bluuebunny/crossref_metadata_2025 huggingface dataset:
Naturopathic community clinics: an international cross-sectional survey
Authors: Lloyd Iva , Gerontakos Sophia , Cardozo Valentina
Published: August 2021

Background

Globally, naturopathic practitioners offer services in 98 countries, reaching every world region and providing care to diverse populations for a range of acute and chronic health conditions. Community clinics provide free or low-cost healthcare services and play a key role in providing necessary primary healthcare for underprivileged or marginalized populations. However, the reach and impact of naturopathic community clinics (NCCs) has not yet been examined. The aim of this study was to identify the characteristics of NCCs around the world, determine the types of services they offer and provide insight into the populations being served.

Methods

Two online cross-sectional surveys were administered using purposive and snowball sampling. A 6-item screening survey was administered first to identify clinics and institutions who fit the criteria for NCC services, followed by a 40-item follow-up survey. Descriptive analysis was conducted using frequencies and means.

Results

The screening survey returned a total of 37 responses from six world regions. Of those respondents who indicated involvement in NCCs, 74% went on to complete the follow-up survey. The majority of the responding NCCs were located in North America (50%), followed by Western Pacific (17%), Europe (10%), Asia (13%), Latin America (7%) and Africa (3%). The vast majority (71%) of the NCCs that have been in operation for more than 10 years are located in North America, while 43% of the NCCs that have been operational less than 5 years are in the Western Pacific Region. 80% of the responding NCCs were affiliated with a naturopathic school. The majority of respondents (76%) mentioned that they aim to serve underserved and/or marginalized populations, with 34% indicating that their target population is low-income families, 21% focusing on serving immigrants and refugees, 21% on serving people experiencing homelessness, 14% on serving Indigenous peoples, 14% on serving those with specific gender differences, 10% on serving seniors and 10% on serving drug users.

Conclusion

The naturopathic profession offers free or significantly low-cost naturopathic services through community clinics around the world. The findings of this survey provide insight into the important role of the naturopathic profession in primary health care and provide rationale for exploring this topic in greater detail.
Modelling the cost of place of birth: a pathway analysis
Authors: Scarf Vanessa L. , Yu Serena , Viney Rosalie , Cheah Seong Leang , Dahlen Hannah , Sibbritt David , Thornton Charlene , Tracy Sally , Homer Caroline
Published: August 2021

Background

In New South Wales (NSW), Australia there are three settings available for women at low risk of complications to give birth: home, birth centre and hospital. Between 2000 and 2012, 93.6% of babies were planned to be born in hospital, 6.0% in a birth centre and 0.4% at home. Availability of alternative birth settings is limited and the cost of providing birth at home or in a birth centre from the perspective of the health system is unknown.

Objectives

The objective of this study was to model the cost of the trajectories of women who planned to give birth at home, in a birth centre or in a hospital from the public sector perspective.

Methods

This was a population-based study using linked datasets from NSW, Australia. Women included met the following selection criteria: 37-41 completed weeks of pregnancy, spontaneous onset of labour, and singleton pregnancy at low risk of complications. We used a decision tree framework to depict the trajectories of these women and Australian Refined-Diagnosis Related Groups (AR-DRGs) were applied to each trajectory to estimate the cost of birth. A scenario analysis was undertaken to model the cost for 30 000 women in one year.

Findings

496 387 women were included in the dataset. Twelve potential outcome pathways were identified and each pathway was costed using AR-DRGs. An overall cost was also calculated by place of birth: $AUD4802 for homebirth, $AUD4979 for a birth centre birth and $AUD5463 for a hospital birth.

Conclusion

The findings from this study provides some clarity into the financial saving of offering more options to women seeking an alternative to giving birth in hospital. Given the relatively lower rates of complex intervention and neonatal outcomes associated with women at low risk of complications, we can assume the cost of providing them with homebirth and birth centre options could be cost-effective.
Toolkit and distance coaching strategies: a mixed methods evaluation of a trial to implement care coordination quality improvement projects in primary care
Authors: Penney Lauren S. , Bharath Purnima S. , Miake-Lye Isomi , Leng Mei , Olmos-Ochoa Tanya T. , Finley Erin P. , Chawla Neetu , Barnard Jenny M. , Ganz David A.
Published: August 2021

Background

Care coordination tools and toolkits can be challenging to implement. Practice facilitation, an active but expensive strategy, may facilitate toolkit implementation. We evaluated the comparative effectiveness of distance coaching, a form of practice facilitation, for improving the implementation of care coordination quality improvement (QI) projects.

Methods

We conducted a mixed methods evaluation of the Coordination Toolkit and Coaching (CTAC) initiative. Twelve matched US Veterans Health Administration primary care clinics were randomized to receive coaching and an online care coordination toolkit (“coached”;n = 6) or access to the toolkit only (“non-coached”;n = 6). We did interviews at six, 12, and 18 months. For coached sites, we‘ly collected site visit fieldnotes, prospective coach logs, retrospective coach team debriefs, and project reports. We employed matrix analysis using constructs from the Consolidated Framework for Implementation Research and a taxonomy of outcomes. We assessed each site’s project(s) using an adapted Complexity Assessment Tool for Systematic Reviews.

Results

Eleven sites implemented a local CTAC project. Eight sites (5 coached, 3 non-coached) used at least one tool from the toolkit. Coached sites implemented significantly more complex projects than non-coached sites (11.5 vs 7.5, 95% confidence interval 1.75–6.25,p < 0.001); engaged in more formal implementation processes (planning, engaging, reflecting and evaluating); and generally had larger, more multidisciplinary QI teams. Regardless of coaching status, sites focused on internal organizational improvement and low-intensity educational projects rather than the full suite of care coordination tools. At 12 months, half the coached and non-coached sites had clinic-wide project implementation; the remaining coached sites had implemented most of their project(s), while the remaining non-coached sites had either not implemented anything or conducted limited pilots. At 18 months, coached sites reported ongoing effort to monitor, adapt, and spread their CTAC projects, while non-coached sites did not report much continuing work. Coached sites accrued benefits like improved clinic relationships and team QI skill building that non-coached sites did not describe.

Conclusions

Coaching had a positive influence on QI skills of (and relationships among) coached sites’ team members, and the scope and rigor of projects. However, a 12-month project period was potentially too short to ensure full project implementation or to address cross-setting or patient-partnered initiatives.

Trial registration

NCT03063294.
Birth preparedness and related factors: a cross-sectional study in Tanzania City area
Authors: Shimpuku Yoko , Mwilike Beatrice , Ito Keiko , Mwakawanga Dorkasi , Hirose Naoki , Kubota Kazumi
Published: August 2021

Background

Birth preparedness could be the key factor that influences the choice of birthplace with skilled birth attendants. To reduce the high maternal mortality of Tanzania, a large study was planned to develop a smartphone app to promote birth preparedness in a city area of Tanzania. This study aimed to identify factors that influence birth preparedness in the city area of Tanzania.

Methods

Pregnant women were asked to complete the Birth Preparedness Questionnaire during antenatal visits using tablets. Multiple linear regression analyses were performed to determine the sociodemographic and obstetric characteristics that influenced the factors.

Results

A total of 211 participants were included in the analysis. Distance from the nearest health facility negatively influenced the total score of the Birth Preparedness Assessment (β= 0.7,p = 0.02). Education higher than college positively influenced the total score (β = 4.76,p = 0.01). Decision-making of birthplace by other people (not women) negatively influencedFamily Support(β=1.18,p = 0.03). Having jobs negatively influencedPreparation of Money and Food(β=-1.02,p < 0.01) and positively influenced the knowledge (β = 0.75,p = 0.03). Being single positively influencedPreparation of Money and Food(β = 0.35,p = 0.19) andPreference of Skilled Birth Attendants(β = 0.42,p = 0.04). Experience of losing a baby negatively influenced the knowledge (β=0.80,p < 0.01) andPreference of Skilled Birth Attendants(β=0.38,p = 0.02).

Conclusions

The findings showed an updated information on pregnant Tanzanian women living in an urban area where rapid environmental development was observed. Birth preparedness was negatively affected when women reside far from the health facilities, the birthplace decision-making was taken by others beside the women, women have jobs, and when women have experienced the loss of a baby. We hope to use the information from this study as content in our future study, in which we will be applying a smartphone app intervention for healthy pregnancy and birth preparedness. This information will also help in guiding the analysis of this future study. Although generalization of the study needs careful consideration, it is important to reconsider issues surrounding birth preparedness as women’s roles both in the family and society, are more, especially in urban settings.
Professionals’ responses to the introduction of AI innovations in radiology and their implications for future adoption: a qualitative study
Authors: Chen Yaru , Stavropoulou Charitini , Narasinkan Radhika , Baker Adrian , Scarbrough Harry
Published: August 2021

Background

Artificial Intelligence (AI) innovations in radiology offer a potential solution to the increasing demand for imaging tests and the ongoing workforce crisis. Crucial to their adoption is the involvement of different professional groups, namely radiologists and radiographers, who work interdependently but whose perceptions and responses towards AI may differ. We aim to explore the knowledge, awareness and attitudes towards AI amongst professional groups in radiology, and to analyse the implications for the future adoption of these technologies into practice.

Methods

We conducted 18 semi-structured interviews with 12 radiologists and 6 radiographers from four breast units in National Health Services (NHS) organisations and one focus group with 8 radiographers from a fifth NHS breast unit, between 2018 and 2020.

Results

We found that radiographers and radiologists vary with respect to their awareness and knowledge around AI. Through their professional networks, conference attendance, and contacts with industry developers, radiologists receive more information and acquire more knowledge of the potential applications of AI. Radiographers instead rely more on localized personal networks for information. Our results also show that although both groups believe AI innovations offer a potential solution to workforce shortages, they differ significantly regarding the impact they believe it will have on their professional roles. Radiologists believe AI has the potential to take on more repetitive tasks and allow them to focus on more interesting and challenging work. They are less concerned that AI technology might constrain their professional role and autonomy. Radiographers showed greater concern about the potential impact that AI technology could have on their roles and skills development. They were less confident of their ability to respond positively to the potential risks and opportunities posed by AI technology.

Conclusions

In summary, our findings suggest that professional responses to AI are linked to existing work roles, but are also mediated by differences in knowledge and attitudes attributable to inter-professional differences in status and identity. These findings question broad-brush assertions about the future deskilling impact of AI which neglect the need for AI innovations in healthcare to be integrated into existing work processes subject to high levels of professional autonomy.
Characterization of porcine sapelovirus prevalent in western Jiangxi, China
Authors: Yang Taotao , Zhang Lingqian , Lu Yingmei , Guo Minhong , Zhang Zhibang , Lin Anqi
Published: August 2021

Background

Porcine sapelovirus (PSV) infection can lead severe polioencephalomyelitis with high morbidity and mortality, which result in significant economic losses. Infection with the PSV is believed to be common yet limited information is available on the prevalence and molecular characterization of PSV in China. Therefore, the objective of this study was to characterize the prevalence and genome of PSV strains identified in the western Jiangxi province of China.

Results

A high specificity and sensitivity SYBR Green I-based RT-PCR method for PSV detection was developed. Two hundred and ninety four fecal samples were collected from December 2018 to March 2019 in 4 farms. An overall PSV-positivity rate of 11.22% (33/294) was detected with the real-time RT-PCR method, and a high infection rate and viral load of PSV were found in nursery pigs. In total, complete VP1 gene sequences of 11 PSV strains (PSV-YCs) were obtained. Homology comparisons of the VP1 gene of the 11 PSV-YCs with previously reported PSVs revealed nucleotide sequence identities ranging from 63% to 96.8%, and deduced amino acid sequence identities from 61.4% to 99.7%. Phylogenetic analyses based on the VP1 gene exhibited 2 main clades corresponding to PSV-1 and PSV-2, and all PSV-YCs prevalent in western Jiangxi belonged to the traditional genotype (PSV-1). In addition, the pairwise distances of VP1 gene sequences between PSV-YCs ranged from 0.009 to 0.198, which indicating that substantial genetic diversity among the PSVs in western Jiangxi.

Conclusions

To the authors’ knowledge, this is the first description of PSV in the Jiangxi province pig herds in China, and it is crucial to understand the epidemiology of the viruses in China. The results also provide an important theoretical foundation for diagnosis and early warning of epidemic diseases caused by PSVs prevailing in this region.
Bacterioferritin: a key iron storage modulator that affects strain growth and butenyl-spinosyn biosynthesis in Saccharopolyspora pogona
Authors: Tang Jianli , Zhu Zirong , He Haocheng , Liu Zhudong , Xia Ziyuan , Chen Jianming , Hu Jinjuan , Cao Li , Rang Jie , Shuai Ling , Liu Yang , Sun Yunjun , Ding Xuezhi , Hu Shengbiao , Xia Liqiu
Published: August 2021

Background

Butenyl-spinosyn, produced by Saccharopolyspora pogona, is a promising biopesticide due to excellent insecticidal activity and broad pesticidal spectrum. Bacterioferritin (Bfr, encoded by bfr) regulates the storage and utilization of iron, which is essential for the growth and metabolism of microorganisms. However, the effect of Bfr on the growth and butenyl-spinosyn biosynthesis in S. pogona has not been explored.

Results

Here, we found that the storage of intracellular iron influenced butenyl-spinosyn biosynthesis and the stress resistance of S. pogona, which was regulated by Bfr. The overexpression of bfr increased the production of butenyl-spinosyn by 3.14-fold and enhanced the tolerance of S. pogona to iron toxicity and oxidative damage, while the knockout of bfr had the opposite effects. Based on the quantitative proteomics analysis and experimental verification, the inner mechanism of these phenomena was explored. Overexpression of bfr enhanced the iron storage capacity of the strain, which activated polyketide synthase genes and enhanced the supply of acyl-CoA precursors to improve butenyl-spinosyn biosynthesis. In addition, it induced the oxidative stress response to improve the stress resistance of S. pogona.

Conclusion

Our work reveals the role of Bfr in increasing the yield of butenyl-spinosyn and enhancing the stress resistance of S. pogona, and provides insights into its enhancement on secondary metabolism, which provides a reference for optimizing the production of secondary metabolites in actinomycetes.
Elevated exosome-derived miRNAs predict osimertinib resistance in non-small cell lung cancer
Authors: Li Xinying , Chen Cen , Wang Zimu , Liu Jiaxin , Sun Wei , Shen Kaikai , Lv Yanling , Zhu Suhua , Zhan Ping , Lv Tangfeng , Song Yong
Published: August 2021

Background

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations will inevitably develop drug resistance after being treated with the third-generation EGFR-tyrosine kinase inhibitor (TKI), osimertinib. Recently, the drug resistance information transmitted by exosomal miRNAs has attracted much attention. However, the mechanism of exosome-derived miRNAs in osimertinib resistance remains unexplored.

Methods

We extracted and sequenced exosomes from the supernatant of the osimertinib-resistant cell line, H1975-OR, and the sensitive cell line, H1975. The results were compared with plasma exosome sequencing before and after the appearance of drug resistance in three NSCLC clinical patients treated with oral osimertinib. Exosome-derived miRNAs that had significantly increased expression levels after osimertinib resistance were screened for expanded validation in other 64 NSCLC patients.

Results

Cluster analysis of the target genes revealed that exosomal miRNAs participate in osimertinib resistance mechanisms through the activation of bypass pathways (RAS-MAPK pathway abnormality and PI3K pathway activation). Exosome-derived miR-184 and miR-3913-5p expression levels increased significantly after the onset of osimertinib resistance. Exosomal miR-3913-5p was associated with TNM stage, platelet count, tumor marker carcinoembryonic antigen, and distant metastases. In patients with EGFR exon 21 L858R mutation, the increased expression levels of miR-184 and miR-3913-5p derived from serum exosomes indicated osimertinib resistance. Similarly, for T790M-positive patients, the level of exosome-derived miR-3913-5p can be used as a predictive marker for osimertinib resistance.

Conclusions

The expression levels of miR-184 and miR-3913-5p derived from exosomes in the peripheral blood of NSCLC patients could be used as biomarkers to indicate osimertinib resistance.

Graphic Abstract
Nivolumab monotherapy or combination therapy with ipilimumab for lung cancer: a systemic review and meta-analysis
Authors: Jiang Huihui , Xu Aiqun , Xia Wanli , Xia Xingyuan , Li Pulin , Zhang Binbin , Zhu Ke , Zhou Sijing , Wang Ran
Published: August 2021

Background

The high incidence and mortality of lung cancer have seriously affected human life and health. Nivolumab is a monoclonal antibody that can inhibit programmed death 1 (PD-1) and Ipilimumab is a monoclonal antibody against CTLA-4(cytotoxic T lymphocyte-associated antigen 4), both of which can prevent the immune escape of tumor cells. Our goal was to synthesize evidence from published randomized controlled trials involving the safety and efficacy of either Nivolumab alone or in combination for the treatment of unresectable lung cancer.

Methods

We searched the following electronic databases: PubMed, Embase, and Cochrane libraries, and screened the retrieved records for eligibility. We used the Stata16 software for the analyses. The results of the analysis are expressed as hazard ratios (HRs) or risk ratios (RRs) and their corresponding 95% confidence intervals (CI).

Results

The final analysis included seven trials involving 3817 patients. Among patients with advanced lung cancer, patients using immunotherapy had better overall survival (OS), progression-free survival (PFS), and an objective response rate (ORR) than patients receiving chemotherapy. The HR of Nivolumab monotherapy or combination therapy with OS was compared with that of chemotherapy (HR: 0.73, 95% CI 0.64–0.83; HR: 0.67, 95% CI 0.55–0.81), and the HR of PFS was (HR: 0.81, 95% CI 0.69–0.94; HR: 0.67, 95% CI 0.55–0.82).

Conclusions

Immunotherapy has been shown to have more clinically meaningful survival benefits for patients with lung cancer, whether monotherapy or combination immunotherapy.

CRD42020213440
LINC01410 leads the migration, invasion and EMT of bladder cancer cells by modulating miR-4319 / Snail1
Authors: Guo Wei , Gai Qimei , Ma Yue , Shan Zhengfei , Wu Jitao
Published: August 2021

Background

Several previous studies have implied the significance of lncRNA1410 (LINC01410) in gastric cancer, rectal cancer, and cervical cancer. Nevertheless, the potential of LINC01410 in bladder cancer (BC) development has not been addressed.

Methods

The related mechanisms were explored by qRT-PCR analysis, CCK-8 assay, cell transfection assay, Transwell assay, Western Blot analysis, Luciferase reporter assay and RNA pull-down assay.

Results

In the following study, LINC01410, characterized as an oncogene, exhibited high levels of expression in BC tissues as compared to normal tissues and its expression leads to a reduced prognosis of BC. Functional characterization of LINC01410 showed that knocking down LINC01410 could markedly reduce the invasion and proliferation capacity of T24 and 5637 cells. Mechanistically, LINC01410 served as a sponge for miR-4319 and the findings were further attested through luciferase reporter assay. Analysis of miR-4319 demonstrated its low expression in BC tissues as compared to normal tissues and knocking down LINC01410 significantly increased miR-4319. Data obtained from rescue assay discovered that silencing of miR-4319 in T24 and 5637 cells restored the proliferation and invasion capacity of LINC01410.

Conclusions

Taken together, this study is the first report on the oncogenic potential of LINC01410 in BC development by upregulating Snail1 protein and downregulating miR-4319.

Trial registrationRetrospectively registered.
Increased primaquine total dose prevents Plasmodium vivax relapses in patients with impaired CYP2D6 activity: report of three cases
Authors: de Pina-Costa Anielle , Silvino Ana Carolina Rios , dos Santos Edwiges Motta , Pedro Renata Saraiva , Moreira José , Umana Gabriela Liseth , da Silva Ana Danielle Tavares , da Rosa Santos Otília Helena Lupi , de Deus Henriques Karina Medeiros , Daniel-Ribeiro Cláudio Tadeu , Brasil Patrícia , Sousa Tais Nobrega , Siqueira André M.
Published: August 2021

Background

The relapsing nature ofPlasmodium vivaxinfection is a major barrier to its control and elimination. Factors such as adequate dosing, adherence, drug quality, and pharmacogenetics can impact the effectiveness of radical cure ofP. vivaxand need to be adequately evaluated. CYP2D6 pathway mediates the activation of primaquine (primaquine) into an active metabolite(s) in hepatocytes, and impaired activity has been linked to a higher risk of relapse.

Cases presentation

Three patients diagnosed withP. vivaxmalaria presented repeated relapses after being initially treated with chloroquine (25 mg/kg) and primaquine (3.5 mg/kg in 14 days) at a non-endemic travel clinic. Recurring episodes were subsequently treated with a higher dose of primaquine (7 mg/kg in 14 days), which prevented further relapses in two patients. However, one patient still presented two episodes after a higher primaquine dose and was prescribed 300 mg of chloroquine weekly to prevent further episodes. Impaired CYP2D6 function was observed in all of them.

Conclusion

Lack of response to primaquine was associated with impaired CYP2D6 activity in three patients presenting multiple relapses followed in a non-endemic setting. Higher primaquine dosage was safe and effectively prevented relapses in two patients and should be further investigated as an option in Latin America. It is crucial to investigate the factors associated with unsuccessful radical cures and alternative therapeutic options.
Dynamics of inequality in child under-nutrition in Ethiopia
Authors: Yayo Negasi Mengesha
Published: August 2021

Introduction

Although Ethiopia has already achieved a remarkable progress in reducing under-five mortality in the last decades, undernutrition among children is still a common problem in this country. Socioeconomic inequalities in health outcomes in Ethiopia have been thus of focus in academia and policy spheres for a while now. This study provides new evidence on child undernutrition inequalities in Ethiopia using longitudinal perspective.

Method

Using three round of household panel survey (from 2012 to 2016), we use concentration index (associated curve), different mobility index approaches for measuring inequalities and its dynamics, and decomposition method to identify contributing factors.

Results

In all concentration index computing approaches and socioeconomic status ranking variables, the concentration indices are significant with negative value. This implies that in either of short-run or long-run inequality estimates, the burden of unequal distribution of undernutrition remains on the poor with significant difference across regions. While employing different SES ranking variables, the difference in the concentration indices is only found significant in case of Height-for-age Z-score. It signifies that relatively higher inequality is measured using consumption as ranking variable. Significant difference in inequality is also shown across regions. With respect to dynamics of inequalities, results on mobility indices computed based on Allanson et al. (Longitudinal analysis of income-related health inequality. Dundee Discussion Working Paper No. 214, 2010) approach show that inequality remain stable (persistent) in Height-for- age Z-score, and reduction of inequality in Weight-for- age Z-score while in case of Weight-for- height Z-score, there is no clear trend over subsequent waves. Results on decomposition of inequalities show that the major contributors are wealth index, consumption and mother’s education.

Conclusion

The argument of the choice of welfare indicator can have a large and significant impact on measured socioeconomic inequalities in a health variable which it depends on the variable examined. Employing longitudinal perspective rather than weighted average of cross-sectional data is justifiable to see the dynamic of inequality in child malnutrition. In both socioeconomic status ranking variables, the bulk of inequality in malnutrition is caused by inequality in socioeconomic status in which it disfavours the poor in both cases. This calls for enhancing the policy measures that narrow socioeconomic gaps between groups in the population and targeting on early childhood intervention and nutrition sensitive.
Socioeconomic inequalities in health behaviors: exploring mediation pathways through material conditions and time orientation
Authors: Mudd Andrea L. , van Lenthe Frank J. , Verra Sanne E. , Bal Michèlle , Kamphuis Carlijn B. M.
Published: August 2021

Background

Socioeconomic inequalities in health behaviors have been attributed to both structural and individual factors, but untangling the complex, dynamic pathways through which these factors influence inequalities requires more empirical research. This study examined whether and how two factors, material conditions and time orientation, sequentially impact socioeconomic inequalities in health behaviors.

Methods

Dutch adults 25 and older self-reported highest attained educational level, a measure of socioeconomic position (SEP); material conditions (financial strain, housing tenure, income); time orientation; health behaviors including smoking and sports participation; and health behavior-related outcomes including body mass index (BMI) and self-assessed health in three surveys (2004, 2011, 2014) of the longitudinal GLOBE (Dutch acronym for “Health and Living Conditions of the Population of Eindhoven and surroundings”) study. Two hypothesized pathways were investigated during a ten-year time period using sequential mediation analysis, an approach that enabled correct temporal ordering and control for confounders such as baseline health behavior.

Results

Educational level was negatively associated with BMI, positively associated with sports participation and self-assessed health, and not associated with smoking in the mediation models. For smoking, sports participation, and self-assessed health, a pathway from educational level to the outcome mediated by time orientation followed by material conditions was observed.

Conclusions

Time orientation followed by material conditions may play a role in determining socioeconomic inequalities in certain health behavior-related outcomes, providing empirical support for the interplay between structural and individual factors in socioeconomic inequalities in health behavior. Smoking may be determined by prior smoking behavior regardless of SEP, potentially due to its addictive nature. While intervening on time orientation in adulthood may be challenging, the results from this study suggest that policy interventions targeted at material conditions may be more effective in reducing socioeconomic inequalities in certain health behaviors when they account for time orientation.
A novel multi-functionalized multicellular nanodelivery system for non-small cell lung cancer photochemotherapy
Authors: Zhang Yongtai , Xia Qing , Wu Tong , He Zehui , Li Yanyan , Li Zhe , Hou Xuefeng , He Yuanzhi , Ruan Shuyao , Wang Zhi , Sun Jia , Feng Nianping
Published: August 2021

Background

A red blood cell membrane (RBCm)-derived drug delivery system allows prolonged circulation of an antitumor treatment and overcomes the issue of accelerated blood clearance induced by PEGylation. However, RBCm-derived drug delivery systems are limited by low drug-loading capacities and the lack of tumor-targeting ability. Thus, new designs of RBCm-based delivery systems are needed.

Results

Herein, we designed hyaluronic acid (HA)–hybridized RBCm (HA&RBCm)-coated lipid multichambered nanoparticles (HA&RBCm-LCNPs) to remedy the limitations of traditional RBCm drug delivery systems. The inner core co-assembled with phospholipid-regulated glycerol dioleate/water system in HA&RBCm-LCNPs met the required level of blood compatibility for intravenous administration. These newly designed nanocarriers had a honeycomb structure with abundant spaces that efficiently encapsulated paclitaxel and IR780 for photochemotherapy. The HA&RBCm coating allowed the nanocarriers to overcome the reticuloendothelial system barrier and enhanced the nanocarriers specificity to A549 cells with high levels of CD44. These properties enhanced the combinatorial antitumor effects of paclitaxel and IR780 associated with microtubule destruction and the mitochondrial apoptotic pathway.

Conclusions

The multifunctional HA&RBCm-LCNPs we designed expanded the functionality of RBCm and resulted in a vehicle for safe and efficient antitumor treatment.

Graphical abstract
A nitroxides-based macromolecular MRI contrast agent with an extraordinary longitudinal relaxivity for tumor imaging via clinical T1WI SE sequence
Authors: Guo Shiwei , Wang Xiaoming , Li Zhiqian , Pan Dayi , Dai Yan , Ye Yun , Tian Xiaohe , Gu Zhongwei , Gong Qiyong , Zhang Hu , Luo Kui
Published: August 2021

Background

Macromoleculization of nitroxides has been an effective strategy to improve low relaxivities and poor in vivo stability, however, nitroxides-based metal-free magnetic resonance imaging (MRI) macromolecular contrast agents (mCAs) are still under-performed. These mCAs do not possess a high nitroxides content sufficient for a cumulative effect. Amphiphilic nanostructures in these mCAs are not stable enough for highly efficient protection of nitroxides and do not have adequate molecular flexibility for full contact of the paramagnetic center with the peripheral water molecules. In addition, these mCAs still raise the concerns over biocompatibility and biodegradability due to the presence of macromolecules in these mCAs.

Results

Herein, a water-soluble biodegradable nitroxides-based mCA (Linear pDHPMA-mPEG-Ppa-PROXYL) was prepared via covalent conjugation of a nitroxides (2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl, PROXYL) onto an enzyme-sensitive linear di-block poly[N-(1, 3-dihydroxypropyl) methacrylamide] (pDHPMA). A high content of PROXYL up to 0.111 mmol/g in Linear pDHPMA-mPEG-Ppa-PROXYL was achieved and a stable nano-sized self-assembled aggregate in an aqueous environment (ca. 23 nm) was formed. Its longitudinal relaxivity (r1 = 0.93 mM− 1 s− 1) was the highest compared to reported nitroxides-based mCAs. The blood retention time of PROXYL from the prepared mCA in vivo was up to ca. 8 h and great accumulation of the mCA was realized in the tumor site due to its passive targeting ability to tumors. Thus, Linear pDHPMA-mPEG-Ppa-PROXYL could provide a clearly detectable MRI enhancement at the tumor site of mice via the T1WI SE sequence conventionally used in clinical Gd3+-based contrast agents, although it cannot be compared with DTPA-Gd in the longitudinal relaxivity and the continuous enhancement time at the tumor site of mice. Additionally, it was demonstrated to have great biosafety, hemocompatibility and biocompatibility.

Conclusions

Therefore, Linear pDHPMA-mPEG-Ppa-PROXYL could be a potential candidate as a substitute of metal-based MRI CAs for clinical application.

Graphic Abstract
“It’s like ‘liquid handcuffs”: The effects of take-home dosing policies on Methadone Maintenance Treatment (MMT) patients’ lives
Authors: Frank David , Mateu-Gelabert Pedro , Perlman David C. , Walters Suzan M. , Curran Laura , Guarino Honoria
Published: August 2021

Background

Methadone Maintenance Treatment (MMT) is widely recognized as one of the most effective ways of reducing risk of overdose, arrest, and transmission of blood-borne viruses like HIV and HCV among people that use opioids. Yet, MMT’s use of restrictive take-home dose policies that force most patients to attend their clinic on a daily, or near-daily, basis may be unpopular with many patients and lead to low rates of treatment uptake and retention. In response, this article examines how clinics’ take-home dosing policies have affected patients’ experiences of treatment and lives in general.

Methods

This article is based on semi-structured, qualitative interviews with a variety of stakeholders in MMT. Interviews explored: reasons for engaging with, or not engaging with MMT; how MMT is conceptualized by patients and treatment providers (e.g., as harm reduction or route to abstinence and/or recovery); experiences with MMT; perception of barriers to MMT (e.g., organizational/regulatory, social) and how MMT might be improved to support peoples’ substance use treatment needs and goals.

Results

Nearly all of the patients with past or present MMT use were highly critical of the limited access to take-home doses and consequent need for daily or near daily clinic attendance. Participants described how the use of restrictive take-home dose policies negatively impacted their ability to meet day-to-day responsibilities and also cited the need for daily attendance as a reason for quitting or avoiding OAT. Responses also demonstrate how such policies contribute to an environment of cruelty and stigma within many clinics that exposes this already-stigmatized population to additional trauma.

Conclusions

Take-home dose policies in MMT are not working for a substantial number of patients and are reasonably seen by participants as degrading and dehumanizing. Revision of MMT regulations and policies regarding take home doses are essential to improve patient satisfaction and the quality and effectiveness of MMT as a key evidence-based treatment and harm reduction strategy.
Reliability and validity of the Korean version of the MacNew heart disease Health-related Quality of Life questionnaire
Authors: Bae Sun Hyoung , Yoon Myeong-Ho , Park Jin-Hee
Published: August 2021

Background

Myocardial infarction and unstable angina are prevalent in Korea. The MacNew Heart Disease health-related quality of life questionnaire is a widely used patient-reported outcome measure for patients with heart disease in several countries. In this study, we tested the validity and reliability of the Korean version of the MacNew (K-MacNew).

Methods

Participants were 200 patients who had experienced unstable angina or myocardial infarction, and were recruited from a tertiary hospital in Korea. The K-MacNew was developed using forward–backward translation techniques. Construct validity (including discriminative validity), concurrent validity, and internal consistency reliability of the K-MacNew were assessed. Discriminative validity was assessed by examining the between-group differences in the K-MacNew scores according to functional capacity, anxiety, and depression levels. Concurrent validity was examined by correlating the K-MacNew dimensions with the physical and mental health domains of the 36-item Short Form Health Survey Instrument (SF-36).

Results

Factor analysis results of the K-MacNew demonstrated a three-factor structure (emotional, physical, and social) that explained 57.92% of the variance. Significant differences in the K-MacNew scores were observed according to patients’ functional capacity, anxiety, and depression levels. The SF-36 physical health domain score showed a moderate positive correlation with the physical dimension score of the K-MacNew (r = 0.517, P < 0.001), and the SF-36 mental health domain score showed a strong positive correlation with the emotional dimension of K-MacNew (r = 0.745, P < 0.001). The K-MacNew showed good internal consistency, with a Cronbach’s α of 0.947 for the global scale.

Conclusion

The K-MacNew demonstrated good reliability and validity for use as a patient-reported outcome measure and is ready for the assessment of the health-related quality of life of patients with coronary artery disease in Korea. To establish the clinical validity of the K-MacNew, additional studies should be conducted to verify the validity and reliability of the K-MacNew in a number of participants, including those with various types of coronary artery disease.
Cost-effectiveness of using amyloid positron emission tomography in individuals with mild cognitive impairment
Authors: Lee Young-Sil , Youn HyunChul , Jeong Hyun-Ghang , Lee Tae-Jin , Han Ji Won , Park Joon Hyuk , Kim Ki Woong
Published: August 2021

Background

Amyloid positron emission tomography (PET) makes it possible to diagnose Alzheimer’s disease (AD) in its prodromal phase including mild cognitive impairment (MCI). This study evaluated the cost-effectiveness of including amyloid-PET for assessing individuals with MCI.

Methods

The target population was 60-year-old patients who were diagnosed with MCI. We constructed a Markov model for the natural history of AD with the amyloid positivity (AP). Because amyloid-PET can detect the AP MCI state, AD detection can be made faster by reducing the follow-up interval for a high-risk group. The health outcomes were evaluated in quality-adjusted life years (QALYs) and the final results of cost-effectiveness analysis were presented in the form of the Incremental Cost-Effectiveness Ratio (ICER). To handle parameter uncertainties, one-way sensitivity analyses for various variables were performed.

Results

Our model showed that amyloid-PET increased QALYs by 0.003 in individuals with MCI. The estimated additional costs for adopting amyloid-PET amounted to a total of 1250 USD per patient when compared with the cost when amyloid-PET is not adopted. The ICER was 3,71,545 USD per QALY. According to the sensitivity analyses, treatment effect of Donepezil and virtual intervention effect in MCI state were the most influential factors.

Conclusions

In our model, using amyloid-PET at the MCI stage was not cost-effective. Future advances in management of cognitive impairment would enhance QALYs, and consequently improve cost-effectiveness.
PI3K-AKT, JAK2-STAT3 pathways and cell–cell contact regulate maspin subcellular localization
Authors: Longhi M. T. , Silva L. E. , Pereira M. , Magalhães M. , Reina J. , Vitorino F. N. L. , Gumbiner B. M. , da Cunha J. P. C. , Cella N.
Published: August 2021

Background

Maspin (SERPINB5) is a potential tumor suppressor gene with pleiotropic biological activities, including regulation of cell proliferation, death, adhesion, migration and gene expression. Several studies indicate that nuclear localization is essential for maspin tumor suppression activity. We have previously shown that the EGFR activation leads to maspin nuclear localization in MCF-10A cells. The present study investigated which EGFR downstream signaling molecules are involved in maspin nuclear localization and explored a possible role of cell–cell contact in this process.

Methods

MCF-10A cells were treated with pharmacological inhibitors against EGFR downstream pathways followed by EGF treatment. Maspin subcellular localization was determined by immunofluorescence. Proteomic and interactome analyses were conducted to identify maspin-binding proteins in EGF-treated cells only. To investigate the role of cell–cell contact these cells were either treated with chelating agents or plated on different cell densities. Maspin and E-cadherin subcellular localization was determined by immunofluorescence.

Results

We found that PI3K-Akt and JAK2-STAT3, but not MAP kinase pathway, regulate EGF-induced maspin nuclear accumulation in MCF-10A cells. We observed that maspin is predominantly nuclear in sparse cell culture, but it is redistributed to the cytoplasm in confluent cells even in the presence of EGF. Proteomic and interactome results suggest a role of maspin on post-transcriptional and translation regulation, protein folding and cell–cell adhesion.

Conclusions

Maspin nuclear accumulation is determined by an interplay between EGFR (via PI3K-Akt and JAK2-STAT3 pathways) and cell–cell contact.
The context matters - not all prolonged sitting bouts are equally related to momentary affective states: an ambulatory assessment with sedentary-triggered E-diaries
Authors: Kanning Martina , Niermann Christina , Ebner-Primer Ulrich , Giurgiu Marco
Published: August 2021

Background

Sedentary behaviors (SB) and especially prolonged sitting bouts are highly prevalent in daily life and studies indicated an association with an increased risk for several non-communicable diseases. Consequently, guidelines to reduce SB were developed. At the same time, an in-depth knowledge regarding SB such as where, what and with whom people spend time sedentary as well as correlates such as affective states of prolonged sitting bouts, is still lacking. A more differentiated view on SB is necessary to identify detrimental and modifiable sedentary bouts. We addressed this gap by conducting an ambulatory assessment study including accelerometer and sedentary-triggered e-diaries that captures data during prolonged sitting bouts (> 20 min). We investigated how contextual factors of prolonged sitting bouts are associated with momentary affective states.

Method

Four studies were combined with a final sample of 308 participants (50.3% female, Mage, 27.4, range, 17–66). SB was assessed objectively with thigh-worn accelerometers for four to five days. Whenever a participant was sitting for 20 or 30 min the accelerometer triggered questions assessing social (not alone vs. alone) and environmental (leisure vs. working) factors as well as momentary affective states (valence, energetic arousal and calmness). Multilevel analyses were used to examine within-person associations between different contexts and mood during prolonged sitting.

Results

Momentary affective states varied significantly due to different social and environmental contexts (ps < 0.001): Sitting together with others was associated with higher levels of valence and energetic arousal. Furthermore, sitting during leisure time was associated with higher levels of valence and calmness and lower levels of energetic arousal. Significant interaction analyses revealed that participants had the highest ratings while sitting during leisure episodes together with others.

Conclusion

Findings showed that prolonged sitting bouts differ regarding their association with affect. Sitting with others, sitting during leisure time and especially sitting during leisure time and with others, was associated with higher levels of momentary affective states, respectively. Thus, SB guidelines should focus on reducing those SB episodes that are associated with lower levels of affect, for example during working episodes.
First molecular characterization of poxviruses in cattle, sheep, and goats in Botswana
Authors: Modise Boitumelo Magret , Settypalli Tirumala Bharani Kumar , Kgotlele Tebogo , Xue Dingrong , Ntesang Kebonyemodisa , Kumile Kago , Naletoski Ivancho , Nyange John Frederick , Thanda Carter , Macheng Kenny Nametso , Marobela-Raborokgwe Chandapiwa , Viljoen Gerrit Johannes , Cattoli Giovanni , Lamien Charles Euloge
Published: August 2021

Background

Poxviruses within theCapripoxvirus,Orthopoxvirus, andParapoxvirusgenera can infect livestock, with the two former having zoonotic importance. In addition, they induce similar clinical symptoms in common host species, creating a challenge for diagnosis. Although endemic in the country, poxvirus infections of small ruminants and cattle have received little attention in Botswana, with no prior use of molecular tools to diagnose and characterize the pathogens.

Methods

A high-resolution melting (HRM) assay was used to detect and differentiate poxviruses in skin biopsy and skin scab samples from four cattle, one sheep, and one goat. Molecular characterization of capripoxviruses and parapoxviruses was undertaken by sequence analysis of RPO30 and GPCR genes.

Results

The HRM assay revealed lumpy skin disease virus (LSDV) in three cattle samples, pseudocowpox virus (PCPV) in one cattle sample, and orf virus (ORFV) in one goat and one sheep sample. The phylogenetic analyses, based on the RPO30 and GPCR multiple sequence alignments showed that the LSDV sequences of Botswana were similar to common LSDV field isolates encountered in Africa, Asia, and Europe. The Botswana PCPV presented unique features and clustered between camel and cattle PCPV isolates. The Botswana ORFV sequence isolated from goat differed from the ORFV sequence isolated from sheep.

Conclusions

This study is the first report on the genetic characterization of poxvirus diseases circulating in cattle, goats, and sheep in Botswana. It shows the importance of molecular methods to differentially diagnose poxvirus diseases of ruminants.
Circulating SARS-CoV-2 variants in Italy, October 2020–March 2021
Authors: Lai Alessia , Bergna Annalisa , Menzo Stefano , Zehender Gianguglielmo , Caucci Sara , Ghisetti Valeria , Rizzo Francesca , Maggi Fabrizio , Cerutti Francesco , Giurato Giorgio , Weisz Alessandro , Turchi Chiara , Bruzzone Bianca , Ceccherini Silberstein Francesca , Clementi Nicola , Callegaro Annapaola , Sagradi Fabio , Francisci Daniela , Venanzi Rullo Emmanuele , Vicenti Ilaria , Clementi Massimo , Galli Massimo ,   collaborative group SCIRE SARS-CoV-2 Italian Research Enterprise, Balotta Claudia , Gori Maria , Bagnarelli Patrizia , Baj Andreina , Novazzi Federica , Orsi Andrea , Caligiuri Patrizia , Boccotti Simona , Bellocchi Maria Concetta , Sarmati Loredana , Andreoni Massimo , Mancini Nicasio , Criscuolo Elena , Gallitelli Rosa , Testa Sophie , Dragoni Filippo , Zazzi Maurizio
Published: August 2021

A growing number of emerging SARS-CoV-2 variants is being identified worldwide, potentially impacting the effectiveness of current vaccines. We report the data obtained in several Italian regions involved in the SARS-CoV-2 variant monitoring from the beginning of the epidemic and spanning the period from October 2020 to March 2021.