bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth and tolerance of healthy, term infants fed lower protein extensively hydrolyzed or amino acid-based formula: double-blind, randomized, controlled trial
Authors: Adams Craig B. , Johnston William H. , Deulofeut Harold , Leader Joseph , Rhodes Robbie , Yeiser Michael , Harris Cheryl L. , Wampler Jennifer L. , Hill Rebecca J. , Cooper Timothy 
Published: July 2021

Abstract
Background
Optimal protein level in hypoallergenic infant formulas is an area of ongoing investigation. The aim was to evaluate growth of healthy term infants who received extensively hydrolyzed (EH) or amino acid (AA)-based formulas with reduced protein.

Methods
In this prospective, multi-center, double-blind, controlled, parallel group study, infants were randomized to receive a marketed EH casein infant formula at 2.8 g protein/100 kcal (Control) or one of two investigational formulas: EH casein formula at 2.4 g protein/100 kcal (EHF) or AA-based formula at 2.4 g total protein equivalents/100 kcal (AAF). Control and EHF each had 2 × 107 CFU Lactobacillus rhamnosus GG/100 kcal. Anthropometrics were measured and recall of formula intake, tolerance, and stool characteristics was collected at 14, 30, 60, 90, 120 days of age. Primary outcome was weight growth rate (g/day) between 14 and 120 days of age (analyzed by ANOVA). Medically confirmed adverse events were recorded throughout the study.

Results
No group differences in weight or length growth rate from 14 to 120 days were detected. With the exception of significant differences at several study time points for males, no group differences were detected in mean head circumference growth rates. However, mean achieved weight, length, and head circumference demonstrated normal growth throughout the study period. No group differences in achieved weight or length (males and females) and head circumference (females) were detected and means were within the WHO growth 25th and 75th percentiles from 14 to 120 days of age. With the exception of Day 90, there were no statistically significant group differences in achieved head circumference for males; means remained between the WHO 50th and 75th percentiles for growth at Days 14, 30, and 60 and continued along the 75th percentile through Day 120. No differences in study discontinuation due to formula were detected. The number of participants for whom at least one adverse event was reported was similar among groups.

Conclusions
This study demonstrated hypoallergenic infant formulas at 2.4 g protein/100 kcal were safe, well-tolerated, and associated with appropriate growth in healthy term infants from 14 to 120 days of age.

Trial registration
ClinicalTrials.gov, ClinicalTrials.gov Identifier: NCT01354366. Registered 13 May 2011.
Neonatal mortality prediction with routinely collected data: a machine learning approach
Authors: Batista André F. M. , Diniz Carmen S. G. , Bonilha Eliana A. , Kawachi Ichiro , Chiavegatto Filho Alexandre D. P. 
Published: July 2021

Abstract
Background
Recent decreases in neonatal mortality have been slower than expected for most countries. This study aims to predict the risk of neonatal mortality using only data routinely available from birth records in the largest city of the Americas.

Methods
A probabilistic linkage of every birth record occurring in the municipality of São Paulo, Brazil, between 2012 e 2017 was performed with the death records from 2012 to 2018 (1,202,843 births and 447,687 deaths), and a total of 7282 neonatal deaths were identified (a neonatal mortality rate of 6.46 per 1000 live births). Births from 2012 and 2016 (N = 941,308; or 83.44% of the total) were used to train five different machine learning algorithms, while births occurring in 2017 (N = 186,854; or 16.56% of the total) were used to test their predictive performance on new unseen data.

Results
The best performance was obtained by the extreme gradient boosting trees (XGBoost) algorithm, with a very high AUC of 0.97 and F1-score of 0.55. The 5% births with the highest predicted risk of neonatal death included more than 90% of the actual neonatal deaths. On the other hand, there were no deaths among the 5% births with the lowest predicted risk. There were no significant differences in predictive performance for vulnerable subgroups. The use of a smaller number of variables (WHO’s five minimum perinatal indicators) decreased overall performance but the results still remained high (AUC of 0.91). With the addition of only three more variables, we achieved the same predictive performance (AUC of 0.97) as using all the 23 variables originally available from the Brazilian birth records.

Conclusion
Machine learning algorithms were able to identify with very high predictive performance the neonatal mortality risk of newborns using only routinely collected data.
Delaying sexual onset: outcome of a comprehensive sexuality education initiative for adolescents in public schools
Authors: Ramírez-Villalobos Dolores , Monterubio-Flores Eric Alejandro , Gonzalez-Vazquez Tonatiuh Tomás , Molina-Rodríguez Juan Francisco , Ruelas-González Ma. Guadalupe , Alcalde-Rabanal Jacqueline Elizabeth 
Published: July 2021

Abstract
Background
A common risk behavior in adolescence is the early initiation of unprotected sex that exposes adolescents to an unplanned pregnancy or sexually transmitted infections. Schools are an ideal place to strengthen adolescents’ sexual knowledge and modify their behavior, guiding them to exercise responsible sexuality. The purpose of this article was to evaluate the knowledge of public secondary school teachers who received training in comprehensive education in sexuality (CES) and estimate the counseling’s effect on students’ sexual behavior.

Methods
Seventy-five public school teachers were trained in participatory and innovative techniques for CES. The change in teacher knowledge (n = 75) was assessed before and after the training using t-tests, Wilcoxon ranks tests and a Generalized Estimate Equation model. The students’ sexual and reproductive behavior was evaluated in intervention (n = 650) and comparison schools (n = 555). We fit a logistic regression model using the students’ sexual debut as a dependent variable.

Results
Teachers increased their knowledge of sexuality after training from 5.3 to 6.1 (p < 0.01). 83.3% of students in the intervention school reported using a contraceptive method in their last sexual relation, while 58.3% did so in the comparison schools. The students in comparison schools were 4.7 (p < 0.01) times more likely to start sexual initiation than students in the intervention schools.

Conclusion
Training in CES improved teachers’ knowledge about sexual and reproductive health. Students who received counseling from teachers who were trained in participatory and innovative techniques for CES used more contraceptive protection and delayed sexual debut.
A cross-sectional survey assessing the influence of theoretically informed behavioural factors on hand hygiene across seven countries during the COVID-19 pandemic
Authors: Schmidtke K. A. , Drinkwater K. G. 
Published: July 2021

Abstract
Background
Human hygiene behaviours influence the transmission of infectious diseases. Changing maladaptive hygiene habits has the potential to improve public health. Parents and teachers can play an important role in disinfecting surface areas and in helping children develop healthful handwashing habits. The current study aims to inform a future intervention that will help parents and teachers take up this role using a theoretically and empirically informed behaviour change model called the Capabilities-Opportunities-Motivations-Behaviour (COM-B) model.

Methods
A cross-sectional online survey was designed to measure participants’ capabilities, opportunities, and motivations to [1] increase their children’s handwashing with soap and [2] increase their cleaning of surface areas. Additional items captured how often participants believed their children washed their hands. The final survey was administered early in the coronavirus pandemic (May and June 2020) to 3975 participants from Australia, China, India, Indonesia, Saudi Arabia, South Africa, and the United Kingdom. Participants self-identified as mums, dads, or teachers of children 5 to 10 years old. ANOVAs analyses were used to compare participant capabilities, opportunities, and motivations across countries for handwashing and surface disinfecting. Multiple regressions analyses were conducted for each country to assess the predictive relationship between the COM-B components and children’s handwashing.

Results
The ANOVA analyses revealed that India had the lowest levels of capability, opportunity, and motivation, for both hand hygiene and surface cleaning. The regression analyses revealed that for Australia, Indonesia, and South Africa, the capability component was the only significant predictor of children’s handwashing. For India, capability and opportunity were significant. For the United Kingdom, capability and motivation were significant. Lastly, for Saudi Arabia all components were significant.

Conclusions
The discussion explores how the Behaviour Change Wheel methodology could be used to guide further intervention development with community stakeholders in each country. Of the countries assessed, India offers the greatest room for improvement, and behaviour change techniques that influence people’s capability and opportunities should be prioritised there.
Environmental assessment of pediatric Lead exposure in Tehran; a prospective cross-sectional study
Authors: Ahangar Hedieh , Karimdoost Afsoon , Salimi Amir , Akhgari Maryam , Phillips Scott , Zamani Nasim , Hassanpour Nasibeh , Kolahi Ali-Asghar , Krieger Gary R. , Hassanian-Moghaddam Hossein 
Published: July 2021

Abstract
Background
Ingestion and inhalation are common routes of exposure for lead in humans. Developing countries still have unacceptably high rates of lead toxicity, especially in children. Studies on probable risk factors of lead poisoning in Iranian children are insufficient. In this study, we aimed to evaluate possible environmental factors in children with high blood lead concentrations living in Tehran and neighboring cities.

Methods
In a prospective cross-sectional study between March 2018 and March 2019 we followed all children referred from two pediatric gastrointestinal clinics with blood lead level (BLL) > 5 μg/dL in metropolitan Tehran to investigate possible environmental risk factors in their home. Household specimens including scratched wall paint, house floor dust, windowsill dust, tap water, and consumed spice were evaluated using atomic absorption method to detect lead concentrations. Epidemiological and environmental data collected through in-depth interviews with parents/guardians. Industrial areas were defined based on municipality maps on industrial places.

Results
Thirty of 56 parents/guardians with BLL > 5 μg/dL agreed to be followed through environmental investigation. The only categorical statistically significant risk factor was a history of lead poisoning in the family and living in an industrial zone. There was a positive correlation between BLL and interior windowsills dust lead level, r = 0.46, p = 0.01. Scratched paint lead level and BLL showed a significant positive correlation, r = 0.50, p = 0.005. House floor dust lead level (median = 77.4, p < 0.001) and interior windowsill dust lead level (median = 291, p = 0.011) were both significantly higher than the environmental protection agency (EPA) standards of 40 μg/ft2, 250 μg/ft2. Interior windowsill dust lead concentrations were significantly higher in industrial areas (p = 0.026).

Conclusion
Children’s playing environment should be cleaned more often to reduce dust. Moreover, specific rules may need to be implemented for paint lead concentrations and air pollution, especially in industrial areas.
Beliefs and barriers associated with COVID-19 vaccination among the general population in Saudi Arabia
Authors: Magadmi Rania M. , Kamel Fatemah O. 
Published: July 2021

Abstract
Background
Developing a vaccine against COVID-19 is considered a key strategy to end the pandemic. However, public acceptance is reliant on beliefs and perception toward the vaccine. Therefore, the study aimed to assess the beliefs and barriers associated with COVID-19 vaccination among the Saudi population.

Methods
An online self-administered questionnaire was distributed across the main regions of Saudi Arabia on May 2020. The questionnaire addressed the socio-demographic variables, beliefs toward COVID-19 vaccination, and potential barriers that may prevent participants from being vaccinated. The association between COVID-19 vaccine acceptance and sociodemographic variables were analyzed. Logistic regression analysis was used to identify the predicting variables of vaccine acceptance.

Results
Out of 3101 participants, 44.7% were accepting of COVID-19 vaccination if available, whereas 55.3% admitted hesitancy. Younger, male, who received seasonal influenza vaccine were more likely to accept taking the vaccine. The study found that concerns about side effects were the key barrier for vaccine acceptance. Furthermore, the majority of refusers may accept the vaccine if additional studies confirmed safety and effectiveness.

Conclusion
Results can be utilized in planning vaccination campaigns while waiting for vaccine development.
Exposure–safety analyses of nintedanib in patients with chronic fibrosing interstitial lung disease
Authors: Schmid Ulrike , Weber Benjamin , Sarr Celine , Freiwald Matthias 
Published: July 2021

Abstract
Background
Nintedanib reduces the rate of decline in forced vital capacity in patients with idiopathic pulmonary fibrosis (IPF), other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype and systemic sclerosis-associated ILD (SSc-ILD). The recommended dose of nintedanib is 150 mg twice daily (BID).

Methods
Data from Phase II and III trials in IPF and Phase III trials in SSc-ILD and progressive fibrosing ILDs other than IPF were analyzed to investigate the relationship between nintedanib plasma concentrations (exposure) and safety (liver enzyme elevations [defined as transaminase elevations equal or greater than 3 times the upper limit of normal] and diarrhea).

Results
Using data from 1403 subjects with IPF treated with 50–150 mg nintedanib BID, a parametric time-to-first-event model for liver enzyme elevations was established. Besides exposure, gender was a significant covariate, with a three–fourfold higher exposure-adjusted risk in females than males. Subsequent analysis of combined data from IPF, SSc-ILD (n = 576) and progressive fibrosing ILD (n = 663) studies suggested a consistent exposure–liver enzyme elevation relationship across studies. No exposure–diarrhea relationship was found using data from the various fibrosing ILDs, but diarrhea risk was dependent on dose administered.

Conclusions
The positive correlation between exposure and risk of liver enzyme elevations was consistent across nintedanib studies in IPF, SSc-ILD and progressing fibrosing ILDs other than IPF. The effect size does not warrant a priori dose adjustment in patients with altered plasma exposure (excluding hepatic impairment patients, where there are specific labelling recommendations). For diarrhea, dose administered was a better predictor than exposure.
Medical Assistance in Dying in patients with advanced cancer and their caregivers: a mixed methods longitudinal study protocol
Authors: Li Madeline , Shapiro Gilla K. , Klein Roberta , Barbeau Anne , Rydall Anne , Bell Jennifer A. H. , Nissim Rinat , Hales Sarah , Zimmermann Camilla , Wong Rebecca K. S. , Rodin Gary 
Published: July 2021

AbstractBackgroundThe legal criteria for medical assistance in dying (MAiD) for adults with a grievous and irremediable medical condition were established in Canada in 2016. There has been concern that potentially reversible states of depression or demoralization may contribute to the desire for death (DD) and requests for MAiD. However, little is known about the emergence of the DD in patients, its impact on caregivers, and to what extent supportive care interventions affect the DD and requests for MAiD. The present observational study is designed to determine the prevalence, predictors, and experience of the DD, requests for MAiD and MAiD completion in patients with advanced or metastatic cancer and the impact of these outcomes on their primary caregivers.MethodsA cohort of patients with advanced or metastatic solid tumour cancers and their primary caregivers will be recruited from a large tertiary cancer centre in Toronto, Ontario, Canada, to a longitudinal, mixed methods study. Participants will be assessed at baseline for diagnostic information, sociodemographic characteristics, medical history, quality of life, physical and psychological distress, attitudes about the DD and MAiD, communication with physicians, advance care planning, and use of psychosocial and palliative care interventions. Measures will subsequently be completed every six months and at the time of MAiD requests. Quantitative assessments will be supplemented by qualitative interviews in a subset of participants, selected using quota sampling methods.DiscussionThis study has the potential to add importantly to our understanding of the prevalence and determinants of the DD, MAiD requests and completions in patients with advanced or metastatic cancer and of the experience of both patients and caregivers in this circumstance. The findings from this study may also assist healthcare providers in their conversations about MAiD and the DD with patients and caregivers, inform healthcare providers to ensure appropriate access to MAiD, and guide modifications being considered to broaden MAiD legislation and policy.
Evaluating the implementation of a chronic obstructive pulmonary disease management program using the Consolidated Framework for Implementation Research: a case study
Authors: Paciocco Stefan , Kothari Anita , Licskai Christopher J. , Ferrone Madonna , Sibbald Shannon L. 
Published: July 2021

AbstractBackgroundChronic obstructive pulmonary disease (COPD) is a prevalent chronic disease that requires comprehensive approaches to manage; it accounts for a significant portion of Canada’s annual healthcare spending. Interprofessional teams are effective at providing chronic disease management that meets the needs of patients. As part of an ongoing initiative, a COPD management program, the Best Care COPD program was implemented in a primary care setting. The objectives of this research were to determine site-specific factors facilitating or impeding the implementation of a COPD program in a new setting, while evaluating the implementation strategy used.MethodsA qualitative case study was conducted using interviews, focus groups, document analysis, and site visits. Data were deductively analyzed using the Consolidated Framework for Implementation Research (CFIR) to assess the impact of each of its constructs on Best Care COPD program implementation at this site.ResultsEleven CFIR constructs were determined to meaningfully affect implementation. Five were identified as the most influential in the implementation process. Cosmopolitanism (partnerships with other organizations), networks and communication (amongst program providers), engaging (key individuals to participate in program implementation), design quality and packaging (of the program), and reflecting and evaluating (throughout the implementation process). A peer-to-peer implementation strategy included training of registered respiratory therapists (RRT) as certified respiratory educators and the establishment of a communication network among RRTs to discuss experiences, collectively solve problems, and connect with the program lead.ConclusionsThis study provides a practical example of the various factors that facilitated the implementation of the Best Care COPD program. It also demonstrates the potential of using a peer-to-peer implementation strategy. Focusing on these factors will be useful for informing the continued spread and success of the Best Care COPD program and future implementation of other chronic care programs.
Identification of NOTCH4 mutation as a response biomarker for immune checkpoint inhibitor therapy
Authors: Long Junyu , Wang Dongxu , Yang Xu , Wang Anqiang , Lin Yu , Zheng Mingjun , Zhang Haohai , Sang Xinting , Wang Hanping , Hu Ke , Zhao Haitao 
Published: July 2021

Abstract
Background
Immune checkpoint inhibitor (ICI) therapy elicits durable antitumor responses in patients with many types of cancer. Genomic mutations may be used to predict the clinical benefits of ICI therapy. NOTCH homolog-4 (NOTCH4) is frequently mutated in several cancer types, but its role in immunotherapy is still unclear. Our study is the first to study the association between NOTCH4 mutation and the response to ICI therapy.

Methods
We tested the predictive value of NOTCH4 mutation in the discovery cohort, which included non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, esophagogastric cancer, and bladder cancer patients, and validated it in the validation cohort, which included non-small cell lung cancer, melanoma, renal cell carcinoma, colorectal cancer, esophagogastric cancer, glioma, bladder cancer, head and neck cancer, cancer of unknown primary, and breast cancer patients. Then, the relationships between NOTCH4 mutation and intrinsic and extrinsic immune response mechanisms were studied with multiomics data.

Results
We collected an ICI-treated cohort (n = 662) and found that patients with NOTCH4 mutation had better clinical benefits in terms of objective response rate (ORR: 42.9% vs 25.9%, P = 0.007), durable clinical benefit (DCB: 54.0% vs 38.1%, P = 0.021), progression-free survival (PFS, hazard ratio [HR] = 0.558, P < 0.001), and overall survival (OS, HR = 0.568, P = 0.006). In addition, we validated the prognostic value of NOTCH4 mutation in an independent ICI-treated cohort (n = 1423). Based on multiomics data, we found that NOTCH4 mutation is significantly associated with enhanced immunogenicity, including a high tumor mutational burden, the expression of costimulatory molecules, and activation of the antigen-processing machinery, and NOTCH4 mutation positively correlates activated antitumor immunity, including infiltration of diverse immune cells and various immune marker sets.

Conclusions
Our findings indicated that NOTCH4 mutation serves as a novel biomarker correlated with a better response to ICI therapy.