bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine
Authors: Han Shulan , Ma Wenyan , Jiang Dawei , Sutherlin Logan , Zhang Jing , Lu Yu , Huo Nan , Chen Zhao , Engle Jonathan W. , Wang Yanping , Xu Xiaojie , Kang Lei , Cai Weibo , Wang Lianyan 
Published: November 2021

Abstract
Background
Poly(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles have potential applications as a vaccine adjuvant and delivery system due to its unique advantages as biodegradability and biocompatibility.

Experimental
We fabricated cationic solid lipid nanoparticles using PLGA and dimethyl-dioctadecyl-ammonium bromide (DDAB), followed by loading of model antigen OVA (antigen ovalbumin, OVA257-264) to form an OVA@DDAB/PLGA nano-vaccine. And we investigated the intracellular signaling pathway in dendritic cells in vitro and antigen transport pathway and immune response in vivo mediated by an OVA@DDAB/PLGA nano-vaccine.

Results
In vitro experiments revealed that the antigen uptake of BMDCs after nanovaccine incubation was two times higher than pure OVA or OVA@Al at 12 h. The BMDCs were well activated by p38 MAPK signaling pathway. Furthermore, the nano-vaccine induced antigen escape from lysosome into cytoplasm with 10 times increased cross-presentation activity than those of OVA or OVA@Al. Regarding the transport of antigen into draining lymph nodes (LNs), the nano-vaccine could rapidly transfer antigen to LNs by passive lymphatic drainage and active DC transport. The antigen+ cells in inguinal/popliteal LNs for the nano-vaccine were increased over two folds comparing to OVA@Al and OVA at 12 h. Moreover, the antigen of nano-vaccine stayed in LNs for over 7 days, germinal center formation over two folds higher than those of OVA@Al and OVA. After immunization, the nano-vaccine induced a much higher ratio of IgG2c/IgG1 than OVA@Al. It also effectively activated CD4+ T, CD8+ T and B cells for immune memory with a strong cellular response.

Conclusion
These results indicated that DDAB/PLGA NP was a potent platform to improve vaccine immunogenicity by p38 signaling pathway in BMDCs, enhancing transport of antigens to LNs, and higher immunity response.

Graphical Abstract
Reactive oxygen species (ROS)-responsive nanoprobe for bioimaging and targeting therapy of osteoarthritis
Authors: Shen Chong , Gao Ming , Chen Haimin , Zhan Yanting , Lan Qiumei , Li Zhimin , Xiong Wei , Qin Zainen , Zheng Li , Zhao Jinmin 
Published: November 2021

AbstractStimulus-responsive therapy that allows precise imaging-guided therapy is limited for osteoarthritis (OA) therapy due to the selection of proper physiological markers as stimulus. Based on that the over-production of Reactive Oxygen Species (ROS) is associated with the progression in OA, we selected ROS as markers and designed a cartilage targeting and ROS-responsive theranostic nanoprobe that can be used for effective bioimaging and therapy of OA. This nanoprobe was fabricated by using PEG micelles modified with ROS-sensitive thioketal linkers (TK) and cartilage-targeting peptide, termed TKCP, which was then encapsulated with Dexamethasone (DEX) to form TKCP@DEX nanoparticles. Results showed that the nanoprobe can smartly “turn on” in response to excessive ROS and “turn off” in the normal joint. By applying different doses of ROS inducer and ROS inhibitor, this nanoprobe can emit ROS-dependent fluorescence according to the degree of OA severity, helpful to precise disease classification in clinic. Specifically targeting cartilage, TKCP@DEX could effectively respond to ROS and sustained release DEX to remarkably reduce cartilage damage in the OA joints. This smart, sensitive and endogenously activated ROS-responsive nanoprobe is promising for OA theranostics.
Graphical Abstract
Hepatic small extracellular vesicles promote microvascular endothelial hyperpermeability during NAFLD via novel-miRNA-7
Authors: Zuo Rui , Ye Li-Feng , Huang Yi , Song Zi-Qing , Wang Lei , Zhi Hui , Zhang Min-Yi , Li Jie-Yi , Zhu Li , Xiao Wen-Jing , Shang Hong-Cai , Zhang Yang , He Rong-Rong , Chen Yang 
Published: November 2021

Abstract
Background
A recent study has reported that patients with nonalcoholic fatty liver disease (NAFLD) are more susceptible to coronary microvascular dysfunction (CMD), which may predict major adverse cardiac events. However, little is known regarding the causes of CMD during NAFLD. In this study, we aimed to explore the role of hepatic small extracellular vesicles (sEVs) in regulating the endothelial dysfunction of coronary microvessels during NAFLD.

Results
We established two murine NAFLD models by feeding mice a methionine-choline-deficient (MCD) diet for 4 weeks or a high-fat diet (HFD) for 16 weeks. We found that the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-dependent endothelial hyperpermeability occurred in coronary microvessels during both MCD diet and HFD-induced NAFLD. The in vivo and in vitro experiments proved that novel-microRNA(miR)-7-abundant hepatic sEVs were responsible for NLRP3 inflammasome-dependent endothelial barrier dysfunction. Mechanistically, novel-miR-7 directly targeted lysosomal associated membrane protein 1 (LAMP1) and promotes lysosomal membrane permeability (LMP), which in turn induced Cathepsin B-dependent NLRP3 inflammasome activation and microvascular endothelial hyperpermeability. Conversely, a specific novel-miR-7 inhibitor markedly improved endothelial barrier integrity. Finally, we proved that steatotic hepatocyte was a significant source of novel-miR-7-contained hepatic sEVs, and steatotic hepatocyte-derived sEVs were able to promote NLRP3 inflammasome-dependent microvascular endothelial hyperpermeability through novel-miR-7.

Conclusions
Hepatic sEVs contribute to endothelial hyperpermeability in coronary microvessels by delivering novel-miR-7 and targeting the LAMP1/Cathepsin B/NLRP3 inflammasome axis during NAFLD. Our study brings new insights into the liver-to-microvessel cross-talk and may provide a new diagnostic biomarker and treatment target for microvascular complications of NAFLD.

Graphical Abstract
M2 macrophage microvesicle-inspired nanovehicles improve accessibility to cancer cells and cancer stem cells in tumors
Authors: Wang Yuqi , Gong Xiang , Li Jie , Wang Hong , Xu Xiaoxuan , Wu Yao , Wang Jiaoying , Wang Siling , Li Yaping , Zhang Zhiwen 
Published: November 2021

AbstractCancer cells and cancer stem cells (CSCs) are the major players of cancer malignancy and metastasis, but they are extremely difficult to access. Inspired by the vital role of macrophages and microvesicle-mediated cell–cell communication in tumors, we herein designed M2 macrophage microvesicle-inspired nanovehicle of cabazitaxel (M-CFN) to promote accessibility to cancer cells and CSCs in tumors. In the 4T1 tumor model, M-CFN flexibly permeated the tumor mass, accessed cancer cells and CD90-positive cells, and significantly promoted their entry into CSC fractions in tumors. Moreover, M-CFN treatment profoundly eliminated aldehyde dehydrogenase (ALDH)-expressing CSCs in 4T1 and MCF-7 tumors, produced notable depression of tumor growth and caused 93.86% suppression of lung metastasis in 4T1 models. Therefore, the M2 macrophage microvesicle-inspired nanovehicle provides an encouraging strategy to penetrate the tumor tissues and access these insult cells in tumors for effective cancer therapy.
Graphical Abstract
Association between supportive supervision and performance of community health workers in India: a longitudinal multi-level analysis
Authors: Gopalakrishnan Lakshmi , Diamond-Smith Nadia , Avula Rasmi , Menon Purnima , Fernald Lia , Walker Dilys , Patil Sumeet 
Published: November 2021

Abstract
Introduction
Community health workers (CHWs) deliver services at-scale to reduce maternal and child undernutrition, but often face inadequate support from the health system to perform their job well. Supportive supervision is a promising intervention that strengthens the health system and can enable CHWs to offer quality services.

Objectives
We examined if greater intensity of supportive supervision as defined by monitoring visits to Anganwadi Centre, CHW-supervisor meetings, and training provided by supervisors to CHWs in the context of Integrated Child Services Development (ICDS), a national nutrition program in India, is associated with higher performance of CHWs. Per program guidelines, we develop the performance of CHWs measure by using an additive score of nutrition services delivered by CHWs. We also tested to see if supportive supervision is indirectly associated with CHW performance through CHW knowledge.

Methods
We used longitudinal survey data of CHWs from an impact evaluation of an at-scale technology intervention in Madhya Pradesh and Bihar. Since the inception of ICDS, CHWs have received supportive supervision from their supervisors to provide services in the communities they serve. Mixed-effects logistic regression models were used to test if higher intensity supportive supervision was associated with improved CHW performance. The model included district fixed effects and random intercepts for the sectors to which supervisors belong.

Results
Among 809 CHWs, the baseline proportion of better performers was 45%. Compared to CHWs who received lower intensity of supportive supervision, CHWs who received greater intensity of supportive supervision had 70% higher odds (AOR 1.70, 95% CI 1.16, 2.49) of better performance after controlling for their baseline performance, CHW characteristics such as age, education, experience, caste, timely payment of salaries, Anganwadi Centre facility index, motivation, and population served in their catchment area. A test of mediation indicated that supportive supervision is associated indirectly with CHW performance through improvement in CHW knowledge.

Conclusion
Higher intensity of supportive supervision is associated with improved CHW performance directly and through knowledge of CHWs. Leveraging institutional mechanisms such as supportive supervision could be important in improving service delivery to reach beneficiaries and potentially better infant and young child feeding practices and nutritional outcomes.
Trial registration : Trial registration number: https://doi.org/10.1186/ISRCTN83902145
Factors influencing the performance of community health volunteers working within urban informal settlements in low- and middle-income countries: a qualitative meta-synthesis review
Authors: Ogutu Michael , Muraya Kui , Mockler David , Darker Catherine 
Published: November 2021

Abstract
Background
There is limited information on community health volunteer (CHV) programmes in urban informal settlements in low- and middle-income countries (LMICs). This is despite such settings accounting for a high burden of disease. Many factors intersect to influence the performance of CHVs working in urban informal settlements in LMICs. This review was conducted to identify both the programme level and contextual factors influencing performance of CHVs working in urban informal settlements in LMICs.

Methods
Four databases were searched for qualitative and mixed method studies focusing on CHVs working in urban and peri-urban informal settlements in LMICs. We focused on CHV programme outcome measures at CHV individual level. A total of 13 studies met the inclusion criteria and were double read to extract relevant data. Thematic coding was conducted, and data synthesized across ten categories of both programme and contextual factors influencing CHV performance. Quality was assessed using both the Critical Appraisal Skills Programme (CASP) and the Mixed Methods Assessment Tool (MMAST); and certainty of evidence evaluated using the Confidence in the Evidence from Reviews of Qualitative research (CERQual) approach.

Results
Key programme-level factors reported to enhance CHV performance in urban informal settlements in LMICs included both financial and non-financial incentives, training, the availability of supplies and resources, health system linkage, family support, and supportive supervision. At the broad contextual level, factors found to negatively influence the performance of CHVs included insecurity in terms of personal safety and the demand for financial and material support by households within the community. These factors interacted to shape CHV performance and impacted on implementation of CHV programmes in urban informal settlements.

Conclusion
This review identified the influence of both programme-level and contextual factors on CHVs working in both urban and peri-urban informal settlements in LMICs. The findings suggest that programmes working in such settings should consider adequate remuneration for CHVs, integrated and holistic training, adequate supplies and resources, adequate health system linkages, family support and supportive supervision. In addition, programmes should also consider CHV personal safety issues and the community expectations.
The State of the World’s Midwifery 2021 report: findings to drive global policy and practice
Authors: Nove Andrea , ten Hoope-Bender Petra , Boyce Martin , Bar-Zeev Sarah , de Bernis Luc , Lal Geeta , Matthews Zoë , Mekuria Million , Homer Caroline S. E. 
Published: November 2021

AbstractThe third global State of the World’s Midwifery report (SoWMy 2021) provides an updated evidence base on the sexual, reproductive, maternal, newborn and adolescent health (SRMNAH) workforce. For the first time, SoWMy includes high-income countries (HICs) as well as low- and middle-income countries. This paper describes the similarities and differences between regions and income groups, and discusses the policy implications of these variations. SoWMy 2021 estimates a global shortage of 900,000 midwives, which is particularly acute in low-income countries (LICs) and in Africa. The shortage is projected to improve only slightly by 2030 unless additional investments are made. The evidence suggests that these investments would yield important returns, including: more positive birth experiences, improved health outcomes, and inclusive and equitable economic growth. Most HICs have sufficient SRMNAH workers to meet the need for essential interventions, and their education and regulatory environments tend to be strong. Upper-middle-income countries also tend to have strong policy environments. LICs and lower-middle-income countries tend to have a broader scope of practice for midwives, and many also have midwives in leadership positions within national government. Key regional variations include: major midwife shortages in Africa and South-East Asia but more promising signs of growth in South-East Asia than in Africa; a strong focus in Africa on professional midwives (rather than associate professionals: the norm in many South-East Asian countries); heavy reliance on medical doctors rather than midwives in the Americas and Eastern Mediterranean regions and parts of the Western Pacific; and a strong educational and regulatory environment in Europe but a lack of midwife leaders at national level. SoWMy 2021 provides stakeholders with the latest data and information to inform their efforts to build back better and fairer after COVID-19. This paper provides a number of policy responses to SoWMy 2021 that are tailored to different contexts, and suggests a variety of issues to consider in these contexts. These suggestions are supported by the inclusion of all countries in the report, because it is clear which countries have strong SRMNAH workforces and enabling environments and can be viewed as exemplars within regions and income groups.
Associations of neighborhood built, safety, and social environment with walking to and from school among elementary school-aged children in Chiba, Japan
Authors: Hino Kimihiro , Ikeda Erika , Sadahiro Saiko , Inoue Shigeru 
Published: November 2021

Abstract
Background
Although it is globally known that Japan has high prevalence of active school travel among children, there are few international studies on Japanese children’s school travel. Moreover, only few studies have focused on the differences in their mode of travel between to-school and from-school. This study examined the associations of neighborhood built, safety, and social environments with walking to/from school among elementary school-aged children in Chiba, Japan.

Methods
We conducted an online survey with 1545 parents of children aged 6–12 years residing in Chiba between 25 and 27 November 2020 during the COVID-19 pandemic. A neighborhood was defined as the area of a postcode provided by the participants. Each neighborhood environment was assessed based on the built environment (new town designation, walkability, distance to school, population density), social environment (neighborhood cohesion and connection), and safety (CCTVs, a road section for walking alone, safety volunteers). Neighborhood walkability was measured using subscales of the Neighborhood Environment Walkability Scale (youth and abbreviated versions) including crime safety and traffic safety. Parents’ perceived influence of COVID-19 on school commuting and after-school activities were also included in the model as covariates. Walking to and from school were separately analyzed using multinomial logistic regressions, where new towns and walkability were computed separately as explanatory variables.

Results
Four fifths of children walked to and from school daily. Walking to school was positively associated with crime safety, neighborhood connections, and schools sited in new towns. Walking from school had positive associations with traffic safety, neighborhood cohesion, and CCTVs, but negative associations with safety volunteers and after-school activities. The presence of a section for walking alone and perceived influence of COVID-19 had negative associations with walking to and from school.

Conclusions
Recent social changes such as declining birthrate, decline in public elementary schools, and increasing after-school activities may change parental attitudes toward children’s walking to/from school, and subsequently, their mode of school travel over time. To maintain the high prevalence of walking to/from school in Japan, multidisciplinary approaches involving different stakeholders from education, public health, and urban planning are required to overcome sectionalism and support this behavior in the long term.
Mediterranean diet and depression: a population-based cohort study
Authors: Yin Weiyao , Löf Marie , Chen Ruoqing , Hultman Christina M. , Fang Fang , Sandin Sven 
Published: November 2021

Abstract
Background
Depression imposes immense public health burden, demonstrating an urgent need of the identification of modifiable risk factors. Only a few cohort studies have analyzed the association between Mediterranean dietary pattern (MDP) and depression but with mixed results. We examined the impact of MDP on clinically ascertained depression in a large population-based dataset.

Methods
In 1991/92, detailed information on diet, using a food frequency questionnaire, and potential confounding factors (body weight, height, educational attainment, smoking, previous diabetes and hypertension, and physical activity) was collected, in a random sample of 49,261 Swedish women aged 29-49. Adherence to MDP was calculated. Clinical depression was extracted from the National Patient Register. Study participants were followed up through 2012.

Results
During an average follow-up of 20.4 years, 1677 incident cases of depression were diagnosed. We observed a lower risk of depression for medium (score 4-5) and high (6-9) adherence to MDP, compared with low (0-3) adherence (Medium: hazard ratio (HR) = 0.90, 95% confidence interval (CI) = 0.81-1.00; High: HR = 0.82, 95%CI = 0.71-0.94). Per unit increase of adherence, the risk of depression was reduced by 5% (HR = 0.95, 95%CI = 0.92-0.98). The association became stronger when restricting to severe form of depression (HR = 0.51, 95%CI = 0.33-0.76). The HRs were higher from age 50 onward both over the first and the second 10-year follow-up period, compared with before age 50, indicating stronger association with increasing age. Results remained after extensive sensitivity analyses.

Conclusion
Higher adherence to a Mediterranean diet at middle age was associated with a lower risk of depression later in life among Swedish women.
Barriers to translational research in Windsor Ontario: a survey of clinical care providers and health researchers
Authors: Senecal Justin B. , Metcalfe Karen , Wilson Kaila , Woldie Indryas , Porter Lisa A. 
Published: November 2021

Abstract
Background
Translational research is an ideology focussed on streamlining the transition of novel research into clinical practice to ultimately benefit populations. Central to this approach is overcoming barriers to research involvement and interdisciplinary collaboration. Identifying barriers has been the subject of several studies focused on communities with large academic hospitals. The Windsor-Essex region is currently built around community hospitals which have less of an emphasis on research, employ fewer physicians holding academic appointments and generally do not provide incentivised time for research and training. In this study, we surveyed clinicians and researchers working in Windsor-Essex to gain insight into barriers to translational research important to those working in smaller sized, community-based research networks.

Methods
Using an anonymous close-ended Qualtrics survey distributed via email, we surveyed faculty members from The University of Windsor and clinical care providers from Windsor-Essex (n = 68). This included 24 physicians, 14 allied health professionals, and 30 non-clinician researchers.

Results
Managing competing interests, lack of time, funding, infrastructure, and networks were identified by greater than 75% of participants as barriers to research involvement. 62% of physicians identified the lack of permanent post-graduate medical trainees as a barrier. Clinicians were consistently less experienced in research skills compared to others; particularly in publishing results and applying for funding (p < 0.001). Schedule incompatibility, funding issues and identifying interested collaborators with overlapping interests were identified as barriers to interdisciplinary collaboration by 80% of participants. Moreover, 46% of those surveyed were unhappy with their research involvement and these individuals were 13% more likely to perceive research as important for their career progression (p = 0.244).

Conclusions
This study identifies several important barriers to translational research in Windsor-Essex and suggests that many motivated researchers are unhappy with their current involvement. These results will inform decision making in the research community of Windsor-Essex and provides insight for communities of similar size and research capacity. Ultimately, enabling the translation of clinical research in all communities is required to ensure equitable access to cutting edge care.