bluuebunny/crossref_metadata_2025_split huggingface dataset:
How do common conditions impact health-related quality of life for children? Providing guidance for validating pediatric preference-based measures
Authors: Xiong Xiuqin , Dalziel Kim , Huang Li , Mulhern Brendan , Carvalho Natalie 
Published: January 2023

AbstractBackgroundThere is increasing interest in the validation of pediatric preference-based health-related quality of life measurement instruments. It is critical that children with various degrees of health-related quality of life (HRQoL) impact are included in validation studies. To inform patient sample selection for validation studies from a pragmatic perspective, this study explored HRQoL impairments between known-groups and HRQoL changes over time across 27 common chronic child health conditions and identified conditions with the largest impact on HRQoL.MethodsThe health dimensions of two common preference-based HRQoL measures, the EQ-5D-Y and CHU9D, were constructed using Pediatric Quality of Life Inventory items that overlap conceptually. Data was from the Longitudinal Study of Australian Children, a nationally representative sample with over 10,000 children at baseline. Seven waves of data were included for the analysis, with child age ranging from 2 to18 years. Impacts to specific health dimensions and overall HRQoL between those having a specific condition versus not were compared using linear mixed effects models. HRQoL changes over time were obtained by calculating the HRQoL differences between two consecutive time points, grouped by “Improved” and “Worsened” health status. Comparison among various health conditions and different age groups (2–4 years, 5–12 years and 13–18 years) were made.ResultsConditions with the largest statistically significant total HRQoL impairments of having a specific condition compared with not having the condition were recurrent chest pain, autism, epilepsy, anxiety/depression, irritable bowel, recurrent back pain, recurrent abdominal pain, and attention deficit hyperactivity disorder (ADHD) for the total sample (2–18 years). Conditions with largest HRQoL improvement over time were anxiety/depression, ADHD, autism, bone/joint/muscle problem, recurrent abdominal pain, recurrent pain in other part, frequent headache, diarrhea and day-wetting. The dimensions included in EQ-5D-Y and CHU9D can generally reflect HRQoL differences and changes. The HRQoL impacts to specific health dimensions differed by condition in the expected direction. The conditions with largest HRQoL impacts differed by age group.ConclusionsThe conditions with largest HRQoL impact were identified. This information is likely to be valuable for recruiting patient samples when validating pediatric preference-based HRQoL instruments pragmatically.
Limitations of COVID-19 testing and case data for evidence-informed health policy and practice
Authors: Alvarez Elizabeth , Bielska Iwona A. , Hopkins Stephanie , Belal Ahmed A. , Goldstein Donna M. , Slick Jean , Pavalagantharajah Sureka , Wynfield Anna , Dakey Shruthi , Gedeon Marie-Carmel , Alam Edris , Bouzanis Katrina 
Published: January 2023

Abstract
Background
Coronavirus disease 2019 (COVID-19) became a pandemic within a matter of months. Analysing the first year of the pandemic, data and surveillance gaps have subsequently surfaced. Yet, policy decisions and public trust in their country’s strategies in combating COVID-19 rely on case numbers, death numbers and other unfamiliar metrics. There are many limitations on COVID-19 case counts internationally, which make cross-country comparisons of raw data and policy responses difficult.

Purpose and conclusions
This paper presents and describes steps in the testing and reporting process, with examples from a number of countries of barriers encountered in each step, all of which create an undercount of COVID-19 cases. This work raises factors to consider in COVID-19 data and provides recommendations to inform the current situation with COVID-19 as well as issues to be aware of in future pandemics.
DeepMPF: deep learning framework for predicting drug–target interactions based on multi-modal representation with meta-path semantic analysis
Authors: Ren Zhong-Hao , You Zhu-Hong , Zou Quan , Yu Chang-Qing , Ma Yan-Fang , Guan Yong-Jian , You Hai-Ru , Wang Xin-Fei , Pan Jie 
Published: January 2023

Abstract
Background
Drug-target interaction (DTI) prediction has become a crucial prerequisite in drug design and drug discovery. However, the traditional biological experiment is time-consuming and expensive, as there are abundant complex interactions present in the large size of genomic and chemical spaces. For alleviating this phenomenon, plenty of computational methods are conducted to effectively complement biological experiments and narrow the search spaces into a preferred candidate domain. Whereas, most of the previous approaches cannot fully consider association behavior semantic information based on several schemas to represent complex the structure of heterogeneous biological networks. Additionally, the prediction of DTI based on single modalities cannot satisfy the demand for prediction accuracy.

Methods
We propose a multi-modal representation framework of ‘DeepMPF’ based on meta-path semantic analysis, which effectively utilizes heterogeneous information to predict DTI. Specifically, we first construct protein–drug-disease heterogeneous networks composed of three entities. Then the feature information is obtained under three views, containing sequence modality, heterogeneous structure modality and similarity modality. We proposed six representative schemas of meta-path to preserve the high-order nonlinear structure and catch hidden structural information of the heterogeneous network. Finally, DeepMPF generates highly representative comprehensive feature descriptors and calculates the probability of interaction through joint learning.

Results
To evaluate the predictive performance of DeepMPF, comparison experiments are conducted on four gold datasets. Our method can obtain competitive performance in all datasets. We also explore the influence of the different feature embedding dimensions, learning strategies and classification methods. Meaningfully, the drug repositioning experiments on COVID-19 and HIV demonstrate DeepMPF can be applied to solve problems in reality and help drug discovery. The further analysis of molecular docking experiments enhances the credibility of the drug candidates predicted by DeepMPF.

Conclusions
All the results demonstrate the effectively predictive capability of DeepMPF for drug-target interactions. It can be utilized as a useful tool to prescreen the most potential drug candidates for the protein. The web server of the DeepMPF predictor is freely available at http://120.77.11.78/DeepMPF/, which can help relevant researchers to further study.
Phenylalanine free infant formula in the dietary management of phenylketonuria
Authors: Yilmaz Ozlem , Cochrane Barbara , Wildgoose Jo , Pinto Alex , Evans Sharon , Daly Anne , Ashmore Catherine , MacDonald Anita 
Published: January 2023

Abstract
Background
Phenylalanine-free infant formula is an essential source of safe protein in a phenylalanine restricted diet, but its efficacy is rarely studied. We report a multicentre, open, longitudinal, prospective intervention study on a phenylalanine-free infant formula (PKU Start: Vitaflo International Ltd.).

Results
This was a 2-part study: part I (28 days short term evaluation) and part II (12 months extension). Data was collected on infant blood phenylalanine concentrations, dietary intake, growth, and gastrointestinal tolerance. Ten infants (n = 8 males, 80%), with a median age of 14 weeks (range 4–36 weeks) were recruited from 3 treatment centres in the UK. Nine of ten infants completed the 28-day follow-up (one caregiver preferred the usual phenylalanine-free formula and discontinued the study formula after day 14) and 7/9 participated in study part II. The phenylalanine-free infant formula contributed a median of 57% (IQR 50–62%) energy and 53% (IQR 33–66%) of total protein intake from baseline to the end of the part II extension study. During the 12-month follow-up, infants maintained normal growth and satisfactory blood phenylalanine control. Any early gastrointestinal symptoms (constipation, colic, vomiting and poor feeding) improved with time.

Conclusion
The study formula was well tolerated, helped maintain good metabolic control, and normal growth in infants with PKU. The long-term efficacy of phenylalanine-free infant formula should continue to be observed and monitored.
Validation of the brief Adjustment Disorder New Modules with Australian oncology patients
Authors: Harris Bernadette E. , Rice Kylie , Murray Clara V. , Thorsteinsson Einar B. 
Published: January 2023

Abstract
Background
Evidence suggests that up to 30% of cancer patients may meet the criteria for adjustment disorder. However, no assessment instruments have been validated for use with cancer patients. The Adjustment Disorder New Module (ADNM)-8 and ADNM-4 are brief screening tools for adjustment disorder mapped directly to the new ICD-11 criteria. The aim of this study was to investigate the factor structure and validity of both instruments in an Australian sample of adult oncology patients.

Methods
A total of 405 participants with a cancer diagnosis were recruited online from across Australia. Participants reported cancer-specific information, such as time since diagnosis, treatment stage, cancer stage, type of cancer, and the following questionnaires: 8-item Adjustment Disorder New Module (ADNM-8), the World Health Organisation Well-Being Index (WHO-5), and the short form Depression Anxiety and Stress Scale (DASS-21). The predictiveness of stressors was assessed using multiple regression analysis and the structure of the ADNM-8 and the ADNM-4 was tested using confirmatory factor analysis.

Results
Six previously tested models were examined, and the results suggested a 2-factor structure reflecting the two ICD-11 diagnostic criteria clusters of preoccupation with the stressor and failure to adapt was a good fit for both scales. The ADNM-4 outperformed the longer version of the scale on numerous fit indices though the ADNM-8 and ADNM-4 were highly correlated. Correlations of both scales with the psychological distress scale, the stress subscale, and the wellbeing index indicated good construct validity.

Conclusions
Our results suggest that the ADNM-8 and ADNM-4 are useful screening tools for assessing adjustment disorder symptoms in cancer patients. The prompt screening of cancer patients encourages early intervention for those at risk of adaptation difficulties and informs research and clinical decisions regarding appropriate treatments.
β-actin mediated H3K27ac changes demonstrate the link between compartment switching and enhancer-dependent transcriptional regulation
Authors: Mahmood Syed Raza , Said Nadine Hosny El , Gunsalus Kristin C. , Percipalle Piergiorgio 
Published: January 2023

Abstract
Background
Recent work has demonstrated that three-dimensional genome organization is directly affected by changes in the levels of nuclear cytoskeletal proteins such as β-actin. The mechanisms which translate changes in 3D genome structure into changes in transcription, however, are not fully understood. Here, we use a comprehensive genomic analysis of cells lacking nuclear β-actin to investigate the mechanistic links between compartment organization, enhancer activity, and gene expression.

Results
Using HiC-Seq, ATAC-Seq, and RNA-Seq, we first demonstrate that transcriptional and chromatin accessibility changes observed upon β-actin loss are highly enriched in compartment-switching regions. Accessibility changes within compartment switching genes, however, are mainly observed in non-promoter regions which potentially represent distal regulatory elements. Our results also show that β-actin loss induces widespread accumulation of the enhancer-specific epigenetic mark H3K27ac. Using the ABC model of enhancer annotation, we then establish that these epigenetic changes have a direct impact on enhancer activity and underlie transcriptional changes observed upon compartment switching. A complementary analysis of fibroblasts undergoing reprogramming into pluripotent stem cells further confirms that this relationship between compartment switching and enhancer-dependent transcriptional change is not specific to β-actin knockout cells but represents a general mechanism linking compartment-level genome organization to gene expression.

Conclusions
We demonstrate that enhancer-dependent transcriptional regulation plays a crucial role in driving gene expression changes observed upon compartment-switching. Our results also reveal a novel function of nuclear β-actin in regulating enhancer function by influencing H3K27 acetylation levels.
Plasmodium malariae contributes to high levels of malaria transmission in a forest–savannah transition area in Cameroon
Authors: Nguiffo-Nguete Daniel , Nongley Nkemngo Francis , Ndo Cyrille , Agbor Jean-Pierre , Boussougou-Sambe Stravensky T. , Salako Djogbénou Luc , Ntoumi Francine , Adegnika Ayôla A. , Borrmann Steffen , Wondji Charles S. 
Published: January 2023

Abstract
Background
Malaria control efforts are highly skewed towards Plasmodium falciparum while overlooking other Plasmodium species such as P. malariae. A better understanding of the role of Plasmodium species other than P. falciparum is needed to strengthen malaria elimination initiatives. The aim of the present study was to elucidate the contribution of P. malariae to malaria transmission in Cameroon.

Methods
The study was conducted in the Ngatti Health District, a forest–savannah transition area in the Adamawa Region, Cameroon. A total of 497 individuals aged from 1 to 85 years were diagnosed with malaria in November 2020 using a rapid diagnostic test (RDT) and microscopy. Adult mosquitoes were collected between September 2019 and March 2020 by indoor aspiration and identified morphologically and molecularly. The infection status of Plasmodium spp. was also determined by quantitative PCR, and dried blood spots were collected from 156 participants with the aim to detect different Plasmodium species by nested PCR.

Results
The overall Plasmodium prevalence was 50.3%, 51.8% and 64.7%, as detected by microscopy, the RDT and PCR, respectively. Based on the PCR results, P. falciparum was the most prevalent species (43%); followed by co-infections P. falciparum/P. malariae (17%), P. falciparum/P. ovale (1.3%), P. falciparum/P. ovale/P. malariae (1.3%); and then by P. malariae mono-infection (2.5%). The same trend was observed using microscopy, with 35% of participants infected with P. falciparum, 11% co-infected with P. falciparum/P. malariae and 4% infected with P. malariae. The prevalence and parasite density of malaria infection varied significantly with age group (P < 0.05), with the highest prevalence rate observed in children aged 6–10 years (P = 0.0001) while the density of Plasmodium infection increased significantly in children aged < 5 years compared to the other age groups (P = 10−3). Among the 757 Anopheles mosquitoes collected, 737 (97.35%) were An. funestus sensu stricto, 15 (1.9%) were An. gambiae and 5 (0.6%) were An. hancocki. The Plasmodium species recorded at the head/thorax level were P. falciparum and P. malariae, with a sporozoite infection rate of 8.4%; the highest sporozoite infection rate was recorded at Mibellon village (13.6%).

Conclusion
The results of this study reveal the significant contribution of P. malariae, in addition to P. falciparum, to the high malaria transmission rate in this region. These findings highlight the need to deploy initiatives to also tackle this Plasmodium species to eliminate malaria in the region.

Graphical Abstract
Dynamic changes in whole genome DNA methylation, chromatin and gene expression during mouse lens differentiation
Authors: Chang William , Zhao Yilin , Rayêe Danielle , Xie Qing , Suzuki Masako , Zheng Deyou , Cvekl Ales 
Published: January 2023

Abstract
Background
Cellular differentiation is marked by temporally and spatially coordinated gene expression regulated at multiple levels. DNA methylation represents a universal mechanism to control chromatin organization and its accessibility. Cytosine methylation of CpG dinucleotides regulates binding of methylation-sensitive DNA-binding transcription factors within regulatory regions of transcription, including promoters and distal enhancers. Ocular lens differentiation represents an advantageous model system to examine these processes as lens comprises only two cell types, the proliferating lens epithelium and postmitotic lens fiber cells all originating from the epithelium.

Results
Using whole genome bisulfite sequencing (WGBS) and microdissected lenses, we investigated dynamics of DNA methylation and chromatin changes during mouse lens fiber and epithelium differentiation between embryos (E14.5) and newborns (P0.5). Histone H3.3 variant chromatin landscapes were also generated for both P0.5 lens epithelium and fibers by chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq). Tissue-specific features of DNA methylation patterns are demonstrated via comparative studies with embryonic stem (ES) cells and neural progenitor cells (NPCs) at Nanog, Pou5f1, Sox2, Pax6 and Six3 loci. Comparisons with ATAC-seq and RNA-seq data demonstrate that reduced methylation is associated with increased expression of fiber cell abundant genes, including crystallins, intermediate filament (Bfsp1 and Bfsp2) and gap junction proteins (Gja3 and Gja8), marked by high levels of histone H3.3 within their transcribed regions. Interestingly, Pax6-binding sites exhibited predominantly DNA hypomethylation in lens chromatin. In vitro binding of Pax6 proteins showed Pax6’s ability to interact with sites containing one or two methylated CpG dinucleotides.

Conclusions
Our study has generated the first data on methylation changes between two different stages of mammalian lens development and linked these data with chromatin accessibility maps, presence of histone H3.3 and gene expression. Reduced DNA methylation correlates with expression of important genes involved in lens morphogenesis and lens fiber cell differentiation.
Extraction and surface modification of cellulose fibers and its reinforcement in starch-based film for packaging composites
Authors: Hafid Halimatun Saadiah , Omar Farah Nadia , Bahrin Ezyana Kamal , Wakisaka Minato 
Published: January 2023

Abstract
Background
Cellulose extraction from gloss art paper (GAP) waste is a recycling strategy for the abundance of gloss art paper waste. Here, a study was conducted on the impact of ultrasonic homogenization for cellulose extraction from GAP waste to improve the particle size, crystallinity, and thermal stability.

Results
At treatment temperature of 75.8 °C, ultrasonic power level of 70.3% and 1.4 h duration, cellulose with properties of 516.4 nm particle size, 71.5% crystallinity, and thermal stability of 355.2 °C were extracted. Surface modification of cellulose GAP waste with H3PO4 hydrolysis and 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO) oxidation was done followed by starch reinforcement. Surface hydrophobicity and mechanical strength were increased for H3PO4 hydrolysis and TEMPO oxidation starch–cellulose. No reduction of thermal properties observed during the treatment, while increment of crystallinity index up to 47.65–59.6% was shown. Neat starch film was more transparent, followed by starch–TEMPO film and starch–H3PO4 film, due to better homogeneity.

Conclusions
The cellulose GAP reinforced starch film shows potential in developing packaging materials and simultaneously provide an alternative solution of GAP waste recycling.

Graphical Abstract
Taking Care of Us© (TCU) study protocol: feasibility and acceptability of a dyadic intervention for couples living with heart failure
Authors: Lyons Karen S. , Whitlatch Carol J. , Vest Amanda R. , Upshaw Jenica N. , Johnson Stacy Hutton , Morelock Jeremiah , Lee Christopher S. 
Published: January 2023

Abstract
Background
There are more than 1 million hospital admissions and 3 million emergency visits for heart failure in the USA annually. Although spouse/partners make substantial contributions to the management of heart failure and experience poor health and high levels of care strain, they are rarely the focus of heart failure interventions. This protocol describes a pilot randomized controlled trial that tests the feasibility, acceptability, and preliminary change in outcomes of a seven-session couple-based intervention called Taking Care of Us© (TCU). The TCU© intervention is grounded in the theory of dyadic illness management and was developed to promote collaborative illness management and better physical and mental health of adults with heart failure and their partners.

Methods
A two-arm randomized controlled trial will be conducted. Eligible adults with heart failure and their co-residing spouse/partner will be recruited from a clinical site in the USA and community/social media outreach and randomized to either the TCU© intervention or to a control condition (SUPPORT©) that offers education around heart failure management. The target sample is 60 couples (30 per arm). TCU© couples will receive seven sessions over 2 months via Zoom; SUPPORT© couples will receive three sessions over 2 months via Zoom. All participants will complete self-report measures at baseline (T1), post-treatment (T2), and 3 months post-treatment (T3). Acceptability and feasibility of the intervention will be examined using both closed-ended and open-ended questions as well as enrollment, retention, completion, and satisfaction metrics. Preliminary exploration of change in outcomes of TCU© on dyadic health, dyadic appraisal, and collaborative management will also be conducted.

Discussion
Theoretically driven, evidence-based dyadic interventions are needed to optimize the health of both members of the couple living with heart failure. Results from this study will provide important information about recruitment and retention and benefits and drawbacks of the TCU© program to directly inform any needed refinements of the program and decision to move to a main trial.

Trial registration
ClinicalTrials.gov (NCT04737759) registered on 27 January 2021.
Identification of the prognostic value of Th1/Th2 ratio and a novel prognostic signature in basal-like breast cancer
Authors: Xiao Yu , Huang Yi , Jiang Jianping , Chen Yan , Wei Changyuan 
Published: January 2023

Abstract
Background

Breast cancer is a heterogeneous group of diseases. The polarization of CD4+ T helper (Th) lymphocytes (mainly Th1 and Th2) may differ in breast cancers with different outcomes, but this has not been fully validated.

Methods
This study is a bioinformatic analysis, in which differentially expressed genes (DEGs) were identified in patients with low and high Th1/Th2 ratios. And then, DEG functions, hub genes and independent predictors were determined.

Results
Low Th1/Th2 ratio was associated with poor outcome in Luminal A and basal-like breast cancer (p < 0.05). GSEA and KEGG analysis of DEGs obtained from comparing low and high Th1/Th2 ratios illuminated downregulation of immune-related gene sets and pathways affecting Th1/Th2 balance toward Th2 polarization (p < 0.05). Survival and Cox analyses of all the DEGs confirmed CCL1 and MYH6 were independent protective factors and IFNK and SOAT2 were independent risk factors for basal-like breast cancer (95%CI: 1.06–2.5, p = 0.026). Then a four-gene signature was constructed and achieved a promising prognostic value (C-index = 0.82; AUC = 0.826).

Conclusions
Low Th1/Th2 ratio predicts poor outcome in Luminal A and Basal-like breast cancer, and downregulation of immune-related gene sets and pathways contribute to Th1/Th2 balance toward Th2 polarization. CCL1, MYH6, IFNK, and SOAT2 have an independent prognostic value of survival outcome and might be novel markers in basal-like breast cancer.