bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of region-of-interest size and location on quantitative contrast-enhanced ultrasound of canine splenic perfusion
Authors: Morabito Simona , Di Pietro Simona , Cicero Luca , Falcone Annastella , Liotta Luigi , Crupi Rosalia , Cassata Giovanni , Macrì Francesco
Published: August 2021

Background

During contrast enhanced ultrasound (CEUS), the features of the regions of interest (ROI) can affect the value of the perfusion-related parameters obtained from a time intensity curve (TIC). In veterinary medicine, conflicting have been reported on the influence of ROI size and location on renal CEUS. There are some disagreeing evidences regarding the optimal method for selecting ROI in quantitative analysis of renal perfusion using CEUS.

The aim of this study was to evaluate the effect of the size and location of ROIs in the spleen of conscious dogs on perfusion variables determined using sulphur hexafluoride contrast-enhanced ultrasounds.

Results

A prospective observational study on 15 client-owned mixed-breed adult dogs was performed using a system equipped with contrast-tuned imaging technology. Qualitative and quantitative assessments of the spleen enhancement pattern were carried out. Three square ROIs (0.05 cm2) were manually drawn in a row and spaced 1 mm apart, placing adjacent ROIs at three different depths. Three medium rectangular ROIs (0.3 cm2) include the 3 smallest ROIs in each row, indicated by the letters A, B and C, and a single large square ROI (1 cm2) was drawn containing all previous ROIs. Software analysis of time-intensity curves generated within each ROI allowed us to calculate the perfusion-related parameters: peak enhancement, time to peak, regional blood flow, mean transit time and regional blood volume.

The coefficient of variation for all blood-related parameters was always lower in the larger ROI than in the other smaller ROIs. ROI A and B, positioned proximally and medially, levels respectively, showed similar coefficients of variation to the largest ROI. The analysis of variance model exhibited a significant effect of location and size of the ROIs in the quantitative analysis of canine spleen perfusion, with a reduction of perfusion-related parameters in the distal ROI.

Conclusions

The recommendation for a quantitative CEUS examination of a dog’s spleen is to analyze splenic perfusion by drawing a sufficiently large ROI proximal to the ultrasound beam on the splenic parenchyma. This may be of clinical relevance in the diagnosis of splenic diseases.
More natural more better: triple natural anti-oxidant puerarin/ferulic acid/polydopamine incorporated hydrogel for wound healing
Authors: Ou Qianmin , Zhang Shaohan , Fu Chuanqiang , Yu Le , Xin Peikun , Gu Zhipeng , Cao Zeyuan , Wu Jun , Wang Yan
Published: August 2021

Background

During wound healing, the overproduction of reactive oxygen species (ROS) can break the cellular oxidant/antioxidant balance, which prolongs healing. The wound dressings targeting the mitigation of ROS will be of great advantages for the wound healing. puerarin (PUE) and ferulic acid (FA) are natural compounds derived from herbs that exhibit multiple pharmacological activities, such as antioxidant and anti-inflammatory effects. Polydopamine (PDA) is made from natural dopamine and shows excellent antioxidant function. Therefore, the combination of natural antioxidants into hydrogel dressing is a promising therapy for wound healing.

Results

Hydrogel wound dressings have been developed by incorporating PUE or FA via PDA nanoparticles (NPs) into polyethylene glycol diacrylate (PEG-DA) hydrogel.

This hydrogel can load natural antioxidant drugs and retain the drug in the gel network for a long period due to the presence of PDA NPs. Under oxidative stress, this hydrogel can improve the activity of superoxide dismutase and glutathione peroxidase and reduce the levels of ROS and malondialdehyde, thus preventing oxidative damage to cells, and then promoting wound healing, tissue regeneration, and collagen accumulation.

Conclusion

Overall, this triple antioxidant hydrogel accelerates wound healing by alleviating oxidative injury. Our study thus provides a new way about co-delivery of multiple antioxidant natural molecules from herbs via antioxidant nanoparticles for wound healing and skin regeneration.

Graphic Abstract
Intranasal immunization with O-2′-Hydroxypropyl trimethyl ammonium chloride chitosan nanoparticles loaded with Newcastle disease virus DNA vaccine enhances mucosal immune response in chickens
Authors: Zhao Kai , Sun Beini , Shi Ci , Sun Yanwei , Jin Zheng , Hu Gaowei
Published: August 2021

Background

There has been a great interest in developing strategies for enhancing antigen delivery to the mucosal immune system as well as identifying mucosal active immunostimulating agents. To elevate the potential of O-2ʹ-Hydroxypropyl trimethyl ammonium chloride chitosan (O-2ʹ-HACC) as an adjuvant and mucosal immune delivery carrier for DNA vaccine, we prepared the O-2ʹ-HACC loaded with Newcastle disease virus (NDV) F gene plasmid DNA and C3d6 molecular adjuvant (O-2ʹ-HACC/pFDNA microparticles).

Results

The O-2ʹ-HACC/pFDNA exhibited a regular spherical morphology with a particle size of 202.3 ± 0.52 nm, a zeta potential of 50.8 ± 8.21 mV, encapsulation efficiency of 90.74 ± 1.10%, and a loading capacity of 49.84 ± 1.20%. The plasmid DNA could be sustainably released from the O-2ʹ-HACC/pFDNA after an initial burst release. Intranasal vaccination of chickens immunized with O-2ʹ-HACC/pFDNA not only induced higher anti-NDV IgG and sIgA antibody titers but also significantly promoted lymphocyte proliferation and produced higher levels of IL-2, IL-4, IFN-γ, CD4+, and CD8 + T lymphocytes compared with the NDV commercial live attenuated vaccine. Intranasal delivery of the O-2ʹ-HACC/pFDNA enhanced humoral, cellular, and mucosal immune responses and protected chickens from the infection of highly virulent NDV compared with the intramuscular delivery.

Conclusions

Collectively, our findings indicated that the O-2ʹ-HACC could be used as a vaccine adjuvant and delivery system for mucosal immunity and have an immense application promise.

Graphic Abstract
Evaluation of the feasibility and sustainability of the joint human and animal vaccination and its integration to the public health system in the Danamadji health district, Chad
Authors: Abakar Mahamat Fayiz , Seli Djimet , Lechthaler Filippo , Crump Lisa , Mancus Arielle , Tran Nhan , Zinsstag Jakob , Muñoz Daniel Cobos
Published: August 2021

Background

One Health approaches such as the Joint human and animal vaccination programmes (JHAVP) are shown to be feasible and to increase health care access to hard-to-reach communities such as mobile pastoralists. However, the financial sustainability and the integration into the public health systems at the district level of such programmes are still challenging. The main objective of the present study was to give insight to the feasibility and financial sustainability of JHAVP integrated as part of the public health system in Chad.

Methods

We conducted a mixed methods study using semi-structured key informant interviews, focus group discussions and budget impact analysis. Strengths, weaknesses, opportunities, and threats were analysed regarding the feasibility and sustainability of the implementation of JHAVP in Danamadji health district in Chad. Feasibility was further analysed using three dimensions: acceptability, implementation, and adaptation. Financial sustainability of JHAVP was analysed through budget impact analysis of implementation of the programme at district level.

Results

The acceptability of this approach was regularly assessed by immunization campaign teams through evaluation meetings which included pastoralists. The presence of authorities in the meetings and workshops of the programme had an incentive effect since they represent a mark of consideration these populations generally declared to be lacking. The coordination between the public health and veterinary services at central and decentralized level seemed to be a key element in the success of the implementation of the programme. Regarding financial sustainability, the total incremental budget impact was 27% slightly decreasing to 26% after five years, which accounts for up to one third of the total budget of the district health office. Also, given that most of the costs for each round are recurrent costs, efficiency gains from scale effects over time are limited.

Conclusion

Based on these findings, we conclude that for JHAVP to be routinely delivered at the district health level, a considerable increase in financial resources would be required. The district could benefit from joint immunization to maintain contact with mobile pastoralists to promote the use of available immunization services at district level.
The influence of linkages, feedback mechanisms, and caregiver mobility on immunization follow-up visits in Lideta sub-city of Addis Ababa, Ethiopia: a qualitative study
Authors: Zewde Thewodros , Teklu Alula , Bedada Diriba , Tsehaye Yoseph
Published: August 2021

Background

Losing children to follow-up is one of the major barriers identified in Ethiopia’s immunization programme. In many urban slum areas like Lideta sub-city, Addis Ababa, several demand- and supply-side factors affect the follow-up visits for routine immunization services, so this study aimed to explore the influence of linkages, a feedback mechanism, and caregiver mobility on immunization follow-up visits.

Methods

The study team employed a qualitative method and conducted 30 in-depth interviews with caregivers, 26 interviews with key informants, and five focus group discussions with health officials and decision-makers. A deductive content and thematic analysis was carried out by importing the transcripts into OpenCodes, applying the a priori codes, and identifying new codes and themes.

Results

The linkages among health facilities included those from hospitals to health centres, from hospitals to hospitals, and from health centres to health centres within and outside the sub-city. Using these linkages, most vaccinators transfer caregivers without providing multi-dose vial (MDV) vaccines, mainly bacille Calmette–Guérin (BCG) and measles-containing vaccines (MCV), “to minimize wastage” and thus successfully reduce vaccine wastage rates; yet most caregivers wasted their time, energy, and money travelling from one health facility to another. Despite some efforts to transfer caregivers using “transferal slips” and informal phone calls to vaccinators’ friends, unfortunately, there was no formally established system for obtaining feedback about the arrival of caregivers and continuation of the follow-up visits. Overall, the transfer process lacked uniformity, used various approaches, and was not systematic.

Conclusions

Transferal of caregivers for the sake of minimizing wastage of MDV vaccines without checking the vaccination schedules of the receiving health facilities, using various informal types of tools and approaches, along with a poor follow-up and feedback system, were major identified challenges which cost caregivers extra money, energy, and time in getting timely immunization services. Therefore, the Federal Ministry of Health should strengthen the linkages among facilities, ensure the establishment of formal communications by developing guidelines and standardized tools – transferal slips and approaches – and initiate a fast feedback provision system using SMS text messages.
Unveiling and addressing implementation barriers to routine immunization in the peri-urban slums of Karachi, Pakistan: a mixed-methods study
Authors: Yazdani Amna Tanweer , Muhammad Ameer , Nisar Muhammad Imran , Khan Uzma , Shafiq Yasir
Published: August 2021

Background

Great disparities in immunization coverage exist in Pakistan between urban and rural areas. However, coverage estimates for large peri-urban slums in Sindh are largely unknown and implementation challenges remain unexplored. This study explores key supply- and demand-side immunization barriers in peri-urban slums, as well as strategies to address them. It also assesses immunization coverage in the target slums.

Methods

Conducted in four peri-urban slums in Karachi, this mixed-methods study consists of a baseline cross-sectional coverage survey of a representative sample of 840 caregivers of children aged 12–23 months, and 155 in-depth interviews (IDIs) through purposive sampling of respondents (caregivers, community influencers and immunization staff). After identifying the barriers, a further six IDIs were then conducted with immunization policy-makers and policy influencers to determine strategies to address these barriers, resulting in the development of an original validated implementation framework for immunization in peri-urban slums. A thematic analysis approach was applied to qualitative data.

Results

The survey revealed 49% of children were fully vaccinated, 43% were partially vaccinated and 8% were unvaccinated. Demand-side immunization barriers included household barriers, lack of knowledge and awareness, misconceptions and fears regarding vaccines and social and religious barriers. Supply-side barriers included underperformance of staff, inefficient utilization of funds, unreliable immunization and household data and interference of polio campaigns with immunization. The implementation framework’s policy recommendations to address these barriers include: (1) improved human resource management; (2) staff training on counselling; (3) re-allocation of funds towards incentives, outreach, salaries and infrastructure; (4) a digital platform integrating birth registry and vaccination tracking systems for monitoring and reporting by frontline staff; (5) use of digital platform for immunization targets and generating dose reminders; and (6) mutual sharing of resources and data between the immunization, Lady Health Worker and polio programmes for improved coverage.

Conclusions

The implementation framework is underpinned by the study of uncharted immunization barriers in complex peri-urban slums, and can be used by implementers in Pakistan and other developing countries to improve immunization programmes in limited-resource settings, with possible application at a larger scale. In particular, a digital platform integrating vaccination tracking and birth registry data can be expanded for nationwide use.
Using health data for decision-making at each level of the health system to achieve universal health coverage in Ethiopia: the case of an immunization programme in a low-resource setting
Authors: Tilahun Binyam , Teklu Alemayehu , Mancuso Arielle , Endehabtu Berhanu F. , Gashu Kassahun D. , Mekonnen Zeleke A.
Published: August 2021

Background

For evidence-based decision-making, there is a need for quality, timely, relevant and accessible information at each level of the health system. Limited use of local data at each level of the health system is reported to be a main challenge for evidence-based decision-making in low- and middle-income countries. Although evidence is available on the timeliness and quality of local data, we know little about how it is used for decision-making at different levels of the health system. Therefore, this study aimed to assess the level of data use and its effect on data quality and shared accountability at different levels of the health system.

Methods

An implementation science study was conducted using key informants and document reviews between January and September 2017. A total of 21 key informants were selected from community representatives, data producers, data users and decision-makers from the community to the regional level. Reviewed documents include facility reports, district reports, zonal reports and feedback in supervision from the district. Thematic content analysis was performed for the qualitative data.

Results

Respondents reported that routine data use for routine decision-making was low. All health facilities and health offices have a performance monitoring team, but these were not always functional. Awareness gaps, lack of motivating incentives, irregularity of supportive supervision, lack of community engagement in health report verification as well as poor technical capacity of health professionals were found to be the major barriers to data use. The study also revealed that there are no institutional or national-level regulations or policies on the accountability mechanisms related to health data. The community-level Health Development Army programme was found to be a strong community engagement approach that can be leveraged for data verification at the source of community data.

Conclusion

The culture of using routine data for decision-making at the local level was found to be low. Strengthening the capacity of health workers and performance monitoring teams, introducing incentive mechanisms for data use, engaging the community in data verification and introducing accountability mechanisms for health data are essential to improve data use and quality.
Using participatory action research to improve immunization utilization in areas with pockets of unimmunized children in Nigeria
Authors: Akwataghibe Ngozi N. , Ogunsola Elijah A. , Popoola Oluwafemi A. , Agbo Adanna I. , Dieleman Marjolein A.
Published: August 2021

Background

In 2005, Nigeria adopted the Reaching Every Ward strategy to improve vaccination coverage for children 0–23 months of age. By 2015, Ogun state had full coverage (100%) in 12 of its 20 local government areas, but eight had pockets of unimmunized children, with the highest burden (37%) in Remo North. A participatory action research (PAR) approach was used to facilitate implementation of local solutions to contextual barriers to immunization in Remo North. This article assesses and seeks to explain the outcomes of the PAR implemented in Remo North to understand whether and possibly how it improved immunization utilization.

Methods

The PAR intervention took place from 2016 to 2017. It involved two (4-month) cycles of dialogue and action between community members, frontline health workers and local government officials in two wards of Remo North, facilitated by the research team. The PAR was assessed using a pre/post-intervention-only design with mixed methods. These included household surveys of caregivers of 215 and 213 children, respectively, 25 semi-structured interviews with stakeholders involved in immunization service delivery and 16 focus group discussions with community members. Data were analysed using the Strategic Advisory Group of Experts (SAGE) vaccine hesitancy framework.

Results

Collaboration among the three stakeholder groups enabled the development and implementation of solutions to identified problems related to access to and use of immunization services. At endline, assessment by card for children older than 9 months revealed a significant increase in those fully immunized, from 60.7% at baseline to 90.9% (p < .05). A significantly greater number of caregivers visited fixed government health facilities for routine immunization at endline (83.2%) than at baseline (54.2%) (p < .05). The reasons reported by caregivers for improved utilization of routine immunization services were increased community mobilization activities and improved responsiveness of the health workers. Spillover effects into maternal health services enhanced the use of immunization services by caregivers. Spontaneous scale-up of actions occurred across Remo North due to the involvement of local government officials.

Conclusion

The PAR approach achieved contextual solutions to problems identified by communities. Collection and integration of evidence into discussions/dialogues with stakeholders can lead to change. Leveraging existing structures and resources enhanced effectiveness.
Prospective relations between maternal emotional eating, feeding to soothe, and infant appetitive behaviors
Authors: Temmen Chelsie D. , Lipsky Leah M. , Faith Myles S. , Nansel Tonja R.
Published: August 2021

Background

Infant obesogenic appetitive behaviors are associated with greater infant weight and child obesity, yet little is known about maternal influences on infant appetitive behaviors. This study examines the relations between maternal eating behaviors, feeding to soothe, and infant appetitive behaviors in a longitudinal sample of United States mothers.

Methods

Pregnant women were recruited in the first trimester (< 12 weeks) and followed through 1 year postpartum. Mothers reported their own eating behaviors (eating competence, restrained, emotional, and external eating) in pregnancy; feeding to soothe their infant at 2, 6, and 12 months postpartum; and their infants’ appetitive behaviors (enjoyment of food, food responsiveness, slowness in eating, and satiety responsiveness) at 6 months. Three path models were estimated to examine the direct relations of maternal eating behaviors with infant appetitive behaviors, the indirect relations of maternal eating behaviors with infant appetitive behaviors through feeding to soothe, and the longitudinal relations between feeding to soothe and infant appetitive behaviors.

Results

Maternal eating behaviors and infant appetitive behaviors were directly and indirectly related in all three models. Greater maternal eating competence was related to greater enjoyment of food but was not related to feeding to soothe. Greater maternal restrained and external eating were not directly related to infant appetitive behaviors but were indirectly related to greater infant responsiveness to food through more frequent feeding to soothe. Additionally, several longitudinal relations between feeding to soothe behaviors and infant appetitive behaviors were present. More frequent feeding to soothe at 2 months was related to greater responsiveness to food at 6 months, which was then related to more frequent feeding to soothe at 6 months. Furthermore, greater satiety responsiveness, faster eating speed, and greater responsiveness to food at 6 months were related to more frequent feeding to soothe at 12 months.

Conclusions

Maternal eating behaviors were related to infant appetitive behaviors directly and indirectly through feeding to soothe. Additionally, results suggest feeding to soothe and infant appetitive behaviors may be bidirectionally linked. These results underscore the need to examine how parental feeding behaviors are influenced both by parental eating behaviors and child appetitive behaviors throughout infancy.

Trial registration

Clinicaltrials.gov. Registration ID – NCT02217462. Date of registration – August 13, 2014.
A three-dimensional printed model in preoperative consent for ventricular septal defect repair
Authors: Deng Xicheng , He Siping , Huang Peng , Luo Jinwen , Yang Guangxian , Zhou Bing , Xiao Yunbin
Published: August 2021

Background

The 3D printing technology in congenital cardiac surgery has been widely utilized to improve patients’ understanding of their disease. However, there has been no randomized controlled study on its usefulness in surgical consent for congenital heart disease repair.

Methods

A randomized controlled study was performed during consent process in which guardians of candidates for ventricular septal defect repair were given detailed explanation of the anatomy, indication for surgery and potential complication and risks using 3D print ventricular septal defect model (n = 20) versus a conventional 2D diagram (n = 20). A questionnaire was finished by each guardian of the patients. Data collected from questionnaires as well as medical records were statistically analyzed.

Results

Statistically significant improvements in ratings of understanding of ventricular septal defect anatomy (p = 0.02), and of the surgical procedure and potential complications (p = 0.02) were noted in the group that used the 3D model, though there was no difference in overall ratings of the consent process (p = 0.09). There was no difference in questionnaire score between subjects with different education levels. The clinical outcomes, as represented by the duration of intensive care unit stay, intubation duration was comparable between the two groups.

Conclusions

The results indicated that it was an effective tool which may be used to consent for congenital heart surgery. Different education levels do not affect guardians’ understanding in consent. The impact of 3D printing used in this scenario on long term outcomes remains to be defined.
Survival and long-term outcomes following in-hospital cardiac arrest in a Swiss university hospital: a prospective observational study
Authors: Fuchs Alexander , Käser Dominic , Theiler Lorenz , Greif Robert , Knapp Jürgen , Berger-Estilita Joana
Published: August 2021

Background

Incidence of in-hospital cardiac arrest is reported to be 0.8 to 4.6 per 1,000 patient admissions. Patient survival to hospital discharge with favourable functional and neurological status is around 21–30%. The Bern University Hospital is a tertiary medical centre in Switzerland with a cardiac arrest team that is available 24 h per day, 7 days per week. Due to lack of central documentation of cardiac arrest team interventions, the incidence, outcomes and survival rates of cardiac arrests in the hospital are unknown. Our aim was to record all cardiac arrest team interventions over 1 year, and to analyse the outcome and survival rates of adult patients after in-hospital cardiac arrests.

Methods

We conducted a prospective single-centre observational study that recorded all adult in-hospital cardiac arrest team interventions over 1 year, using an Utstein-style case report form. The primary outcome was 30-day survival after in-hospital cardiac arrest. Secondary outcomes were return of spontaneous circulation, neurological status (after return of spontaneous circulation, after 24 h, after 30 days, after 1 and 5 years), according to the Glasgow Outcomes Scale, and functional status at 30 days and 1 year, according to the Short-form-12 Health Survey.

Results

The cardiac arrest team had 146 interventions over the study year, which included 60 non-life-threatening alarms (41.1%). The remaining 86 (58.9%) acute life-threatening situations included 68 (79.1%) as patients with cardiac arrest. The mean age of these cardiac arrest patients was 68 ± 13 years, with a male predominance (51/68; 75.0%). Return of spontaneous circulation was recorded in 49 patients (72.1%). Over one-third of the cardiac arrest patients (27/68) were alive after 30 days with favourable neurological outcome. The patients who survived the first year lived also to 5 years after the event with favourable neurological and functional status.

Conclusions

The in-hospital cardiac arrest incidence on a large tertiary Swiss university hospital was 1.56 per 1000 patient admissions. After a cardiac arrest, about a third of the patients survived to 5 years with favourable neurological and functional status. Alarms unrelated to life-threatening situations are common and need to be taken into count within a low-threshold alarming system.

Trial Registration: The trial was registered in clinicaltrials.gov (NCT02746640).
The NUDGE trial pragmatic trial to enhance cardiovascular medication adherence: study protocol for a randomized controlled trial
Authors: Glasgow Russell E. , Knoepke Christopher E. , Magid David , Grunwald Gary K. , Glorioso Thomas J. , Waughtal Joy , Marrs Joel C. , Bull Sheana , Ho P. Michael
Published: August 2021

Background

Nearly half of patients do not take their cardiovascular medications as prescribed, resulting in increased morbidity, mortality, and healthcare costs. Mobile and digital technologies for health promotion and disease self-management offer an opportunity to adapt behavioral “nudges” using ubiquitous mobile phone technology to facilitate medication adherence. The Nudge pragmatic clinical trial uses population-level pharmacy data to deliver nudges via mobile phone text messaging and an artificial intelligent interactive chat bot with the goal of improving medication adherence and patient outcomes in three integrated healthcare delivery systems.

Methods

The Theory of mHealth, the Expanded RE-AIM/PRISM, and the PRECIS-2 frameworks were used for program planning, implementation, and evaluation, along with a focus on dissemination and cost considerations. During the planning phase, the Nudge study team developed and piloted a technology-based nudge message and chat bot of optimized interactive content libraries for a range of diverse patients. Inclusion criteria are very broad and include patients in one of three diverse health systems who take medications to treat hypertension, atrial fibrillation, coronary artery disease, diabetes, or hyperlipidemia. A target of approximately 10,000 participants will be randomized to one of 4 study arms: usual care (no intervention), generic nudge (text reminder), optimized nudge, and optimized nudge plus interactive AI chat bot. The PRECIS-2 tool indicated that the study protocol is very pragmatic, although there is variability across PRECIS-2 dimensions.

Discussion

The primary effectiveness outcome is medication adherence defined by the proportion of days covered (PDC) using pharmacy refill data. Implementation outcomes are assessed using the RE-AIM framework, with a particular focus on reach, consistency of implementation, adaptations, cost, and maintenance/sustainability. The project has limitations including limited power to detect some subgroup effects, medication complications (bleeding), and longer-term outcomes (myocardial infarction). Strengths of the study include the diverse healthcare systems, a feasible and generalizable intervention, transparent reporting using established pragmatic research and implementation science frameworks, strong stakeholder engagement, and planning for dissemination and sustainment.

Trial registration

ClinicalTrials.govNCT03973931. Registered on 4 June 2019. The study was funded by the NIH; grant number is 4UH3HL144163-02 issued 4/5/19.
C-STICH2: emergency cervical cerclage to prevent miscarriage and preterm birth—study protocol for a randomised controlled trial
Authors: Hodgetts-Morton Victoria , Hewitt Catherine A. , Jones Laura , Leighton Lisa , Pilarski Nicole , Molloy Eleanor , Hinshaw Kim , Norman Jane , Waugh Jason , Stock Sarah , Thornton Jim , Toozs-Hobson Philip , Johnston Tracey , Coomarasamy Arri , Thangaratinam Shakila , Mol Ben , Pajkrt Eva , Marlow Neil , Roberts Tracy , Middleton Lee , Brocklehurst Peter , Morris Katie
Published: August 2021

Background

Cervical cerclage is a recognised treatment to prevent late miscarriage and pre-term birth (PTB). Emergency cervical cerclage (ECC) for cervical dilatation with exposed unruptured membranes is less common and the potential benefits of cerclage are less certain. A randomised control trial is needed to accurately assess the effectiveness of ECC in preventing pregnancy loss compared to an expectant approach.

Methods

C-STICH2 is a multicentre randomised controlled trial in which women presenting with cervical dilatation and unruptured exposed membranes at 16 + 0 to 27 + 6 weeks gestation are randomised to ECC or expectant management. Trial design includes 18 month internal pilot with embedded qualitative process evaluation, minimal data set and a within-trial health economic analysis.

Inclusion criteria are ≥16 years, singleton pregnancy, exposed membranes at the external os, gestation 16 + 0–27 + 6 weeks, and informed consent. Exclusion criteria are contraindication to cerclage, cerclage in situ or previous cerclage in this pregnancy.

Randomisation occurs via an online service in a 1:1 ratio, using a minimisation algorithm to reduce chance imbalances in key prognostic variables (site, gestation and dilatation). Primary outcome is pregnancy loss; a composite including miscarriage, termination of pregnancy and perinatal mortality defined as stillbirth and neonatal death in the first week of life. Secondary outcomes include all core outcomes for PTB. Two-year development outcomes will be assessed using general health and Parent Report of Children’s Abilities-Revised (PARCA-R) questionnaires. Intended sample size is 260 participants (130 each arm) based on 60% rate of pregnancy loss in the expectant management arm and 40% in the ECC arm, with 90% power and alpha 0.05. Analysis will be by intention-to-treat.

Discussion

To date there has been one small trial of ECC in 23 participants which included twin and singleton pregnancies. This small trial along with the largest observational study (n = 161) found ECC to prolong pregnancy duration and reduce deliveries before 34 weeks gestation. It is important to generate high quality evidence on the effectiveness of ECC in preventing pregnancy loss, and improve understanding of the prevalence of the condition and frequency of complications associated with ECC. An adequately powered RCT will provide the highest quality evidence regarding optimum care for these women and their babies.

Trial registration

ISRCTN Registry ISRCTN12981869. Registered on 13th June 2018.
RETRACTED ARTICLE: Mesenchymal stem cell-derived exosomal miR-146a reverses diabetic β-cell dedifferentiation
Authors: He Qin , Song Jia , Cui Chen , Wang Jinbang , Hu Huiqing , Guo Xinghong , Yang Mengmeng , Wang Lingshu , Yan Fei , Liang Kai , Liu Zhaojian , Liu Fuqiang , Sun Zheng , Dong Ming , Hou Xinguo , Chen Li
Published: August 2021

Background

Mesenchymal stem cells (MSCs) show promising therapeutic potential in treating type 2 diabetes mellitus (T2DM) in clinical studies. Accumulating evidence has suggested that the therapeutic effects of MSCs are not due to their direct differentiation into functional β-cells but are instead mediated by their paracrine functions. Among them, exosomes, nano-sized extracellular vesicles, are important substances that exert paracrine functions. However, the underlying mechanisms of exosomes in ameliorating T2DM remain largely unknown.

Methods

Bone marrow mesenchymal stem cell (bmMSC)-derived exosomes (bmMDEs) were administrated to T2DM rats and high-glucose-treated primary islets in order to detect their effects on β-cell dedifferentiation. Differential miRNAs were then screened via miRNA sequencing, and miR-146a was isolated after functional verification. TargetScan, reporter gene detection, insulin secretion assays, and qPCR validation were used to predict downstream target genes and involved signaling pathways of miR-146a.

Results

Our results showed that bmMDEs reversed diabetic β-cell dedifferentiation and improved β-cell insulin secretion both in vitro and in vivo. Results of miRNA sequencing in bmMDEs and subsequent functional screening demonstrated that miR-146a, a highly conserved miRNA, improved β-cell function. We further found that miR-146a directly targeted Numb, a membrane-bound protein involved in cell fate determination, leading to activation of β-catenin signaling in β-cells. Exosomes derived from miR-146a-knockdown bmMSCs lost the ability to improve β-cell function.

Conclusions

These findings demonstrate that bmMSC-derived exosomal miR-146a protects against diabetic β-cell dysfunction by acting on the NUMB/β-catenin signaling pathway, which may represent a novel therapeutic strategy for T2DM.
MSCs from polytrauma patients: preliminary comparative study with MSCs from elective-surgery patients
Authors: López Raúl , Martí-Chillón Gerardo J. , Blanco Juan F. , da Casa Carmen , González-Robledo Javier , Pescador David , Preciado Silvia , Muntión Sandra , Sánchez-Guijo Fermín
Published: August 2021

Background

Polytrauma is a major clinical problem due to its impact on morbidity and mortality, especially among the younger population. Its pathophysiology is not completely elucidated, and the study of the involvement of certain cell populations with therapeutic potential, such as mesenchymal stromal cells (MSCs), is an area of growing interest, as mesenchymal cells have anti-inflammatory, immunoregulatory, and osteogenic potential.

Methods

In the present preliminary work, we have evaluated the characteristics of MSCs in terms of proliferation, immunophenotype, cell cycle, clonogenic capacity, and multilineage differentiation ability in a series of 18 patients with polytrauma and compared them to those from otherwise healthy patients undergoing elective spinal surgery.

Results

MSCs from polytrauma patients displayed higher proliferative potential with significantly higher cumulative population doublings, increased expression of some important cell adhesion molecules (CD105, CD166), and an early pre-osteogenic differentiation ability compared to those of the control group.

Conclusions

MSCs could potentially be of help in the repair process of polytrauma patients contribute to both cell-tissue repair and anti-inflammatory response. This potential should be further explored in larger studies.
New insights into mitophagy and stem cells
Authors: Lin Qingyin , Chen Jiaqi , Gu Lifang , Dan Xingang , Zhang Cheng , Yang Yanzhou
Published: August 2021

Mitophagy is a specific autophagic phenomenon in which damaged or redundant mitochondria are selectively cleared by autophagic lysosomes. A decrease in mitophagy can accelerate the aging process. Mitophagy is related to health and longevity and is the key to protecting stem cells from metabolic stress damage. Mitophagy decreases the metabolic level of stem cells by clearing active mitochondria, so mitophagy is becoming increasingly necessary to maintain the regenerative capacity of old stem cells. Stem cell senescence is the core problem of tissue aging, and tissue aging occurs not only in stem cells but also in transport amplifying cell chambers and the stem cell environment. The loss of the autophagic ability of stem cells can cause the accumulation of mitochondria and the activation of the metabolic state as well as damage the self-renewal ability and regeneration potential of stem cells. However, the claim remains controversial. Mitophagy is an important survival strategy against nutrient deficiency and starvation, and mitochondrial function and integrity may affect the viability, proliferation and differentiation potential, and longevity of normal stem cells. Mitophagy can affect the health and longevity of the human body, so the number of studies in this field has increased, but the mechanism by which mitophagy participates in stem cell development is still not fully understood. This review describes the potential significance of mitophagy in stem cell developmental processes, such as self-renewal, differentiation and aging. Through this work, we discovered the role and mechanism of mitophagy in different types of stem cells, identified novel targets for killing cancer stem cells and curing cancer, and provided new insights for future research in this field.
A systematic summary of survival and death signalling during the life of hair follicle stem cells
Authors: Hu Xi-Min , Li Zhi-Xin , Zhang Dan-Yi , Yang Yi-Chao , Fu Shen-ao , Zhang Zai-Qiu , Yang Rong-Hua , Xiong Kun
Published: August 2021

Hair follicle stem cells (HFSCs) are among the most widely available resources and most frequently approved model systems used for studying adult stem cells. HFSCs are particularly useful because of their self-renewal and differentiation properties. Additionally, the cyclic growth of hair follicles is driven by HFSCs. There are high expectations for the use of HFSCs as favourable systems for studying the molecular mechanisms that contribute to HFSC identification and can be applied to hair loss therapy, such as the activation or regeneration of hair follicles, and to the generation of hair using a tissue-engineering strategy. A variety of molecules are involved in the networks that critically regulate the fate of HFSCs, such as factors in hair follicle growth and development (in the Wnt pathway, Sonic hedgehog pathway, Notch pathway, and BMP pathway), and that suppress apoptotic cues (the apoptosis pathway). Here, we review the life cycle, biomarkers and functions of HFSCs, concluding with a summary of the signalling pathways involved in HFSC fate for promoting better understanding of the pathophysiological changes in the HFSC niche. Importantly, we highlight the potential mechanisms underlying the therapeutic targets involved in pathways associated with the treatment of hair loss and other disorders of skin and hair, including alopecia, skin cancer, skin inflammation, and skin wound healing.
Axon regeneration after optic nerve injury in rats can be improved via PirB knockdown in the retina
Authors: Yang Mei , Jian Lan , Fan Wei , Chen Xing , Zou Huan , Huang Yanming , Chen Xiaofan , Zhou Yuan-Guo , Yuan Rongdi
Published: August 2021

Background

In the central nervous system (CNS), three types of myelin-associated inhibitors (MAIs) exert major inhibitory effects on nerve regeneration: Nogo-A, myelin-associated glycoprotein (MAG), and oligodendrocyte-myelin glycoprotein (OMgp). MAIs have two co-receptors, Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PirB). Existing studies confirm that inhibiting NgR only exerted a modest disinhibitory effect in CNS. However, the inhibitory effects of PirB on nerve regeneration after binding to MAIs are controversial too. We aimed to further investigate the effect of PirB knockdown on the neuroprotection and axonal regeneration of retinal ganglion cells (RGCs) after optic nerve injury in rats.

Methods

The differential expression of PirB in the retina was observed via immunofluorescence and western blotting after 1, 3, and 7 days of optic nerve injury (ONI). The retina was locally transfected with adeno-associated virus (AAV) PirB shRNA, then, the distribution of virus in tissues and cells was observed 21 days after AAV transfection to confirm the efficiency of PirB knockdown. Level of P-Stat3 and expressions of ciliary neurotrophic factor (CNTF) were detected via western blotting. RGCs were directly labeled with cholera toxin subunit B (CTB). The new axons of the optic nerve were specifically labeled with growth associated protein-43 (GAP43) via immunofluorescence. Flash visual evoked potential (FVEP) was used to detect the P1 and N1 latency, as well as N1-P1, P1-N2 amplitude to confirm visual function.

Results

PirB expression in the retina was significantly increased after ONI. PirB knockdown was successful and significantly promoted P-Stat3 level and CNTF expression in the retina. PirB knockdown promoted the regeneration of optic nerve axons and improved the visual function indexes such as N1-P1 and P1-N2 amplitude.

Conclusions

PirB is one of the key molecules that inhibit the regeneration of the optic nerve, and inhibition of PirB has an excellent effect on promoting nerve regeneration, which allows the use of PirB as a target molecule to promote functional recovery after ONI.
Dubhe: a deep-learning-based B5G coverage analysis method
Authors: Xu Haoyan , Xu Xiaolong , Xiao Fu
Published: August 2021

In recent years, with the rapid development of various technologies such as the Internet of Things and the Internet, the demand for massive device connections and a variety of differentiated new business applications has continued to increase. In order to better cope with the rapid growth of mobile data in the future, 5G also came into being. Then, B5G was proposed and applied in industries such as traditional voice/video, smart city, automotive car or ship, unmanned aerial vehicle, marine monitoring, IoT, and intelligent industry. In these scenarios, B5G is required to achieve seamless global coverage. As these scenarios are complex and changeable, analysis of the coverage of 5G base stations has become a challenge. We decompose the environment around the base station into multiple grids, and analyze the signal strength of each grid. A signal propagation model needs to be constructed to predict whether each grid is covered. The commonly used wireless propagation model is an empirical model based on a mathematical formula for statistical analysis of a large amount of test data during the establishment of a 5G local area network. It has universal applicability, but has insufficient prediction accuracy for specific scenarios. Therefore, it is necessary to calibrate and modify the typical propagation model according to the specific environment to obtain an accurate propagation model that matches the current area. We improved the traditional wireless communication model, and proposed a deep-learning-based B5G coverage analysis method namedDubhewhich is one of the planets of the Big Dipper. In a real cell scenario, the mean square error of the link budget of the typical UMa model is 17.9 dBm, while the mean square error of the proposedDubhemodel constructed in this article is only 6.78 dBm. The recognition rate of weak coverage can reach 42.86%.
On optimal number of cognitive radios considering co-site electromagnetic compatibility
Authors: Liao Mingxue
Published: August 2021

With the development and wide applications of wireless communication technology, the limited spectrum resources and the fixed spectrum allocation policy could no longer satisfy the demand for wireless communication. Just for this reason, many spectrum resources become spectrum holes because they are allocated but not used. Cognitive radio is now becoming one of the most important techniques for high utility of these spectrum holes. If the holes available to cognitive users are abundant over a certain time, it is a worth consideration to increase network throughputs by orthogonal multiplexing as many as spectrum holes. A multi-transceiver configuration is one of the possible solutions for this purpose. With such a schema, all transceivers within a cognitive user work in a concurrent or parallel mode, by which the throughput of the network can be increased. However, co-site working cognitive radios may incur electromagnetic interference between each other. When more cognitive radios are equipped, much electromagnetic interference may be incurred. Many techniques are proposed to mitigate such so-siting interference; however, none of them have addressed the probability that the interference will happen. If the probability could be estimated in advance, the user will make a better planning on the configurations of the co-siting working radios. Based on an elaboratedn-fold multiple integral model, we propose a novel method to decide how many cognitive radios can be installed for one cognitive user at most. This is our main contribution with this work, providing an enhanced ability to determine the optimal number of cognitive radios installed within each cognitive user. We make a strict deduction on electromagnetic compatibility probability with various parameters of cognitive radios. Simulations are performed and the results show that the electromagnetic compatibility of the simulated cognitive radio system meets the deducted probability by this method very well.