bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilization, quality, and spending for pediatric Medicaid enrollees with primary care in health centers vs non-health centers
Authors: Volerman Anna , Carlson Bradley , Wan Wen , Murugesan Manoradhan , Asfour Nour , Bolton Joshua , Chin Marshall H. , Sripipatana Alek , Nocon Robert S.
Published: February 2024

Background

Limited research has explored the performance of health centers (HCs) compared to other primary care settings among children in the United States. We evaluated utilization, quality, and expenditures for pediatric Medicaid enrollees receiving care in HCs versus non-HCs.

Methods

This national cross-sectional study utilized 2012 Medicaid Analytic eXtract (MAX) claims to examine children 0–17 years with a primary care visit, stratified by whether majority (> 50%) of primary care visits were at HCs or non-HCs. Outcome measures include utilization (primary care visits, non-primary care outpatient visits, prescription claims, Emergency Department (ED) visits, hospitalizations) and quality (well-child visits, avoidable ED visits, avoidable hospitalizations). For children enrolled in fee-for-service Medicaid, we also measured expenditures. Propensity score-based overlap weighting was used to balance covariates.

Results

A total of 2,383,270 Medicaid-enrolled children received the majority of their primary care at HCs, while 18,540,743 did at non-HCs. In adjusted analyses, HC patients had 20% more primary care visits, 15% less non-primary care outpatient visits, and 21% less prescription claims than non-HC patients. ED visits were similar across the two groups, while HC patients had 7% lower chance of hospitalization than non-HC. Quality of care outcomes favored HC patients in main analyses, but results were less robust when excluding managed care beneficiaries. Total expenditures among the fee-for-service subpopulation were lower by $239 (8%) for HC patients.

Conclusions

In this study of nationwide claims data to evaluate healthcare utilization, quality, and spending among Medicaid-enrolled children who receive primary care at HCs versus non-HCs, findings suggest primary care delivery in HCs may be associated with a more cost-effective model of healthcare for children.
Examining the referral of patients with elevated blood pressure to health resources in an under-resourced community in South Africa
Authors: McNulty Lia K. , Stoutenberg Mark , Kolkenbeck-Ruh Andrea , Harrison Amy , Mmoledi Thabiso , Katiyo Daniel , Mhlaba Mimi , Kubheka Delisile , Ware Lisa J.
Published: February 2024

Background

Low-and-middle income countries face a disproportionate burden of non-communicable diseases (NCDs) that threaten to overwhelm under-resourced health systems. Community health workers (CHWs) can promote NCD prevention, reach patients, and connect them to local community health resources; however, little has been done to examine how referrals to these resources are utilized by community members. The purpose of this study is to examine the use of referrals to community-based health resources and investigate the factors influencing patient utilization of referrals connecting them to appropriate health resources for elevated blood pressure (BP).

Methods

CHWs conducted home visits, which included BP screening and brief counseling, with community members in Soweto, South Africa. Participants with elevated (systolic BP: 121–139/ diastolic BP: 81–89 mmHg) or high (≥ 140/90 mmHg) BP were referred to either a local, community-based physical activity (PA) program managed by a non-governmental organization or local health clinics. The number of participants that received and utilized their referrals was tracked. Follow-up interviews were conducted with individuals given a referral who: (1) went to the PA program, (2) did not go to the PA program, (3) went to a clinic, and (4) did not go to a clinic. Interviews were transcribed and analyzed to identify common themes and differences between groups regarding their decisions to utilize the referrals.

Results

CHWs visited 1056 homes, with 1001 community members consenting to the screening; 29.2% (n = 292) of adults were classified as having optimal BP (≤120/80 mmHg), 35.8% (n = 359) had elevated BP, and 35.0% (n = 350) had high BP. One hundred and seventy-three participants accepted a referral to the PA program with 46 (26.6%) enrolling. Five themes emerged from the interviews: (1) prior knowledge and thoughts on BP, (2) psychosocial factors associated with BP control, (3) perception about receiving the referral, (4) contextual factors influencing referral utilization, and (5) perceived benefits of utilizing the referral.

Conclusion

CHWs can successfully increase community members’ access to health resources by providing appropriate referrals. However, greater attention needs to address community members’ barriers and hesitancy to utilize health resources.
Association of social vulnerability index and masking adherence among children enrolled in COVID-19 community research partnership study
Authors: Dantuluri Keerti L. , Buahin Asare , Uschner Diane , DeWitt Michael E. , Rossman Whitney , Dunn Connell O. , Hetherington Timothy C. , Priem Jennifer , Castri Paola , Lagarde William H. , Gibbs Michael , Ahmed Amina ,   The COVID-19 Community Research Partnership
Published: February 2024

Background

Individuals with high social vulnerability index (SVI) have poorer outcomes with COVID-19. Masking reduces transmission of COVID-19 among children, but how SVI plays a role in masking behavior is unknown. We aimed to measure the association of SVI with masking adherence among children during the COVID-19 pandemic.

Methods

We conducted a multi-site, prospective syndromic surveillance study among children aged 2 – 17 years in the Southeastern United States by daily electronic surveys which solicited symptoms of COVID-19-like illness, infection with or exposure to SARS-CoV-2, masking habits, and any receipt of COVID-19 vaccines. Parents/guardians submitted surveys for their children; adolescents 13 years and older could opt to submit their own surveys. Multivariable and univariate linear models were used to measure the associations of different predictors such as SVI with masking adherence.

Results

One thousand four hundred sixty-one children from 6 states and 55 counties predominately from North and South Carolina were included in the analysis. Most children in the cohort were 5 – 11 years old, non-Hispanic White, from urban counties, and with low-moderate SVI. Overall masking adherence decreased over time, and older children had higher masking adherence throughout the study period compared with younger children. Children who resided in urban counties had greater masking adherence throughout the study period than those who resided in suburban or rural counties. Masking adherence was higher among children with both low and medium SVI than those with high SVI.

Conclusions

Despite being at risk for more severe outcomes with COVID-19, children with high SVI had lower levels of masking adherence compared to those with low SVI. Our findings highlight opportunities for improved and targeted messaging in these vulnerable communities.
The most influential articles on stem cells in intervertebral disc degeneration
Authors: Ye Shuxi , Chen Rongchun , Shi Jiangyou , Wu Yaohong
Published: February 2024

Background

Stem cell-related studies have been increasingly conducted to facilitate the regeneration of degenerative discs. However, analyses of high-impact articles focused on this topic are rare. This study aimed to determine and summarize the most-cited studies examining stem cells in the context of intervertebral disc degeneration (IDD).

Methods

We searched the Web of Science (WoS) database for stem cell-related articles in IDD, and the 50 highest-cited papers were summarized. A correlation analysis was conducted to determine the relationship among WoS citations, Altmetric Attention Score (AAS), and Dimensions.

Results

The number of citations of the top 50 manuscripts ranged from 92 to 370. The top three countries were the United States (14), China (10), and Japan (9). Spine (12) was the most prevalent journal, and this was followed by Biomaterials (6). Bone marrow-derived stem cells were the most common subject (38), and they were followed by nucleus pulposus-derived stem cells (4) and annulus fibrosus-derived stem cells (4). Humans were the most studied species (31), and the next most studied were rabbits (9) and rats (7). There was a very high correlation between WoS and Dimension citations (p < 0.001, r = 0.937).

Conclusions

For the first time, the highest impact articles examining stem cells in the context of IDD were assessed together. The current study provides a deepened understanding of historical studies focused on stem cells in IDD and is beneficial for future studies in this field.
Strain-specific features of Pleurotus ostreatus growth in vitro and some of its biological activities
Authors: Krupodorova Tetiana , Barshteyn Victor , Tsygankova Victoria , Sevindik Mustafa , Blume Yaroslav
Published: February 2024

Background

The production of Pleurotus ostreatus mycelium as a promising object for use in food and other industries is hampered by a lack of information about the strain-specificity of this fungus mycelium growth and its acquisition of various biological activities. Therefore, this research aimed to investigate mycelial growth of different P. ostreatus strains on varies solid and liquid media as well as to evaluate strains antagonistic, antibacterial, antiradical scavenging activities, and total phenolic content.

Results

Potato Dextrose Agar medium was suitable for all strains except P. ostreatus strain 2460. The best growth rate of P. ostreatus 2462 strain on solid culture media was 15.0 ± 0.8 mm/day, and mycelia best growth on liquid culture media—36.5 ± 0.2 g/l. P. ostreatus strains 551 and 1685 were more susceptible to positive effect of plant growth regulators Ivin, Methyur and Kamethur. Using of nutrient media based on combination of natural waste (amaranth flour cake and wheat germ, wheat bran, broken vermicelli and crumbs) has been increased the yield of P. ostreatus strains mycelium by 2.2–2.9 times compared to the control. All used P. ostreatus strains displayed strong antagonistic activity in co-cultivation with Aspergillus niger, Candida albicans, Issatchenkia orientalis, Fusarium poae, Microdochium nivale in dual-culture assay. P. ostreatus 2462 EtOAc mycelial extract good inhibited growth of Escherichia coli (17.0 ± 0.9 mm) while P. ostreatus 2460 suppressed Staphylococcus aureus growth (21.5 ± 0.5 mm) by agar well diffusion method. The highest radical scavenging effect displayed both mycelial extracts (EtOH and EtOAc) of P. ostreatus 1685 (61 and 56%) by DPPH assay as well as high phenolic content (7.17 and 6.73 mg GAE/g) by the Folin-Ciocalteu’s method. The maximal total phenol content (7.52 mg GAE/g) demonstrated of P. ostreatus 2461 EtOH extract.

Conclusions

It is found that the growth, antibacterial, antiradical scavenging activity as well as total phenolic content were dependent on studied P. ostreatus strains in contrast to antagonistic activity. The proposed culture mediums of natural waste could be an alternative to commercial mediums for the production mycelial biomass of P. ostreatus strains.
Unique case of lymphocytic hypophysitis with normal pituitary hormone serology mimicking a non-functioning pituitary adenoma
Authors: Shen Kyle , Cadang Catherine , Phillips Daniel , Babu Varsha
Published: February 2024

Background

Lymphocytic hypophysitis is a rare autoimmune condition that usually presents during pregnancy and causes inflammation of the pituitary gland. Although the pathophysiology is not well understood, it often presents with headaches, visual disturbances, and symptoms of hypopituitarism. However, not all cases may present with hypopituitarism which can make this rare disease with an incidence of ~ 1 in 9 million much more difficult to diagnose.

Case Presentation

We present a 35-year-old G4P4 woman with progressive vision loss and intermittent frontal headaches during her first trimester through 2 months postpartum. She presented with no symptoms of hypopituitarism and her hormone panel only showed elevated prolactin, possibly due to her breastfeeding. She was treated with a right pterional craniotomy with decompression of both optic nerves, partial resection of the suprasellar mass, and glucocorticoid therapy for headaches and visual disturbances.

Conclusion

This case is notable for a presentation of lymphocytic hypophysitis without symptoms of hypopituitarism. This is important for outpatient providers to be aware of, especially those that care for pregnant patients so that unfavorable outcomes can be avoided.
Astragalus polysaccharides attenuate rat aortic endothelial senescence via regulation of the SIRT-1/p53 signaling pathway
Authors: Miao Xinyu , Rong Lingjun , Fu Bo , Cui Shaoyuan , Gu Zhaoyan , Hu Fan , Lu Yanhui , Yan Shuangtong , Sun Banruo , Jiang Wenli , Zhang Yuting , Gong Yanping , Li Chunlin
Published: February 2024

Background

Astragalus polysaccharides (APS) have been verified to have antioxidative and antiaging activities in the mouse liver and brain. However, the effect of APS on aortic endothelial senescence in old rats and its underlying mechanism are currently unclear. Here, we aimed to elucidate the effects of APS on rat aortic endothelial oxidative stress and senescence in vitro and in vivo and investigate the potential molecular targets.

Methods

Twenty-month-old natural aging male rats were treated with APS (200 mg/kg, 400 mg/kg, 800 mg/kg daily) for 3 months. Serum parameters were tested using corresponding assay kits. Aortic morphology was observed by staining with hematoxylin and eosin (H&E) and Verhoeff Van Gieson (VVG). Aging-related protein levels were evaluated using immunofluorescence and western blot analysis. Primary rat aortic endothelial cells (RAECs) were isolated by tissue explant method. RAEC mitochondrial function was evaluated by the mitochondrial membrane potential (MMP) measured with the fluorescent lipophilic cationic dye JC‑1. Intracellular total antioxidant capacity (T-AOC) was detected by a commercial kit. Cellular senescence was assessed using senescence-associated-β-galactosidase (SA-β-Gal) staining.

Results

Treatment of APS for three months was found to lessen aortic wall thickness, renovate vascular elastic tissue, improve vascular endothelial function, and reduce oxidative stress levels in 20-month-old rats. Primary mechanism analysis showed that APS treatment enhanced Sirtuin 1 (SIRT-1) protein expression and decreased the levels of the aging marker proteins p53, p21 and p16 in rat aortic tissue. Furthermore, APS abated hydrogen peroxide (H2O2)-induced cell senescence and restored H2O2-induced impairment of the MMP and T-AOC in RAECs. Similarly, APS increased SIRT-1 and decreased p53, p21 and p16 protein levels in senescent RAECs isolated from old rats. Knockdown of SIRT-1 diminished the protective effect of APS against H2O2-induced RAEC senescence and T-AOC loss, increased the levels of the downstream proteins p53 and p21, and abolished the inhibitory effect of APS on the expression of these proteins in RAECs.

Conclusion

APS may reduce rat aortic endothelial oxidative stress and senescence via the SIRT-1/p53 signaling pathway.
Nurses’ perceptions of the transition to 100% single-occupancy patient rooms in a university hospital in the Netherlands: an uncontrolled before and after study
Authors: Pruijsten Ralph , Ista Erwin , Maben Jill , van Heel Liesbeth , van Dijk Monique
Published: February 2024

Background

To improve patients’ privacy, comfort and infection control, newly built hospitals increasingly offer 100% single-occupancy patient rooms. Our study examines how nurses perceived the transition from a hospital with multi-bedded patient rooms to one with solely single-occupancy patient rooms designed according to principles of a healing environment.

Methods

In a single-centre, before-after survey study, nurses completed a questionnaire of 21 items in three domains: perceived patient safety and monitoring, nurses’ working conditions and patient environment. Before-measurements (n = 217) were compared with two after-measurements in the new hospital, respectively after one (n = 483) and two years (n = 191).

Results

Nurses considered the single rooms in the new hospital worse for visibility and monitoring but this had improved somewhat after two years. In either setting, the majority perceived working conditions (walking distances and designated rest area) as unfavourable. The patient environment in the new hospital was generally perceived as much better than in the former hospital.

Conclusion

The transition to solely single-occupancy patient rooms was largely considered positive by nurses in terms of patient environment. However, monitoring of patients and working conditions remain a concern. When designing new hospitals, attention should be paid to optimal working conditions for nurses. To improve monitoring of patients, we recommend the use of remote-sensoring.
Development and validation of the nurses sexual harassment scale in Iran
Authors: Zeighami Maryam , Malakoutikhah Alireza , Shahrbabaki Parvin Mangolian , Al-Oliamat Kamlah , Dehghan Mahlagha
Published: February 2024

Introduction

In recent years, the prevalence of sexual harassment has become a global problem, and nursing, like other professions, has not been immune to this issue. By having a valid and reliable instrument, healthcare personnel can be helped in preventing and managing this problem and reduce its negative consequences on mental health and well-being. The aim of this study was developing and psychometrically measuring the Nurses Sexual Harassment Scale.

Materials and methods

This study is the second phase of a mixed method study. Initially in the first phase, a qualitative approach with conventional content analysis was used to explain nurses’ experiences of sexual harassment in the workplace. To design the Nurses Sexual Harassment Scale, qualitative data and literature were reviewed. In the quantitative phase (second phase), the target scale was psychometrically evaluated using content validity (14 experts), face validity (12 nurses with being sexually harassed), construct validity (316 nurses working in hospitals affiliated to Kerman University of Medical Sciences), and reliability (internal consistency and repeatability).

Results

A 15-item scale with two components: “latent sexual harassment” (9 items) and “manifest sexual harassment” (6 items), which explained 68.4% of the total variance was developed. Also, due to the strong correlation between the Nurses Sexual Harassment Scale and the Impact of Event Scale-Revised (r = 0.67), convergent validity was confirmed. Also, the scale of the present study had good reliability (Cronbach’s alpha coefficient = 0.94, Omega coefficient = 0.94, and ICC = 0.92).

Conclusion

Given the importance of sexual harassment among nurses, measuring the dimensions of this problem may allow professionals to plan interventions to prevent it. Overall, the results of the present study showed that the psychometric properties of the " Nurses Sexual Harassment Scale” with 15 items are acceptable and this scale can be used in the clinical environment. A further study within the nursing community is recommended to confirm the findings.
A cost-effectiveness analysis of a universal, preventative-focused, parent and infant programme
Authors: Crealey Gráinne E. , Hickey Gráinne , McGilloway Sinead
Published: February 2024

Background

This study assessed whether a relatively newly developed Parent and Infant (PIN) parenting support programme was cost-effective when compared to services as usual (SAU).

Methods

The cost-effectiveness of the PIN programme versus SAU was assessed from an Irish health and social care perspective over a 24-month timeframe and within the context of a non-randomised, controlled before-and-after trial. In total, 163 parent-infant dyads were included in the study (86 intervention, 77 control). The primary outcome measure for the economic evaluation was the Parenting Sense of Competence Scale (PSOC).

Results

The average cost of the PIN programme was €647 per dyad. The mean (SE) cost (including programme costs) was €7,027 (SE €1,345) compared to €4,811 (SE €593) in the control arm, generating a (non-significant) mean cost difference of €2,216 (bootstrap 95% CI -€665 to €5,096; p = 0.14). The mean incremental cost-effectiveness of the PIN service was €614 per PSOC unit gained (bootstrap 95% CI €54 to €1,481). The probability that the PIN programme was cost-effective, was 87% at a willingness-to-pay of €1,000 per one unit change in the PSOC.

Conclusions

Our findings suggest that the PIN programme was cost-effective at a relatively low willingness-to-pay threshold when compared to SAU. This study addresses a significant knowledge gap in the field of early intervention by providing important real world evidence on the implementation costs and cost-effectiveness of a universal early years parenting programme. The challenges involved in assessing the cost-effectiveness of preventative interventions for very young children and their parents are also discussed.

Trial registration

ISRCTN17488830 (Date of registration: 27/11/15). This trial was retrospectively registered.
Electronic Integrated Management of Childhood Illness (eIMCI): a randomized controlled trial to evaluate an electronic clinical decision-making support system for management of sick children in primary health care facilities in South Africa
Authors: Horwood C. , Haskins L. , Mapumulo S. , Connolly C. , Luthuli S. , Jensen C. , Pansegrouw D. , McKerrow N.
Published: February 2024

Background

Electronic clinical decision-making support systems (eCDSS) aim to assist clinicians making complex patient management decisions and improve adherence to evidence-based guidelines. Integrated management of Childhood Illness (IMCI) provides guidelines for management of sick children attending primary health care clinics and is widely implemented globally. An electronic version of IMCI (eIMCI) was developed in South Africa.

Methods

We conducted a cluster randomized controlled trial comparing management of sick children with eIMCI to the management when using paper-based IMCI (pIMCI) in one district in KwaZulu-Natal. From 31 clinics in the district, 15 were randomly assigned to intervention (eIMCI) or control (pIMCI) groups. Computers were deployed in eIMCI clinics, and one IMCI trained nurse was randomly selected to participate from each clinic. eIMCI participants received a one-day computer training, and all participants received a similar three-day IMCI update and two mentoring visits. A quantitative survey was conducted among mothers and sick children attending participating clinics to assess the quality of care provided by IMCI practitioners. Sick child assessments by participants in eIMCI and pIMCI groups were compared to assessment by an IMCI expert.

Results

Self-reported computer skills were poor among all nurse participants. IMCI knowledge was similar in both groups. Among 291 enrolled children: 152 were in the eIMCI group; 139 in the pIMCI group. The mean number of enrolled children was 9.7 per clinic (range 7-12). IMCI implementation was sub-optimal in both eIMCI and pIMCI groups. eIMCI consultations took longer than pIMCI consultations (median duration 28 minutes vs 25 minutes; p = 0.02). eIMCI participants were less likely than pIMCI participants to correctly classify children for presenting symptoms, but were more likely to correctly classify for screening conditions, particularly malnutrition. eIMCI participants were less likely to provide all required medications (124/152; 81.6% vs 126/139; 91.6%, p= 0.026), and more likely to prescribe unnecessary medication (48/152; 31.6% vs 20/139; 14.4%, p = 0.004) compared to pIMCI participants.

Conclusions

Implementation of eIMCI failed to improve management of sick children, with poor IMCI implementation in both groups. Further research is needed to understand barriers to comprehensive implementation of both pIMCI and eIMCI. (349)

Clinical trials registration

Clinicaltrials.gov ID: BFC157/19, August 2019.
Strategies to improve care for older adults who present to the emergency department: a systematic review
Authors: Testa Luke , Richardson Lieke , Cheek Colleen , Hensel Theresa , Austin Elizabeth , Safi Mariam , Ransolin Natália , Carrigan Ann , Long Janet , Hutchinson Karen , Goirand Magali , Bierbaum Mia , Bleckly Felicity , Hibbert Peter , Churruca Kate , Clay-Williams Robyn
Published: February 2024

Background

The aim of this systematic review was to examine the relationship between strategies to improve care delivery for older adults in ED and evaluation measures of patient outcomes, patient experience, staff experience, and system performance.

Methods

A systematic review of English language studies published since inception to December 2022, available from CINAHL, Embase, Medline, and Scopus was conducted. Studies were reviewed by pairs of independent reviewers and included if they met the following criteria: participant mean age of ≥ 65 years; ED setting or directly influenced provision of care in the ED; reported on improvement interventions and strategies; reported patient outcomes, patient experience, staff experience, or system performance. The methodological quality of the studies was assessed by pairs of independent reviewers using The Joanna Briggs Institute critical appraisal tools. Data were synthesised using a hermeneutic approach.

Results

Seventy-six studies were included in the review, incorporating strategies for comprehensive assessment and multi-faceted care (n = 32), targeted care such as management of falls risk, functional decline, or pain management (n = 27), medication safety (n = 5), and trauma care (n = 12). We found a misalignment between comprehensive care delivered in ED for older adults and ED performance measures oriented to rapid assessment and referral. Eight (10.4%) studies reported patient experience and five (6.5%) reported staff experience.

Conclusion

It is crucial that future strategies to improve care delivery in ED align the needs of older adults with the purpose of the ED system to ensure sustainable improvement effort and critical functioning of the ED as an interdependent component of the health system. Staff and patient input at the design stage may advance prioritisation of higher-impact interventions aligned with the pace of change and illuminate experience measures. More consistent reporting of interventions would inform important contextual factors and allow for replication.
Insulin receptor alternative splicing in breast and prostate cancer
Authors: Li Jinyu , Huang Gena
Published: February 2024

Cancer etiology represents an intricate, multifactorial orchestration where metabolically associated insulin-like growth factors (IGFs) and insulin foster cellular proliferation and growth throughout tumorigenesis. The insulin receptor (IR) exhibits two splice variants arising from alternative mRNA processing, namely IR-A, and IR-B, with remarkable distribution and biological effects disparities. This insightful review elucidates the structural intricacies, widespread distribution, and functional significance of IR-A and IR-B. Additionally, it explores the regulatory mechanisms governing alternative splicing processes, intricate signal transduction pathways, and the intricate association linking IR-A and IR-B splicing variants to breast and prostate cancer tumorigenesis. Breast cancer and prostate cancer are the most common malignant tumors with the highest incidence rates among women and men, respectively. These findings provide a promising theoretical framework for advancing preventive strategies, diagnostic modalities, and therapeutic interventions targeting breast and prostate cancer.
Diet in secondary prevention: the effect of dietary patterns on cardiovascular risk factors in patients with cardiovascular disease: a systematic review and network meta-analysis
Authors: Bonekamp N. E. , Cruijsen E. , Geleijnse J. M. , Winkels R. M. , Visseren F. L. J. , Morris P. B. , Koopal C.
Published: February 2024

Background

Improving dietary habits is a first-line recommendation for patients with cardiovascular disease (CVD). It is unclear which dietary pattern most effectively lowers cardiovascular risk factors and what the short- and long-term effects are. Therefore, this network meta-analysis compared the effects of popular dietary patterns on cardiovascular risk factors in patients with established CVD.

Methods

A systematic search of PubMed, Embase, the Cochrane library, SCOPUS and Web of Science was conducted up to 1 April 2023. Randomized controlled trials (RCTs) comparing the effect of popular dietary patterns (Mediterranean, moderate carbohydrate, low glycemic index, low-fat and minimal dietary intervention) on cardiovascular risk factors (body weight, systolic blood pressure, lipids) in CVD populations were selected. A random-effects network meta-analysis was performed.

Results

Seventeen RCTs comprising 6,331 participants were included. The moderate carbohydrate diet had the most beneficial effect on body weight (-4.6 kg, 95%CrI -25.1; 15.8) and systolic blood pressure (-7.0 mmHg 95%CrI -16.8; 2.7) compared to minimal intervention. None of the included dietary patterns had a favorable effect on low-density lipoprotein cholesterol. After 12 months, the effects were attenuated compared to those at < 6 months.

Conclusions

In this network meta-analysis of 17 randomized trials, potentially clinically relevant effects of dietary interventions on CV risk factors were observed, but there was considerable uncertainty due to study heterogeneity, low adherence, or actual diminished effects in the medically treated CVD population. It was not possible to select optimal dietary patterns for secondary CVD prevention. Given recent clinical trials demonstrating the potential of dietary patterns to significantly reduce cardiovascular event risk, it is likely that these effects are effectuated through alternative physiological pathways.
Associations of residential green space with internalizing and externalizing behavior in early childhood
Authors: Hazlehurst Marnie F. , Hajat Anjum , Tandon Pooja S. , Szpiro Adam A. , Kaufman Joel D. , Tylavsky Frances A. , Hare Marion E. , Sathyanarayana Sheela , Loftus Christine T. , LeWinn Kaja Z. , Bush Nicole R. , Karr Catherine J.
Published: February 2024

Background

Green space exposures may promote child mental health and well-being across multiple domains and stages of development. The aim of this study was to investigate associations between residential green space exposures and child mental and behavioral health at age 4–6 years.

Methods

Children’s internalizing and externalizing behaviors in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) cohort in Shelby County, Tennessee, were parent-reported on the Child Behavior Checklist (CBCL). We examined three exposures—residential surrounding greenness calculated as the Normalized Difference Vegetation Index (NDVI), tree cover, and park proximity—averaged across the residential history for the year prior to outcome assessment. Linear regression models were adjusted for individual, household, and neighborhood-level confounders across multiple domains. Effect modification by neighborhood socioeconomic conditions was explored using multiplicative interaction terms.

Results

Children were on average 4.2 years (range 3.8-6.0) at outcome assessment. Among CANDLE mothers, 65% self-identified as Black, 29% as White, and 6% as another or multiple races; 41% had at least a college degree. Higher residential surrounding greenness was associated with lower internalizing behavior scores (-0.66 per 0.1 unit higher NDVI; 95% CI: -1.26, -0.07) in fully-adjusted models. The association between tree cover and internalizing behavior was in the hypothesized direction but confidence intervals included the null (-0.29 per 10% higher tree cover; 95% CI: -0.62, 0.04). No associations were observed between park proximity and internalizing behavior. We did not find any associations with externalizing behaviors or the attention problems subscale. Estimates were larger in neighborhoods with lower socioeconomic opportunity, but interaction terms were not statistically significant.

Conclusions

Our findings add to the accumulating evidence of the importance of residential green space for the prevention of internalizing problems among young children. This research suggests the prioritization of urban green spaces as a resource for child mental health.
The pathogenic mutations of APOA5 in Chinese patients with hyperlipidemic acute pancreatitis
Authors: Liu Yuxin , Dai Si , Qin Shuqi , Zhou Jing , Wang Zhendan , Yin Guojian
Published: February 2024

Background and aims

To study the role of gene mutations in the development of severe hypertriglyceridemia (HTG) in patients with hyperlipidemic acute pancreatitis (HLAP), especially different apolipoprotein A5 (APOA5) mutations.

Methods

Whole-exome sequencing was performed on 163 patients with HLAP and 30 patients with biliary acute pancreatitis (BAP). The pathogenicity of mutations was then assessed by combining clinical information, predictions of bioinformatics programs, information from multiple gene databases, and residue location and conservation. The pathogenic mutations ofAPOA5were visualized using the software.

Results

1. Compared with BAP patients, pathogenic mutations ofAPOA5were frequent in HLAP patients; among them, the heterozygous mutation of p.G185C was the most common.

2. All six pathogenic mutations ofAPOA5identified in this study (p.S35N, p.D167V, p.G185C, p.K188I, p.R223C, and p.H182fs) were positively correlated with severe HTG; they were all in the important domains of apolipoprotein A-V (apoA-V). Residue 223 is strictly conserved in multiple mammals and is located in the lipoprotein lipase (LPL)-binding domain (Pro215–Phe261). When Arg 223 is mutated to Cys 223, the positive charge of this residue is reduced, which is potentially destructive to the binding function of apoA-V to LPL.

3. Four newAPOA5mutations were identified, namely c.563A > T, c.667C > T, c.788G > A, and c.544_545 insGGTGC.

Conclusions

The pathogenic mutations ofAPOA5were specific to the patients with HLAP and severe HTG in China, and identifying such mutations had clinical significance in elucidating the etiology and subsequent treatment.

Graphical Abstract
Polydopamine-assisted aptamer-carrying tetrahedral DNA microelectrode sensor for ultrasensitive electrochemical detection of exosomes
Authors: Jiang Bowen , Zhang Tenghua , Liu Silan , Sheng Yan , Hu Jiaming
Published: February 2024

Background

Exosomes are nanoscale extracellular vesicles (30–160 nm) with endosome origin secreted by almost all types of cells, which are considered to be messengers of intercellular communication. Cancerous exosomes serve as a rich source of biomarkers for monitoring changes in cancer-related physiological status, because they carry a large number of biological macromolecules derived from parental tumors. The ultrasensitive quantification of trace amounts of cancerous exosomes is highly valuable for non-invasive early cancer diagnosis, yet it remains challenging. Herein, we developed an aptamer-carrying tetrahedral DNA (Apt-TDNA) microelectrode sensor, assisted by a polydopamine (PDA) coating with semiconducting properties, for the ultrasensitive electrochemical detection of cancer-derived exosomes.

Results

The stable rigid structure and orientation of Apt-TDNA ensured efficient capture of suspended exosomes. Without PDA coating signal amplification strategy, the sensor has a linear working range of 102–107 particles mL−1, with LOD of ~ 69 exosomes and ~ 42 exosomes for EIS and DPV, respectively. With PDA coating, the electrochemical signal of the microelectrode is further amplified, achieving single particle level sensitivity (~ 14 exosomes by EIS and ~ 6 exosomes by DPV).

Conclusions

The proposed PDA-assisted Apt-TDNA microelectrode sensor, which integrates efficient exosome capture, sensitive electrochemical signal feedback with PDA coating signal amplification, provides a new avenue for the development of simple and sensitive electrochemical sensing techniques in non-invasive cancer diagnosis and monitoring treatment response.

Graphical Abstract
Underreporting of non-study cigarette use by study participants confounds the interpretation of results from ambulatory clinical trial of reduced nicotine cigarettes
Authors: Zhang Mingda , Wang Jingzhu , Edmiston Jeffery
Published: February 2024

Background

As part of its comprehensive plan to significantly reduce the harm from tobacco products, the US Food and Drug Administration is establishing a product standard to lower nicotine in conventional cigarettes to make them “minimally addictive or non-addictive". Many clinical studies have investigated the potential impact of such a standard on smoking behavior and exposure to cigarette constituents. These ambulatory studies required participants who smoke to switch to reduced nicotine study cigarettes. In contrast to clinical trials on pharmaceuticals or medical devices, participants had ready access to non-study conventional nicotine cigarettes and high rates of non-study cigarette use were consistently reported. The magnitude of non-compliance, which could impact the interpretation of the study results, was not adequately assessed in these trials.

Methods

We conducted a secondary analysis of data from a large, randomized trial of reduced nicotine cigarettes with 840 participants to estimate the magnitude of non-compliance, i.e., the average number of non-study cigarettes smoked per day by study participants assigned to reduced nicotine cigarettes. Individual participants’ non-study cigarette use was estimated based on his/her urinary total nicotine equivalent level, the nicotine content of the study cigarette assigned and the self-reported number of cigarettes smoked, using a previously published method.

Results

Our analysis showed that (1) there is a large variation in the number of non-study cigarettes smoked by participants within each group (coefficient of variation 90–232%); (2) participants in reduced nicotine cigarette groups underreported their mean number of non-study cigarettes smoked per day by 85–91%; and (3) the biochemical-based estimates indicate no reduction in the mean number of total cigarettes smoked per day for any group assigned to reduced nicotine cigarettes after accounting for non-study cigarettes.

Conclusions

High levels of non-compliance, in both the rate and magnitude of non-study cigarette use, are common in ambulatory reduced nicotine cigarette trials where participants have access to conventional nicotine non-study cigarettes. The potential impact of high non-compliance on study outcomes should be considered when interpreting the results from such ambulatory studies.
Drivers of cervical cancer prevention and management in sub-Saharan Africa: a qualitative synthesis of mixed studies
Authors: Atnafu Desta Debalkie , Khatri Resham , Assefa Yibeltal
Published: February 2024

Background

Cervical cancer is a public health concern in the sub-Saharan Africa region. Cervical cancer screening is one of the strategies for detecting early precancerous lesions. However, many women have poor access to and utilization of screening services in the region. This review aimed to synthesize evidence on the challenges and opportunities of screening, early detection and  management of cervical cancer in sub-Saharan Africa.

Methods

We conducted a structured narrative review of studies published in English. We included studies published from 1 January 2013 to mid-2022. Studies were selected following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Key search terms (detractors and enablers, cervical cancer screening, sub-Saharan Africa) were employed to identify studies from three electronic databases (HINARI, Science Direct, and PubMed). We also conducted searches on Google Scholar to identify relevant grey literatures. A thematic analysis was conducted and themes were identified, then explained using a socio-ecological framework (intrapersonal, interpersonal, organizational, community, policy levels).

Results

We identified 60 studies in the final review. Cervical cancer screening and early detection and management programmes are influenced by drivers at multiple levels. Individual-level drivers included a lack of knowledge about cervical cancer and screening literacy, and a low risk in perception, attitude, susceptibility and perceived fear of test results, as well as sociodemographic characteristics of women. Interpersonal drivers were community embarrassment, women’s relationships with health workers, support and encouragement, the presence of peers or relatives to model preventive behaviour, and the mothers’ networks with others. At the organizational level, influencing factors were related to providers (cervical cancer screening practice, training, providers’ profession type, skill of counselling and sex, expert recommendation and work commitments). At the community level, drivers of cervical cancer screening included stigma, social–cultural norms, social networks and beliefs. System- and policy-level drivers were lack of nearby facilities and geographic remoteness, resource allocation and logistics management, cost of screening, promotion policy, ownership and management, lack of decentralized cancer policy and lack of friendly infrastructure.

Conclusions

There were several drivers in the implementation of cervical cancer screening programmes at multiple levels. Prevention and management of cervical cancer programmes requires multilevel strategies to be implemented  across the individual level (users), community and organizational levels (providers and community users), and system and policy levels. The design and implementation of policies and programmes need to address the multilevel challenges.
The scaffold of neutrophil extracellular traps promotes CCA progression and modulates angiogenesis via ITGAV/NFκB
Authors: Zhang Congyi , Wu Dehai , Dong Bowen , Liao Guanqun , Yu Yang , Huang Shizhuan , Luo Feng , Zhang Bin , Wu Haotian , Li Tianwei , Wen Dixiang , Tai Sheng
Published: February 2024

Neutrophil extracellular traps (NETs) have garnered attention for their dual role in host defense and tumor promotion. With their involvement documented across a spectrum of tumors, their influence on the progression of cholangiocarcinoma (CCA) is of paramount interest. We employed immunohistochemistry and immunofluorescence to detect NET deposition in CCA tissues. Through in vitro and in vivo investigation, including CCA organoid and transposon-based models in PAD4 KO mice, we explored the effects of NETs on cell proliferation and metastasis. Molecular insights were gained through RNA sequencing, enzyme linked immunosorbent assay, and chromatin immunoprecipitation. Elevated intratumoral NET deposition within CCA tissues was associated with poor survival. The influence of NETs on CCA proliferation, migration and invasion was primarily mediated by NET-DNA. RNA sequencing unveiled the activation of the NFκB signaling pathway due to NET-DNA stimulation. NET-DNA pull-down assay coupled with mass spectrometry revealed the interaction between NET-DNA and αV integrin (ITGAV), culmination in the activation of the NFκB pathway. Furthermore, NET-DNA directly upregulated the expression of VEGF-A in cancer cells. The study unequivocally establishes NETs as facilitators of CCA progression, orchestrating proliferation, metastasis, and angiogenesis through ITGAV/NFκB pathway activation. This novel insight positions NETs as prospective therapeutic targets for managing CCA patients. By implementing a variety of methodologies and drawing intricate connections between NETs, DNA interactions, and signaling pathways, this research expands our comprehension of the complex interplay between the immune system and cancer progression, offering promising avenues for intervention.
Adjunctive interventions: change methods directed at recipients that support uptake and use of health innovations
Authors: Smith Justin D. , Li Dennis H. , Merle James L. , Keiser Brennan , Mustanski Brian , Benbow Nanette D.
Published: February 2024

Background

Implementation science groups change methods into two categories: (1) clinical, behavioral, or biomedical intervention targeting recipient’s health outcomes and (2) implementation strategies targeting the delivery system. Differentiating interventions from strategies based on their intended functions is critical to accurately attributing their effects to health or implementation outcomes. However, in coordinating 200+ HIV implementation research projects and conducting systematic reviews, we identified change methods that had characteristics of both interventions and strategies that were inconsistently categorized. To alleviate confusion and improve change method specification, we propose that implementation science should adopt an extant but rarely used term—adjunctive interventions—to classify change methods that are distinct from the common intervention/strategy taxonomy.

Main text

Adjunctive interventions as change methods that target recipients (e.g., patients, participants) of a health intervention but are designed to increase recipients’ motivation, self-efficacy, or capacity for initiating, adhering to, complying with, or engaging with the health intervention over time. In two of our published reviews on implementation of HIV interventions, 25 out of 45 coded change methods fell into this gray area between strategy and intervention. We also noted instances in which the same change method was labelled as the intervention (“the thing”), as an adjunctive intervention, or an implementation strategy in different studies—further muddying the waters. Adjunctive interventions are distinguished from other change methods by their intended targets, desired outcomes, and theory of action and causal processes. Whereas health interventions target recipients and have a direct, causal effect on the health outcome, adjunctive interventions enhance recipients’ attitudes and behaviors to engage with the intervention and have an indirect causal link to the health outcome via increasing the probability of recipients’ utilization and adherence to the intervention. Adjunctive interventions are incapable of directly producing the health outcome and will themselves require implementation strategies to effectively impact sustained uptake, utilization, and adherence. Case examples, logic modeling, and considerations (e.g., relationship to consumer engagement strategies) for adjunctive intervention research are provided.

Conclusion

Conceptualizing adjunctive interventions as a separate type of change method will advance implementation research by improving tests of effectiveness, and the specification of mechanisms and outcomes.