to have each of six screening procedures were specifically associated with higher frequencies of services (P = 0.001). Conclusions: Demonstration of intervention impact may have been limited because the rates of prevention services were significantly higher in this study than have been reported elsewhere. These results might be explained by selection biases inherent in studying patients with a regular provider, overall practice trends for changes in provision of the studied services, and the study methods.
Endogenous Hormones and Ovarian Cancer: Epidemiology and Current Hypotheses
Authors: Lukanova Annekatrin , Kaaks Rudolf 
Published: June 2022

Abstract
The effect of major epidemiologic risk factors for ovarian cancer has been reviewed in the light of several hormonal hypotheses, including the gonadotropin, androgens, progesterone, estrogens, insulin-like growth factor-I, and insulin hypotheses. The role of inclusion cyst formation and Mullerian epithelium differentiation in the pathology of the disease are also briefly outlined. Although based on limited data, the observed tendency in current evidence suggests possible etiologic roles for elevated androgens and estrogens and decreased progesterone in the pathogenesis of ovarian cancer. A direct effect of gonadotropins cannot be entirely ruled out, but it is plausible that their effect on ovarian cancer risk is mediated by stimulation of ovarian steroidogenesis. Insulin-like growth factor-I also emerges as a hormone that may be directly involved in the pathogenesis of the disease, but thus far only one prospective study has examined this association. Hyperinsulinemia is an unlikely risk factor for ovarian cancer. The observed tendency for an increased risk with androgens from ovarian origin (in premenopausal women), the lack of association with adrenal androgens, and the relatively weak associations observed with obesity, hormonal replacement therapy use, and endogenous hormones after menopause suggest that ovarian synthesis of sex steroids rather than their circulating levels may be etiologically important. More data from prospective studies will be crucial to improve our understanding of the etiologic role of endogenous hormones in the pathogenesis of ovarian cancer. Such data will ultimately provide opportunities for research targeted; at early detection and preventive interventions.
Virtual Venues and International Negotiations: Lessons from the COVID-19 Pandemic
Authors: Bjola Corneliu , Coplen Michaela 
Published: June 2022

Abstract
The COVID-19 pandemic has altered international diplomacy, with many negotiations now conducted in ‘virtual venues’ facilitated by videoconferencing platforms such as Zoom, Microsoft Teams, Webex, and Interprefy. Drawing on a survey of diplomats with experience in virtual venue negotiation, we analyze respondents’ perceptions of efficacy, tactics, and legitimacy in these venues. We find that virtual venues not only affect the format, but also the substance of negotiations. In general, perceptions of efficacy are related to diplomats’ ability to ‘read the room’. Virtual venues also impact negotiations at the tactical level. We find that coercive approaches (including novel tactics) are more common than persuasive approaches. Overall, these venues are afforded the same legitimacy as face-to-face negotiations. We conclude that, as virtual venues will be a feature of international diplomacy for the foreseeable future, further research is required to inform increased diplomatic adaptation and hybridity.
Deconstructing the Relation between Law and Authoritarianism: How Law Consolidated Authoritarianism in Post-2011 Egypt
Authors: Elgohari Mohamed 
Published: June 2022

Abstract
This article argues that law and legal mechanisms in Egypt have not simply reinforced authoritarianism but have also been the avenue through which embryonic moves toward the rule of law have been halted and even reversed. The political regime has utilized law to consolidate its rule, boost its legitimacy, crack down on opposition and dissent, and restrict freedoms and rights. In Egypt, law and authoritarianism have not only co-existed but also have intersected and been mutually supportive. The political regime has used laws to legalize its autocratic policies and practices as a pretext to restore order and stability and fight terrorism. Since 2013, the law has been a tool not simply for authoritarianism in general but also for the ruling regime and military institution to assert control over society, to place themselves out of reach of legal/constitutional mechanisms and accountability either by issuing new laws and executive orders or altering existing ones.
The implementation of a whole school approach to mental health and well-being promotion in the Irish primary school context
Authors: Higgins Edel , Booker Roger 
Published: June 2022

Background: Schools are well recognised as critical contexts for the promotion of mental health and well-being and offer the potential to reach a large number of children at an early age, at a time when they are developing important attitudes and behaviours that may influence their future health. Ensuing from a number of large-scale epidemiological studies which have found that young Irish people are significantly struggling with their mental health and well-being, the Government of Ireland has committed to prioritising mental health promotion in schools through a multicomponent, preventive, whole school approach. Objectives: To obtain a detailed and integrated account of the implementation of a whole school approach to mental health and well-being promotion in the Irish primary school context. Method: A qualitative case study approach was undertaken employing in depth semi-structured interviews, document analysis and field notes. Thematic analysis was applied to all interview data and emerging themes were mapped on to the Theoretical Domains Framework (TDF) domains. Setting: Three Irish primary schools. Results: Facilitators and barriers that emerged from the data related primarily to the schools’ economic and political context, organisational context, and internal and external partnerships and relationships. Conclusion: This study has demonstrated that the implementation process in ‘real-world’ practice settings, such as schools, is dynamic, complex and exists within a multi-level system and requires careful consideration of the numerous ecological factors that can influence implementation.
Temporal Trends in Tobacco Product Use Among US Middle and High School Students: National Youth Tobacco Survey, 2011-2020
Authors: Jebai Rime , Osibogun Olatokunbo , Li Wei , Gautam Prem , Bursac Zoran , Ward Kenneth D. , Maziak Wasim 
Published: June 2022

Objectives: Despite significant declines in cigarette smoking during the past decade, other tobacco products gained popularity among middle and high school students. This study examined temporal trends in exclusive and concurrent use of tobacco products among middle and high school students in the United States from 2011 through 2020. Methods: We used multiple annual datasets from the National Youth Tobacco Survey from 2011 through 2020 (N = 193 350) to examine trends of current (past 30 days) exclusive, dual, and poly use of tobacco products (ie, cigarettes, electronic cigarettes [e-cigarettes], cigars, hookahs, and smokeless tobacco). We used joinpoint regression models to calculate log-linear trends in annual percentage change (APC). Results: During 2011-2020, exclusive use of any tobacco product decreased significantly, except for e-cigarettes, which increased significantly at an APC of 226.8% during 2011-2014 and 14.6% during 2014-2020. This increase was more pronounced among high school students (APC = 336.6% [2011-2014] and 15.7% [2014-2020]) than among middle school students (APC = 10.4% [2014-2020]) and among male students (APC = 252.8% [2011-2014] and 14.8% [2014-2020]) than among female students (APC = 13.6% [2014-2020]). During 2011-2020, we also found upward trends in dual use of e-cigarettes and cigarettes (APC = 17.3%). Poly use of e-cigarettes, cigarettes, and any other tobacco products increased significantly at an APC of 57.1% during 2011-2014. Conclusions: The emergence of new tobacco products such as e-cigarettes in the US market has shifted the landscape of tobacco use among adolescents in the last decade toward poly product use, in which e-cigarettes are a prominent component. Our findings underscore the increasing complexity of tobacco use among adolescents in the United States and the need for strong policies and regulations adapted to evolving trends in cigarette and noncigarette tobacco products.
Prolonged durability of extensive contiguous spinal metastasis stabilization in non-small cell lung cancer patients receiving targeted therapy: two case reports and a literature review
Authors: Jaipanya Pilan , Chanplakorn Pongsthorn 
Published: June 2022

Contiguous spinal metastasis poses a challenge for spine surgeons. In patients with a short remaining life expectancy, surgery may be discouraged. However, in select cases, surgery may be inevitable to eliminate pain and improve the patient’s quality of life. Additionally, with advancements in systemic cancer therapy, the efficacy and duration of tumor control have improved significantly. Consequently, a patient’s life expectancy may be difficult to estimate with existing prognostic scores. Because patients may achieve prolonged survival, spinal metastasis surgery could greatly benefit a patient’s quality of life. In this report, we present the details of two patients with non-small lung cancer with contiguous spinal metastasis who underwent spinal surgery for their metastatic disease. After surgery and targeted therapy with epidermal growth factor tyrosine kinase inhibitors (EGFR TKI), the patients attained substantial healing of their previously lytic spines and achieved prolonged survival of up to 42 months. With modern systemic therapy for lung cancer, the treatment of spinal metastatic disease can achieve decent outcomes, even in poor surgical candidates. Mini-abstract In this report, we present two cases of contiguous spinal metastatic disease in non-small cell lung cancer patients who achieved prolonged survival and stable spinal fixation after treatment with EGFR TKIs.
Occupational therapy incorporating dogs for autistic children and young people: Parent perspectives
Authors: Richardson Kathleen , Mackenzie Lynette , Lovarini Meryl , Dickson Claire 
Published: June 2022

Introduction Dogs may elicit positive therapy outcomes for children/adolescents with autism spectrum disorder (ASD). However, little is known about the parent perspectives of the use of dogs as part of an occupational therapy program for ASD. This study aimed to explore parent perspectives about the Animal Assisted Therapy (AAT) component of the occupational therapy intervention their child/adolescent received across five weekly sessions. Method Using a phenomenological approach, 16 semi-structured interviews were conducted with parents (13 mothers and four fathers) following an AAT occupational therapy program. Thematic analysis was conducted. Results Three themes were identified relating to the value parents attributed to the AAT occupational therapy program with dogs for their child/adolescent: 1. Stress and anxiety management; 2. Participation and engagement and 3. Social communication. Positive outcomes identified by parents included the dogs being a calming influence and facilitating the participation of their child/adolescent in life-skill activities. Conclusion Parents valued AAT occupational therapy involving dogs. Future studies should investigate how to best target this occupational therapy approach for autistic children and adolescents.
Prediction of ESBL-producing E coli for suspected urinary tract infection
Authors: Higuchi Hiroshi , Nakamura Tsukasa , Mashino Junji , Imada Toshihiro , Morimoto Takeshi 
Published: June 2022

Aim: The widespread existence of extended-spectrum β-lactamase (ESBL) producing Escherichia coli ( E. coli) has become a critical threat in developed countries. Prediction rule for ESBL producing E. coli is relevant to see patients with suspected urinary tract infection. Materials and methods: We collected clinical and laboratory data and constructed multivariate logistic regression models to develop a clinical prediction rule in the derivation cohort with 1185 patients with urine cultures and validated the rule in the validation cohort with 516 patients. Results: ESBL-producing E. coli was found in 185 patients (16%) in the derivation cohort. When assigning 14 points for being female (odds ratio (OR): 4.2), six points for CRP >5 mg/dl (OR: 1.87), and four points for a history of urinary tract infection (OR: 1.52), the area under the curve (AUC) had 0.67 (95% confidence interval (CI): 0.63–0.70) in the derivation cohort and 0.64 (95% CI: 0.59–0.69] in the validation cohort. Conclusions: The developed prediction rule had moderate accuracy to predict ESBL-producing E. coli in patients with suspected urinary tract infection.
Role of the pre- to postoperative alpha-fetoprotein ratio in the prognostic evaluation of liver cancer after radiofrequency ablation
Authors: Luo Biwei , Liu Linsen , Bi Jian’gang , Bao Shiyun , Zhang Yusen 
Published: June 2022

Objective This study aimed to investigate the role of the alpha fetoprotein (AFP) ratio before and after radiofrequency ablation (RFA) in the prognosis of patients with liver cancer. Methods A total of 368 patients who underwent RFA for liver cancer in Shenzhen People's Hospital from 2010 to 2020 were randomly divided into the training group and the validation group. Levels of AFP before and after RFA were recorded and their ratios were calculated. Results Using the X-tile software, it was found that the optimal cut-off value of the AFP ratio in the training group was 37.9. Both in the training group and the validation group, the relapse-free survival and overall survival of patients with an AFP ratio <37.9 (high-risk group) were significantly shorter than those with an AFP ratio >37.9 (low-risk group) (training group, relapse-free survival, P = 0.0003; overall survival, P = 0.0186; validation group, relapse-free survival, P = 0.0490, overall survival, P = 0.0031). An AFP ratio <37.9 was an independent risk factor for recurrence and survival of liver cancer after RFA. Conclusion The AFP ratio can predict the prognosis of patients with liver cancer after RFA. An AFP ratio <37.9 is an independent risk factor for tumor recurrence and survival after RFA.