bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Bayesian hierarchical framework to integrate dietary exposure and biomarker measurements into aetiological models
Authors: Pittavino M. , Plummer M. , Johansson M. , Ferrari P. 
Published: April 2022

AbstractIn nutritional epidemiology, self-reported assessments of dietary exposure are prone to measurement errors, which is responsible for bias in the association between dietary factors and risk of disease. In this study, self-reported dietary assessments were complemented by biomarkers of dietary intake. Dietary and serum measurements of folate and vitamin-B6 from two nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC) study were integrated in a Bayesian model to explore the measurement error structure of the data, and relate dietary exposures to risk of site-specific cancer. A Bayesian hierarchical model was developed, which included: 1) an exposure model, to define the distribution of unknown true exposure (X); 2) a measurement model, to relate observed assessments, in turn, dietary questionnaires (Q), 24-hour recalls (R) and biomarkers (M) to X measurements; 3) a disease model, to estimate exposures/cancer relationships. The marginal posterior distribution of model parameters was obtained from the joint posterior distribution, using Markov Chain Monte Carlo (MCMC) sampling techniques in JAGS. The study included 554 and 882 case/control pairs for kidney and lung cancer, respectively. In the measurement error component, the error correlation between Q measurements of vitamin-B6 and folate was estimated to be equal to 0.82 (95% CI: 0.76, 0.87). After adjustment for age, center, sex, BMI and smoking status, the kidney cancer odds ratios (OR) were 0.55 (0.16, 1.31) and 1.07 (0.33, 3.44) for one standard deviation increase of vitamin-B6 and folate, respectively. For lung cancer ORs were 0.85 (0.27, 2.42) for vitamin-B6 and 0.55 (0.14, 1.39) for folate. Bayesian models offer powerful solutions to handle complex data structures. After accounting for the role of measurement error, folate and vitamin-B6 were not associated to the risk of kidney and lung cancer.
Novel discoveries and enhanced genomic prediction from modelling genetic risk of cancer age-at-onset
Authors: Maksimova Ekaterina S. , Ojavee Sven E. , Läll Kristi , Sadler Marie C. , Mägi Reedik , Kutalik Zoltan , Robinson Matthew R. 
Published: April 2022

AbstractGenome-wide association studies seek to attribute disease risk to DNA regions and facilitate subject-specific prediction and patient stratification. For later-life diseases, inference from case-control studies is hampered by the uncertainty that control group subjects might later be diagnosed. Time-to-event analysis treats controls as right-censored, making no additional assumptions about future disease occurrence and represents a more sound conceptual alternative for more accurate inference. Here, using data on 11 common cancers from the UK and Estonian Biobank studies, we provide empirical evidence that discovery and genomic prediction are greatly improved by analysing age-at-diagnosis, compared to a case-control model of association. We replicate previous findings from large-scale case-control studies and find an additional 7 previously unreported independent genomic regions, out of which 3 replicated in independent data. Our novel discoveries provide new insights into underlying cancer pathways, and our model yields a better understanding of the polygenicity and genetic architecture of the 11 tumours. We find that heritable germline genetic variation plays a vital role in cancer occurrence, with risk attributable to many thousands of underlying genomic regions. Finally, we show that Bayesian modelling strategies utilising time-to-event data increase prediction accuracy by an average of 20% compared to a recent summary statistic approach (LDpred-funct). As sample sizes increase, incorporating time-to-event data should be commonplace, improving case-control studies by using richer information about the disease process.
Genetically personalised organ-specific metabolic models in health and disease
Authors: Foguet Carles , Xu Yu , Ritchie Scott C. , Lambert Samuel A. , Persyn Elodie , Nath Artika P. , Davenport Emma E. , Roberts David J. , Paul Dirk S. , Angelantonio Emanuele Di , Danesh John , Butterworth Adam S. , Yau Christopher , Inouye Michael 
Published: April 2022

AbstractUnderstanding how genetic variants influence disease risk and complex traits (variant-to-function) is one of the major challenges in human genetics. Here we present a model-driven framework to leverage human genome-scale metabolic networks to define how genetic variants affect biochemical reaction fluxes across major human tissues, including skeletal muscle, adipose, liver, brain and heart. As proof of concept, we build personalised organ-specific metabolic flux models for 524,615 individuals of the INTERVAL and UK Biobank cohorts and perform a fluxome-wide association study (FWAS) to identify 4,411 associations between personalised flux values and the concentration of metabolites in blood. Furthermore, we apply FWAS to identify 97 metabolic fluxes associated with the risk of developing coronary artery disease, many of which are linked to processes previously described to play in role in the disease. Our work demonstrates that genetically personalised metabolic models can elucidate the downstream effects of genetic variants on biochemical reactions involved in common human diseases.
Serum DNA methylome of the colorectal cancer serrated pathway
Authors: Gallardo-Gómez María , Costas-Ríos Lara , Garcia-Prieto Carlos A. , Álvarez-Rodríguez Lara , Bujanda Luis , Barrero Maialen , Castells Antoni , Balaguer Francesc , Jover Rodrigo , Esteller Manel , Baiges Antoni Tardío , Fojón Joaquín González-Carreró , Cubiella Joaquín , De Chiara Loretta 
Published: April 2022

ABSTRACTObjectiveThe clinical relevance of the serrated pathway of colorectal carcinogenesis is evident but the screening of serrated lesions remains challenging. We aimed to characterize the serum methylome of the serrated pathway, and to evaluate circulating cell-free DNA (cfDNA) methylation as a source of biomarkers for the non-invasive screening and diagnosis of serrated lesions.DesignWe collected serum samples from individuals with serrated adenocarcinoma (SAC), traditional serrated adenomas, sessile serrated lesions, hyperplastic polyps and with no colorectal findings. First, epigenome-wide methylation was quantified in cfDNA pooled samples with the MethylationEPIC array. Then, methylation profiles were compared to tissue and serum cfDNA datasets. Finally, biomarker utility of serum cfDNA methylation was evaluated.ResultsWe identified a differential methylation profile that can distinguish high-risk serrated lesions from the absence of serrated neoplasia, showing concordance with tissue methylation from SAC and sessile serrated lesions (external datasets). We report that the methylation profiles in serum cfDNA are pathway-specific, clearly separating serrated lesions from conventional adenomas. Among the differentially methylated regions (DMR) we report, the combination of two DMRs within the genes NINJ2 and ERICH1 discriminated high-risk serrated lesions and SAC with 91.4% sensitivity and 64.4% specificity, while methylation from a DMR within ZNF718 reported 100% sensitivity for the detection of SAC at 96% specificity.ConclusionThis is the only study available to date exploring the serum methylome of serrated lesions. We have identified a differential methylation profile in serum specific to the serrated pathway. The serum methylome may serve as a source of non-invasive biomarkers for screening and detection of high-risk serrated lesions.
Evaluation of cold pain tolerance in patients with fibromyalgia and opioid use by survival analysis
Authors: Deng Eden Z. , Weikel Daniel P. , Martucci Katherine T. 
Published: April 2022

AbstractPurposeCold pain tolerance is traditionally measured using the cold pressor test (CPT), a clinical pain research method in which participants immerse an extremity (i.e., hand or foot) into cold water for as long as tolerable. Prior research studies have investigated cold pain tolerance in patients with chronic pain, yet few have used survival analysis, which allows for proper handling of data censoring and therefore, the optimal statistical method for CPT data analysis. The goal of the present study was to use survival analysis to evaluate cold pain tolerance in patients with fibromyalgia. Furthermore, we aimed to model relationships between psychological and clinical variables as well as opioid medication use and cold pain tolerance.Patients and MethodsA total of 85 patients with fibromyalgia (42 who were taking opioids) and 47 healthy pain-free controls were involved in two studies that provided CPT and questionnaire data. Survival analysis using Cox regression models evaluated group effects (patients vs. controls) and effects of psychological, clinical, and medication factors on cold pain tolerance.ResultsPatients with fibromyalgia, as compared to healthy controls, exhibited significantly lower CPT survival (HR = 2.17, 95% CI: [1.42, 3.31], p = 0.00035). Cox regression models indicated that the psychological and clinical measures included did not strongly mediate this relationship (p > 0.05). When comparing across patient cohorts (Study 1 vs. Study 2), results were consistent across non-opioid-taking patient and healthy control groups, while differences in CPT survival were observed across the groups of patients taking opioid pain medications.ConclusionReduced cold pain tolerance in patients with fibromyalgia is identified by survival analysis, an optimal method for time-to-event pain measures. While our selected psychological and clinical measures do not appear to be significantly associated with cold pain tolerance, opioid medication use may impart greater cold pain tolerance among some patients.
Strain-stream model of epidemic spread in application to COVID-19
Authors: Trigger S.A. , Ignatov A.M. 
Published: April 2022

The recently developed model of the epidemic spread of two virus stains in a closed population is generalized for situation typical for the couple of strains delta and omicron, when there is high probability for omicron infection enough soon after recovering from delta infection. This model can be considered as some kind of weave of SIR and SIS models for the case of competition of two strains of the same virus having different contagiousness in a population.PACS number(s)02.50.-r, 05.60.-k, 82.39.-k, 87.19.Xx
A COMPARATIVE EVALUATION OF NON-INCISED PAPILLAE AND ENTIRE PAPILLA PRESERVATION SURGICAL APPROACHES IN TREATMENT OF INTRABONY DEFECTS – A CLINICAL AND RADIOGRAPHIC STUDY
Authors: Elenora Martina Bandi Divya , Chandra Rampalli Viswa , Santosh Vallabhdas , Reddy Gollapalle Prabhandh , Reddy Aileni Amarender 
Published: April 2022

ABSTRACTAim & ObjectivesThe aim of the present study was to clinically and radiographically compare and evaluate the NIPSA (Non-Incised Papillae Surgical Approach) and EPP (Entire Papilla Preservation) techniques in the treatment of intra bony defects.Patients and methodsFrom this initial patient pool of 156 patients, 44 individuals satisfying the inclusion criteria were selected. One site in each subject was assigned into each of the following experimental groups which were treated with the relevant procedure; NIPSA and EPP groups. Clinical parameters included the recording of pocket probing depths (PPD), clinical attachment levels (CAL) and papilla loss. The evaluation of bone fill was performed at the end of 3 & 6-months by using Image J® software.ResultsNIPSA and EPP resulted in highly significant CAL gains(4.00±1.00vs5.25 ± 1.47mm;p≤0.001)and PPD reductions(3.352±0.70vs3.625±1.024mm;p≤0.001)at 6-months post-surgery. From the start to the end of study period, NIPSA resulted in almost no papilla loss (1.71±0.47 to 1.73±0.77mm) while EPP technique showed minimal and insignificant(1.57±0.52 to 1.48±0.71mm;p≥0.05)papilla loss. The EPP group revealed a highly significant(0.459±0.16vs0.269±0.16cm2;p≤0.001)bone fill over NIPSA group at 6-months.ConclusionFrom this trial conducted over a period of 6-months, NIPSA and EPP both resulted in significant improvements in clinical outcomes. NIPSA and EPP showed favourable outcomes in terms papilla loss and bone fill respectively. Both the techniques achieve the aims outlined earlier and broaden the choice available to a periodontist in the management of intrabony defects.
Global Reports of Myocarditis Following COVID-19 Vaccination: A Systematic Review and Meta-Analysis
Authors: Ahmed Sirwan Khalid , Mohamed Mona Gamal , Essa Rawand Abdulrahman , Ahmed Rashad Eman Abdelaziz , Ibrahim Peshraw Khdir , Khdir Awat Alla , Wsu Zhiar Hussen 
Published: April 2022

AbstractIn December 2020, the FDA granted emergency approval to Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) COVID-19 vaccines. There have been recent media reports of myocarditis after receiving COVID-19 vaccines, particularly the messenger RNA (mRNA) vaccines, causing public concern. This review summarizes information from published case series and case reports, with a strong emphasis on reporting patient and disease characteristics, investigation, and clinical outcome, to provide a comprehensive picture of the condition. Forty studies, including 147 cases, participated in this systematic review. The median age was 28.9 years; 93.9% were male and 6.1% were female. 72.1% of patients received the Pfizer-BioNTech (BNT162b2) vaccine, 24.5% of patients received the Moderna COVID-19 Vaccine (mRNA-1273), and the rest of the 3.3% received other types of vaccines. Furthermore, most myocarditis cases (87.1%) occurred after the second vaccine dose, after a median time interval of 3.3 days. The most frequently reported symptoms were chest pain, myalgia/body aches and fever. Troponin levels were consistently elevated in 98.6%. The admission ECG was abnormal in 88.5% of cases, and the left LVEF was lower than 50% in 26.5% of cases. The vast majority of patients (93.2%) resolved symptoms and recovered, and only 3 patients died. These findings may help public health policy to consider myocarditis in the context of the benefits of COVID-19 vaccination as well as to assess the cardiac condition before the choice of vaccine, which is offered to male adults. In addition, it must be carefully weighed against the very substantial benefit of vaccination.
Comparison of procedures performed and costs between an outsourced dental health plan with fee-for-service payment and an evidence-based, in-house dental health service with salaried professionals
Authors: Da Costa Filho Luiz Cesar , Da Costa Carolina Covolo , Polanczyk Carisi Anne , Duncan Bruce Bartholow 
Published: April 2022

ABSTRACTIt was evaluated a dental care services provided to almost 4,000 users (employees and their families) of a company (Moinhos de Vento Hospital, Brazil). The analysis was divided into two periods of time: from January 2000 to December 2002, during which time the dental care provided to employees (and families) was outsourced to a dental plan which operates with an accredited network, and from March 2003 to June 2005, when the dental care was provided by an in-house dental care service with preventive and evidence-based dentistry guidelines. Economic data were collected, as well as the type and number of procedures performed.ConclusionsAn in-house service with evidence-based clinical protocols, as compared with an accredited network, decreased costs and also increased the number of procedures done, changed the profile of care for a less invasive dentistry and one more geared toward the causes of diseases, while still preserving the customers’ satisfaction.
Statins and antidepressants induce similar in vitro gene expression responses
Authors: Jiang Jiayue-Clara , Hu Chenwen , McIntosh Andrew M , Shah Sonia 
Published: April 2022

AbstractBackgroundBased on observational studies and small-scale randomized controlled trials, it is uncertain whether cholesterol-lowering statins have any beneficial or adverse effects on depressive symptoms. In this study we investigate this question using a genomics approach.MethodsTo compare the pharmacological effects of statin and antidepressant exposure and identify commonly perturbed biological pathways, we interrogated Connectivity Map (CMap), a database of gene expression signatures from drug-treated human cell lines. We used Mendelian randomization, a statistical genomics approach, to investigate the potential causal on-target (HMGCR inhibition) and off-target effects of statin exposure on depression, depressive symptoms, and traits related to the shared pathways identified from CMap analysis.ResultsCompounds inducing highly similar gene expression responses to statins (as indicated by an average CMap connectivity score with statins > 90) were enriched for antidepressants (12 out of 38 antidepressants; p < 1E-05). Genes perturbed in the same direction by both statins and antidepressants were significantly enriched for diverse cellular and metabolic pathways, and various immune activation, development and response processes. Genetically proxied HMGCR inhibition was significantly associated with monocyte and platelet-related metrics.ConclusionsOur study is the first to directly compare gene expression responses to statins and antidepressants, demonstrating perturbation of shared immune pathways. We further show that statin exposure is strongly associated with alterations in monocyte and platelet measures, both of which have previously been implicated in depression. Our findings warrant further investigation into the use of statins for treating depression, particularly in patients with raised blood biomarkers of inflammation.
Ensuring a successful transition from Pap to HPV-based primary screening in Canada: a study protocol to investigate the psychosocial correlates of women’s screening intentions
Authors: Griffin-Mathieu Gabrielle , Haward Ben , Tatar Ovidiu , Zhu Patricia , Perez Samara , Shapiro Gilla K. , McBride Emily , Thompson Erika L. , Smith Laurie W. , Lofters Aisha K. , Daley Ellen M. , Guichon Juliet R. , Waller Jo , Steben Marc , Decker Kathleen M. , Mayrand Marie-Hélène , Brotherton Julia M. L. , Ogilvie Gina S. , Zimet Gregory D. , Norris Teresa , Rosberger Zeev 
Published: April 2022

AbstractIntroductionThe Human Papillomavirus (HPV) test has emerged as a significant improvement over cytology for primary cervical cancer screening. In Canada, provinces and territories are moving towards implementing HPV testing in cervical cancer screening programs. While an abundance of research exists on the benefits of HPV-based screening, there is a dearth of research examining women’s understanding of HPV testing. In other countries, failure to adequately address women’s concerns about changes has disrupted implementation of HPV-based screening. This study protocol describes a multi-step approach to develop psychometrically valid measures and to investigate psychosocial correlates of women’s intentions to participate in HPV-based cervical cancer screening.Materials and MethodsWe conducted a web-based survey of Canadian women to assess the acceptability and feasibility of a questionnaire, including validation of scales examining: cervical cancer knowledge, HPV testing knowledge, HPV testing attitudes and beliefs, and HPV test self-sampling attitudes and beliefs. Preferences for cervical cancer screening were assessed using Best-Worst Scaling methodology.A second web-based survey will be administered to a national sample of Canadian women in June-July of 2022 using the validated scales. Differences in the knowledge, attitudes, beliefs, and preferences of women who are currently either underscreened or adequately screened for cervical cancer will be examined through bivariate analyses. Multinomial logistic regression will be used to estimate the associations between psychosocial and sociodemographic factors and intentions to screen using HPV-based screening.Study Impact and DisseminationFindings will provide direction for Canadian public health authorities to align guidelines to address women’s concerns and optimize acceptability and uptake of HPV-based primary screening. Validated scales can be used by other researchers to improve and standardize measurement of psychosocial factors impacting HPV test acceptability. Study results will be disseminated through peer-reviewed journal articles, conference presentations, and direct communication with researchers, clinicians, policymakers, media, and specialty organizations.
A 21L/BA.2-21K/BA.1 “MixOmicron” SARS-CoV-2 hybrid undetected by qPCR that screen for variant in routine diagnosis
Authors: Colson Philippe , Delerce Jeremy , Marion-Paris Elise , Lagier Jean-Christophe , Levasseur Anthony , Fournier Pierre-Edouard , La Scola Bernard , Raoult Didier 
Published: April 2022

ABSTRACTAmong the multiple SARS-CoV-2 variants identified since summer 2020, several have co-circulated, creating opportunities for coinfections and potentially genetic recombinations that are common in coronaviruses. Viral recombinants are indeed beginning to be reported more frequently. Here, we describe a new SARS-CoV-2 recombinant genome that is mostly that of a Omicron 21L/BA.2 variant but with a 3’ tip originating from a Omicron 21K/BA.1 variant. Two such genomes were obtained in our institute from adults sampled in February 2022 in university hospitals of Marseille, southern France, by next-generation sequencing carried out with the Illumina or Nanopore technologies. The recombination site was located between nucleotides 26,858-27,382. In the two genomic assemblies, mean sequencing depth at mutation-harboring positions was 271 and 1,362 reads and mean prevalence of the majoritary nucleotide was 99.3±2.2% and 98.8±1.6%, respectively. Phylogeny generated trees with slightly different topologies according to whether genomes were depleted or not of the 3’ tip. This 3’ terminal end brought in the Omicron 21L/BA.2 genome a short transposable element of 41 nucleotides named S2m that is present in most SARS-CoV-2 except a few variants among which the Omicron 21L/BA.2 variant and may be involved in virulence. Importantly, this recombinant is not detected by currently used qPCR that screen for variants in routine diagnosis. The present observation emphasizes the need to survey closely the genetic pathways of SARS-CoV-2 variability by whole genome sequencing, and it could contribute to gain a better understanding of factors that lead to observed differences between epidemic potentials of the different variants.
Weakly supervised learning for multi-organ adenocarcinoma classification in whole slide images
Authors: Tsuneki Masayuki , Kanavati Fahdi 
Published: April 2022

AbstractThe primary screening by automated computational pathology algorithms of the presence or absence of adenocarcinoma in biopsy specimens (e.g., endoscopic biopsy, transbronchial lung biopsy, and needle biopsy) of possible primary organs (e.g., stomach, colon, lung, and breast) and radical lymph node dissection specimen is very useful and should be a powerful tool to assist surgical pathologists in routine histopathological diagnostic workflow. In this paper, we trained multi-organ deep learning models to classify adenocarcinoma in biopsy and radical lymph node dissection specimens whole slide images (WSIs). We evaluated the models on seven independent test sets (stomach, colon, lung, breast, lymph nodes) to demonstrate the feasibility in multiorgan and lymph nodes specimens from different medical institutions and international public datasets, achieving receiver operating characteristic areas under the curves (ROC-AUCs) in the range of 0.91-0.99.