bluuebunny/crossref_metadata_2025_split huggingface dataset:
Faecal haemoglobin concentrations are associated with all-cause mortality and cause of death in colorectal cancer screening
Authors: Kaalby Lasse , Deding Ulrik , Al-Najami Issam , Berg-Beckhoff Gabriele , Bjørsum-Meyer Thomas , Laurberg Tinne , Shaukat Aasma , Steele Robert J. C. , Koulaouzidis Anastasios , Rasmussen Morten , Kobaek-Larsen Morten , Baatrup Gunnar 
Published: January 2023

Abstract
Background
Colorectal cancer (CRC) screening reduces all-cause and CRC-related mortality. New research demonstrates that the faecal haemoglobin concentration (f-Hb) may indicate the presence of other serious diseases not related to CRC. We investigated the association between f-Hb, measured by a faecal immunochemical test (FIT), and both all-cause mortality and cause of death in a population-wide cohort of screening participants.

Methods
Between 2014 and 2018, 1,262,165 participants submitted a FIT for the Danish CRC screening programme. We followed these participants, using the Danish CRC Screening Database and several other national registers on health and population, until December 31, 2018. We stratified participants by f-Hb and compared them using a Cox proportional hazards regression on all-cause mortality and cause of death reported as adjusted hazard ratios (aHRs). We adjusted for several covariates, including comorbidity, socioeconomic factors, demography and prescription medication.

Results
We observed 21,847 deaths in the study period. Our multivariate analyses indicated an association relationship between increasing f-Hb and the risk of dying in the study period. This risk increased steadily from aHR 1.38 (95% CI: 1.32, 1.44) in those with a f-Hb of 7.1–11.9 μg Hb/g faeces to 2.20 (95% CI: 2.10, 2.30) in those with a f-Hb ≥60.0 μg Hb/g faeces, when compared to those with a f-Hb ≤7.0 μg Hb/g faeces. The pattern remained when excluding CRC from the analysis. Similar patterns were observed between incrementally increasing f-Hb and the risk of dying from respiratory disease, cardiovascular disease and cancers other than CRC. Furthermore, we observed an increased risk of dying from CRC with increasing f-Hb.

Conclusions
Our findings support the hypothesis that f-Hb may indicate an elevated risk of having chronic conditions if causes for the bleeding have not been identified. The mechanisms still need to be established, but f-Hb may be a potential biomarker for several non-CRC diseases.
Nasal TSLP and periostin in infants with severe bronchiolitis and risk of asthma at 4 years of age
Authors: Garcia-Garcia Maria Luz , Sastre Beatriz , Arroyas Maria , Beato Maite , Alonso Patricia , Rodrigo-Muñoz José Manuel , Del Pozo Victoria , Casas Inmaculada , Calvo Cristina 
Published: January 2023

Abstract
Background
Severe bronchiolitis is often associated with subsequent respiratory morbidity, mainly recurrent wheezing and asthma. However, the underlying immune mechanisms remain unclear. The main goal of this study was to investigate the association of nasal detection of periostin and thymic stromal lymphopoietin (TSLP) during severe bronchiolitis with the development of asthma at 4 years of age.

Methods
Observational, longitudinal, post-bronchiolitis, hospital-based, follow-up study. Children hospitalized for bronchiolitis between October/2013 and July/2017, currently aged 4 years, included in a previous study to investigate the nasal airway secretion of TSLP and periostin during bronchiolitis, were included. Parents were contacted by telephone, and were invited to a clinical interview based on a structured questionnaire to obtain information on the respiratory evolution. The ISAAC questionnaire for asthma symptoms for 6–7-year-old children, was also employed.

Results
A total of 248 children were included (median age 4.4 years). The mean age at admission for bronchiolitis was 3.1 (IQR: 1.5–6.5) months. Overall, 21% had ever been diagnosed with asthma and 37% had wheezed in the last 12 months. Measurable nasal TSLP was detected at admission in 27(11%) cases and periostin in 157(63%). The detection of nasal TSLP was associated with the subsequent prescription of maintenance asthma treatment (p = 0.04), montelukast (p = 0.01), and the combination montelukast/inhaled glucocorticosteroids (p = 0.03). Admissions for asthma tended to be more frequent in children with TSLP detection (p = 0.07). In the multivariate analysis, adjusting for potential confounders, the detection of TSLP remained independently associated with chronic asthma treatment prescription (aOR:2.724; CI 1.051–7.063, p:0.04) and with current asthma (aOR:3.41; CI 1.20–9.66, p:0.02).
Nasal detection of periostin was associated with lower frequency of ever use of short-acting beta2-agonists (SABA) (p = 0.04), lower prevalence of current asthma (p = 0.02), less prescription of maintenance asthma treatment in the past 12 months (p = 0.02, respectively). In the multivariate analysis, periostin was associated with lower risk of asthma at 4 years, independently of the atopic status (aOR:0.511 CI 95% 0.284–0.918, p:0.025).

Conclusions
Our results show a positive correlation between nasal TSLP detection in severe bronchiolitis and the presence of current asthma, prescription of asthma maintenance treatment and respiratory admissions up to the age of 4 years. By contrast, we found a protective association between nasal periostin detection and current asthma at 4 years, ever diagnosis of asthma, maintenance asthma treatment prescription, and respiratory admissions.
Action on the social determinants for advancing health equity in the time of COVID-19: perspectives of actors engaged in a WHO Special Initiative
Authors: Solar Orielle , Valentine Nicole , Castedo Antia , Brandt Gonzalo Soto , Sathyandran Jaitra , Ahmed Zahra , Cheh Paul , Callon Emma , Porritt Felicity , Espinosa Isabel , Fortune Kira , Kubota Shogo , Elliott Elizabeth , David April Joy , Bigdeli Maryam , Hachri Hafid , Bodenmann Patrick , Morisod Kevin , Biehl Molly , Nambiar Devaki , Williams Carmel , Allen Jessica , Goldblatt Peter , Placella Erika , Marmot Michael , Rasanathan Kumanan 
Published: January 2023

AbstractSince the 2008 publication of the reports of the Commission on Social Determinants of Health and its nine knowledge networks, substantial research has been undertaken to document and describe health inequities. The COVID-19 pandemic has underscored the need for a deeper understanding of, and broader action on, the social determinants of health. Building on this unique and critical opportunity, the World Health Organization is steering a multi-country Initiative to reduce health inequities through an action-learning process in ‘Pathfinder’ countries. The Initiative aims to develop replicable and reliable models and practices that can be adopted by WHO offices and UN staff to address the social determinants of health to advance health equity. This paper provides an overview of the Initiative by describing its broad theory of change and work undertaken in three regions and six Pathfinder countries in its first year-and-a-half. Participants engaged in the Initiative describe results of early country dialogues and promising entry points for implementation that involve model, network and capacity building. The insights communicated through this note from the field will be of interest for others aiming to advance health equity through taking action on the social determinants of health, in particular as regards structural determinants.
Radiogenomic analysis of prediction HER2 status in breast cancer by linking ultrasound radiomic feature module with biological functions
Authors: Cui Hao , Sun Yue , Zhao Dantong , Zhang Xudong , Kong Hanqing , Hu Nana , Wang Panting , Zuo Xiaoxuan , Fan Wei , Yao Yuan , Fu Baiyang , Tian Jiawei , Wu Meixin , Gao Yue , Ning Shangwei , Zhang Lei 
Published: January 2023

Abstract
Background
Human epidermal growth factor receptor 2 (HER2) overexpressed associated with poor prognosis in breast cancer and HER2 has been defined as a therapeutic target for breast cancer treatment. We aimed to explore the molecular biological information in ultrasound radiomic features (URFs) of HER2-positive breast cancer using radiogenomic analysis. Moreover, a radiomics model was developed to predict the status of HER2 in breast cancer.

Methods
This retrospective study included 489 patients who were diagnosed with breast cancer. URFs were extracted from a radiomics analysis set using PyRadiomics. The correlations between differential URFs and HER2-related genes were calculated using Pearson correlation analysis. Functional enrichment of the identified URFs-correlated HER2 positive-specific genes was performed. Lastly, the radiomics model was developed based on the URF-module mined from auxiliary differential URFs to assess the HER2 status of breast cancer.

Results
Eight differential URFs (p < 0.05) were identified among the 86 URFs extracted by Pyradiomics. 25 genes that were found to be the most closely associated with URFs. Then, the relevant biological functions of each differential URF were obtained through functional enrichment analysis. Among them, Zone Entropy is related to immune cell activity, which regulate the generation of calcification in breast cancer. The radiomics model based on the Logistic classifier and URF-module showed good discriminative ability (AUC = 0.80, 95% CI).

Conclusion
We searched for the URFs of HER2-positive breast cancer, and explored the underlying genes and biological functions of these URFs. Furthermore, the radiomics model based on the Logistic classifier and URF-module relatively accurately predicted the HER2 status in breast cancer.
A novel mutation in the proteoglycan 4 gene causing CACP syndrome: two sisters report
Authors: Bağrul İlknur , Ceylaner Serdar , Yildiz Yasemin Tasci , Tuncez Serife , Aydin Elif Arslanoglu , Bağlan Esra , Ozdel Semanur , Bülbül Mehmet 
Published: January 2023

Abstract
Background
Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome, caused by biallelic pathogenic mutations in the proteoglycan 4 (PRG4) gene, is characterized by early-onset camptodactyly, noninflammatory arthropathy, coxa vara deformity, and rarely, pericardial effusion. This syndrome can mimic juvenile idiopathic arthritis. CACP syndrome is caused by mutations in the proteoglycan 4 (PRG4) gene. To date, only 36 pathogenic mutations have been reported in this gene, but none have been reported from Azerbaijan.

Case presentation
Herein, we report two siblings presented with chronic polyarthritis, had a prior diagnosis of juvenile idiopathic arthritis, but was subsequently diagnosed as CACP syndrome with novel mutation in the PRG4 gene.

Conclusion
Our report expands the knowledge of PRG4 mutations, which will aid in CACP patient counseling.
Conspiracy beliefs and COVID-19 guideline adherence in adolescent psychiatric outpatients: the predictive role of adverse childhood experiences
Authors: Goreis Andreas , Pfeffer Bettina , Zesch Heidi Elisabeth , Klinger Diana , Reiner Tamara , Bock Mercedes M. , Ohmann Susanne , Sackl-Pammer Petra , Werneck-Rohrer Sonja , Eder Harald , Skala Katrin , Czernin Klara , Mairhofer Dunja , Rohringer Bernhard , Bedus Carolin , Lipp Ronja , Vesely Christine , Plener Paul L. , Kothgassner Oswald D. 
Published: January 2023

Abstract
Background
Conspiracy beliefs have become widespread throughout the COVID-19 pandemic. Previous studies have shown that endorsing conspiracy beliefs leads to lower protective guideline adherence (i.e., wearing face masks), posing a threat to public health measures. The current study expands this research across the lifespan, i.e., in a sample of adolescents with mental health problems. Here, we investigated the association between conspiracy beliefs and guideline adherence while also exploring the predictors of conspiracy beliefs.

Methods
N = 93 adolescent psychiatric outpatients (57% female, mean age: 15.8) were assessed using anonymous paper–pencil questionnaires. Endorsement of generic and COVID-19 conspiracy beliefs was assessed, in addition to items measuring adherence to protective guidelines and mental health (stress, depressive symptoms, emotional/behavioral problems, and adverse childhood experiences). Multiple regressions and supervised machine learning (conditional random forests) were used for analyses.

Results
Fourteen percent of our sample fully endorsed at least one COVID-19 conspiracy theory, while protective guidelines adherence was relatively high (M = 4.92, on a scale from 1 to 7). The endorsement of COVID-19 conspiracy beliefs—but not of generic conspiracy beliefs—was associated with lower guideline adherence (β = − 0.32, 95% CI − 0.53 to − 0.11, p < .001). Conditional random forests suggested that adverse childhood experiences and peer and conduct problems were relevant predictors of both conspiracy belief categories.

Conclusion
While a significant proportion of our sample of adolescents in psychiatric treatment endorsed conspiracy beliefs, the majority did not. Furthermore, and to some degree, contrary to public perception, we found that adolescents show relatively good adherence to public health measures—even while experiencing a high degree of mental distress. The predictive value of adverse childhood experiences and peer/conduct problems for conspiracy beliefs might be explained by compensatory mechanisms to ensure the safety, structure, and inclusion that conspiracies provide.
A model for predicting both breast cancer risk and non-breast cancer death among women > 55 years old
Authors: Schonberg Mara A. , Wolfson Emily A. , Eliassen A. Heather , Bertrand Kimberly A. , Shvetsov Yurii B. , Rosner Bernard A. , Palmer Julie R. , Ngo Long H. 
Published: January 2023

Abstract
Background
Guidelines recommend shared decision making (SDM) for mammography screening for women ≥ 75 and not screening women with < 10-year life expectancy. High-quality SDM requires consideration of women’s breast cancer (BC) risk, life expectancy, and values but is hard to implement because no models simultaneously estimate older women’s individualized BC risk and life expectancy.

Methods
Using competing risk regression and data from 83,330 women > 55 years who completed the 2004 Nurses’ Health Study (NHS) questionnaire, we developed (in 2/3 of the cohort, n = 55,533) a model to predict 10-year non-breast cancer (BC) death. We considered 60 mortality risk factors and used best-subsets regression, the Akaike information criterion, and c-index, to identify the best-fitting model. We examined model performance in the remaining 1/3 of the NHS cohort (n = 27,777) and among 17,380 Black Women’s Health Study (BWHS) participants, ≥ 55 years, who completed the 2009 questionnaire. We then included the identified mortality predictors in a previously developed competing risk BC prediction model and examined model performance for predicting BC risk.

Results
Mean age of NHS development cohort participants was 70.1 years (± 7.0); over 10 years, 3.1% developed BC, 0.3% died of BC, and 20.1% died of other causes; NHS validation cohort participants were similar. BWHS participants were younger (mean age 63.7 years [± 6.7]); over 10-years 3.1% developed BC, 0.4% died of BC, and 11.1% died of other causes. The final non-BC death prediction model included 21 variables (age; body mass index [BMI]; physical function [3 measures]; comorbidities [12]; alcohol; smoking; age at menopause; and mammography use). The final BC prediction model included age, BMI, alcohol and hormone use, family history, age at menopause, age at first birth/parity, and breast biopsy history. When risk factor regression coefficients were applied in the validation cohorts, the c-index for predicting 10-year non-BC death was 0.790 (0.784–0.796) in NHS and 0.768 (0.757–0.780) in BWHS; for predicting 5-year BC risk, the c-index was 0.612 (0.538–0.641) in NHS and 0.573 (0.536–0.611) in BWHS.

Conclusions
We developed and validated a novel competing-risk model that predicts 10-year non-BC death and 5-year BC risk. Model risk estimates may help inform SDM around mammography screening.
Isoniazid preventive therapy completion in children under 5 years old who are contacts of tuberculosis cases in Lima, Peru: study protocol for an open-label, cluster-randomized superiority trial
Authors: Otero L. , Zetola N. , Campos M. , Zunt J. , Bayer A. , Curisinche M. , Ochoa T. , Reyes M. , Vega V. , Van der Stuyft P. , Sterling TR. 
Published: January 2023

AbstractBackgroundChildren < 5 years old in contact with TB cases are at high risk for developing severe and fatal forms of TB. Contact investigation, BCG vaccination, and isoniazid preventive therapy (IPT) are the most effective strategies to prevent TB among children. However, the implementation of IPT faces challenges at several stages of the cascade of care of TB infection among children, particularly those less than 5 years old. In Peru, a large proportion of children do not complete IPT, which highlights the need to design effective interventions that enhance preventive therapy adherence and completion. Although the body of evidence for such interventions has grown, interventions in medium TB incidence settings are lacking. This study aims to test the effectiveness, acceptability, and feasibility of an intervention package to increase information and motivation to complete IPT among children < 5 who have been prescribed IPT.MethodsAn open-label, cluster-randomized superiority trial will be conducted in two districts in South Lima, Peru. Thirty health facilities will be randomized as clusters, 10 to the intervention and 20 to control (standard of care). We aim to recruit 10 children from different households in each cluster. Participants will be caretakers of children aged < 5 years old who initiated IPT. The intervention consists of educational material, and short message services (SMS) reminders and motivators. The primary outcomes will be the proportion of children who picked up > 90% of the 24 weeks of IPT (22 pick-ups) and the proportion of children who picked up the 24 weeks of IPT. The standard of care is a weekly pick-up with monthly check-ups in a health facility. Feasibility and acceptability of the intervention will be assessed through an interview with the caretaker.DiscussionUnfavorable outcomes of TB in young children, high effectiveness of IPT, and low rates of IPT completion highlight the need to enhance adherence and completion of IPT among children < 5 years old. Testing of a context-adapted intervention is needed to improve IPT completion rates and therefore TB prevention in young children.Trial registrationClinicalTrials.gov NCT03881228. Registered on March 19, 2019.
Temporal transcriptomic changes in microRNAs involved in the host immune response and metabolism during Neospora caninum infection
Authors: Chen Jin-Ming , Zhao Shan-Shan , Tao De-Liang , Li Jing-Yu , Yang Xin , Fan Ying-Ying , Song Jun-Ke , Liu Qun , Zhao Guang-Hui 
Published: January 2023

AbstractBackgroundNeospora caninuminfection is a major cause of abortion in cattle, which results in serious economic losses to the cattle industry. However, there are no effective drugs or vaccines for the control ofN. caninuminfections. There is increasing evidence that microRNAs (miRNAs) are involved in many physiological and pathological processes, and dysregulated expression of host miRNAs and the biological implications of this have been reported for infections by various protozoan parasites. However, to our knowledge, there is presently no published information on host miRNA expression duringN. caninuminfection.MethodsThe expression profiles of miRNAs were investigated by RNA sequencing (RNA-seq) in caprine endometrial epithelial cells (EECs) infected withN. caninumat 24 h post infection (pi) and 48 hpi, and the functions of differentially expressed (DE) miRNAs were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The transcriptome data were validated by using quantitative real-time polymerase chain reaction. One of the upregulated DEmiRNAs, namely chi-miR-146a, was selected to study the effect of DEmiRNAs on the propagation ofN. caninumtachyzoites in caprine EECs.ResultsRNA-seq showed 18 (17 up- and one downregulated) and 79 (54 up- and 25 downregulated) DEmiRNAs at 24 hpi and 48 hpi, respectively. Quantitative real-time polymerase chain reaction analysis of 13 randomly selected DEmiRNAs (10 up- and three downregulated miRNAs) confirmed the validity of the RNA-seq data. A total of 7835 messenger RNAs were predicted to be potential targets for 66 DEmiRNAs, and GO and KEGG enrichment analysis of these predicted targets revealed that DEmiRNAs altered byN. caninuminfection may be involved in host immune responses (e.g. Fc gamma R-mediated phagocytosis, Toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, transforming growth factor-β signaling pathway, mitogen-activated protein kinase signaling pathway) and metabolic pathways (e.g. lysine degradation, insulin signaling pathway, AMP-activated protein kinase signaling pathway, Rap1 signaling pathway, calcium signaling pathway). Upregulated chi-miR-146a was found to promoteN. caninumpropagation in caprine EECs.ConclusionsThis is, to our knowledge, the first report on the expression profiles of host miRNAs during infection withN. caninum, and shows that chi-miR-146a may promoteN. caninumpropagation in host cells. The novel findings of the present study should help to elucidate the interactions between host cells andN. caninum.Graphical Abstract
Phthalates impact on the epigenetic factors contributed specifically by the father at fertilization
Authors: Swanson G. M. , Nassan F. L. , Ford J. B. , Hauser R. , Pilsner J. R. , Krawetz S. A. 
Published: January 2023

Abstract
Background
Preconception exposure to phthalates such as the anti-androgenic dibutyl-phthalate (DBP) impacts both male and female reproduction, yet how this occurs largely remains unknown. Previously we defined a series of RNAs expressly provided by sperm at fertilization and separately, and in parallel, those that responded to high DBP exposure. Utilizing both populations of RNAs, we now begin to unravel the impact of high-DBP exposure on those RNAs specifically delivered by the father.

Results
Enrichment of RNAs altered by DBP exposure within the Molecular Signature Database highlighted cellular stress, cell cycle, apoptosis, DNA damage response, and gene regulation pathways. Overlap within each of these five pathways identified those RNAs that were specifically (≥ fivefold enriched) or primarily (≥ twofold enriched) provided as part of the paternal contribution compared to the oocyte at fertilization. Key RNAs consistently altered by DBP, including CAMTA2 and PSME4, were delivered by sperm reflective of these pathways. The majority (64/103) of overlapping enriched gene sets were related to gene regulation. Many of these RNAs (45 RNAs) corresponded to key interconnected CRREWs (Chromatin remodeler cofactors, RNA interactors, Readers, Erasers, and Writers). Modeling suggests that CUL2, PHF10, and SMARCC1 may coordinate and mechanistically modulate the phthalate response.

Conclusions
Mediated through a CRREW regulatory network, the cell responded to exposure presenting stressed-induced changes in the cell cycle—DNA damage—apoptosis. Interestingly, the majority of these DBP-responsive epigenetic mediators’ direct acetylation or deacetylation, impacting the sperm's cargo delivered at fertilization and that of the embryo.