bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of RNA-seq and Ribosome Profiling to Characterize Transcriptional and Translational Estrogen Responses of Genes in Human Breast Cancer
Authors: Choo Siew Woh , Zhong Yu , Sendler Edward , Goustin Anton Scott , Cai Juan , Ju Donghong , Brown James Bentley , Kosir Mary Ann , Lipovich Leonard 
Published: September 2020

Abstract
BackgroundEstrogen is a hormone that is frequently essential in breast cancer to drive key transcriptional programs by interacting with the estrogen receptor alpha that upregulates proliferative and oncogenic genes and represses apoptotic and tumor suppressor genes. Protein-coding targets of estrogen regulation in breast cancer are well-defined. However, long non-coding RNA (lncRNA) genes account for the majority of human gene catalogs. The coding status of these genes – their accidental, or regulated, translation by ribosomes, under the influence of estrogen – remains a controversial topic. MethodsHere, we performed comprehensive transcriptome analysis using RNA-Seq, as well as ribosome profiling using Ribo-Seq, on the same samples: biological replicates of human estrogen receptor alpha (ERa) positive MCF7 breast cancer cells before and after estrogen treatment. We correlated these two datasets, globally highlighting protein-coding and lncRNA differentially expressed genes and transcripts that were positively as well as negatively responsive to estrogen, separately at the transcriptional level and the translational (as approximated by ribosome binding) level.ResultsOur data showed that some transcripts were more robustly detected in RNA-Seq than in the ribosome-profiling data, and vice versa, suggesting distinct gene-specific estrogen responses at the transcriptional and the translational level, respectively. Certain differentially expressed transcripts may point to the regulation of alternative splicing by estrogen. Several pseudogenes were co- and anti-regulated with their cancer-functional parental genes. Gene ontology analysis highlighted cancer-relevant pathways enriched after estrogen treatment in cells.ConclusionsOur study represents a significant advance in the estrogen receptor biology, because we demonstrated global effects of estrogen on splicing and translation that are distinct from, and not always correlated with, its effects on transcription, and that differ globally for protein-coding and lncRNA genes. We have also highlighted for the first time the transcriptional and translational response of expressed pseudogenes to estrogen, pointing to new perspectives for biomarker and drug-target development for breast cancer in future.
Evaluation of the Relationship Between Cytochrome P450 Polymorphisms and T2DM&nbsp;Risk
Authors: Zhao QingBin , Wei Huiyi , Li Zhiying , Wei Haoyang 
Published: September 2020

Abstract
Background: Recent studies have identified some genetic polymorphisms of CYP2C8 and CYP2D6 related to disease susceptibility. However, it has not been reported whether polymorphisms in CYP2C8 and CYP2D6 are associated with the risk of type 2 diabetes mellitus (T2DM). We designed a case-control study to evaluate the relationship between those CYP polymorphisms and T2DM risk. Methods: Four single nucleotide polymorphisms (SNPs) of CYP2C8 and CYP2D6 were genotyped from 512 patients and 515 healthy controls using Agena MassARRAY. The chi-square test was used to compare the differences in allele and genotype frequencies between the two groups. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression analysis to evaluate the relationship between polymorphism and T2DM risk. Results: The results found that the rs1065852 in CYP2D6 was correlated with the T2DM risk in overall (A vs. G: OR = 1.22, 95% CI: 1.03–1.45, P = 0.024; AA vs.GG: OR = 1.46, 95% CI: 1.04–2.06, P = 0.031; AA-AG vs. GG: OR = 1.36, 95% CI: 1.04–1.79, P = 0.026; additive: OR = 1.21, 95% CI: 1.02–1.44, P = 0.027). Gender stratification analysis results demonstrated that the rs1065852 in CYP2D6 was related with an increased the risk of T2DM in male and age < 59 years old. However, no statistical significance relation was found between CYP2C8 SNPs and T2DM risk. Conclusions: This study revealed that CYP2D6 (rs1065852) could be potential genetic markers of susceptibility to T2DM. Further studies are required to confirm our findings.
Socio-demographic, clinical and health facility-related predictors of delayed HIV diagnosis among patients newly diagnosed with HIV in Northwest Ethiopia: a multilevel analysis
Authors: Moges Nurilign Abebe , Berhane Yemane , AKINYEMI Joshua Odunayo , Okunlola Micheal A. , Adesina Olubukola Adeponle 
Published: September 2020

Abstract
Background

Ethiopia recently implemented the ‘test and treat’ strategy for all HIV-infected individuals receiving a diagnosis at the health facility level. However, the impact of this policy in terms of timely HIV diagnosis and factors associated with it were not evaluated. Therefore, this study aimed to determine the magnitude and predictors of delayed HIV diagnosis among newly diagnosed people living with HIV in the northwest, Ethiopia.
Methods

In this cross-sectional study, a total of 759 newly diagnosed patients were recruited consecutively. The multistage sampling technique was employed to select health facilities and all newly diagnosed patients were included. Delayed HIV diagnosis was defined when there is an established AIDS-defining clinical condition (WHO clinical stage III or IV), irrespective of CD4 count. Data were entered into Epi-Data version 3.5 and exported to STATA version 14 for further analysis. Taking into account the nested structure of the data, multilevel logistic regression analysis has been employed. Four models containing variables of interest were fitted. Multivariate multilevel logistic regression analysis was performed to estimate the adjusted odds ratios (AOR) at a 95% confidence interval (CI).
Results

A one-fourth of newly diagnosed HIV patients diagnosed at advanced disease stage. After controlling for other individual and health facility level factors, factors associated with delayed HIV diagnosis were: Patients who had completed secondary school or higher (AOR = 2.08, 95% CI = 1.06, 4.08), patients who presented to health facilities with HIV symptoms (AOR = 5.87, 95% CI = 3.57, 9.62), being non-working functional status (AOR = 4.80, 95% CI = 2.58, 8.92) and HIV diagnosis at hospitals (AOR = 2.16, 95% CI = 1.08, 4.31).
Conclusion

The magnitude of delayed HIV diagnosis was improved. In addition to individual-level factors, it is important to address health facility-related factors to improve earlier HIV diagnosis. Here, we recommend using both clinical and laboratory characteristics of a patient particularly, baseline CD4 count and viral load to identify patients diagnosed with advanced disease stage. Moreover, public health interventions are important targeted on factors associated with delayed HIV diagnosis.
Factors Associated With Self-efficacy Toward Healthy Eating and Physical Activity Among Kuwaiti Adolescent Girls&nbsp;
Authors: AlGhanim Latifa , Alkazemi Dalal Usamah Zaid 
Published: September 2020

Abstract

Background: The factors that may influence adolescents’ health-related behaviors in Kuwait are unclear. We hypothesized that girls’ self-efficacy would be negatively associated with their weight statuses and positively associated with healthy eating-related behaviors. This study aimed to measure healthy eating-related parameters, including self-efficacy, dietary habits, dietary beliefs, nutrition knowledge, and physical activity, in a sample of Kuwaiti adolescent girls and assess the correlates of self-efficacy, including weight status and dietary and health behaviors. Methods: In this cross-sectional, self-administered survey at the school level, we evaluated students of three schools in different governorate locations in Kuwait. The participants were adolescent girls (n=301; mean age, 16.6±1.2 years) who attended secondary schools. The main outcome measures were self-efficacy, dietary habits, dietary beliefs, nutrition knowledge, physical activity, and weight status per body mass index (BMI) categories. Pearson’s correlation analysis was performed to determine the associations among the healthy behavior related parameter scores. The independent samples t-test was used to examine the differences in scores between participants’ characteristics and self-efficacy scores (SES). Multivariate regression analysis was used to determine the final independent correlates of SES.Results: Only 19.9% of the participants had high self-efficacy toward healthy eating behaviors, 20.9% had “satisfactory eating habits,” 11.3% had a good comprehension of the meanings of healthy and unhealthy dietary habits and food, 16.3% had good nutrition knowledge, and 29.2% had an active lifestyle. SES was negatively correlated with BMI (r=-0.074, P=0.03) and positively correlated with all domains of healthy eating and physical activity. However, SES was not associated with nutritional knowledge. The independent correlates of SES in the multivariate regression analysis were governorate, eating beliefs, healthy eating score, and physical activity (R2=38.3%).Conclusions: Adolescent girls in Kuwait demonstrated a high level of self-efficacy toward healthy eating and behaviors and had firm nutritional beliefs; however, they failed to translate their beliefs into good nutritional habits. It is necessary to develop interventional nutrition programs at the school level that aim at improving healthy behaviors among adolescents.
Systematic Review and Meta-analysis of the Safety of Chloroquine and Hydroxychloroquine From Randomized Controlled Trials on Malarial and Non-malarial Conditions
Authors: Botelho Mayra Souza , Bolfi Fernanda , Leite Renata Giacomini Occhiuto Ferreira , Leite Mauro Salles Ferreira , Banzato Luisa Rocco , Soares Luiza Teixeira , Olivatti Thaina Oliveira Felicio , Mangolim Amanda Sampaio , Oliveira Flávia Ramos Kazan , Abbade Luciana Patrícia Fernandes , Abbade Joelcio Francisco , Almeida Ricardo Augusto Monteiro de Barros , Galendi Julia Simões Correa , Thabane Lehana , Nogueira Vania dos Santos Nunes 
Published: September 2020

Abstract
Background: Despite the expectations regarding the effectiveness of chloroquine (CQ) and hydroxychloroquine (HCQ) for coronavirus disease (COVID-19) management, concerns about their adverse events have remained. Objectives: The objective of this systematic review was to evaluate the safety of CQ and HCQ from malarial and non-malarial randomized clinical trials (RCTs). Methods: The primary outcomes were the frequencies of serious adverse events (SAEs), retinopathy, and cardiac complications. Search strategies were applied to MEDLINE, EMBASE, LILACS, CENTRAL, Scopus, and Trip databases. We used random-effects model to pool results across studies and Peto one-step odds ratio (OR) for event rates below 1 %. Both-armed zero-event studies were excluded from the meta-analyses. We used the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate the certainty of evidence.Results: Ninety-two RCTs were included. We found no significant difference between CQ/HCQ and control (placebo or non-CQ/HCQ) in the frequency of SAEs (OR: 0.98, 95 % confidence interval [CI]: 0.71–1.36, 25 trials, 11,605 participants, moderate certainty of evidence). No clear relationship was observed between CQ/HCQ and retinopathy (OR: 1,63, 95 % CI: -0.4–6.57, 5 trials, 344 participants, very low certainty of evidence). There was a low certainty of evidence of the effect of CQ/HCQ versus control on cardiac complications (Relative risk: 1.48, 95 % CI: 1.1–1.98, 8 trials, 5,970 participants).Conclusions: CQ and HCQ might be safe, with low frequency of SAEs on malarial and non-malarial conditions. No clear effect of their use on the incidence of retinopathy and cardiac complications was observed.The protocol for this systematic review was registered with PROSPERO (registration number: CRD42020177818)
The How, Why, and for Whom Mindfulness-based Programs and Practices Produce Change in the General Population: A Scoping Review Protocol
Authors: Maloney Shannon , Montero-Marin Jesus , Kuyken Willem 
Published: September 2020

Abstract
Background: Despite growing evidence for the salutary effects of mindfulness-based programs (MBPs), there is limited understanding of the how, why, and for whom these programs work in the general population. To better understand these questions, one must implement design and data-analytic approaches that can elucidate potential mediators, mechanisms, and moderators. These variables explain the processes through which treatments, such as MBPs, produce change (mediators/mechanisms) and illuminate in which contexts these programs work best (moderators). The extant literature has investigated these variables predominately in pre-post analyses of MBPs. However, there are other ways to explore these processes or ‘pathways of change.’ One option is to implement dismantling trials and investigate the effects of core components of MBPs (e.g. mindfulness practice). Understanding how key elements operate in isolation will help specify ‘active ingredients’ and how the MBP framework works on the whole. The primary objective of the current scoping review will be to comprehensively evaluate studies that have explored pathways of change in MBPs and individual mindfulness practices to further our understanding of how to best adapt these programs and maximise benefits across the general population. Methods: Five electronic databases (PubMed, PsycINFO, Embase, Scopus, and the Cochrane Central) will be systematically searched for eligible studies. Studies will be included if they investigate a MBP or practice in the general population (adults aged 18 and over). Eligible studies must evaluate a proposed mediator, mechanism, or moderator of a MBP or practice. The following information will be extracted for charting: (a) Name of author(s), (b) year of publication (c) sample characteristics (d) sampling method (e) reported mediators, mechanisms, and moderators, (f) design approach, (g) data-analytic approach, (h) adherence to methodological requirements, (i) description of MBP or practice, (j) treatment dosage, (k) delivery mode, (l) effect sizes and outcomes. A qualitative narrative summary of the results will be described in accordance with the information extracted for charting.Discussion: The results from this review will help inform mindfulness teachers, researchers, and health-care professionals who intend to adapt MBPs or practices.Systematic review registration: Open Science Framework, DOI: 10.17605/OSF.IO/XJDSU
KRAS mutation effects on the 2-[18F]FDG PET uptake of colorectal adenocarcinoma metastases in the liver
Authors: Popovic Marko , Talarico Olga , Hoff Jörg van den , Kunin Henry , Zhang Zhigang , Lafontaine Daniel , Dogan Snjezana , Leung Johnny , Kaye Elena , Czmielewski Christian , Mayerhoefer Marius E. , Zanzonico Pat , Yaeger Rona , Schöder Heiko , Humm John L. , Solomon Stephen B. , Sofocleous Constantinos T. , Kirov Assen S. 
Published: September 2020

Abstract
Background: Deriving individual tumor genomic characteristics from patient imaging analysis is desirable. We explore the predictive value of 2-[18F]FDG uptake with regards to the KRAS mutational status of colorectal adenocarcinoma liver metastases (CLM). Methods : 2-[18F]FDG PET/CT images, surgical pathology and molecular diagnostic reports of 37 patients who underwent PET/CT-guided biopsy of CLM were reviewed under an IRB-approved retrospective research protocol. Sixty CLM in 39 interventional PET scans of the 37 patients were segmented using two different auto-segmentation tools implemented in different commercially available software packages. PET standard uptake values (SUV) were corrected for: 1) partial volume effect (PVE) using cold wall-corrected contrast recovery coefficients derived from phantom spheres with variable diameter; and 2) variability of arterial tracer supply and variability of uptake time after injection until start of PET scan derived from the tumor-to-blood standard uptake ratio (SUR) approach. The correlations between the KRAS mutational status and the mean, peak, and maximum SUV were investigated using Student ’ s t-test, Wilcoxon rank sum test with continuity correction, logistic regression and receiver operation characteristic (ROC) analysis. These correlation analyses were also performed for the ratios of the mean, peak and maximum tumor uptake to the mean blood activity concentration at the time of scan: SUR_mean, SUR_peak, and SUR_max , respectively. Results: Fifteen patients harbored KRAS missense mutations ( KRAS+ ) while another 3 harbored KRAS gene amplification. For 31 lesions the mutational status was derived from the PET/CT-guided biopsy. The Student ’ s-t p-values for separating KRAS mutant cases decreased after applying PVE correction to all uptake metrics of each lesion and when applying correction for uptake time variability to the SUR metrics. The observed correlations were strongest when both corrections were applied to SUR MAX and when the patients harboring gene amplification were grouped with the wild type: p ≤ 0.001; ROC area under the curve (AUC) = 0.77 and 0.75 for the two different segmentations respectively with a mean specificity of 0.69 and sensitivity of 0.85. Conclusions: The correlations observed after applying the described corrections show potential for assigning probabilities for the KRAS missense mutation status in CLM using 2-[18F]FDG PET images.
Protocol Development for HMU! (HIV Prevention for Methamphetamine Users), a Study of Peer Navigation and Text Messaging to Promote Pre-Exposure Prophylaxis Adherence and Persistence Among People Who Use Methamphetamine: Qualitative Focus Group and Interview Study
Authors: McMahan Vanessa M , Frank Noah , Buckler Smitty , Violette Lauren R , Baeten Jared M , Banta-Green Caleb J , Barnabas Ruanne V , Simoni Jane , Stekler Joanne D 
Published: September 2020

Background
Cisgender men who have sex with men (MSM) and transgender people (TGP) who use methamphetamine are disproportionately impacted by HIV acquisition. Pre-exposure prophylaxis (PrEP) is highly effective at preventing HIV, and interventions that support PrEP persistence and adherence should be evaluated among MSM and TGP who use methamphetamine.

Objective
We conducted formative work to inform the development of text messaging and peer navigation interventions to support PrEP persistence and adherence among MSM and TGP who use methamphetamine. In this paper, we describe how the findings from these focus groups and interviews were used to refine the study interventions and protocol for the Hit Me Up! study (HMU!; HIV Prevention in Methamphetamine Users).

Methods
Between October 2017 and March 2018, we conducted two focus groups and three in-depth interviews with MSM and TGP who use methamphetamine or who have worked with people who use methamphetamine. During these formative activities, we asked participants about their opinions on the proposed interventions, education and recruitment materials, and study design. We focused on how we could develop peer navigation and text messaging interventions that would be culturally appropriate and acceptable to MSM and TGP who use methamphetamine. Transcripts were reviewed by two authors who performed a retrospective content analysis to describe which specific opinions and recommendations influenced protocol development and the refinement of the interventions.

Results
Overall, participants thought that MSM and TGP would be interested in participating in the study, although they expected recruitment and retention to be challenging. Participants thought that the peer navigator should be someone who is nonjudgmental, has experience with people who use methamphetamine, and is patient and flexible. There was consensus that three text messages per day were appropriate, adherence reminders should be straightforward, all messages should be nonjudgmental, and participants should be able to tailor the timing and content of the text messages. These suggestions were incorporated into the study interventions via the hiring and training process and into the development of the text library, platform selection, and customizability of messages.

Conclusions
It is important to include the opinions and insights of populations most impacted by HIV to develop PrEP interventions with the greatest chance of success. Our formative work generated several recommendations that were incorporated into the interventions and protocol development for our ongoing study.

Trial Registration
ClinicalTrials.gov NCT03584282; https://clinicaltrials.gov/ct2/show/NCT03584282
Standalone Smartphone Cognitive Behavioral Therapy–Based Ecological Momentary Interventions to Increase Mental Health: Narrative Review
Authors: Marciniak Marta Anna , Shanahan Lilly , Rohde Judith , Schulz Ava , Wackerhagen Carolin , Kobylińska Dorota , Tuescher Oliver , Binder Harald , Walter Henrik , Kalisch Raffael , Kleim Birgit 
Published: September 2020

Background
A growing number of psychological interventions are delivered via smartphones with the aim of increasing the efficacy and effectiveness of these treatments and providing scalable access to interventions for improving mental health. Most of the scientifically tested apps are based on cognitive behavioral therapy (CBT) principles, which are considered the gold standard for the treatment of most mental health problems.

Objective
This review investigates standalone smartphone-based ecological momentary interventions (EMIs) built on principles derived from CBT that aim to improve mental health.

Methods
We searched the MEDLINE, PsycINFO, EMBASE, and PubMed databases for peer-reviewed studies published between January 1, 2007, and January 15, 2020. We included studies focusing on standalone app-based approaches to improve mental health and their feasibility, efficacy, or effectiveness. Both within- and between-group designs and studies with both healthy and clinical samples were included. Blended interventions, for example, app-based treatments in combination with psychotherapy, were not included. Selected studies were evaluated in terms of their design, that is, choice of the control condition, sample characteristics, EMI content, EMI delivery characteristics, feasibility, efficacy, and effectiveness. The latter was defined in terms of improvement in the primary outcomes used in the studies.

Results
A total of 26 studies were selected. The results show that EMIs based on CBT principles can be successfully delivered, significantly increase well-being among users, and reduce mental health symptoms. Standalone EMIs were rated as helpful (mean 70.8%, SD 15.3; n=4 studies) and satisfying for users (mean 72.6%, SD 17.2; n=7 studies).

Conclusions
Study quality was heterogeneous, and feasibility was often not reported in the reviewed studies, thus limiting the conclusions that can be drawn from the existing data. Together, the studies show that EMIs may help increase mental health and thus support individuals in their daily lives. Such EMIs provide readily available, scalable, and evidence-based mental health support. These characteristics appear crucial in the context of a global crisis such as the COVID-19 pandemic but may also help reduce personal and economic costs of mental health impairment beyond this situation or in the context of potential future pandemics.