bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative genomics analyses reveal sequence determinants underlying interspecies variations in injury-responsive enhancers
Authors: Ji Luzhang , Shi Yuanyuan , Bian Qian 
Published: April 2023

Abstract
Background
Injury induces profound transcriptional remodeling events, which could lead to only wound healing, partial tissue repair, or perfect regeneration in different species. Injury-responsive enhancers (IREs) are cis-regulatory elements activated in response to injury signals, and have been demonstrated to promote tissue regeneration in some organisms such as zebrafish and flies. However, the functional significances of IREs in mammals remain elusive. Moreover, whether the transcriptional responses elicited by IREs upon injury are conserved or specialized in different species, and what sequence features may underlie the functional variations of IREs have not been elucidated.

Results
We identified a set of IREs that are activated in both regenerative and non-regenerative neonatal mouse hearts upon myocardial ischemia-induced damage by integrative epigenomic and transcriptomic analyses. Motif enrichment analysis showed that AP-1 and ETS transcription factor binding motifs are significantly enriched in both zebrafish and mouse IREs. However, the IRE-associated genes vary considerably between the two species. We further found that the IRE-related sequences in zebrafish and mice diverge greatly, with the loss of IRE inducibility accompanied by a reduction in AP-1 and ETS motif frequencies. The functional turnover of IREs between zebrafish and mice is correlated with changes in transcriptional responses of the IRE-associated genes upon injury. Using mouse cardiomyocytes as a model, we demonstrated that the reduction in AP-1 or ETS motif frequency attenuates the activation of IREs in response to hypoxia-induced damage.

Conclusions
By performing comparative genomics analyses on IREs, we demonstrated that inter-species variations in AP-1 and ETS motifs may play an important role in defining the functions of enhancers during injury response. Our findings provide important insights for understanding the molecular mechanisms of transcriptional remodeling in response to injury across species.
Comparative protein analysis of two maize genotypes with contrasting tolerance to low temperature
Authors: Ramazan Salika , Jan Nelofer , John Riffat 
Published: April 2023

Abstract
Background
Low temperature (LT) stress is one of the major environmental stress factors affecting the growth and yield of maize (Zea mays L.). Hence, it is important to unravel the molecular mechanisms behind LT stress tolerance to improve molecular breeding in LT tolerant genotypes. In the present study, two maize genotypes viz. Gurez local from Kashmir Himalaya and tropical grown GM6, were dissected for their LT stress response in terms of accumulation of differentially regulated proteins (DRPs). Leaf proteome analysis at three-leaf stage of maize seedlings subjected to LT stress of 6 °C for a total of 12 h duration was performed using two dimensional gel electrophoresis (2D-PAGE) followed by subsequent identification of the proteins involved.

Results
After MALDI-TOF (Matrix-assisted laser desorption/ionization-time of flight) and bioinformatics analysis, 19 proteins were successfully identified in Gurez local, while as 10 proteins were found to get successful identification in GM6. The interesting observations from the present investigation is the identification of three novel proteins viz. threonine dehydratase biosynthetic chloroplastic, thylakoidal processing peptidase 1 chloroplastic, and nodulin-like protein, whose role in abiotic stress tolerance, in general, and LT stress, in particular, has not been reported so far. It is important to highlight here that most of LT responsive proteins including the three novel proteins were identified from Gurez local only, owing to its exceptional LT tolerance. From the protein profiles, obtained in both genotypes immediately after LT stress perception, it was inferred that stress responsive protein accumulation and their expression fashion help the Gurez local in seedling establishment and withstand unfavorable conditions as compared to GM6. This was inferred from the findings of pathway enrichment analysis like regulation of seed growth, timing of floral transition, lipid glycosylation, and aspartate family amino acid catabolic processes, besides other key stress defense mechanisms. However, in GM6, metabolic pathways enriched were found to be involved in more general processes including cell cycle DNA replication and regulation of phenylpropanoid metabolism. Furthermore, majority of the qRT-PCR results of the selected proteins demonstrated positive correlation between protein levels and transcript abundance, thereby strengthening our findings.

Conclusions
In conclusion, our findings reported majority of the identified proteins in Gurez local exhibiting up-regulated pattern under LT stress as compared to GM6. Furthermore, three novel proteins induced by LT stress were found in Gurez local, requiring further functional validation. Therefore, our results offer more insights for elucidating the molecular networks mediating LT stress tolerance in maize.
Longitudinal association between N-terminal B-type natriuretic peptide, anxiety and social support in patients with HFpEF: results from the multicentre randomized controlled Aldo-DHF trial
Authors: Wilke Marieke R. , Broschmann Daniel , Sandek Anja , Wachter Rolf , Edelmann Frank , Herrmann-Lingen Christoph 
Published: April 2023

Abstract
Background
Higher plasma levels of natriuretic peptides (NPs) have been associated with reduced anxiety in experimental research and a number of patient samples. As NP levels are elevated in heart failure patients, we investigate whether this elevation is related to anxiety in patients with heart failure with preserved ejection fraction (HFpEF).

Methods
Post-hoc regression and mediation analyses were conducted, using data of 422 patients with HFpEF from the randomized, placebo-controlled, double-blinded, two-armed, multicentre aldosterone in diastolic heart failure trial, testing associations and their mediators between the N-terminal B-type natriuretic peptide (NT-proBNP) and anxiety at baseline and over 12-month follow-up. Anxiety was measured by the Hospital Anxiety and Depression Scale (HADS), social support by the ENRICHD Social Support Inventory and physical functioning by the Short Form 36 Health Survey.

Results
The mean age of the study population was 66.8 ± 7.6 years, 47.6% were male and 86.0% had NYHA class II. NT-proBNP showed a weak negative correlation with HADS anxiety scores at baseline (r = − 0.087; p = 0.092), which was significant (r = − 0.165; p = 0.028) in men but not in women. NT-proBNP also tended to predict lower anxiety at 12-months in men. On the other hand, higher anxiety at baseline was associated with lower NT-proBNP scores 12 months later (r = − 0.116; p = 0.026). All associations lost significance in multivariate regression for age, perceived social support (ESSI), physical function (SF-36) and study arm. Mediation analyses revealed that social support acts as a full mediator for the link between NT-proBNP levels and anxiety.

Conclusion
The mechanisms linking NT-proBNP to anxiety may be more complex than originally assumed. While effects of NT-proBNP on anxiety may be mediated by perceived social support, there may be an additional negative effect of anxiety on NT-proBNP. Future research should consider this possible bi-directionality of the association and assess the potential influence of gender, social support, oxytocin and vagal tone on the interaction of anxiety and natriuretic peptide levels.
Trial Registrationhttp://www.controlled-trials.com (ISRCTN94726526) on 07/11/2006.
Eudra-CT-number: 2006–002,605-31.
Trends in predicted 10-year risk for cardiovascular diseases among patients with type 2 diabetes in Thailand, from 2014 to 2018
Authors: Lertsakulbunlue Sethapong , Mungthin Mathirut , Rangsin Ram , Kantiwong Anupong , Sakboonyarat Boonsub 
Published: April 2023

Abstract
Background
Cardiovascular diseases (CVD) are the leading causes of death globally, including Thailand. Approximately one-tenth of Thai adults have type 2 diabetes (T2D), a significantly increasing CVD. Our study aimed to determine the trends of predicted 10-year CVD risk among patients with T2D.

Methods
A series of hospital-based cross-sectional studies were conducted in 2014, 2015 and 2018. We included Thai patients with T2D aged 30–74-year-old without a history of CVD. The predicted 10-year risk for CVD was calculated based on Framingham Heart Study equations both with simple office-based nonlaboratory and laboratory-based. Age- and sex-adjusted means and proportions of predicted 10-year risk for CVD were calculated.

Results
A total of 84,602 patients with T2D were included in the present study. The average SBP among study participants was 129.3 ± 15.7 mmHg in 2014 and rose to 132.6 ± 14.9 mmHg in 2018. Likewise, the average body mass index was 25.7 ± 4.5 kg/m2 in 2014 and elevated to 26.0 ± 4.8 kg/m2 in 2018. The age- and sex-adjusted mean of the predicted 10-year CVD risk (simple office-based) was 26.2% (95% CI: 26.1–26.3%) in 2014 and rose to 27.3% (95% CI: 27.2–27.4%) in 2018 (p-for trend < 0.001). While the age- and sex-adjusted mean of the predicted 10-year CVD risk (laboratory-based) ranged from 22.4–22.9% from 2014 to 2018 (p-for trend < 0.001). The age- and sex-adjusted prevalence of the high predicted 10-year CVD risk (simple office-based) was 67.2% (95% CI: 66.5–68.0%) in 2014 and significantly rose to 73.1% (95% CI: 72.4–73.7%) in 2018 (p-for trend < 0.001). Nevertheless, the age- and sex-adjusted prevalence of the high predicted 10-year CVD risk (laboratory-based) ranged from 46.0–47.4% from 2014 to 2018 (p-for trend = 0.405). However, among patients with available laboratory results, a significantly positive correlation was noted between predicted 10-year CVD risk, simple office-based and laboratory-based (r = 0.8765, p-value < 0.001).

Conclusion
Our study demonstrated significant rising trends in the predicated 10-year CVD risk among Thai patients with T2D. In addition, the results empowered further improved modifiable CVD risks, especially regarding high BMI and high blood pressure.
A new data driven method for summarising multiple cause of death data
Authors: Dobson Annette , McElwee Paul , Baneshi Mohammad Reza , Eynstone-Hinkins James , Moran Lauren , Waller Michael 
Published: April 2023

Abstract
Background
National mortality statistics are based on a single underlying cause of death. This practice does not adequately represent the impact of the range of conditions experienced in an ageing population in which multimorbidity is common.

Methods
We propose a new method for weighting the percentages of deaths attributed to different causes that takes account of the patterns of associations among underlying and contributing causes of death. It is driven by the data and unlike previously proposed methods does not rely on arbitrary choices of weights which can over-emphasise the contribution of some causes of death. The method is illustrated using Australian mortality data for people aged 60 years or more.

Results
Compared to the usual method based only on the underlying cause of death the new method attributes higher percentages of deaths to conditions like diabetes and dementia that are frequently mentioned as contributing causes of death, rather than underlying causes, and lower percentages to conditions to which they are closely related such as ischaemic heart disease and cerebrovascular disease. For some causes, notably cancers, which are usually recorded as underlying causes with few if any contributing causes the new method produces similar percentages to the usual method. These different patterns among groups of related conditions are not apparent if arbitrary weights are used.

Conclusion
The new method could be used by national statistical agencies to produce additional mortality tables to complement the current tables based only on underlying causes of death.
Associations between diabetes status and grip strength trajectory sub-groups in adulthood: findings from over 16 years of follow-up in the MRC National Survey of Health and Development
Authors: Norris T. , Johnson W. , Cooper R. , Pereira S. M. Pinto 
Published: April 2023

Abstract
Background
Cross-sectional studies suggest a relationship between diabetes status and weaker grip strength (GS) in adulthood and limited evidence from longitudinal studies has focussed on the association with average change in GS. We aimed to investigate whether diabetes status was related to membership of distinct GS trajectories in mid-to-late adulthood in 2,263 participants in the Medical Research Council National Survey of Health and Development.

Methods
Grip strength (kg) was measured at 53, 60–64 and 69 years. Pre-/diabetes was defined at 53 years based on HbA1c > 5.6% and/or doctor-diagnosis of diabetes. Sex-specific latent class trajectory models were developed and multinomial logistic regression was used to investigate the association between pre-/diabetes status and membership into GS trajectory classes.

Results
For both males and females, a 3-class solution (‘High’, ‘Intermediate’, ‘Low’) provided the best representation of the GS data and the most plausible solution. There was no evidence that pre-/diabetes status was associated with class membership in either sex: e.g., adjusted odds ratios of being in the ‘Low’ class (vs. ‘High’) for males with pre-/diabetes (vs. no-diabetes) was 1.07 (95% CI:0.45,2.55).

Conclusion
Using a flexible data-driven approach to identify GS trajectories between 53 and 69 years, we observed three distinct GS trajectories, all declining, in both sexes. There was no association between pre-/diabetes status at 53 years and membership into these GS trajectories. Understanding the diabetes status―GS trajectories association is vital to ascertain the consequences that projected increases in pre-/diabetes prevalence’s are likely to have.
Prevalence of early postpartum depression and associated risk factors among selected women in southern Malawi: a nested observational study
Authors: Moya E , Mzembe G , Mwambinga M , Truwah Z , Harding R , Ataide R , Larson Leila M , Fisher J , Braat S , Pasricha SR , Mwangi MN , Phiri KS 
Published: April 2023

Abstract
Background
The birth of a child should be a time of celebration. However, for many women, childbirth represents a time of great vulnerability to becoming mentally unwell, a neglected maternal morbidity. This study aimed to determine the prevalence of early postpartum depression (PPD) and its associated risk factors among women giving birth at health facilities in southern Malawi. Identifying women vulnerable to PPD will help clinicians provide appropriately targeted interventions before discharge from the maternity ward.

Method
We conducted a nested cross-sectional study. Women were screened for early PPD using a locally validated Edinburgh Postpartum Depression Scale (EPDS) as they were discharged from the maternity ward. The prevalence of moderate or severe (EPDS ≥ 6) and severe (EPDS ≥ 9) PPD was determined, including 95% confidence intervals (CI). Data on maternal age, education and marital status, income source, religion, gravidity, and HIV status, among others, were collected during the second trimester of pregnancy, and obstetric and infant characteristics during childbirth were examined as potential risk factors for early PPD using univariable and multivariable logistic regression analyses.

Results
Data contributed by 636 women were analysed. Of these women, 9.6% (95% CI; 7.4–12.1%) had moderate to severe early PPD using an EPDS cut-off of ≥ 6, and 3.3% (95% CI; 2.1–5.0%) had severe early PPD using an EPDS cut-off of ≥ 9. Multivariable analyses indicated that maternal anaemia at birth (aOR; 2.65, CI; 1.49–4.71, p-value; 0.001) was associated with increased risk for moderate and/or severe early PPD, while live birth outcome (aOR; 0.15, 95% CI; 0.04–0.54, p-value; 0.004), being single compared to divorced/widowed (aOR; 0.09, 95% CI; 0.02–0.55, p-value; 0.009), and lower education level (aOR; 0.36, 95% CI; 0.20–0.65, p-value; 0.001) were associated with decreased risk. Being HIV positive (aOR; 2.88, 95% CI; 1.08–7.67, p-value; 0.035) was associated with severe PPD only.

Conclusion
The prevalence of early PPD was slightly lower in our selected sample compared to previous reports in Malawi and was associated with maternal anaemia at birth, non-live birth, being divorced/widowed and HIV-positive status. Therefore, health workers should screen for depressive symptoms in women who are at increased risk as they are discharged from the maternity ward for early identification and treatment.
Co-occurrence of depression, anxiety, and perinatal posttraumatic stress in postpartum persons
Authors: Howard Shelby , Witt Caitlin , Martin Karla , Bhatt Ateshi , Venable Emily , Buzhardt Sarah , Chapple Andrew G. , Sutton Elizabeth F. 
Published: April 2023

Abstract
Background
The study aim was to describe the incidence of depression, anxiety, perinatal-post-traumatic stress disorder (PTSD), and their co-occurrences in the early postpartum period in a low-resource OB/GYN clinic serving majority Medicaid-eligible persons. We hypothesized that postpartum persons screening positive for depression will have an increased risk of a positive screen for anxiety and perinatal PTSD.

Methods
A retrospective study of postpartum persons receiving care in Baton Rouge, Louisiana was conducted using responses abstracted from the electronic medical record (EMR) of the Patient Health Questionnaire-9 (PHQ9), Generalized Anxiety Disorder-7 (GAD7), and Perinatal Post Traumatic Stress Disorder Questionnaire-II (PPQII). Categorical distributions were compared using Fisher exact tests, while t-tests were used to compare continuous covariates. Multivariable logistic regression was used to predict anxiety (GAD7) and perinatal PTSD (PPQII) scores while adjusting for potential confounders, as well as to predict continuous PPQII and GAD7 based on continuous PHQ9 scores.

Results
There were 613 birthing persons 4–12 weeks postpartum that completed mental health screening (PHQ9, GAD7, and PPQII) between November 2020 and June 2022 as part of routine postpartum care in the clinic. The incidence of screening positive for symptoms of depression (PHQ9 > 4) was 25.4% (n = 156), while the incidence of positive screening for symptoms of anxiety (GAD7 > 4) and perinatal PTSD (PPQII $$\ge$$
≥
19) were 23.0% (n = 141) and 5.1% (n = 31) respectively. Postpartum patients with mild anxiety or more (i.e. GAD7 > 4) had 26 times higher odds of screening positive for symptoms of depression (PHQ9 > 4) (adjusted odds ratio [aOR] 26.3; 95% confidence interval [CI] 15.29–46.92; p < 0.001). Postpartum persons with a PPQII score indicating symptoms of perinatal PTSD (PPQII $$\ge$$
≥
19) had 44 times higher odds of screening positive for symptoms of depression (PHQ > 4) (aOR 44.14; 95%CI 5.07–5856.17; p < 0.001).

Conclusions
Depression, anxiety, and perinatal PTSD are each independent risk factors for each other. To comply with the American College of Obstetricians and Gynecologists (ACOG) recommendations, providers should universally screen postpartum persons with validated screening tools for mood disturbances. However, if a complete full mood assessment is not feasible, this study provides evidence to support screening patients for depression, and if the patient screens positive, prompt additional screening for anxiety and perinatal PTSD.
The potential of PARP as a therapeutic target across pediatric solid malignancies
Authors: Keller Kaylee M. , Koetsier Joost , Schild Linda , Amo-Addae Vicky , Eising Selma , van den Handel Kim , Ober Kimberley , Koopmans Bianca , Essing Anke , van den Boogaard Marlinde L. , Langenberg Karin P. S. , Jäger Natalie , Kool Marcel , Pfister Stefan , Dolman M. Emmy M. , Molenaar Jan J. , van Hooff Sander R. 
Published: April 2023

Abstract
Background
Pediatric cancer is the leading cause of disease-related death in children and the need for better therapeutic options remains urgent. Due to the limited number of patients, target and drug development for pediatrics is often supplemented by data from studies focused on adult cancers. Recent evidence shows that pediatric cancers possess different vulnerabilities that should be explored independently from adult cancers.

Methods
Using the publicly available Genomics of Drug Sensitivity in Cancer database, we explore therapeutic targets and biomarkers specific to the pediatric solid malignancies Ewing sarcoma, medulloblastoma, neuroblastoma, osteosarcoma, and rhabdomyosarcoma. Results are validated using cell viability assays and high-throughput drug screens are used to identify synergistic combinations.

Results
Using published drug screening data, PARP is identified as a drug target of interest across multiple different pediatric malignancies. We validate these findings, and we show that efficacy can be improved when combined with conventional chemotherapeutics, namely topoisomerase inhibitors. Additionally, using gene set enrichment analysis, we identify ribosome biogenesis as a potential biomarker for PARP inhibition in pediatric cancer cell lines.

Conclusion
Collectively, our results provide evidence to support the further development of PARP inhibition and the combination with TOP1 inhibition as a therapeutic approach in solid pediatric malignancies. Additionally, we propose ribosome biogenesis as a component to PARP inhibitor sensitivity that should be further investigated to help maximize the potential utility of PARP inhibition and combinations across pediatric solid malignancies.
Aberrant methylation in neurofunctional gene serves as a hallmark of tumorigenesis and progression in colorectal cancer
Authors: Li Xuan , Cai Du , Huang Yaoyi , Xie Yumo , Shen Dingcheng , Yuan Ze , Liu Xiaoxia , Huang Meijin , Luo Yanxin , Yu Huichuan , Wang Xiaolin 
Published: April 2023

Abstract
Background
DNA methylation is one of the most promising biomarkers in predicting the prognosis of colorectal cancer (CRC). We aimed to develop a DNA methylation biomarker that could evaluate the prognosis of CRC.

Methods
A promising DNA methylation biomarker was developed by hypermethylated genes in cancer tissue that were identified from Illumina EPIC methylation arrays. A cohort comprising 30 pairs of snap-frozen tumor tissue and adjacent normal tissue was used for correlation analysis between the methylation and expression status of the marker. The other cohort comprising 254 formalin-fixed paraffin-embedded (FFPE) tumor tissue from 254 CRC patients was used for prognosis analysis.

Results
Regulating synaptic membrane exocytosis 2 (RIMS2) was hypermethylated and lowly expressed in CRC comparing to adjacent normal tissue. Hypermethylation of RIMS2 in CRC was correlated with less frequent KRAS mutant and high differentiation. RIMS2 promoter methylation showed independent predictive value for survival outcome (P = 0.015, HR 1.992, 95% CI [(1.140–3.48)]), and a combination of RIMS2 methylation with KRAS status could predict prognosis better.

Conclusions
RIMS2 is frequently hypermethylated in CRC, which can silence the expression of RIMS2. RIMS2 methylation is a novel biomarker for predicting the prognosis of CRC.