bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melatonin and cancer suppression: insights into its effects on DNA methylation
Authors: Davoodvandi Amirhossein , Nikfar Banafsheh , Reiter Russel J. , Asemi Zatollah 
Published: September 2022

AbstractMelatonin is an important naturally occurring hormone in mammals. Melatonin-mediated biological effects include the regulation of circadian rhythms, which is important for optimal human health. Also, melatonin has a broad range of immunoenhancing actions. Moreover, its oncostatic properties, especially regarding breast cancer, involve a variety cancer-inhibitory processes and are well documented. Due to their promising effects on the prognosis of cancer patients, anti-cancer drugs with epigenetic actions have attracted a significant amount of attention in recent years. Epigenetic modifications of cancers are categorized into three major processes including non-coding RNAs, histone modification, and DNA methylation. Hence, the modification of the latter epigenetic event is currently considered an effective strategy for treatment of cancer patients. Thereby, this report summarizes the available evidence that investigated melatonin-induced effects in altering the status of DNA methylation in different cancer cells and models, e.g., malignant glioma and breast carcinoma. Also, we discuss the role of artificial light at night (ALAN)-mediated inhibitory effects on melatonin secretion and subsequent impact on global DNA methylation of cancer cells.
The long-term impact of the earthquake on substance use
Authors: Amiri Hadis , Riyahifar Sevda , Nakhaee Nouzar , Nekoei-Moghadam Mahmoud 
Published: September 2022

AbstractEarthquake is associated with several health conditions such as posttraumatic stress disorder (PTSD), depression, and cardiovascular disease. However, the association between earthquakes and substance use has been less studied to date. We conducted a historical cohort study 17 years after the Bam earthquake by enrolling 818 households using multi-stage cluster sampling. The sample consisted of earthquake-exposed and non-exposed citizens. The ASSIST screening test was used to determine substance use. Logistic regression analysis was used to evaluate the association of variables of interest with substance use. Nearly 60% of the study subjects were female and the mean ± SD age of the sample was 46.6 ± 11.5 years. The prevalence of tobacco, alcohol, and other drug use in the exposed group was 19.5%, 24.9%, and 21.6%, respectively. The corresponding figures in the non-exposed group were 15.6%, 19.3%, and 20.1%, respectively (P > 0.05). The logistic regression model found no association between the history of earthquake exposure and the risk of any current drug use. Our results showed those 17 years after the Bam earthquake, there was no relationship between earthquake exposure and substance use.
Variation of the element composition of municipal sewage sludges in the context of new regulations on phosphorus recovery in Germany
Authors: Sichler Theresa Constanze , Montag David , Barjenbruch Matthias , Mauch Tatjana , Sommerfeld Thomas , Ehm Jan-Hendrik , Adam Christian 
Published: September 2022

AbstractPhosphorus (P) recovery is obligatory for all sewage sludges with more than 20 g P/kg dry matter (DM) from 2029 in Germany. Nine wastewater treatment plants (WWTPs) were chosen to investigate variations of phosphorus contents and other parameters in sewage sludge over the year. Monthly sewage sludge samples from each WWTP were analyzed for phosphorus and other matrix elements (C, N, H, Ca, Fe, Al, etc.), for several trace elements (As, Cr, Mo, Ni, Pb, Sn) and loss of ignition. Among the nine WWTPs, there are four which have phosphorus contents both above and below the recovery limit of 20 g/kg DM along the year. Considering the average phosphorus content over the year, only one of them is below the limit. Compared to other matrix elements and parameters, phosphorus fluctuations are low with an average of 7% over all nine WWTPs. In total, only hydrogen and carbon are more constant in the sludge. In several WWTPs with chemical phosphorus elimination, phosphorus fluctuations showed similar courses like iron and/or aluminum. WWTPs with chamber filter presses rather showed dilution effects of calcium dosage. As result of this study, monthly phosphorus measurement is highly recommended to determine whether a WWTP is below the 20 g/kg DM limit.
Graphical Abstract
Hazardous chemicals in non-polar extracts from paper and cardboard food packaging: an effect-based evaluation
Authors: Selin Erica , Wänn Mimmi , Svensson Kettil , Gravenfors Erik , Giovanoulis Georgios , Oskarsson Agneta , Lundqvist Johan 
Published: September 2022

Abstract
Background
Food contact articles are used in our everyday life and information regarding the potential health hazards of migrating chemicals for humans is scarce. In this study, an effect-based evaluation of non-polar extracts of food contact articles made of paper and board was conducted with a panel of eight bioassay endpoints. These, health-relevant endpoints, included oxidative stress, inflammation, genotoxicity, xenobiotic metabolism and hormone receptor effects.

Results
In total, 62 food contact articles were pooled into 19 groups, in which articles intended to be used for similar types of food item(s) were pooled, and extracted with acetone:n-hexane (1:4). These were then tested in the effect-based bioassays. Bioactivities were detected for multiple materials in six out of eight assays, the two assays showing no effects were NFκB and androgen receptor agonistic response. In essence, the detection rates of the tested non-polar extracts were 72% for antagonistic effects on the estrogen receptor, 72% for antagonistic effects on the androgen receptor, 47% for oxidative stress, 28% for agonistic effects on the estrogen receptor and 33% for genotoxicity. The bioequivalent concentrations ranges in extracts of 10 mg food contact article/mL cell culture media were: for oxidative stress from 2.45 to 5.64 µM tBHQ equivalents, estrogen receptor agonistic activity from 1.66 to 6.33 ρM estradiol equivalents, estrogen receptor antagonistic activity from 1.21 × 10–3 to 4.20 × 10–3 μM raloxifene equivalents and androgen antagonistic activity 0.08–0.46 μM hydroxyflutamide equivalents. The extracts that were bioactive in multiple assays were: baking moulds, boxes for popcorn, infant formula/skimmed milk, porridge/flour mixes, pizza, fries’ and hamburgers as well as packages for frozen food.

Conclusion
Non-polar extracts of food contact articles contain compounds that can activate molecular initiating events in toxicity pathways of high relevance to human health. These events included endocrine-disruptive activities, oxidative stress and genotoxicity. Effect-based methods proved to be a valuable tool for evaluating food package articles, as they can detect potentially hazardous effects of both known and unknown chemicals as well as potential cocktail effects.
Evaluating patient-reported outcome measures (PROMs) for clinical trials and clinical practice in adult patients with uveitis or scleritis: a systematic review
Authors: O’Donovan Charles , Panthagani Jesse , Aiyegbusi Olalekan Lee , Liu Xiaoxuan , Bayliss Susan , Calvert Melanie , Pesudovs Konrad , Denniston Alastair , Moore David , Braithwaite Tasanee 
Published: September 2022

AbstractPatient reported outcome measures (PROMs) capture impact of disease and treatment on quality of life, and have an emerging role in clinical trial outcome measurement. This study included a systematic review and quality appraisal of PROMs developed or validated for use in adults with uveitis or scleritis. We searched MEDLINE, EMBASE, PsycINFO, CINAHL and grey literature sources, to 5 November 2021. We used established quality criteria to grade each PROM instrument in multiple domains from A (high quality) to C (low quality), and assessed content development, validity, reliability and responsiveness. For instruments developed using classic test theory-based psychometric approaches, we assessed acceptability, item targeting and internal consistency. For instruments developed using Item Response Theory (IRT) (e.g. Rasch analysis), we assessed response categories, dimensionality, measurement precision, item fit statistics, differential item functioning and targeting. We identified and appraised four instruments applicable to certain uveitis types, but none for scleritis. Specifically, the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ), a 3-part PROM for Birdshot retinochoroiditis (Birdshot Disease & Medication Symptoms Questionnaire [BD&MSQ], the quality of life (QoL) impact of Birdshot Chorioretinopathy [QoL BCR], and the QoL impact of BCR medication [QoL Meds], the Kings Sarcoidosis Questionnaire (KSQ), and a PROM for cytomegalovirus retinitis. These instruments had limited coverage for these heterogeneous conditions, with a focus on very rare subtypes. Psychometric appraisal revealed considerable variability between instruments, limited content development, and only one developed using Item Response Theory. In conclusion, there are few validated PROMs for patients with uveitis and none for scleritis, and existing instruments have suboptimal psychometric performance. We articulate why we do not recommend their inclusion as clinical trial outcome measures for drug licensing purposes, and highlight an unmet need for PROMs applicable to uveitis and scleritis.
Optimal experimental designs for estimating genetic and non-genetic effects underlying infectious disease transmission
Authors: Pooley Christopher , Marion Glenn , Bishop Stephen , Doeschl-Wilson Andrea 
Published: September 2022

AbstractBackgroundThe spread of infectious diseases in populations is controlled by the susceptibility (propensity to acquire infection), infectivity (propensity to transmit infection), and recoverability (propensity to recover/die) of individuals. Estimating genetic risk factors for these three underlying host epidemiological traits can help reduce disease spread through genetic control strategies. Previous studies have identified important ‘disease resistance single nucleotide polymorphisms (SNPs)’, but how these affect the underlying traits is an unresolved question. Recent advances in computational statistics make it now possible to estimate the effects of SNPs on host traits from epidemic data (e.g. infection and/or recovery times of individuals or diagnostic test results). However, little is known about how to effectively design disease transmission experiments or field studies to maximise the precision with which these effects can be estimated.ResultsIn this paper, we develop and validate analytical expressions for the precision of the estimates of SNP effects on the three above host traits for a disease transmission experiment with one or more non-interacting contact groups. Maximising these expressions leads to three distinct ‘experimental’ designs, each specifying a different set of ideal SNP genotype compositions across groups: (a) appropriate for a single contact-group, (b) a multi-group design termed “pure”, and (c) a multi-group design termed “mixed”, where ‘pure’ and ‘mixed’ refer to groupings that consist of individuals with uniformly the same or different SNP genotypes, respectively. Precision estimates for susceptibility and recoverability were found to be less sensitive to the experimental design than estimates for infectivity. Whereas the analytical expressions suggest that the multi-group pure and mixed designs estimate SNP effects with similar precision, the mixed design is preferred because it uses information from naturally-occurring rather than artificial infections. The same design principles apply to estimates of the epidemiological impact of other categorical fixed effects, such as breed, line, family, sex, or vaccination status. Estimation of SNP effect precisions from a given experimental setup is implemented in an online software toolSIRE-PC.ConclusionsMethodology was developed to aid the design of disease transmission experiments for estimating the effect of individual SNPs and other categorical variables that underlie host susceptibility, infectivity and recoverability. Designs that maximize the precision of estimates were derived.
DMRscaler: a scale-aware method to identify regions of differential DNA methylation spanning basepair to multi-megabase features
Authors: Bondhus Leroy , Wei Angela , Arboleda Valerie A. 
Published: September 2022

Abstract
Background
Pathogenic mutations in genes that control chromatin function have been implicated in rare genetic syndromes. These chromatin modifiers exhibit extraordinary diversity in the scale of the epigenetic changes they affect, from single basepair modifications by DNMT1 to whole genome structural changes by PRM1/2. Patterns of DNA methylation are related to a diverse set of epigenetic features across this full range of epigenetic scale, making DNA methylation valuable for mapping regions of general epigenetic dysregulation. However, existing methods are unable to accurately identify regions of differential methylation across this full range of epigenetic scale directly from DNA methylation data.

Results
To address this, we developed DMRscaler, a novel method that uses an iterative windowing procedure to capture regions of differential DNA methylation (DMRs) ranging in size from single basepairs to whole chromosomes. We benchmarked DMRscaler against several DMR callers in simulated and natural data comparing XX and XY peripheral blood samples. DMRscaler was the only method that accurately called DMRs ranging in size from 100 bp to 1 Mb (pearson's r = 0.94) and up to 152 Mb on the X-chromosome. We then analyzed methylation data from rare-disease cohorts that harbor chromatin modifier gene mutations in NSD1, EZH2, and KAT6A where DMRscaler identified novel DMRs spanning gene clusters involved in development.

Conclusion
Taken together, our results show DMRscaler is uniquely able to capture the size of DMR features across the full range of epigenetic scale and identify novel, co-regulated regions that drive epigenetic dysregulation in human disease.
Patients’ health literacy and health behaviour assessment in primary health care: evidence from a cross-sectional survey
Authors: Šulinskaitė Kristina , Zagurskienė Daiva , Blaževičienė Aurelija 
Published: September 2022

AbstractBackgroundHealth literacy is defined as a person's ability to find, understand, and use health-related information when making health-related decisions. Patients with lower health literacy more frequently face difficulties when they have health issues or need medical help. Such patients are less likely to visit health care facilities and receive less help, which subsequently leads to higher hospitalization and mortality rates. Patients with better health literacy skills pay more attention to their health behaviours.MethodsThis is a cross-sectional survey conducted in two primary health care centres—one public and one private—in Lithuania. The study enrolled patients who were visiting family physicians (n = 399). The study used the Health Literacy Survey European Questionnaire (HLS-EU-Q47). Calculation of means and two independent samples were used for statistical analysis, and a correlation coefficient was calculated.ResultsThe majority (40.6%) of respondents had problematic health literacy, while only 7% had excellent health literacy. Better health literacy was observed among younger patients (aged below 30 years), residing in urban areas, having higher education, and living with a partner. Inadequate or problematic health literacy was noted among 83.6% of respondents aged 59 years and older; similar rates were also observed among patients with basic or primary education (76.1%), secondary education (76.6%), and divorced patients (86%). Respondents with better health literacy also had better health behaviours (p < 0.05).ConclusionsHealth literacy is influenced by age, residence, education, and family status. Patients with better health literacy also reported better health behaviours.
Translation, cultural adaptation and validation of the Somatic Symptom Scale-8 (SSS-8) for the Brazilian Portuguese language
Authors: Pollo Camila Fernandes , Meneguin Silmara , Miot Hélio Amante , de Oliveira César 
Published: September 2022

Abstract
Background
Assessment tools are commonly used in different fields of health to assist in the diagnosis, the evaluation of the response to treatment, the measurement of quality of life and the establishment of the prognosis.

Objectives
Translate, culturally adapt and perform the psychometric validation of the Somatic Symptom Scale (SSS-8) for use in the Brazilian population.

Methods
Cross-cultural adaptation followed a combination of guidelines and for psychometric evaluation a sample of 300 patients was recruited. All recommended measurement properties by the Consensus-based Standards for the selection of health status Measurement Instruments were evaluated, including analysis by an expert committee and analysis by the target public. The Skindex-16 was used for the evaluation of convergent validity and Cronbach’s alpha was used for the determination of the internal consistency of the translated version of the SSS-8.

Results
The final version received approval from five experts and the agreement index was 100% for all items. During the pretest, the scale was administered to 300 patients with psoriasis and none of the items needed to be altered. A moderate correlation was found between the Skindex-16 and SSS-8-BRA. In the analysis of internal consistency, Cronbach’s alpha for the SSS-8-BRA was 0.81.

Conclusion
The SSS-8 is a valid and reliable tool for the assessment of somatic symptoms in the Brazilian population.
Transient alterations in plasma sodium concentrations with NER1006 bowel preparation: an analysis of three phase III, randomized clinical trials
Authors: Cash Brooks D. , Allen Christopher , Poppers David M. 
Published: September 2022

Abstract
Background
This analysis characterized changes in sodium levels in patients receiving the 1 L polyethylene glycol-based preparation NER1006.

Methods
Data were pooled from three phase III, randomized clinical trials. A post hoc subanalysis included adults who received a 2-day split-dose (evening/morning) NER1006 regimen, a 1-day split-dose (morning only) regimen, or evening-before regimen and had an increase in sodium concentrations from normal to above the upper limit of normal (143–148 mmol/L) at ≥ 1 of three post-treatment visits. Blood samples were collected at baseline, day of colonoscopy (visit 2), 2 ± 1 days post-colonoscopy (visit 3), and 7 ± 1 days post-colonoscopy (visit 4).

Results
A total of 214 of 1028 patients were included. Of the 214 patients, sodium concentration increased from a mean baseline value of 141.8 mmol/L to a mean of 147.1 mmol/L (median increase from baseline of approximately 5 mmol/L). The mean sodium concentration was within normal range at visit 3 (142.3 mmol/L) and visit 4 (142.4 mmol/L), as was the median sodium concentration. Overall, ~ 90% of patients had a normal serum concentration at visits 3 and 4. Based on day of colonoscopy test results, there were four adverse events involving hypernatremia (0.4% of 1028), which were mild and did not require medical intervention; sodium levels returned to normal range by visit 3.

Conclusion
NER1006 was associated with small, transient increases in sodium levels that were not considered clinically significant.
Trial registration NOCT (ClinicalTrials.gov: NCT02254486 [registered October 2, 2014]), MORA (ClinTrials.gov: NCT02273167 [registered October 23, 2014]; EudraCT number: 2014-002185-78 [registered August 13, 2014]), DAYB (ClinicalTrials.gov: NCT02273141 [registered October 23, 2014]; EudraCT Number: 2014-002186-30 [registered August 12, 2014])
Clinical characteristics and outcomes in those with primary extrahepatic malignancy and malignant ascites
Authors: Alshuwaykh Omar , Cheung Amanda , Goel Aparna , Kwong Allison , Dhanasekaran Renumathy , Ghaziani T. Tara , Ahmed Aijaz , Daugherty Tami , Dronamraju Deepti , Kumari Radhika , Nguyen Mindie , Kim W. Ray , Kwo Paul Yien 
Published: September 2022

Abstract
Background
Malignancy-related ascites accounts for approximately 10% of causes of ascites. Our AIM was to characterize the ascites fluid and correlate clinical outcomes in those with extrahepatic malignancy and ascites.

Methods
241 subjects with extrahepatic solid tumors and ascites were reviewed from 1/1/2000 to 12/31/2019, 119 without liver metastasis and 122 with liver metastasis.

Results
Ascites fluid consistent with peritoneal carcinomatosis (PC) was most common, 150/241 (62%), followed by fluid reflecting the presence of portal hypertension (PH), 69/241 (29%). 22/241 (9%) had low SAAG and low ascites fluid total protein, with evidence of PC on cytology and or imaging in 20/22. Lung cancer was the most common malignancy in subjects with ascites due to PC at 36/150 (24%), pancreatic cancer was the most common in subjects with ascites with features of PH at 16/69 (23%). Chemotherapy or immunotherapy alone was the most common management approach. Significantly higher 5-year, 3-year and 1-year mortality rate were noted in subjects with evidence of PC on cytology/imaging versus subjects with no evidence of PC, and in subjects with liver metastasis compared to subjects without liver metastasis. Subjects with pancreatic cancer and evidence of PC on cytology/imaging had higher 1 and 5-year mortality rates compared to subjects without PC.

Conclusions
Ascites in solid tumor malignancy is most commonly due to PC. We also observed ascites fluid with characteristics of PH in 29% of subjects. Higher mortality rates in subjects with peritoneal carcinomatosis and liver metastasis were noted. These findings may help inform prognosis and treatment strategies.
Poorly differentiated cluster grade-a vital predictor for lymph node metastasis and oncological outcomes in patients with T1 colorectal cancer: a retrospective study
Authors: Ji Xiaolin , Kang Mei , Zhao Xianzhi , Li Xiaoyu , Guo Yingjie , Xie Ping , Yu Yanan , Tian Zibin 
Published: September 2022

Abstract
Background
T1 colorectal cancers have a low lymph node metastasis rate and good prognosis. Thus, endoscopic resection is an attractive choice. This study aimed to describe the value of poorly differentiated cluster grade in identifying endoscopically curable T1 colorectal cancers.

Methods
We included 183 T1 colorectal cancer patients who underwent curative resection. Univariate and multivariate logistic regressions were used to identify lymph node metastasis predictors. The Akaike information criterion was used to determine whether poorly differentiated cluster grade was the best predictor. Backward regression was used to screen the variables. Survival analyses were conducted to determine the prognostic predictive power of poorly differentiated cluster grade. Correlations among predictors and concordance between our pathologists were also investigated.

Results
Poorly differentiated cluster grade was an independent predictor for lymph node metastasis (adjusted odds ratio [OR]G 3 = 0.001; 95% confidence interval [95% CI]G 3 =  < 0.001, 0.139) in T1 colorectal cancer patients; moreover, it had the best predictive value (AIC = 61.626) among all indicators. It was also screened for inclusion in the predictive model. Accordingly, a high poorly differentiated cluster grade independently indicated shorter overall survival (hazard ratio [HR]G 2 = 4.315; 95% CIG 2 = 1.506, 12.568; HRG 3 = 5.049; 95% CIG 3 = 1.326, 19.222) and disease-free survival (HRG 3 = 6.621; 95% CIG 3 = 1.472, 29.786).

Conclusions
Poorly differentiated cluster grade is a vital reference to manage T1 colorectal cancer. It could serve as an indicator to screen endoscopically curable T1 colorectal cancers.