bluuebunny/crossref_metadata_2025 huggingface dataset:
PPARγ activation improves the microenvironment of perivascular adipose tissue and attenuates aortic stiffening in obesity
Authors: Chen Ju-Yi , Wu Yi-Pin , Li Chih-Yi , Jheng Huei-Fen , Kao Ling-Zhen , Yang Ching-Chun , Leu Sy-Ying , Lien I-Chia , Weng Wen-Tsan , Tai Haw-Chih , Chiou Yu-Wei , Tang Ming-Jer , Tsai Pei-Jane , Tsai Yau-Sheng
Published: March 2021

Background

Obesity-related cardiovascular risk, end points, and mortality are strongly related to arterial stiffening. Current therapeutic approaches for arterial stiffening are not focused on direct targeting within the vessel. Perivascular adipose tissue (PVAT) surrounding the artery has been shown to modulate vascular function and inflammation. Peroxisome proliferator-activated receptor γ (PPARγ) activation significantly decreases arterial stiffness and inflammation in diabetic patients with coronary artery disease. Thus, we hypothesized that PPARγ activation alters the PVAT microenvironment, thereby creating a favorable environment for the attenuation of arterial stiffening in obesity.

Methods

Obese ob/ob mice were used to investigate the effect of PPARγ activation on the attenuation of arterial stiffening. Various cell types, including macrophages, fibroblasts, adipocytes, and vascular smooth muscle cells, were used to test the inhibitory effect of pioglitazone, a PPARγ agonist, on the expression of elastolytic enzymes.

Results

PPARγ activation by pioglitazone effectively attenuated arterial stiffening in ob/ob mice. This beneficial effect was not associated with the repartitioning of fat from or changes in the browning of the PVAT depot but was strongly related to improvement of the PVAT microenvironment, as evidenced by reduction in the expression of pro-inflammatory and pro-oxidative factors. Pioglitazone treatment attenuated obesity-induced elastin fiber fragmentation and elastolytic activity and ameliorated the obesity-induced upregulation of cathepsin S and metalloproteinase 12, predominantly in the PVAT. In vitro, pioglitazone downregulated Ctss and Mmp12 in macrophages, fibroblasts, and adipocytes—cell types residing within the adventitia and PVAT. Ultimately, several PPARγ binding sites were found in Ctss and Mmp12 in Raw 264.7 and 3T3-L1 cells, suggesting a direct regulatory mechanism by which PPARγ activation repressed the expression of Ctss and Mmp-12 in macrophages and fibroblasts.

Conclusions

PPARγ activation attenuated obesity-induced arterial stiffening and reduced the inflammatory and oxidative status of PVAT. The improvement of the PVAT microenvironment further contributed to the amelioration of elastin fiber fragmentation, elastolytic activity, and upregulated expression of Ctss and Mmp12. Our data highlight the PVAT microenvironment as an important target against arterial stiffening in obesity and provide a novel strategy for the potential clinical use of PPARγ agonists as a therapeutic against arterial stiffness through modulation of PVAT function.
Foaming of rhamnolipids fermentation: impact factors and fermentation strategies
Authors: Gong Zhijin , Yang Ge , Che Chengchuan , Liu Jinfeng , Si Meiru , He Qiuhong
Published: March 2021

Rhamnolipids have recently attracted considerable attentions because of their excellent biosurfactant performance and potential applications in agriculture, environment, biomedicine, etc., but severe foaming causes the high cost of production, restraining their commercial production and applications. To reduce or eliminate the foaming, numerous explorations have been focused on foaming factors and fermentation strategies, but a systematic summary and discussion are still lacking. Additionally, although these studies have not broken through the bottleneck of foaming, they are conducive to understanding the foaming mechanism and developing more effective rhamnolipids production strategies. Therefore, this review focuses on the effects of fermentation components and control conditions on foaming behavior and fermentation strategies responded to the severe foaming in rhamnolipids fermentation and systematically summarizes 6 impact factors and 9 fermentation strategies. Furthermore, the potentialities of 9 fermentation strategies for large-scale production are discussed and some further strategies are suggested. We hope this review can further facilitate the understanding of foaming factors and fermentation strategies as well as conducive to developing the more effective large-scale production strategies to accelerate the commercial production process of rhamnolipids.
An abdominal-sacral approach with preoperative embolisation for vulvar solitary fibrous tumour: a case report
Authors: Takahashi Akimasa , Nishimura Hiroki , Amano Tsukuru , Deguchi Mari , Yoshino Fumi , Kasei Ryo , Kimura Fuminori , Moritani Suzuko , Murakami Takashi
Published: March 2021

Background

Solitary fibrous tumours (SFTs) in the female genital tract are uncommon. Resection of these tumours is controversial because it can cause life-threatening haemorrhage. We report a case of vulvar SFT that was excised in a combined abdominal-sacral approach after preoperative embolisation.

Case presentation

At another hospital, an inoperable intrapelvic tumour was diagnosed in a 34-year-old woman. Computed tomography and magnetic resonance imaging showed that the uterus, urinary bladder and rectum were compressed laterally by a pelvic tumour with a maximum diameter of 11 cm. This mass was hypervascular and had a well-defined border. Transperineal biopsy was performed, and immunostaining revealed that the mass was an SFT. The tumour was supplied by feeding vessels from the right iliac arteries. First, we embolised the feeding vessels. Second, we performed surgical resection in a combined abdominal-sacral approach; no blood transfusion was necessary, and no perioperative complications occurred. The final pathological diagnosis was SFT that was positive for CD34 and signal transducer and activator of transcription 6 according to immunohistochemical staining.

Conclusion

During a year of follow-up, the disease did not recur. Treatment of pelvic SFT should aim at complete resection through various approaches after careful measures are taken to prevent haemorrhage.
Mapping the burden of diabetes in five small countries in Europe and setting the agenda for health policy and strategic action
Authors: Cuschieri Sarah , Pallari Elena , Terzic Natasa , Alkerwi Ala’a , Sigurðardóttir Árún Kristín
Published: March 2021

Background

Diabetes is a global epidemic affecting every country. Small countries, however, face distinctive challenges related to their health system governance and their ability to implement effective health systems’ reforms. The aim of this research was to perform a comparative assessment of existing diabetes management practices at the population level and explore governmental-related policy for Cyprus, Iceland, Luxembourg, Malta and Montenegro. This is the first time that such an evidence-based review study has been performed in the field of diabetes. The overall purpose was to set the agenda for health policy and inform strategic actions for small countries that can benefit from dealing with the diabetes epidemic at a country level.

Methods

We collected data and synthesized the evidence on dealing with diabetes for each of the five small European countries according to the (1) epidemiology of diabetes and other related metabolic abnormalities, (2) burden of diabetes status and (3) diabetes registers and national plans. We collected data by contacting Ministry representatives and other bodies in each state, and by searching through publicly available information from the respective Ministry of Health website on strategies and policies.

Results

Diabetes rates were highest in Cyprus and Malta. National diabetes registers are present in Cyprus and Montenegro, while national diabetes plans and diabetes-specific strategies have been established in Cyprus, Malta and Montenegro. These three countries also offer a free holistic healthcare service to their diabetes population.

Conclusions

Multistakeholder, national diabetes plans and public health strategies are important means to provide direction on diabetes management and health service provision at the population level. However, political support is not always present, as seen for Iceland. The absence of evidence-based strategies, lack of funding for conducting regular health examination surveys, omission of monitoring practices and capacity scarcity are among the greatest challenges faced by small countries to effectively measure health outcomes. Nevertheless, we identified means of how these can be overcome. For example, the creation of public interdisciplinary repositories enables easily accessible data that can be used for health policy and strategic planning. Health policy-makers, funders and practitioners can consider the use of regular health examination surveys and other tools to effectively manage diabetes at the population level.
A systematic review exploring the bidirectional relationship between puberty and autoimmune rheumatic diseases
Authors: de Gruijter Nina M. , Naja Meena , Peckham Hannah , Radziszewska Anna , Kinsella Matthew , Glenister James , Rosser Elizabeth C. , Butler Gary E. , Jury Elizabeth C. , Ciurtin Coziana
Published: March 2021

Background

Autoimmune rheumatic diseases (ARDs) are associated with a significant sex-bias, which becomes more evident post-puberty. This systematic review aims to elucidate the bidirectional relationship between puberty and ARD-related outcomes.

Methods

Studies published in English until October 2019 were identified using a systematic search of endocrinology and rheumatology literature. Information was extracted on study design, sample size, demographics, puberty outcome measures, disease outcome measures, and main findings. The methodological quality of the studies included was analysed using the Newcastle-Ottawa Scale (NOS).

Results

Sixteen non-randomised studies reporting on the impact of puberty on ARD outcomes (n = 7), ARD impact on puberty-related outcomes (n = 8), or both (n = 1) have been identified. The impact of puberty on ARD outcomes were investigated in patients with juvenile idiopathic arthritis (JIA)-associated uveitis (n = 1), juvenile systemic lupus erythematosus (JSLE) (n = 5) or in healthy controls who developed adult-onset SLE (n = 1) or had non-specific symptoms (n = 1). The impact of ARD on puberty outcomes was explored in JIA (n = 4) and JSLE (n = 3). Quality assessment of studies showed a small to moderate risk of bias overall (NOS 4–9/9). Due to large heterogeneity of the studies it was not possible to perform a meta-analysis. Multiple studies reported on delayed puberty in patients with JIA/JSLE, menstrual and hormonal abnormalities, and lower height and weight than controls. Earlier (pre-pubertal) onset of JSLE was correlated with more severe disease and more need for systemic treatment.

Conclusion

A bidirectional relationship exists between puberty and ARDs; however, more and better research is required to elucidate the complexity of this relationship. We propose puberty-related clinical assessments in patients with ARDs, which can improve patient outcomes and facilitate future research.
Evaluation of genetic stability in olive callus-induced and meristem-induced shoots using flow cytometry and amplified fragment length polymorphism techniques
Authors: Mirzaei Leila , Yadollahi Abbas , Kermani Maryam Jafarkhani , Naderpour Masoud , Zeinanloo Ali Asghar , Farsi Maryam , Davoodi Dariush
Published: March 2021

Background

In vitro culture of olive, as an economically valuable tree, has fundamentally a genotype-dependant low micropropagation rate which needs to be improved in already established and newly released cultivars. Various plant tissue culture media, planting systems and growth factors were evaluated in two promissing Iranian olive cultivars ˈAminˈ and ˈMeshkatˈ and the commercial Spanish cultivar ˈArbequinaˈ.

Results

The results showed that cultivars have their specific optimal media, i.e. ˈAminˈ in the MS with 4 mg/L zeatin, ˈArbequinaˈ in the OM with 1 mg/L zeatin, and ˈMeshkatˈ in the OM and MS with 2 mg/L zeatin, which produced significantly a higher number of axillary shoots than other media. The results also indicated a significant improvement in the growth indices of ˈAminˈ (number of axillary shoots) when cultured using periodical mini bioreactor (PMB) in the VS medium. In comparison with VS, OM did not reveal any significant differences when both culturing systems (PMB and semi-solid media (SSM)) were used.

Regarding the effect of carbon source and light intensity, mannitol and 2000 cd sr m−2 greatly enhanced ˈArbequinaˈ growth indices (main shoot length and growth quality). The results of genetic stability of callus induced shoots (CIS) and meristem induced shoots (MIS) revealed that 2C DNA value assessed by partec flow cytometery (FCM) had 0.01, 0.03 and 0.08 pg discrepencies in ˈAminˈ, ˈArbequinaˈ and ˈMeshkatˈ, repectively. The Amplified Fragment Length Polymorphism (AFLP) results also indicated that the cultivars were classified regardless of the micropropagation origin (CIS or MIS), except for ˈArbequinaˈ. The AFLP findings showed that ˈArbequinaˈ had the highest dispersal (7–38%) in CIS and MIS, while the Iranian cultivar of ˈMeshkatˈ (5–9%) had the highest stability.

Conclusions

This study indicated the importance of in vitro growth parameters for improving the micropropagation indices of olive cultivars. It showed that optimized protocols (OM, PMB, zeatin, mannitol and 2000 cd sr m−2) co-produced larger calli resulting in indirect organogenesis. Based on FCM and AFLP analysis, it can be concluded that true-to-typeness of micropropagated olive was cultivar-dependent.
Is double-strut fibula ankle arthrodesis a reliable reconstruction for bone defect after distal tibia tumor resection?—a finite element study based on promising clinical outcomes
Authors: Zhao Zhiqing , Yan Taiqiang , Guo Wei , Yang Rongli , Tang Xiaodong
Published: March 2021

Background

There are different surgical methods for primary malignant tumor located at distal tibia. Previous studies have reported that double-strut fibula ankle arthrodesis is an alternative option. The purpose of this study was to investigate the biomechanical effect of double-strut fibula ankle arthrodesis by finite element analysis (FEA).

Methods

Computer-aided design software was used to establish three-dimension models. Three different models were constructed: normal tibia-fibula-talus complex (model A), double-strut fibula ankle arthrodesis (model B), and reconstruction by ipsilateral fibula (model C). We used FEA to evaluate and compare the biomechanical characteristics of these constructs. Simulated load of 600 N was applied to the tibial plateau to simulate balanced single-foot standing. Output results representing the model von Mises stress and displacement of the components were analyzed.

Results

Construct stiffness was increased when the internal plate fixation was used. For axial load, model B (1460.5 N/mm) was stiffer than the construct of model A (524.8 N/mm), and model C (636.6 N/mm), indicating model B was more stable. Maximum stress on the fibular graft occurred on the proximal end. The von Mises stress and stress distribution of fibular graft in model B (71.4 MPa) and model C (67.8 MPa) were similar. In model B, the ipsilateral fibula in model B has a higher value of stress (16.1 MPa) than that in model A (0.5 MPa), indicating the ipsilateral fibula shared load after fusion with talus.

Conclusions

Our computational findings suggest that double-strut fibula ankle arthrodesis is an acceptable construct for distal tibia defect and the ipsilateral fibula shares load after fusion with talus.
Validation of a second-generation appropriateness classification system for total knee arthroplasty: a prospective cohort study
Authors: Escobar Antonio , Bilbao Amaia , Bertrand Maria L. , Moreta Jesús , Froufe Miquel A. , Colomina Jordi , Martınez-Cruz Olga , Perera Robert A. , Riddle Daniel L.
Published: March 2021

Background

To test the validity of a second-generation appropriateness system in a cohort of patients undergoing total knee arthroplasty (TKA).

Methods

We applied the RAND/UCLA Appropriateness Method to derive our second-generation system and conducted a prospective study of patients diagnosed with knee osteoarthritis in eight public hospitals in Spain. Main outcome questionnaires were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short-Form-12 (SF-12), and the Knee Society Score satisfaction scale (KSS), completed before and 6 months after TKA. Baseline, changes from baseline to 6 months (journey outcome), and 6-month scores (destination outcome) were compared according to appropriateness category. Percentage of patients attaining the minimal clinically important difference (MCID) and responders according to Outcome Measures in Rheumatology-Osteoarthritis Research Society (OMERACT-OARSI) criteria were also reported.

Results

A total of 282 patients completed baseline and 6-month questionnaires. Of these, 142 (50.4%) were classified as Appropriate, 90 (31.9%) as Uncertain, and 50 (17.7%) as Inappropriate. Patients classified as Appropriate had worse preoperative pain, function, and satisfaction (p < 0.001) and had greater improvements (i.e., journey scores) than those classified as Inappropriate (p < 0.001). At 6 months, destination scores for pain, function, or satisfaction were not significantly different across appropriateness categories. The percentage of patients meeting responder criteria (p < 0.001) and attaining MCID was statistically higher in Appropriate versus Inappropriate groups in pain (p = 0.04) and function (p = 0.004).

Conclusions

The validity of our second-generation appropriateness system was generally supported. The findings highlight a critical issue in TKA healthcare: whether TKA appropriateness should be driven by the extent of improvement, by patient final state, or by both.
The role of Notch ligand Jagged1 in osteosarcoma proliferation, metastasis, and recurrence
Authors: Zhang Jianping , Li Na , Lu Siyu , Chen Yanling , Shan Lequn , Zhao Xingcheng , Xu Yongqing
Published: March 2021

Background

Osteosarcoma is the most common primary bone cancer occurring in young adults and the 5-year survival rate of patients with metastatic osteosarcoma is less than 30% due to high metastatic recurrence and drug resistance. Notch is a highly conserved cell to cell signaling pathway in evolution, and Jagged1 is an important ligand of Notch. Although some studies have found that Notch receptors and ligands including Jagged1 were highly expressed in osteosarcoma tissues and osteosarcoma cells, the role of Jagged1 in osteosarcoma progression and metastasis are still not clear.

Methods

Tumor tissues were collected from 68 patients and immunohistochemical staining was employed to group these patients by expression of Jagged1. Real-time quantitative PCR and Western blotting were used to detect the expression of Jagged1. We used siRNA to knockdown the expression of Jagged1 in F5M2 cells. Colony formation assay and MTT were employed to detect and analyze the proliferation of F5M2 cells with or without knockdown of Jagged1. Transwell assay were used to detect the migration and invasion of F5M2 cells.

Results

In this study, we found that the high expression of Jagged1 is closely related to the metastasis and recurrence of osteosarcoma in 68 clinical specimens. The expression of Jagged1 in F5M2 cells with high metastasis was significantly higher than that in F4 cells with low metastasis. Knockdown of Jagged1 led to lower ability of proliferation, migration, and invasion in F5M2 cells.

Conclusion

The high expression of Jagged1 is closely related to the metastasis and recurrence of osteosarcoma. Knockdown of Jagged1 significantly reduced the proliferation, migration, and invasion of osteosarcoma cells. Our results suggested that knockdown of Jagged1 may be a potentially effective treatment for metastatic osteosarcoma.
Efficacy and safety of short-term chemotherapy for patients with spinal tuberculosis undergoing surgery in Chinese population: a meta-analysis
Authors: Lin Lu , Ke Zhenyong , Cheng Si
Published: March 2021

Objective

The aim of this meta-analysis was to systematically evaluate the clinical efficacy and safety of short-course chemotherapy (≤ 6 months) compared with the standard therapy (9–18 months) for patients with spinal tuberculosis (TB) undergoing surgery in Chinese population.

Methods

In this meta-analysis, we searched electronic databases in the Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang data to determine the equivalence of short-course therapy (group A) and standard therapy (group B) for the drug therapy of TB in Chinese population up to December 24, 2019. Weighted mean difference (WMD), odds risk (OR), and their 95% confidence interval (CI) were calculated. All analyses of relevant outcome indicators were managed by using the Review Manager (RevMan) 5.2 software.

Results

This meta-analysis included six trials published involving 851 patients (group A, 397; group B, 454) with spinal TB. Results showed there were no significant differences between group A and group B in clinical cure rate (OR = 0.61; 95% CI 0.19–2.00, p > 0.05), change of erythrocyte sedimentation rate (ESR) (WMD = − 0.75; 95% CI − 3.33 to 1.83; p > 0.05) and bone graft fusion rate (OR = 2.32; 95% CI 0.36–14.81, p > 0.05). Meanwhile, there were fewer side effects (OR = 0.37; 95% CI 0.24–0.58, p < 0.05) in group A compared with group B.

Conclusions

The results of this meta-analysis showed that for patients with spinal TB undergoing surgery in Chinese population, short-course chemotherapy could be equivalent to the standard chemotherapy in terms of efficacy and have less side effects than the latter.
A multi-feature hybrid classification data mining technique for human-emotion
Authors: Wang Y. , Chu Y. M. , Thaljaoui A. , Khan Y. A. , Chammam W. , Abbas S. Z.
Published: March 2021

Background and objectives

The ideal treatment of illnesses is the interest of every era. Data innovation in medical care has become extremely quick to analyze diverse diseases from the most recent twenty years. In such a finding, past and current information assume an essential job is utilizing and information mining strategies. We are inadequate in diagnosing the enthusiastic mental unsettling influence precisely in the beginning phases. In this manner, the underlying conclusion of misery expressively positions an extraordinary clinical and Scientific research issue. This work is dedicated to tackling the same issue utilizing the AI strategy. Individuals’ dependence on passionate stages has been successfully characterized into various gatherings in the data innovation climate.

Methods

A notable AI multi-include cross breed classifier is utilized to execute half and half order by having the passionate incitement as pessimistic or positive individuals. A troupe learning calculation helps to pick the more appropriate highlights from the accessible classes feeling information on online media to improve order. We split the Dataset into preparing and testing sets for the best proactive model.

Results

The execution assessment is applied to check the proposed framework through measurements of execution assessment. This exploration is done on the Class Labels MovieLens dataset. The exploratory outcomes show that the used group technique gives ideal order execution by picking the highlights’ greatest separation. The supposed results demonstrated the projected framework’s distinction, which originates from the picking-related highlights chosen by the incorporated learning calculation.

Conclusion

The proposed approach is utilized to precisely and successfully analyze the downturn in its beginning phase. It will assist in the recovery and action of discouraged individuals. We presume that the future strategy’s utilization is exceptionally appropriate in all data innovation-based E-medical services for discouraging incitement.
Cardiopulmonary resuscitation (CPR) training strategies in the times of COVID-19: a systematic literature review comparing different training methodologies
Authors: Ali Daniyal Mansoor , Hisam Butool , Shaukat Natasha , Baig Noor , Ong Marcus Eng Hock , Epstein Jonathan L. , Goralnick Eric , Kivela Paul D. , McNally Bryan , Razzak Junaid
Published: March 2021

Background

Traditional, instructor led, in-person training of CPR skills has become more challenging due to COVID-19 pandemic. We compared the learning outcomes of standard in-person CPR training (ST) with alternative methods of training such as hybrid or online-only training (AT) on CPR performance, quality, and knowledge among laypersons with no previous CPR training.

Methods

We searched PubMed and Google Scholar for relevant articles from January 1995 to May 2020. Covidence was used to review articles by two independent researchers. Effective Public Health Practice Project (EPHPP) Quality Assessment Tool was used to assess quality of the manuscripts.

Results

Of the 978 articles screened, twenty met the final inclusion criteria. All included studies had an experimental design and moderate to strong global quality rating. The trainees in ST group performed better on calling 911, time to initiate chest compressions, hand placement and chest compression depth. Trainees in AT group performed better in assessing scene safety, calling for help, response time including initiating first rescue breathing, adequate ventilation volume, compression rates, shorter hands-off time, confidence, willingness to perform CPR, ability to follow CPR algorithm, and equivalent or better knowledge retention than standard teaching methodology.

Conclusion

AT methods of CPR training provide an effective alternative to the standard in-person CPR for large scale public training.
Agreement between continuous and intermittent pulmonary artery thermodilution for cardiac output measurement in perioperative and intensive care medicine: a systematic review and meta-analysis
Authors: Kouz Karim , Michard Frederic , Bergholz Alina , Vokuhl Christina , Briesenick Luisa , Hoppe Phillip , Flick Moritz , Schön Gerhard , Saugel Bernd
Published: March 2021

Background

Pulmonary artery thermodilution is the clinical reference method for cardiac output monitoring. Because both continuous and intermittent pulmonary artery thermodilution are used in clinical practice it is important to know whether cardiac output measurements by the two methods are clinically interchangeable.

Methods

We performed a systematic review and meta-analysis of clinical studies comparing cardiac output measurements assessed using continuous and intermittent pulmonary artery thermodilution in adult surgical and critically ill patients. 54 studies with 1522 patients were included in the analysis.

Results

The heterogeneity across the studies was high. The overall random effects model-derived pooled estimate of the mean of the differences was 0.08 (95%-confidence interval 0.01 to 0.16) L/min with pooled 95%-limits of agreement of − 1.68 to 1.85 L/min and a pooled percentage error of 29.7 (95%-confidence interval 20.5 to 38.9)%.

Conclusion

The heterogeneity across clinical studies comparing continuous and intermittent pulmonary artery thermodilution in adult surgical and critically ill patients is high. The overall trueness/accuracy of continuous pulmonary artery thermodilution in comparison with intermittent pulmonary artery thermodilution is good (indicated by a pooled mean of the differences < 0.1 L/min). Pooled 95%-limits of agreement of − 1.68 to 1.85 L/min and a pooled percentage error of 29.7% suggest that continuous pulmonary artery thermodilution barely passes interchangeability criteria with intermittent pulmonary artery thermodilution.

PROSPERO registration number CRD42020159730.
Community participatory learning and action cycle groups to reduce type 2 diabetes in Bangladesh (D:Clare trial): study protocol for a stepped-wedge cluster randomised controlled trial
Authors: King Carina , Pires Malini , Ahmed Naveed , Akter Kohenour , Kuddus Abdul , Copas Andrew , Haghparast-Bidgoli Hassan , Morrison Joanna , Nahar Tasmin , Shaha Sanjit Kumer , Khan A. K. Azad , Azad Kishwar , Fottrell Edward
Published: March 2021

Background

An estimated 463 million people globally have diabetes, with the prevalence growing in low-and middle-income settings, such as Bangladesh. Given the need for context-appropriate interventions to prevent type 2 diabetes mellitus (T2DM), the ‘Diabetes: Community-led Awareness, Response and Evaluation’ (D:Clare) trial will rigorously evaluate the replication and scale-up of a participatory learning and action (PLA) cycle intervention in Bangladesh, to inform policy on population-level T2DM prevention and control.

Methods

This is a stepped-wedge cluster randomised controlled trial, with integrated process and economic evaluations, conducted from March 2020 to September 2022. The trial will evaluate a community-based four-phase PLA cycle intervention focused on prevention and control of T2DM implemented over 18 months, against a control of usual care. Twelve clusters will be randomly allocated (1:1) to implement the intervention at project month 1 or 12. The intervention will be evaluated through three cross-sectional surveys at months 1, 12 and 24. The trial will be conducted in Alfadanga Upazila, Faridpur district, with an estimated population of 120,000. Clusters are defined as administrative geographical areas, with approximately equal populations. Each of the six unions in Alfadanga will be divided into two clusters, forming 12 clusters in total. Given the risk of inter-cluster contamination, evaluation surveys will exclude villages in border areas. Participants will be randomly sampled, independently for each survey, from a population census conducted in January 2020. The primary outcome is the combined prevalence of intermediate hyperglycaemia and T2DM, measured through fasting and 2-h post-glucose load blood tests. A total of 4680 participants provide 84% power to detect a 30% reduction in the primary outcome, assuming a baseline of 30% and an ICC of 0.07. The analysis will be by intention-to-treat, comparing intervention and control periods across all clusters, adjusting for geographical clustering.

Discussion

This study will provide further evidence of effectiveness for community-based PLA to prevent T2DM at scale in a rural Bangladesh setting. However, we encountered several challenges in applying the stepped-wedge design to our research context, with particular consideration given to balancing seasonality, timing and number of steps and estimation of partial versus full effect.

Trial registration

ISRCTN: ISRCTN42219712. Registered on 31 October 2019
Peritoneal flap for lymphocele prophylaxis following robotic-assisted laparoscopic radical prostatectomy with pelvic lymph node dissection: study protocol and trial update for the randomized controlled PELYCAN study
Authors: Neuberger M. , Kowalewski K. F. , Simon V. , Wessels F. , Siegel F. , Worst T. S. , Westhoff N. , von Hardenberg J. , Kriegmair M. , Michel M. S. , Honeck P. , Nuhn P.
Published: March 2021

Background

Data from interventional studies suggest that a peritoneal flap after pelvic lymph node dissection (LND) during laparoscopic, robotic-assisted radical prostatectomy (RARP) may reduce the rate of symptomatic lymphoceles in transperitoneal approach. However, most of these studies are not conducted in a randomized controlled fashion, thus limiting their scientific value. A recent prospective, randomized, controlled trial (RCT) did not show superiority of a peritoneal flap while further trials are lacking. Therefore, the aim of the presented RCT will be to show that creating a peritoneal flap decreases the rate of symptomatic lymphoceles compared to the current standard procedure without creation of a flap.

Methods/design

PELYCAN is a parallel-group, patient- and assessor-blinded, phase III, adaptive randomized controlled superiority trial. Men with histologically confirmed prostate cancer who undergo transperitoneal RARP with pelvic LND will be randomly assigned in a 1:1 ratio to two groups—either with creating a peritoneal flap (PELYCAN) or without creating a peritoneal flap (control). Sample size calculation yielded a sample size of 300 with a planned interim analysis after 120 patients, which will be performed by an independent statistician. This provides a possibility for early stopping or sample size recalculation.

Patients will be stratified for contributing factors for the development of postoperative lymphoceles. The primary outcome measure will be the rate of symptomatic lymphoceles in both groups within 6 months postoperatively. Patients and assessors will be blinded for the intervention until the end of the follow-up period of 6 months. The surgeon will be informed about the randomization result after performance of vesicourethral anastomosis. Secondary outcome measures include asymptomatic lymphoceles at the time of discharge and within 6 months of follow-up, postoperative complications, mortality, re-admission rate, and quality of life assessed by the EORTC QLQ-C30 questionnaire.

Discussion

The PELYCAN study is designed to assess whether the application of a peritoneal flap during RARP reduces the rate of symptomatic lymphoceles, as compared with the standard operation technique. In case of superiority of the intervention, this peritoneal flap may be suggested as a new standard of care.

Trial registration

German Clinical Trials RegisterDRKS00016794. Registered on 14 May 2019.
Efficient and selective catalytic hydroxylation of unsaturated plant oils: a novel method for producing anti-pathogens
Authors: Senan Ahmed M. , Yin Binru , Zhang Yaoyao , Nasiru Mustapha M. , Lyu Yong‐Mei , Umair Muhammad , Bhat Javaid A. , Zhang Sicheng , Liu Li
Published: March 2021

With the increasing demand for antimicrobial agents and the spread of antibiotic resistance in pathogens, the exploitation of plant oils to partly replace antibiotic emerges as an important source of fine chemicals, functional food utility and pharmaceutical industries. This work introduces a novel catalytic method of plant oils hydroxylation by Fe(III) citrate monohydrate (Fe3+-cit.)/Na2S2O8 catalyst. Methyl (9Z,12Z)-octadecadienoate (ML) was selected as an example of vegetable oils hydroxylation to its hydroxy-conjugated derivatives (CHML) in the presence of a new complex of Fe(II)-species. Methyl 9,12-di-hydroxyoctadecanoate 1, methyl-9-hydroxyoctadecanoate 2 and methyl (10E,12E)-octadecanoate 3 mixtures is produced under optimized condition with oxygen balloon. The specific hydroxylation activity was lower in the case of using Na2S2O8 alone as a catalyst. A chemical reaction has shown the main process converted of plantoils hydroxylation and (+ 16 Da) of OH- attached at the methyl linoleate (ML-OH). HPLC and MALDI-ToF-mass spectrometry were employed for determining the obtained products. It was found that adding oxidizing agents (Na2S2O8) to Fe3+ in the MeCN mixture with H2O would generate the new complex of Fe(II)-species, which improves the C-H activation. Hence, the present study demonstrated a new functional method for better usage of vegetable oils.Producing conjugated hydroxy-fatty acids/esters with better antipathogenic properties. CHML used in food industry, It has a potential pathway to food safety and packaging process with good advantages, fundamental to microbial resistance. Lastly, our findings showed that biological monitoring of CHML-minimum inhibitory concentration (MIC) inhibited growth of various gram-positive and gram-negative bacteria in vitro study. The produced CHML profiles were comparable to the corresponding to previousstudies and showed improved the inhibition efficiency over the respective kanamycin derivatives.
Microbiome profiling of rotavirus infected children suffering from acute gastroenteritis
Authors: Sohail Muhammad U. , Al Khatib Hebah A. , Al Thani Asmaa A. , Al Ansari Khalid , Yassine Hadi M. , Al-Asmakh Maha
Published: March 2021

Background

Rotavirus (RV) is a leading cause of pediatric diarrhea and mortality worldwide. The virus causes acute gastroenteritis characterized by moderate to severe vomiting, diarrhea, dehydration, and fever. Microbial dysbiosis caused by RV infection may significantly influence disease prognosis and the development of other chronic diseases. The gut microbiome plays a vital role in enteric immune response for rotavirus vaccine (RVV) that requires further elucidations. The current study evaluates the gut microbiome of RV positive children and compares gastroenteritis manifestation in children admitted to the Pediatric Emergency Centre, Hamad Medical Cooperation, Doha, Qatar. Stool samples were collected from thirty-nine RV positive and eight healthy control children. 16S rRNA sequence was performed using the Illumina MiSeq platform.

Results

The data demonstrated a significant increase in microbiome diversity denoted by higher relative abundances of phylum Proteobacteria (p = 0.031), Fusobacteria (p = 0.044) and genus Streptococcus (p ≤ 0.001) in the infected group relative to the control. Similarly, district clustering pattern (PERMANOVA p = 0.01) and higher species richness (Shannon entropy p = 0.018) were observed in the children who received two RVV doses compared with the non-vaccinated or single-dose groups. These microbiome changes were represented by over-abundance of phylum Bacteroidetes (p = 0.003) and Verrucomicrobia (p ≤ 0.001), and lower expression of family Enterobacteriaceae in two RVV doses group. However, microbiome composition was not associated with diarrhea, vomiting, and other parameters of gastroenteritis.

Conclusions

The observations assert significant microbial signatures of RVV, which is dose-dependent, and suggest manipulating these microbes as a novel approach for improving RVV efficacy. Further studies are warranted to investigate the immune status of these patients and mechanistic investigation to enhance RVV seroconversion.
Misdiagnosis of chronic pulmonary aspergillosis as pulmonary tuberculosis at a tertiary care center in Uganda: a case series
Authors: Kwizera Richard , Katende Andrew , Bongomin Felix , Nakiyingi Lydia , Kirenga Bruce J.
Published: March 2021

Background

Diagnosis of chronic pulmonary aspergillosis (CPA) is based on a combination of clinical symptomatology, compatible chest imaging findings, evidence of Aspergillus infection and exclusion of alternative diagnosis, all occurring for more than 3 months. Recently, a rapid, highly sensitive and specific point-of-care lateral flow device (LFD) has been introduced for the detection of Aspergillus-specific immunoglobulin (Ig)G, especially in resource-limited settings where CPA is underdiagnosed and often misdiagnosed as smear-negative pulmonary tuberculosis (PTB). Therefore, in our setting, where tuberculosis (TB) is endemic, exclusion of PTB is an important first step to the diagnosis of CPA. We used the recently published CPA diagnostic criteria for resource-limited settings to identify patients with CPA in our center.

Case presentation

Three Ugandan women (45/human immunodeficiency virus (HIV) negative, 53/HIV infected and 18/HIV negative), with a longstanding history of cough, chest pain, weight loss and constitutional symptoms, were clinically and radiologically diagnosed with PTB and empirically treated with an anti-tuberculous regimen despite negative microbiological tests. Repeat sputum Mycobacteria GeneXpert assays were negative for all three patients. On further evaluation, all three patients met the CPA diagnostic criteria with demonstrable thick-walled cavities and fungal balls (aspergilomas) on chest imaging and positive Aspergillus-specific IgG/IgM antibody tests. After CPA diagnosis, anti-TB drugs were safely discontinued for all patients, and they were initiated on capsules of itraconazole 200 mg twice daily with good treatment outcomes.

Conclusions

The availability of simple clinical diagnostic criteria for CPA and a LFD have the potential to reduce misdiagnosis of CPA and in turn improve treatment outcomes in resource-limited settings.
Transplantation of human induced pluripotent stem cell-derived neural crest cells for corneal endothelial regeneration
Authors: Gong Yajie , Duan Haoyun , Wang Xin , Zhao Can , Li Wenjing , Dong Chunxiao , Li Zongyi , Zhou Qingjun
Published: March 2021

Background

The corneal endothelium maintains corneal hydration through the barrier and pump function, while its dysfunction may cause corneal edema and vision reduction. Considering its development from neural crest cells (NCCs), here we investigated the efficacy of the human induced pluripotent stem cell (hiPSC)-derived NCCs for corneal endothelial regeneration in rabbits.

Methods

Directed differentiation of hiPSC-derived NCCs was achieved using the chemically defined medium containing GSK-3 inhibitor and TGF-β inhibitor. The differentiated cells were characterized by immunofluorescence staining, FACS analysis, and in vitro multi-lineage differentiation capacity. For in vivo functional evaluation, 1.0 × 106 hiPSC-derived NCCs or NIH-3 T3 fibroblasts (as control) combined with 100 μM Y-27632 were intracamerally injected into the anterior chamber of rabbits following removal of corneal endothelium. Rabbit corneal thickness and phenotype changes of the transplanted cells were examined at 7 and 14 days with handy pachymeter, dual-immunofluorescence staining, and quantitative RT-PCR.

Results

The hiPSC-derived NCCs were differentiated homogenously through 7 days of induction and exhibited multi-lineage differentiation capacity into peripheral neurons, mesenchymal stem cells, and corneal keratocytes. After 7 days of intracameral injection in rabbit, the hiPSC-derived NCCs led to a gradual recovery of normal corneal thickness and clarity, when comparing to control rabbit with fibroblasts injection. However, the recovery efficacy after 14 days deteriorated and caused the reappearance of corneal edema. Mechanistically, the transplanted cells exhibited the impaired maturation, cellular senescence, and endothelial-mesenchymal transition (EnMT) after the early stage of the in vivo directional differentiation.

Conclusions

Transplantation of the hiPSC-derived NCCs rapidly restored rabbit corneal thickness and clarity. However, the long-term recovery efficacy was impaired by the improper maturation, senescence, and EnMT of the transplanted cells.
miR-133a silencing rescues glucocorticoid-induced bone loss by regulating the MAPK/ERK signaling pathway
Authors: Wang Gang , Wang Fengbin , Zhang Lecheng , Yan Chao , Zhang Yuelei
Published: March 2021

Background

Dysfunction of mesenchymal stem cells (MSCs) is recognized as critical to the pathogenesis of glucocorticoid-induced osteoporosis (GIO), suggesting the potential of MSC-targeting interventions for this disorder. As the miR-133a has been shown to play an important role in bone metabolism, we hypothesized that miR-133a may also be involved in GIO.

Methods

In the in vitro study, we examined the effect of miR-133a antagomir on DEX-treated MSCs, including proliferation, apoptosis, osteoblast, and adipocyte differentiation, then, we explored the mechanism of these effects of miR-133a silencing through measuring the phosphorylation of ERK1/2 and its regulator FGFR1 via western blot and qRT-PCR. In the in vivo study, we developed a GIO rat model by injecting methylprednisolone and modulated the miR-133a expression in the femur by intramedullary injection of the miR-133a antagomir, and then micro-CT analyses and histological staining of the femurs were used to investigate the effect of miR-133a silencing on bone loss of the GIO rats.

Results

qRT-PCR analysis indicated that glucocorticoid induced high miR-133a expression in MSCs and animal models. The in vitro study showed that miR-133a antagomir significantly promoted cell proliferation, viability, and osteoblast differentiation and inhibited adipocyte differentiation in DEX-treated MSCs. Furthermore, the expression of p-ERK1/2 and FGFR1 in DEX-treated MSCs was also upregulated by miR-133a antagomir. Then we investigated the effect of miR-133a silencing on the bone architecture of GIO models, micro-CT analysis showed that miR-133a antagomir attenuated the loss of bone mass and improved the trabecular and cortical parameters induced by methylprednisolone. Histological study showed that miR-133a silencing simultaneously increased bone formation and decreased marrow fat accumulation in GIO rats.

Conclusions

Our findings suggested that miR-133a is strongly associated with GIO and similar disorders induced by glucocorticoids in MSCs. Silencing miR-133a resulted in positive effects on GC-treated MSCs and on bone loss in GIO animal models. Moreover, the FGFR1-MAPK/ERK signaling may be involved in the protective effect of miR-133a silencing.
Clinical performance of lung ultrasound in predicting ARDS morphology
Authors: Costamagna Andrea , Pivetta Emanuele , Goffi Alberto , Steinberg Irene , Arina Pietro , Mazzeo Anna Teresa , Del Sorbo Lorenzo , Veglia Simona , Davini Ottavio , Brazzi Luca , Ranieri V. Marco , Fanelli Vito
Published: March 2021

Background

To assess diagnostic performance of lung ultrasound (LUS) in identifying ARDS morphology (focal vs non-focal), compared with the gold standard computed tomography.

Methods

Mechanically ventilated ARDS patients undergoing lung computed tomography and ultrasound were enrolled. Twelve fields, were evaluated. LUS score was graded from 0 (normal) to 3 (consolidation) according to B-lines extent. Total and regional LUS score as the sum of the four ventral (LUSV), intermediate (LUSI) or dorsal (LUSD) fields, were calculated. Based on lung CT, ARDS morphology was defined as (1) focal (loss of aeration with lobar distribution); (2) non-focal (widespread loss of aeration or segmental loss of aeration distribution associated with uneven lung attenuation areas), and diagnostic accuracy of LUS in discriminating ARDS morphology was determined by AU-ROC in training and validation set of patients.

Results

Forty-seven patients with ARDS (25 training set and 22 validation set) were enrolled. LUSTOT, LUSV and LUSI but not LUSD score were significantly lower in focal than in non-focal ARDS morphologies (p < .01). The AU-ROC curve of LUSTOT, LUSV, LUSI and LUSD for identification of non-focal ARDS morphology were 0.890, 0.958, 0.884 and 0.421, respectively. LUSV value ≥ 3 had the best predictive value (sensitivity = 0.95, specificity = 1.00) in identifying non-focal ARDS morphology. In the validation set, an LUSV score ≥ 3 confirmed to be highly predictive of non-focal ARDS morphology, with a sensitivity and a specificity of 94% and 100%.

Conclusions

LUS had a valuable performance in distinguishing ARDS morphology.
Lightweight authentication protocol in edge-based smart grid environment
Authors: Chen Chien-Ming , Chen Lili , Huang Yanyu , Kumar Sachin , Wu Jimmy Ming-Tai
Published: March 2021

A smart grid (SG) is an advanced power grid system deployed in a cloud center and smart meters (at the consumer end) that provides higher reliability, better data protection, improved power efficiency, automatic monitoring, and effective management of power consumption. However, an SG also poses certain challenges that need to be addressed. For example, data provided by a smart meter are time-sensitive and cannot handle high latency in an SG. Moreover, a smart meter depends on memory, energy, and other factors. Besides, the security between a cloud center and a smart meter is a critical issue that needs to be resolved. Edge computing, an extension of cloud computing deployed in an edge network between a cloud center and the end devices, is an efficient solution to the aforementioned issues. Therefore, in this study, we propose a secure mutual authentication protocol based on edge computing for use in an SG.