bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a Bayesian hierarchical model for a prospective individual patient data meta-analysis with continuous monitoring
Authors: Wu Danni , Goldfeld Keith S. , Petkova Eva
Published: January 2023

Background

Numerous clinical trials have been initiated to find effective treatments for COVID-19. These trials have often been initiated in regions where the pandemic has already peaked. Consequently, achieving full enrollment in a single trial might require additional COVID-19 surges in the same location over several years. This has inspired us to pool individual patient data (IPD) from ongoing, paused, prematurely-terminated, or completed randomized controlled trials (RCTs) in real-time, to find an effective treatment as quickly as possible in light of the pandemic crisis. However, pooling across trials introduces enormous uncertainties in study design (e.g., the number of RCTs and sample sizes might be unknown in advance). We sought to develop a versatile treatment efficacy assessment model that accounts for these uncertainties while allowing for continuous monitoring throughout the study using Bayesian monitoring techniques.

Methods

We provide a detailed look at the challenges and solutions for model development, describing the process that used extensive simulations to enable us to finalize the analysis plan. This includes establishing prior distribution assumptions, assessing and improving model convergence under different study composition scenarios, and assessing whether we can extend the model to accommodate multi-site RCTs and evaluate heterogeneous treatment effects. In addition, we recognized that we would need to assess our model for goodness-of-fit, so we explored an approach that used posterior predictive checking. Lastly, given the urgency of the research in the context of evolving pandemic, we were committed to frequent monitoring of the data to assess efficacy, and we set Bayesian monitoring rules calibrated for type 1 error rate and power.

Results

The primary outcome is an 11-point ordinal scale. We present the operating characteristics of the proposed cumulative proportional odds model for estimating treatment effectiveness. The model can estimate the treatment’s effect under enormous uncertainties in study design. We investigate to what degree the proportional odds assumption has to be violated to render the model inaccurate. We demonstrate the flexibility of a Bayesian monitoring approach by performing frequent interim analyses without increasing the probability of erroneous conclusions.

Conclusion

This paper describes a translatable framework using simulation to support the design of prospective IPD meta-analyses.
A clinicopathological study and survival analysis of 99 breast cancers with HER2/CEP17 ratio ≥ 2.0 and an average HER2 copy number < 4.0 per cell in China
Authors: Zhou Shuling , Lv Hong , Li Anqi , Li Ming , Zhong Siyuan , Lu Hongfen , Zhou Xiaoyan , Bai Qianming , Yang Wentao
Published: January 2023

Background

Breast cancer patients of American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) Group 2 were all HER2-negative according to the 2018 guideline, not HER2-positive as defined in the 2013 guideline.

Methods

We aims to elucidate the unique clinicopathological features of ASCO/CAP Group 2 patients by comparing with classic HER2-nonamplified cancers, and reveal the efficacy of the former to anti-HER2 therapy. The clinicopathological features, treatment and prognosis information of 99 patients between 2014 and 2018 were collected. HER2 status was re-defined using the updated recommendations.

Results

Of the 99 ASCO/CAP Group 2 tumors, 25.5% (25/99) tumors were immunohistochemical (IHC) 0/1+ and 74.7% (74/99) tumors were IHC 2+. According to the updated 2018 guideline, all of them were HER2 negative. When compared to ASCO/CAP Group 5, patients of ASCO/CAP Group 2 displayed higher ratio of histological grade 3 (P = .03), high Ki67 proliferation index (P = .03) and pN3 (more than 9 lymph nodes metastasis, P = .02), and lower estrogen receptor (ER) positivity (P = .04). There was no statistical difference in the survival of patients received anti-HER2 therapy and patients not received anti-HER2 therapy.

Conclusions

Patients of ASCO/CAP Group 2 did not received apparent benefit from anti-HER2 treatment. Although according to the updated guidelines and latest reports, HER2 is negative, but when compared with classic HER2-nonamplified cancers, patients of this group seemed to be more aggressive. We suggest that this group still be regarded as an independent category, in order to accumulate more cases in the future to expand the scope of research.
Active cycle of breathing technique versus oscillating PEP therapy versus walking with huffing during an acute exacerbation of bronchiectasis: a randomised, controlled trial protocol
Authors: Phillips Jennifer , Hing Wayne , Pope Rodney , Canov Ashleigh , Harley Nicole , Lee Annemarie L.
Published: January 2023

Background

Airway clearance techniques (ACTs) for individuals with bronchiectasis are routinely prescribed in clinical practice and recommended by international guidelines, especially during an acute exacerbation. However, there is limited evidence of the efficacy of these techniques during an exacerbation to improve sputum expectoration, health-related quality-of-life (HRQOL) or exercise tolerance. The primary aim of this study is to compare the effects of the active cycle of breathing technique (ACBT), oscillating positive expiratory pressure (O-PEP) therapy, and walking with huffing on sputum expectoration for adults hospitalised with an acute exacerbation of bronchiectasis. Secondary aims are to compare the effects of these interventions on HRQOL, health status, exacerbation rates and hospital admissions in a six-month period following hospital discharge.

Methods

This multi-centre randomised controlled trial will recruit adults with an acute exacerbation of bronchiectasis requiring hospital admission. Participants will be randomised to receive one of three interventions: ACBT, O-PEP therapy, and walking with huffing. Outcome measures including sputum volume during and 1-h post ACT session, and 24-h sputum, as well as health status, HRQOL and exercise capacity will be completed during inpatient stay on day 2 and day 6 of admission, and within 24 h of hospital discharge. Time to first exacerbation, and time to first hospitalisation will be monitored via monthly phone calls for six months post hospital discharge. Health status and HRQOL will be assessed after discharge at two and six months, and exercise capacity will be assessed at six months post hospital discharge.

Discussion

Despite recommendations regarding the importance of ACT for individuals with bronchiectasis during an acute exacerbation, there is a gap in the literature regarding effectiveness of ACT when undertaken by individuals in this clinical state. This study will add to the evidence base regarding the effectiveness of commonly implemented ACTs during a hospital admission with an exacerbation of bronchiectasis. Additionally, it will contribute to knowledge of the long term effects on important and patient-centred outcomes, including incidence of future exacerbations, and HRQOL, which has not been previously established.

Trial registrationRegistered on the Australian and New Zealand Clinical Trials Registry (ACTRN12621000428864).
Assessment of oral health status and related factors in adolescents aged 12–15 years in the Gansu Province of China: a cross-sectional survey
Authors: Zhang Zhidong , Wang Di , Zhao Jian , Wang Dandan , Zhang Baoping
Published: January 2023

Background

The national oral epidemiological survey conducted every decade has become an indispensable means of detecting changes in oral disease patterns. This study was undertaken to investigate the oral health status and related factors in 12–15-year-old students in Gansu, China.

Methods

According to the methodology adopted by the Fourth National Oral Health Survey, a multi-stage, stratified, random sampling method was used to select 3871 adolescents aged 12–15 years from four regions of Gansu Province for oral examination and questionnaire survey. Caries experience was measured using the Decayed, Missing, and Filled Teeth (DMFT) index; and periodontal health examination included gingival bleeding, calculus, periodontal pockets and attachment loss. The questionnaire included questions regarding sociodemographic characteristics, and oral health knowledge and behaviors. SPSS20.0 software was used for statistical analysis of the survey data.

Results

The mean DMFT index was 0.83 ± 1.42. The prevalence of caries experience was 38.6%, filling rate was 1.6%, and pit and fissure sealing rate was 0.5%. Logistic regression analysis showed that female sex, rural district, older age, non-only child, frequency of dental visits, and toothache experience were the risk factors for caries experience, with OR ranging between 1.280 and 3.831 (p < 0.05). Prevalence of healthy periodontium was 29.8%. Female sex, rural district, and younger age were found to be the protective factors for healthy periodontium, with OR ranging between 1.178 and 1.414 (p < 0.05).

Conclusions

Adolescents in Gansu Province had high prevalence of caries experience along with low filling rate, and low prevalence of healthy periodontium. Therefore, it is necessary to vigorously strengthen oral health education, disease prevention and control programs in the province. This would help improve the oral health-related quality of life of these individuals.
A model for design of online health professions education faculty development courses in sub-Saharan Africa
Authors: Keiller L. , Nyoni C. N. , Van Wyk C.
Published: January 2023

The design of faculty development courses requires a contextually aware theoretical foundation. Therefore, the study aimed to determine the feasibility of a specific conjecture map as a model for designing online health professions education faculty development courses in sub-Saharan Africa through a heuristic evaluation approach. The authors hypothesise that using heuristic evaluation strengthens an educational model's theoretical basis and feasibility.

Twenty-five health professions educators from nine sub-Saharan African countries participated in this multi-phased study. In the first phase, the participants completed a survey evaluating the model and the accompanying author-generated heuristics. Then, participants' recommendations were used to make revisions. In the subsequent phase, participants reviewed these revisions and commented on the feasibility of the model within their local context.

All six heuristics were revised following the initial phase, where 80 problems had been identified. Upon revision, the model was deemed feasible by all except one participant. There was a strong relationship and inter-rater agreement of feasibility between 0.84 and 0.95 regarding the model's practicality, demand, acceptability, and adaptability. Revisions to the final model and guidance documents incorporated all changes the participants recommended, confirming the model's feasibility.

Theoretical models are often developed through a top-down approach, omitting the practice-based considerations that could change the formulation of the model. This study demonstrates the convergence of a theoretical and process model with theoretical, expert and end-user data triangulation. Further research is needed to test this empirically developed model.
The psychiatric mental health nurse’s ethical considerations regarding the use of coercive measures – a qualitative interview study
Authors: Manderius Charlotta , Clintståhl Kristofer , Sjöström Karin , Örmon Karin
Published: January 2023

Background

In psychiatric inpatient care, situations arise where it may be necessary to use coercive measures and thereby restrict individual autonomy. The ethical principles of healthcare, i.e., respect for autonomy, beneficence, nonmaleficence, and justice, are recognized as central aspects in healthcare practice, and nurses must be clear about which ethical theories and principles to prioritize and what values are needed for a thorough ethical consideration. The aim of this study is to shed light on psychiatric mental health nurses’ ethical considerations and on the factors influencing them when performing coercive measures.

Methods

This qualitative interview study included twelve psychiatric mental health nurses with experience from psychiatric inpatient care. A content analysis was made. The interviews were audio recorded and transcribed verbatim, and categories were formulated.

Results

The study revealed a duality that created two categories: Ethical considerations that promote the patient’s autonomy and health and Obstacles to ethical considerations. Based on this duality, ethical considerations were made when performing coercive measures to alleviate suffering and promote health. The result shows a high level of ethical awareness in clinical work. However, a request emerged for more theoretical knowledge about ethical concepts that could be implemented among the staff.

Conclusion

The psychiatric mental health nurses in this study strive to do what is best for the patient, to respect the patient’s autonomy as a guiding principle in all ethical considerations, and to avoid coercive measures. An organizational ethical awareness could increase the understanding of the difficult ethical considerations that nurses face with regard to minimizing the use of coercive measures in the long run.
Patient attitudes and beliefs associated with self-referral to physical therapy for musculoskeletal complaints: a qualitative study
Authors: Alshareef Noor , Cozad Melanie , Macauda Mark , Ostermann Jan , Thigpen Charles
Published: January 2023

Background

Non-pharmacologic treatments such as physical therapy (PT) are advocated for musculoskeletal pain. Early access to PT through self-referral has been shown to decrease costs and improve outcomes. Although self-referral is permitted in most U.S. states and supported by some health insurance plans, patients’ utilization of self-referral remains low.

Objective

To identify factors, beyond legislative policies and health insurance, associated with patients’ decisions to access physical therapy through self-referral or provider-referral.

Methods

We recruited 26 females and 6 males whose employer-sponsored insurance benefits included financial incentives for self-referral to physical therapy. Between August 2017 and March 2018, participants completed semi-structured interviews about their beliefs about physical therapy and reasons for choosing self-referral (15 participants) or provider referral (17 participants) for accessing physical therapy. Grounded theory approach was employed to identify themes in the data.

Results

Patients selecting self-referral reported major thematic differences compared to the provider-referral patients including knowledge of the direct access program, attitudes and beliefs about physical therapy and pharmacologic treatment, and prior experiences with physical therapy. Self-referral patients were aware that their plan benefits included reduced cost for self-referral and felt confident in selecting that pathway. They also had negative beliefs about the effectiveness of pharmacological treatments and surgery, and previously had positive direct or indirect experiences with physical therapy.

Conclusion

Knowledge of the ability to self-refer, attitudes and beliefs about treatment, and prior experience with physical therapy were associated with self-referral to physical therapy. Interventions aimed at improving knowledge and changing attitudes toward self-referral to physical therapy to increase utilization appear warranted.
Policy analysis of nutrition stewardship for prevention and control of Non-communicable diseases in Iran
Authors: Amerzadeh Mohammad , Takian Amirhossein , Pouraram Hamed , Sari Ali Akbari , Ostovar Afshin
Published: January 2023

Background

Non- communicable diseases (NCDs) are the main cause of death, which lead to over 73% of death and 62% of DALYs globally. As an unhealthy diet is the leading behavioral risk factor of NCDs, in line with the national action plan for the prevention and control of NCD, this study explored the nutrition-related stewardship problems to reduce the burden of NCDs in Iran.

Methods

This is a qualitative study. We interviewed 30 purposefully identified key informants, i.e., stakeholders, policymakers, and academics, from December 2018 to August 2019. All interviews were recorded and transcribed verbatim. We analyzed data using qualitative content analysis facilitated by MAXQDA 11 software.

Results

Ample policies and laws were identified, most of which were not or partially implemented. Despite some plausible efforts, NCDs do not seem to be a top priority for high-level managers and decision-makers. Besides, the role of non-state actors, i.e., the private sector, is marginal in NCD’s planning and management. Whereas the government, e.g., the Food and Drug Organization (FDO), is the biggest player. Worse still, many harmful products are advertised and easily distributed across the country.

Conclusion

Iran’s government has created a noticeable roadmap to battle NCDs despite imposing many sanctions and related socioeconomic problems. Nevertheless, more interventions are needed to strengthen the stewardship of NCDs by various stakeholders. We recommend the government to monitor the implementation of policies and advertisement of harmful products to prioritize prevention and control of NCDs. In addition, we advocate employing the capacity of non-state actors to reduce the consumption of unhealthy food and the burden of NCDs across the country, ultimately.
Molecular and serological investigation of Hepatitis E virus in pigs slaughtered in Northwestern Italy
Authors: Carella Emanuele , Oberto Francesca , Romano Angelo , Peletto Simone , Vitale Nicoletta , Costa Annalisa , Caruso Claudio , Chiavacci Laura , Acutis Pier Luigi , Pite Ledi , Masoero Loretta
Published: January 2023

Background

Hepatitis E Virus (HEV) is recently considered an emerging public health concern. HEV genotypes 1 and 2 are widely distributed and pathogenic only for humans. In contrast, HEV, genotypes 3 and 4 are observed in swine, deer, wild boars and rabbits and can also be transmitted to humans. The presence of HEV in the liver, muscle, faeces, blood, and bile was detected by real-time RT-PCR in 156 pigs belonging to twenty different farms, ranging from 1 to 8 months of age. The phylogenetic analysis was performed on the viral strain present in the positive biological matrix, with the lowest Ct. HEV-IgG and HEV-IgM in the sera were analysed by two different ELISA kits.

Results

Twenty-one pigs, i.e., 13.46% of them (21/156, 95% CI: 8.53%-19.84%), tested positive for HEV in at least one biological matrix by real-time RT-PCR, while phylogenetic analysis revealed the presence of HEV subtypes 3f and 3c. Pig serums analysed by ELISA showed an overall prevalence of 26.92% (42/156, 95% CI: 20.14%-34.60%) for HEV-IgG, whereas the 28.95% (33/114, 95% CI: 20.84%-38.19%) of them tested negative resulted positive for the HEV-IgM.

Conclusions

The faeces are the biological matrix with the highest probability of detecting HEV. The best concordance value (Kappa Kohen index) and the highest positive correlation (Phi index) were observed for the correlation between bile and liver, even when the number of positive liver samples was lower than the positive bile samples. This finding may suggest that a higher probability of HEV occurs in the bile, when the virus is present in the liver, during the stages of infection. Finally, the presence of HEV in muscle was observed in 11 pigs, usually used for the preparation of some dishes, typical of the Italian tradition, based on raw or undercooked meat. Therefore, their consumption is a possible source of infection for final consumer.
Airway and parenchyma transcriptomics in a house dust mite model of experimental asthma
Authors: Tu Xiaofan , Gomez Henry M. , Kim Richard Y. , Brown Alexandra C. , de Jong Emma , Galvao Izabela , Faiz Alen , Bosco Anthony , Horvat Jay C. , Hansbro Philip , Donovan Chantal
Published: January 2023

Lung transcriptomics studies in asthma have provided valuable information in the whole lung context, however, deciphering the individual contributions of the airway and parenchyma in disease pathogenesis may expedite the development of novel targeted treatment strategies. In this study, we performed transcriptomics on the airway and parenchyma using a house dust mite (HDM)-induced model of experimental asthma that replicates key features of the human disease. HDM exposure increased the expression of 3,255 genes, of which 212 were uniquely increased in the airways, 856 uniquely increased in the parenchyma, and 2187 commonly increased in both compartments. Further interrogation of these genes using a combination of network and transcription factor enrichment analyses identified several transcription factors that regulate airway and/or parenchymal gene expression, including transcription factor EC (TFEC), transcription factor PU.1 (SPI1), H2.0-like homeobox (HLX), metal response element binding transcription factor-1 (MTF1) and E74-like factor 4 (ets domain transcription factor, ELF4) involved in controlling innate immune responses. We next assessed the effects of inhibiting lung SPI1 responses using commercially available DB1976 and DB2313 on key disease outcomes. We found that both compounds had no protective effects on airway inflammation, however DB2313 (8 mg/kg) decreased mucus secreting cell number, and both DB2313 (1 mg/kg) and DB1976 (2.5 mg/kg and 1 mg/kg) reduced small airway collagen deposition. Significantly, both compounds decreased airway hyperresponsiveness. This study demonstrates that SPI1 is important in HDM-induced experimental asthma and that its pharmacological inhibition reduces HDM-induced airway collagen deposition and hyperresponsiveness.
Responsiveness to pulmonary rehabilitation in COPD is associated with changes in microbiota
Authors: Melo-Dias Sara , Cabral Miguel , Furtado Andreia , Souto-Miranda Sara , Mendes Maria Aurora , Cravo João , Almeida Catarina Rodrigues , Marques Alda , Sousa Ana
Published: January 2023

Background

Pulmonary Rehabilitation (PR) is one of the most cost-effective therapies for chronic obstructive pulmonary disease (COPD) management. There are, however, people who do not respond to PR and reasons for non-response are mostly unknown. PR is likely to change the airway microbiota and this could play a role in its responsiveness. In this study we have explored the association between PR effectiveness and specific alterations in oral microbiota and inflammation.

Methods

A prospective longitudinal study was conducted. Data on exercise capacity, dyspnoea, impact of disease and 418 saliva samples were collected from 76 patients, half of whom participated in a 12-weeks PR programme. Responders and non-responders to PR (dyspnoea, exercise-capacity and impact of disease) were defined based on minimal clinically important differences.

Results

Changes in microbiota, including Prevotella melaninogenica and Streptococcus were observed upon PR. Prevotella, previously found to be depleted in severe COPD, increased during the first month of PR in responders. This increase was negatively correlated with Streptococcus and Lautropia, known to be enriched in severe cases of COPD. Simultaneously, an anti-inflammatory commensal of the respiratory tract, Rothia, correlated strongly and negatively with several pro-inflammatory markers, whose levels were generally boosted by PR. Conversely, in non-responders, the observed decline in Prevotella correlated negatively with Streptococcus and Lautropia whose fluctuations co-occurred with several pro-inflammatory markers.

Conclusions

PR is associated with changes in oral microbiota. Specifically, PR increases salivary Prevotella melaninogenica and avoids the decline in Rothia and the increase in Streptococcus and Lautropia in responders, which may contribute to the benefits of PR.
Prevalence of asymptomatic malaria and associated factors among pregnant women at Boset District in East Shoa Zone, Oromia Region, Ethiopia: a cross-sectional study
Authors: Balcha Fufa , Menna Takele , Lombamo Fantu
Published: January 2023

Background

Malaria infection during pregnancy is a significant public health problem that puts pregnant women at risk. Interruption of transmission of asymptomatic malaria among a population remained a challenge and the host serves as a reservoir for the malaria parasite; and is also recognized as a major barrier to malaria elimination. This study aimed to assess the prevalence of asymptomatic malaria and associated factors among pregnant women in the Boset District, East Shoa Zone, Oromia, Ethiopia.

Methods

A community-based cross-sectional study was conducted to assess the prevalence of asymptomatic malaria and associated factors in pregnant women from February to March 2022. Using multistage sample techniques, 328 asymptomatic pregnant women were enrolled. Data were collected using a structured questionnaire. A rapid test and Giemsa-stained blood smear microscopy were used to diagnose Plasmodium infections. Epi info version 7 was used to code, enter, and clean data before being uploaded to SPSS version 25.0 for analysis. Bivariable and multivariable binary logistic regression were employed to find the associated factors. Variables in the multivariable model with a p-value < 0.05 were considered significantly associated with asymptomatic malaria.

Results

Of the total 328 pregnant women who participated in this study, 9(2.74%) and 10(3.05%) were confirmed to be infected with Plasmodium species by microscopy and rapid diagnostic tests, respectively. Asymptomatic malaria during pregnancy was found to be significantly associated with not using an insecticide-treated bed net [(P = 0.002, AOR: 9.61; 95% CI (2.22–41.53)], lack of consultation and health education about malaria prevention during Antenatal care attendance [(P = 0.04, AOR: 4.05; 95% CI (1.02, 16.05)], and living close stagnant water [(P = 0.02, AOR: 4.43; 95% CI (1.17,16.82)].

Conclusions

The current study showed that asymptomatic malaria is prevalent in pregnant women. Not using insecticide-treated bed nets, inadequate health education during antenatal care, and living close to stagnant water are significantly associated with malaria infection. Thus, using insecticide-treated bed nets, health education, and avoiding stagnant water from residential areas could play significant roles in preventing asymptomatic malaria among pregnant women in the study area.
Adipokine chemerin overexpression in trophoblasts leads to dyslipidemia in pregnant mice: implications for preeclampsia
Authors: Tan Lunbo , Ouyang Zijun , Chen Zhilong , Sun Fen , Guo Haichun , Wang Feng , Mulder Monique , Sun Yuan , Lu Xifeng , Zhang Jian V. , Danser A. H. Jan , Verdonk Koen , Fan Xiujun , Yang Qing
Published: January 2023

Background

The adipokine chemerin regulates adipogenesis and the metabolic function of both adipocytes and liver. Chemerin is elevated in preeclamptic women, and overexpression of chemerin in placental trophoblasts induces preeclampsia-like symptoms in mice. Preeclampsia is known to be accompanied by dyslipidemia, albeit via unknown mechanisms. Here, we hypothesized that chemerin might be a contributor to dyslipidemia.

Methods

Serum lipid fractions as well as lipid-related genes and proteins were determined in pregnant mice with chemerin overexpression in placental trophoblasts and chemerin-overexpressing human trophoblasts. In addition, a phospholipidomics analysis was performed in chemerin-overexpressing trophoblasts.

Results

Overexpression of chemerin in trophoblasts increased the circulating and placental levels of cholesterol rather than triglycerides. It also increased the serum levels of lysophosphatidic acid, high-density lipoprotein cholesterol (HDL-C), and and low-density lipoprotein cholesterol (LDL-C), and induced placental lipid accumulation. Mechanistically, chemerin upregulated the levels of peroxisome proliferator-activated receptor g, fatty acid-binding protein 4, adiponectin, sterol regulatory element-binding protein 1 and 2, and the ratio of phosphorylated extracellular signal-regulated protein kinase (ERK)1/2 / total ERK1/2 in the placenta of mice and human trophoblasts. Furthermore, chemerin overexpression in human trophoblasts increased the production of lysophospholipids and phospholipids, particularly lysophosphatidylethanolamine.

Conclusions

Overexpression of placental chemerin production disrupts trophoblast lipid metabolism, thereby potentially contributing to dyslipidemia in preeclampsia.
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

Background

There 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.

Methods

The 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.

Results

Conditions 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.

Conclusions

The 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

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

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

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

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

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

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

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

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