bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perspectives from primary health care providers on their roles for supporting adolescents and young adults transitioning from pediatric services
Authors: Schraeder Kyleigh , Dimitropoulos Gina , McBrien Kerry , Li Jessica Yijia , Samuel Susan 
Published: July 2020

Abstract
Background
Transitioning from pediatric care to adult-oriented care at age 18 (the age of transfer in most countries and jurisdictions) is a complex process for adolescents and young adults affected by chronic physical health and/or mental health conditions. The role of primary health care (PHC) providers for this population is poorly understood. Perspectives from these providers, such as family physicians and other members of the primary care team, have not been explored in depth.

Methods
A total of 18 participants (e.g., family physicians, social workers, nurses) were recruited from 6 Primary Care Networks in Calgary, Alberta, Canada. Semi-structured individual interviews were conducted, and transcribed verbatim. A qualitative description approach was used to analyze the data, and included thematic analysis.

Results
Five distinct, yet overlapping, roles of primary health care providers for adolescents and young adults transitioning to adult care resulted from our analysis: (1) being the “common thread” (continuous accessible care); (2) caring for the “whole patient” (comprehensive care); (3) “knowing families” (family-partnered care); (4) “empowering” adolescents and young adults to develop “personal responsibility” (developmentally-appropriate care); and (5) “quarterbacking” care (coordination of specialist and/or community-based care). Participants identified potential benefits of these roles for adolescents and young adults transitioning to adult care, and barriers in practice (e.g., lack of time, having minimal involvement in pediatric care).

Conclusions
Input from family physicians, who follow their patients across the lifespan and provide the majority of primary care in Canada, are critical for informing and refining recommended transition practices. Our findings provide insights, from PHC providers themselves, to bolster the rationale for primary care involvement during transitions from pediatric specialty and community-based care for AYAs. Solutions to overcome barriers for integrating primary care and specialty care for adolescents and young adults need to be identified, and tested, with input from key stakeholders.
Combined therapy with ceftriaxone and doxycycline does not improve the outcome of meningococcal meningitis in mice compared to ceftriaxone monotherapy
Authors: Ricci Susanna , Grandgirard Denis , Masouris Ilias , Braccini Tiziana , Pozzi Gianni , Oggioni Marco R. , Koedel Uwe , Leib Stephen L. 
Published: July 2020

AbstractBackgroundMeningococcal meningitis (MM) is a life-threatening disease associated with approximately 10% case fatality rates and neurological sequelae in 10–20% of the cases. Recently, we have shown that the matrix metalloproteinase (MMP) inhibitor BB-94 reduced brain injury in a mouse model of MM. The present study aimed to assess whether doxycycline (DOX), a tetracycline that showed a neuroprotective effect as adjuvant therapy in experimental pneumococcal meningitis (PM), would also exert a beneficial effect when given as adjunctive therapy to ceftriaxone (CRO) in experimental MM.MethodsBALB/c mice were infected by the intracisternal route with a group CNeisseria meningitidisstrain. Eighteen h post infection (hpi), animals were randomised for treatment with CRO [100 mg/kg subcutaneously (s.c.)], CRO plus DOX (30 mg/kg s.c.) or saline (control s.c.). Antibiotic treatment was repeated 24 and 40 hpi. Mouse survival and clinical signs, bacterial counts in cerebella, brain damage, MMP-9 and cyto/chemokine levels were assessed 48 hpi.ResultsAnalysis of bacterial load in cerebella indicated that CRO and CRO + DOX were equally effective at controlling meningococcal replication. No differences in survival were observed between mice treated with CRO (94.4%) or CRO + DOX (95.5%), (p > 0.05). Treatment with CRO + DOX significantly diminished both the number of cerebral hemorrhages (p = 0.029) and the amount of MMP-9 in the brain (p = 0.046) compared to untreated controls, but not to CRO-treated animals (p > 0.05). Levels of inflammatory markers in the brain of mice that received CRO or CRO + DOX were not significantly different (p > 0.05). Overall, there were no significant differences in the parameters assessed between the groups treated with CRO alone or CRO + DOX.ConclusionsTreatment with CRO + DOX showed similar bactericidal activity to CRO in vivo, suggesting no antagonist effect of DOX on CRO. Combined therapy significantly improved mouse survival and disease severity compared to untreated animals, but addition of DOX to CRO did not offer significant benefits over CRO monotherapy. In contrast to experimental PM, DOX has no adjunctive activity in experimental MM.
IMMUNEPOTENT CRP induces DAMPS release and ROS-dependent autophagosome formation in HeLa and MCF-7 cells
Authors: Martínez-Torres Ana Carolina , Reyes-Ruiz Alejandra , Calvillo-Rodriguez Kenny Misael , Alvarez-Valadez Karla Maria , Uscanga-Palomeque Ashanti C. , Tamez-Guerra Reyes S. , Rodríguez-Padilla Cristina 
Published: July 2020

Abstract
Background
IMMUNEPOTENT CRP (ICRP) can be cytotoxic to cancer cell lines. However, its widespread use in cancer patients has been limited by the absence of conclusive data on the molecular mechanism of its action. Here, we evaluated the mechanism of cell death induced by ICRP in HeLa and MCF-7 cells.

Methods
Cell death, cell cycle, mitochondrial membrane potential and ROS production were evaluated in HeLa and MCF-7 cell lines after ICRP treatment. Caspase-dependence and ROS-dependence were evaluated using QVD.oph and NAC pre-treatment in cell death analysis. DAMPs release, ER stress (eIF2-α phosphorylation) and autophagosome formation were analyzed as well. Additionally, the role of autophagosomes in cell death induced by ICRP was evaluated using SP-1 pre-treatment in cell death in HeLa and MCF-7 cells.

Results
ICRP induces cell death, reaching CC50 at 1.25 U/mL and 1.5 U/mL in HeLa and MCF-7 cells, respectively. Loss of mitochondrial membrane potential, ROS production and cell cycle arrest were observed after ICRP CC50 treatment in both cell lines, inducing the same mechanism, a type of cell death independent of caspases, relying on ROS production. Additionally, ICRP-induced cell death involves features of immunogenic cell death such as P-eIF2α and CRT exposure, as well as, ATP and HMGB1 release. Furthermore, ICRP induces ROS-dependent autophagosome formation that acts as a pro-survival mechanism.

Conclusions
ICRP induces a non-apoptotic cell death that requires an oxidative stress to take place, involving mitochondrial damage, ROS-dependent autophagosome formation, ER stress and DAMPs’ release. These data indicate that ICRP could work together with classic apoptotic inductors to attack cancer cells from different mechanisms, and that ICRP-induced cell death might activate an immune response against cancer cells.
Real-world efficacy and safety of two doses of cabazitaxel (20 or 25 mg/m2) in patients with castration-resistant prostate cancer: results of a Japanese post-marketing surveillance study
Authors: Matsuyama Hideyasu , Matsubara Nobuaki , Kazama Hirotaka , Seto Takeshi , Tsukube Shoko , Suzuki Kazuhiro 
Published: July 2020

Abstract
Background
The recommended starting dose of cabazitaxel for castration-resistant prostate cancer (CRPC) is 25 mg/m2 in Japan and Europe. Although lower doses are established alternatives based on randomized controlled trials, the safety and efficacy of 25 and 20 mg/m2 in real-world settings are not well established. Therefore, we investigated the safety and efficacy of cabazitaxel at the recommended starting dose or a lower dose (20 mg/m2) in real-world clinical practice.

Methods
We compared the safety and efficacy of cabazitaxel between patients who received cabazitaxel at starting doses of 25 and 20 mg/m2 (C25 and C20, respectively) in a Japanese post-marketing surveillance study of 662 patients with docetaxel-refractory CRPC. Safety was assessed in terms of adverse drug reactions (ADRs). Prostate-specific antigen (PSA) response rate, overall survival (OS), and time-to-treatment failure (TTF) were compared between the C25 and C20 groups in unmatched patients and after applying propensity score matching.

Results
The C20 and C25 groups comprised 190 and 159 patients without matching and 112 patients per group after matching. In unmatched patients, any-grade (C25 vs C20: 89.3% vs 78.4%, Fisher’s p < 0.01) and grade ≥ 3 (81.1% vs 61.1%) ADRs were more frequent in the C25 group. Neutropenia (any grade: 61.6% vs 54.2%; grade ≥ 3: 55.3% vs 42.6%) and febrile neutropenia (grade ≥ 3: 30.2% vs 14.7%) were more frequent in the C25 group. In matched patients, the PSA response rate (reduction in PSA ≥30% from a baseline ≥5 ng/mL) was 26.4 and 32.0% in the C20 and C25 groups, respectively, median OS was 291 days (95% CI 230–not reached) versus not reached (hazard ratio 0.73, 95% CI 0.50–1.08), and TTF favored C25 (hazard ratio 0.75, 95% CI 0.57–0.99).

Conclusions
Clinicians should consider the patient’s risk of clinically significant ADRs and prophylactic granulocyte colony stimulating factor when selecting the starting dose of cabazitaxel for CRPC. Some patients at high risk of ADRs or unfit patients may benefit from a lower starting dose of 20 mg/m2, whereas fit patients may be candidates for a starting dose of 25 mg/m2.

Trial registration
Not applicable.
Global targetome analysis reveals critical role of miR-29a in pancreatic stellate cell mediated regulation of PDAC tumor microenvironment
Authors: Dey Shatovisha , Liu Sheng , Factora Tricia D. , Taleb Solaema , Riverahernandez Primavera , Udari Lata , Zhong Xiaoling , Wan Jun , Kota Janaiah 
Published: July 2020

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms of malignancies with a nearly equal incidence and mortality rates in patients. Pancreatic stellate cells (PSCs) are critical players in PDAC microenvironment to promote the aggressiveness and pathogenesis of the disease. Dysregulation of microRNAs (miRNAs) have been shown to play a significant role in progression of PDAC. Earlier, we observed a PSC-specific downregulation of miR-29a in PDAC pancreas, however, the mechanism of action of the molecule in PSCs is still to be elucidated. The current study aims to clarify the regulation of miR-29a in PSCs and identifies functionally important downstream targets that contribute to tumorigenic activities during PDAC progression.

Methods
In this study, using RNAseq approach, we performed transcriptome analysis of paired miR-29a overexpressing and control human PSCs (hPSCs). Enrichment analysis was performed with the identified differentially expressed genes (DEGs). miR-29a targets in the dataset were identified, which were utilized to create network interactions. Western blots were performed with the top miR-29a candidate targets in hPSCs transfected with miR-29a mimic or scramble control.

Results
RNAseq analysis identified 202 differentially expressed genes, which included 19 downregulated direct miR-29a targets. Translational repression of eight key pro-tumorigenic and -fibrotic targets namely IGF-1, COL5A3, CLDN1, E2F7, MYBL2, ITGA6 and ADAMTS2 by miR-29a was observed in PSCs. Using pathway analysis, we find that miR-29a modulates effectors of IGF-1-p53 signaling in PSCs that may hinder carcinogenesis. We further observe a regulatory role of the molecule in pathways associated with PDAC ECM remodeling and tumor-stromal crosstalk, such as INS/IGF-1, RAS/MAPK, laminin interactions and collagen biosynthesis.

Conclusions
Together, our study presents a comprehensive understanding of miR-29a regulation of PSCs, and identifies essential pathways associated with PSC-mediated PDAC pathogenesis. The findings suggest an anti-tumorigenic role of miR-29a in the context of PSC-cancer cell crosstalk and advocates for the potential of the molecule in PDAC targeted therapies.
Global incidence of Necrotizing Enterocolitis: a systematic review and Meta-analysis
Authors: Alsaied Amer , Islam Nazmul , Thalib Lukman 
Published: July 2020

Abstract
Background
Necrotizing Enterocolitis (NEC) is a major cause of morbidity and mortality in the Neonatal Intensive Care Unit (NICU), yet the global incidence of NEC has not been systematically evaluated. We conducted a systematic review and meta-analysis of cohort studies reporting the incidence of NEC in infants with Very Low Birth Weight (VLBW).

Methods
The databases searched included PubMed, MEDLINE, the Cochrane Library, EMBASE and grey literature. Eligible studies were cohort or population-based studies of newborns including registry data reporting incidence of NEC. Incidence were pooled using Random Effect Models (REM), in the presence of substantial heterogeneity. Additional, bias adjusted Quality Effect Models (QEM) were used to get sensitivity estimates. Subgroup analysis and meta-regression were used to explore the sources of heterogeneity. Funnel plots as appropriate for ratio measures were used to assess publication bias.

Results
A systematic and comprehensive search of databases identified 27 cohort studies reporting the incidence of NEC. The number of neonate included in these studies was 574,692. Of this 39,965 developed NEC. There were substantial heterogeneity between studies (I2 = 100%). The pooled estimate of NEC based on REM was 7.0% (95% CI: 6.0–8.0%). QEM based estimate (6.0%; 95% CI: 4.0–9.0%) were also similar. Funnel plots showed no evidence of publication bias. Although, NEC estimates are similar across various regions, some variation between high and low income countries were noted. Meta regression findings showed a statistically significant increase of NEC over time, quantified by the publication year.

Conclusion
Seven out of 100 of all VLBW infants in NICU are likely to develop NEC. However, there were considerable heterogeneity between studies. High quality studies assessing incidence of NEC along with associated risk factors are warranted.
Parental health literacy and health knowledge, behaviours and outcomes in children: a cross-sectional survey
Authors: de Buhr Elke , Tannen Antje 
Published: July 2020

Abstract
Background
Health literacy (HL) is closely associated with leading health indicators such as engaging in healthy behaviours and experiencing a healthy social environment. Parents represent a critical subgroup among the adult population since they are not only responsible for their own health but also for the health of their children. Previous research suggests that parents with low HL are less likely to meet the preventive and health care needs of their children but there are gaps in the available information and there is not any data available yet for the German context.

Methods
In preparation of an implementation study, a cross-sectional survey was conducted in 28 elementary and secondary schools in Germany. The parent questionnaire was completed by 4217 parents and included the short form of the European Health Literacy Survey Questionnaire (HLS-EU-Q16). The child questionnaire examined children’s health knowledge, behaviours and outcomes. For children between 6 and 10 years, a parent reported on behalf of their children (N = 1518). Students 11 years and older completed a self-administered questionnaire (N = 2776). Bivariate and multivariate analyses were carried out. Spearman’s Rho correlations assess the relationships between household characteristics, parental HL and the health behaviour and outcomes in children.

Results
Among the participating parents, 45.8% showed problematic or inadequate HL. The major determinants of high parental HL were high socio-economic status (SES) (r = .088***, 95% CI [.052, .124]), living in West Germany (r = .064***, 95% CI [.032, .096]) and older parental age (r = .057**, 95% CI [.024, .090]). In the multivariate model, only SES remained significant. High parental HL was associated with positive health behaviours in children including healthier nutrition, regular tooth brushing and more physical activity. The relationships between parental HL and smoking, alcohol, sexual activity among children and children’s weight were not significant.

Conclusions
The results confirm a relationship between low parental HL, SES and some child health behaviours likely to negatively impact their health and wellbeing including less healthy nutrition and less exercise. Strengthening the health knowledge and competencies of parents may contribute to improved child outcomes particularly in the areas of nutrition, exercise and dental health.
Parenting as an inhibitor of gender disparities in alcohol use: the case of early adolescents in China
Authors: Bo Ai , Jaccard James 
Published: July 2020

Abstract
Background
Gender differences in alcohol use are more substantial among early adolescents in China than in the United States, presumably because of more permissive drinking norms for boys than girls in Chinese culture. This study tested a theory that gender differences in early experimentation with alcohol can be reduced through general parenting practices. Whereas traditional research has identified mediators of gender differences in alcohol use, the current research isolated moderators of gender differences and developed their implications for prevention programs.

Methods
The study analyzed the data from the China Global School-Based Student Health Survey (n = 8805 middle school students in four cities). Youth completed anonymous surveys in classroom settings. The study examined interaction effects between gender and parenting variables using multiple regression with robust standard errors.

Results
Early adolescent boys exhibited higher levels of drinking than girls for all drinking outcomes. The gender differences in drinking were negatively associated with the level of perceived parental monitoring, parental involvement in adolescent school performance, and parental empathy in a nonlinear way.

Conclusions
Results suggested that early adolescents’ perceptions of general parenting practice nonlinearly moderated gender disparities in alcohol use.
Use of technology for public health surveillance reporting: opportunities, challenges and lessons learnt from Kenya
Authors: Njeru Ian , Kareko David , Kisangau Ngina , Langat Daniel , Liku Nzisa , Owiso George , Dolan Samantha , Rabinowitz Peter , Macharia Daniel , Ekechi Chinyere , Widdowson Marc-Alain 
Published: July 2020

Abstract
Background
Effective public health surveillance systems are crucial for early detection and response to outbreaks. In 2016, Kenya transitioned its surveillance system from a standalone web-based surveillance system to the more sustainable and integrated District Health Information System 2 (DHIS2). As part of Global Health Security Agenda (GHSA) initiatives in Kenya, training on use of the new system was conducted among surveillance officers. We evaluated the surveillance indicators during the transition period in order to assess the impact of this training on surveillance metrics and identify challenges affecting reporting rates.

Methods
From February to May 2017, we analysed surveillance data for 13 intervention and 13 comparison counties. An intervention county was defined as one that had received refresher training on DHIS2 while a comparison county was one that had not received training. We evaluated the impact of the training by analysing completeness and timeliness of reporting 15 weeks before and 12 weeks after the training. A chi-square test of independence was used to compare the reporting rates between the two groups. A structured questionnaire was administered to the training participants to assess the challenges affecting surveillance reporting.

Results
The average completeness of reporting for the intervention counties increased from 45 to 62%, i.e. by 17 percentage points (95% CI 16.14–17.86) compared to an increase from 49 to 52% for the comparison group, i.e. by 3 percentage points (95% CI 2.23–3.77). The timeliness of reporting increased from 30 to 51%, i.e. by 21 percentage points (95% CI 20.16–21.84) for the intervention group, compared to an increase from 31 to 38% for the comparison group, i.e.by 7 percentage points (95% CI 6.27–7.73). Major challenges for the low reporting rates included lack of budget support from government, lack of airtime for reporting, health workers strike, health facilities not sending surveillance data, use of wrong denominator to calculate reporting rates and surveillance officers having other competing tasks.

Conclusions
Training plays an important role in improving public health surveillance reporting. However, to improve surveillance reporting rates to the desired national targets, other challenges affecting reporting must be identified and addressed accordingly.
Use and value of systematic reviews in English local authority public health: a qualitative study
Authors: South Emily , Lorenc Theo 
Published: July 2020

Abstract
Background
Responsibility for public health in England transferred from the National Health Service to local authorities in 2013, representing a different decision-making environment. Systematic reviews are considered the gold standard of evidence for clinical decision-making but little is known about their use in local government public health. This study aimed to explore the extent to which public health decision-makers in local authorities engage with systematic reviews and how they do so.

Methods
Semi-structured interviews were conducted with senior public health practitioners (n = 14) in Yorkshire and the Humber local authorities. Sampling was purposive and involved contacting Directors of Public Health directly and snowballing through key contacts. Face-to-face or telephone interviews were digitally recorded, transcribed verbatim and analysed using the Framework Method.

Results
Public health practitioners described using systematic reviews directly in decision-making and engaging with them more widely in a range of ways, often through a personal commitment to professional development. They saw themselves as having a role to advocate for the use of rigorous evidence, including systematic reviews, in the wider local authority. Systematic reviews were highly valued in principle and public health practitioners had relevant skills to find and appraise them. However, the extent of use varied by individual and local authority and was limited by the complexity of decision-making and various barriers. Barriers included that there were a limited number of systematic reviews available on certain public health topics, such as the wider determinants of health, and that the narrow focus of reviews was not reflective of complex public health decisions facing local authorities. Reviews were used alongside a range of other evidence types, including grey literature. The source of evidence was often considered an indicator of quality, with specific organisations, such as Public Health England, NICE and Cochrane, particularly trusted.

Conclusions
Research use varies and should be considered within the specific decision-making and political context. There is a need for systematic reviews to be more reflective of the decisions facing local authority public health teams.