bluuebunny/crossref_metadata_2025 huggingface dataset:
Early hepatic artery thrombosis treatments and outcomes: aorto-hepatic arterial conduit interposition or revision of anastomosis?
Authors: Sohrabi Nazari Sahar , Eslamian Mohammad , Sheikhbahaei Erfan , Zefreh Hamidreza , Lashkarizadeh Mohammad Mehdi , Shamsaeefar Alireza , Kazemi Kourosh , Nikoupour Hamed , Nikeghbalian Saman , Vatankhah Pooya
Published: February 2024

Background

Hepatic artery thrombosis (HAT) is one of the critical conditions after an orthotopic liver transplant (OLT) and leads to severe problems if not corrected promptly. However, multiple treatments have been proposed for HAT, in which surgical revascularization with either auto-hepatic conduit interposition (AHCI) or revision of the anastomosis is more familiar indeed indicated for some patients and in specific situations. In this study, we want to evaluate the success and outcomes of treating early HAT (E-HAT), which defines HAT within 30 days after OLT with either of the surgical revascularization techniques.

Method

In this retrospective study, we collected information from the medical records of patients who underwent either of the surgical revascularization procedures for E-HAT after OLT. Patients who needed early retransplantation (RT) or died without surgical intervention for E-HAT were excluded. Demographic data, OLT surgery information, and data regarding E-HAT were gathered. The study outcomes were secondary management for E-HAT in case of improper inflow, biliary complications (BC), RT, and death.

Results

A total of 37 adult patients with E-HAT after OLT included in this study. These E-HATs were diagnosed within a mean of 4.6 ± 3.6 days after OLT. Two patients had their HA revised for the initial management of E-HAT; however, it changed to AHCI intraoperatively and finally needed RT. Two and nine patients from the AHCI and revision groups had re-thrombosis (12.5% vs. 47.3%, respectively, p = 0.03). RT was used to manage rethrombosis in all patients of AHCI and two patients of the revision group (22.2%). In comparison to the AHCI, revision group had statistically insignificant higher rates of BC (47.4% vs. 31.2%); however, RT for nonvascular etiologies (12.5% vs. 5.3%) and death (12.5% vs. 10.5%) were nonsignificantly higher in AHCI group. All patients with more than one HA exploration who were in the revision group had BC; however, 28.5% of patients with just one HA exploration experienced BC (p < 0.001).

Conclusion

Arterial conduit interposition seems a better approach for the initial management of E-HAT in comparison to revision of the HA anastomosis due to the lower risk of re-thrombosis and the number of HA explorations; indeed, BC, RT, and death remain because they are somewhat related to the ischemic event of E-HAT than to a surgical treatment itself.
Giant peritoneal loose body and its protein composition: a case report
Authors: Sang Weicong , Li Yang , Hong Xiaoping , Qu Haihong , Zhu Rujian , Yi Qingtong
Published: February 2024

Peritoneal loose body (PLB) is a kind of lesions located in the abdominal cavity or pelvic cavity, which is rare and difficult to diagnose. The diameter of PLB is mostly 0.5–2.5 cm. Most PLBS are asymptomatic. Here we reported a case of giant PLB in the pelvis and analyzed its structure and protein composition. Surgical exploration revealed a white oval mass (4.5*4*3 cm) in the pelvic cavity. After the mass was removed, the symptoms of hematuria disappeared and the patient was discharged on the second postoperative day. Histochemical staining showed that PLB was mainly composed of collagen and scattered calcification. The protein components of PLB were detected by proteome analysis, and a variety of proteins related to collagen deposition and calcification were identified in PLB.
Photobiomodulation versus corticosteroid in the management of erosive oral lichen planus: a randomized controlled clinical trial
Authors: Mohamed Reem Kamal , Elsayed Naguiba Mahmoud , Mahmoud Sabah Abdelhady , Gaweesh Yasmine Youssri
Published: February 2024

Background

Oral lichen planus (OLP) is a chronic illness of immune origin that is typically treated with corticosteroids as a gold standard therapy. Photobiomodulation (PBM) may represent an alternative remedy that has the potential to treat a variety of pathological conditions by alleviating pain, reducing inflammation, and promoting tissue healing without the drawbacks of steroid therapies. Thus, the aim of the current study was to compare the effect of photobiomodulation to topical 0.1% triamcinolone acetonide on erosive oral lichen planus.

Methods

This randomized controlled clinical trial involved 44 patients complaining of erosive oral lichen planus. Patients were assigned to one of two groups: control group (n = 22) received 0.1% topical triamcinolone acetonide three times daily with miconazole oral gel once daily for 4 weeks, and photobiomodulation group (n = 22) received laser therapy by 980 nm diode laser utilizing output power 300 mW twice weekly for 5 weeks (a total of 10 sessions). The evaluation of patients was performed at baseline, 6 weeks, and 12 weeks postoperatively in terms of pain, clinical scores, and biochemical evaluation of salivary malondialdehyde levels. All recorded data were analyzed using Mann–Whitney test to compare the two studied groups regarding pain, lesion size, and salivary levels of malondialdehyde. Friedman test, followed by post hoc test, was used for comparison of the data within the same group along the 3 periods at baseline, 6 weeks, and 12 weeks.

Results

Both groups showed significant improvement in pain and clinical scores, with no statistical difference between them. Moreover, there was a significant improvement in salivary malondialdehyde levels for both groups, with no significant difference between them.

Conclusions

Photobiomodulation could be a promising therapeutic modality for management of erosive oral lichen planus without the side effects of steroid therapy. The salivary malondialdehyde level could be used as a biomarker to evaluate the disease severity and its response to the treatment.

Trial registration

The study has been registered at ClinicalTrials.gov (NCT05951361) (19/07/2023).
A scoping review of dental practitioners’ perspectives on perceived barriers and facilitators to preventive oral health care in general dental practice
Authors: Leggett H. , Vinall-Collier K. , Csikar J. , Owen J. , Edwebi S. , Douglas G. V.A
Published: February 2024

Background

Oral health has an important role in the general health and well-being of individuals. Dental teams are ideally placed to support patients in preventing ill-health. Understanding the barriers and facilitators to the adoption, promotion and facilitation of preventive advice and treatment is key to improving oral health services. The Theoretical Domains Framework (TDF) is a useful psychological framework to help identify individual, interpersonal and environmental issues which could be impacting clinicians’ ability to provide preventive advice and care. The aim of this review was to identify the perceived barriers and facilitators to preventive oral health care from the perspectives of the oral healthcare team within the general dental practice.

Methods

A search strategy was developed, piloted, and run in: Medline via Ovid, PsycInfo, Web of Science, SCOPUS, EMBASE, Conference Proceedings Citation Index- Science, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews and followed PRISMA guidelines. Identified records were screened independently by two researchers. Data were coded using the Theoretical Domains Framework (TDF) and analysed using narrative data synthesis.

Results

5610 papers were identified, and 19 included in this review. Thirteen papers focussed on dentists. Of the 106 items mapped onto the TDF, 48 were facilitators. The domains most frequently represented were, environmental context and resources, beliefs about consequences, social professional role and identity, skills, beliefs about capabilities and knowledge. Six studies focussed on dental hygienists. There were 47 items mapped onto the TDF, 18 were facilitators. The domains most frequently represented were environmental context and resources, social influences, beliefs about consequences and knowledge.

Conclusions

The review identified that the delivery of preventive activities did not focus solely on the patient and dental professional interaction as many previous studies have highlighted. The review found that multiple factors influence whether prevention is delivered to patients. The largest barrier and facilitator for the dental professionals identified in this review was the environmental context and resources. Further research is needed to evaluate the effectiveness of interventions that aim to promote preventive oral health care in primary care settings to understand whether they address the barriers identified in this review.
Knowledge translation strategies used for sustainability of an evidence-based intervention in child health: a multimethod qualitative study
Authors: Cassidy Christine E. , Flynn Rachel , Campbell Alyson , Dobson Lauren , Langley Jodi , McNeil Deborah , Milne Ella , Zanoni Pilar , Churchill Megan , Benzies Karen M.
Published: February 2024

Background

Sustainability of evidence-based interventions (EBIs) is suboptimal in healthcare. Evidence on how knowledge translation (KT) strategies are used for the sustainability of EBIs in practice is lacking. This study examined what and how KT strategies were used to facilitate the sustainability of Alberta Family Integrated Care (FICare)™, a psychoeducational model of care scaled and spread across 14 neonatal intensive care units, in Alberta, Canada.

Methods

First, we conducted an environmental scan of relevant documents to determine the use of KT strategies to support the sustainability of Alberta FICare™. Second, we conducted semi-structured interviews with decision makers and operational leaders to explore what and how KT strategies were used for the sustainability of Alberta FICare™, as well as barriers and facilitators to using the KT strategies for sustainability. We used the Expert Recommendations for Implementation Change (ERIC) taxonomy to code the strategies. Lastly, we facilitated consultation meetings with the Alberta FICare™ leads to share and gain insights and clarification on our findings.

Results

We identified nine KT strategies to facilitate the sustainability of Alberta FICare™: Conduct ongoing training; Identify and prepare local champions; Research co-production; Remind clinicians; Audit and provide feedback; Change record systems; Promote adaptability; Access new funding; and Involve patients/consumers and family members. A significant barrier to the sustainability of Alberta FICare™ was a lack of clarity on who was responsible for the ongoing maintenance of the intervention. A key facilitator to sustainability of Alberta FICare was its alignment with the Maternal, Newborn, Child & Youth Strategic Clinical Network (MNCY SCN) priorities. Co-production between researchers and health system partners in the design, implementation, and scale and spread of Alberta FICare™ was critical to sustainability.

Conclusion

This research highlights the importance of clearly articulating who is responsible for continued championing for the sustainability of EBIs. Additionally, our research demonstrates that the adaptation of interventions must be considered from the onset of implementation so interventions can be tailored to align with contextual barriers for sustainability. Clear guidance is needed to continually support researchers and health system leaders in co-producing strategies that facilitate the long-term sustainability of effective EBIs in practice.
Work ethics and its relationship with workplace ostracism and counterproductive work behaviours among nurses: a structural equation model
Authors: Elliethey Nancy Sabry , Aly Abou Hashish Ebtsam , Ahmed Mohamed Elbassal Nariman
Published: February 2024

Background

The organization’s work ethics is the cornerstone to promoting positive nurses’ behaviours and overcoming counterproductive ones.

Purpose

The current study aims to explore the relationship between work ethics (WEs) and counterproductive work behaviours (CWB) among nurses and testify to the mediating role of workplace ostracism (WO) in this relationship.

Methods

A descriptive correlational study was conducted in an Egyptian hospital. A convenient sample of staff nurses (N = 369) who agreed to participate in the study answered work ethics, counterproductive work behaviours, and workplace ostracism questionnaires, which were proven to be valid and reliable study measures. Descriptive and inferential statistics were applied, and relationships were presented using structural equation modelling.

Ethical Considerations

Ethics Committee approval, written informed consent, data privacy and confidentiality, and participants’ rights to voluntary participation and withdrawal were maintained.

Results

The majority of nurses (78.5%) perceived a high level of work ethics while majority of nurses reporting low levels of counterproductive work behaviours and workplace ostracism (82.25%, 75.75%), respectively. In addition to the negative correlations, the findings revealed that WEs have a significant negative influence on each of CWB (β − 0.482, p < 0.005) and WO (β − 0.044, p < 0.005). The regression analysis showed that WEs can negatively predict about 15% of the variance in each of CWB and WO. On the other hand, WO has a positive effect on CWB (β 0.035, p < 0.021) and mediates the relationship between WEs and CWB.

Discussion

Ostracism negatively affects the attitudes of nurses, which in turn results in negative behavioural outcomes (i.e., deviant behaviour).

Conclusion

It is imperative for the hospital and nurse managers to establish a work environment that fosters support and cultivate work ethics and ethical work climate with the aim of managing negative work behaviours, enhancing nurses’ retention and satisfaction, and eventually improving the quality of patient care.
The complexity of leadership in coproduction practices: a guiding framework based on a systematic literature review
Authors: Kjellström Sofia , Sarre Sophie , Masterson Daniel
Published: February 2024

Background

As coproduction in public services increases, understanding the role of leadership in this context is essential to the tasks of establishing relational partnerships and addressing power differentials among groups. The aims of this review are to explore models of coproduction leadership and the processes involved in leading coproduction as well as, based on that exploration, to develop a guiding framework for coproduction practices.

Methods

A systematic review that synthesizes the evidence reported by 73 papers related to coproduction of health and welfare.

Results

Despite the fact that models of coleadership and collective leadership exhibit a better fit with the relational character of coproduction, the majority of the articles included in this review employed a leader-centric underlying theory. The practice of coproduction leadership is a complex activity pertaining to interactions among people, encompassing nine essential practices: initiating, power-sharing, training, supporting, establishing trust, communicating, networking, orchestration, and implementation.

Conclusions

This paper proposes a novel framework for coproduction leadership practices based on a systematic review of the literature and a set of reflective questions. This framework aims to help coproduction leaders and participants understand the complexity, diversity, and flexibility of coproduction leadership and to challenge and enhance their capacity to collaborate effectively.
Translational research on drug development and biomarker discovery for hepatocellular carcinoma
Authors: Chew Valerie , Chuang Chien-Huai , Hsu Chiun
Published: February 2024

Translational research plays a key role in drug development and biomarker discovery for hepatocellular carcinoma (HCC). However, unique challenges exist in this field because of the limited availability of human tumor samples from surgery, the lack of homogenous oncogenic driver mutations, and the paucity of adequate experimental models. In this review, we provide insights into these challenges and review recent advancements, with a particular focus on the two main agents currently used as mainstream therapies for HCC: anti-angiogenic agents and immunotherapy. First, we examine the pre-clinical and clinical studies to highlight the challenges of determining the optimal therapeutic combinations with biologically effective dosage for HCC. Second, we discuss biomarker studies focusing on anti-PD1/anti-PD-L1-based combination therapy. Finally, we discuss the progress made in our collective understanding of tumor immunology and in multi-omics analysis technology, which enhance our understanding of the mechanisms underlying immunotherapy, characterize different patient subgroups, and facilitate the development of novel combination approaches to improve treatment efficacy. In summary, this review provides a comprehensive overview of efforts in translational research aiming at advancing our understanding of and improving the treatment of HCC.
Genetic characterization of a novel Salinicola salarius isolate applied for the bioconversion of agro-industrial wastes into polyhydroxybutyrate
Authors: Abdelrahman Shymaa A. , Barakat Olfat S. , Ahmed Marwa N.
Published: February 2024

Background

Polyhydroxybutyrate (PHB) has emerged as a promising eco-friendly alternative to traditional petrochemical-based plastics. In the present study, we isolated and characterized a new strain of Salinicola salarius, a halophilic bacterium, from the New Suez Canal in Egypt and characterized exclusively as a potential PHB producer. Further genome analysis of the isolated strain, ES021, was conducted to identify and elucidate the genes involved in PHB production.

Results

Different PHB-producing marine bacteria were isolated from the New Suez Canal and characterized as PHB producers. Among the 17 bacterial isolates, Salinicola salarius ES021 strain showed the capability to accumulate the highest amount of PHB. Whole genome analysis was implemented to identify the PHB-related genes in Salinicola salarius ES021 strain. Putative genes were identified that can function as phaCAB genes to produce PHB in this strain. These genes include fadA, fabG, and P3W43_16340 (encoding acyl-CoA thioesterase II) for PHB production from glucose. Additionally, phaJ and fadB were identified as key genes involved in PHB production from fatty acids. Optimization of environmental factors such as shaking rate and incubation temperature, resulted in the highest PHB productivity when growing Salinicola salarius ES021 strain at 30°C on a shaker incubator (110 rpm) for 48 h. To maximize PHB production economically, different raw materials i.e., salted whey and sugarcane molasses were examined as cost-effective carbon sources. The PHB productivity increased two-fold (13.34 g/L) when using molasses (5% sucrose) as a fermentation media. This molasses medium was used to upscale PHB production in a 20 L stirred-tank bioreactor yielding a biomass of 25.12 g/L, and PHB of 12.88 g/L. Furthermore, the produced polymer was confirmed as PHB using Fourier-transform infrared spectroscopy (FTIR), gas chromatography-mass spectroscopy (GC–MS), and nuclear magnetic resonance spectroscopy (NMR) analyses.

Conclusions

Herein,Salinicola salarius ES021 strain was demonstrated as a robust natural producer of PHB from agro-industrial wastes. The detailed genome characterization of the ES021 strain presented in this study identifies potential PHB-related genes. However, further metabolic engineering is warranted to confirm the gene networks required for PHB production in this strain. Overall, this study contributes to the development of sustainable and cost-effective PHB production strategies.
Impact of cell wall polysaccharide modifications on the performance of Pichia pastoris: novel mutants with enhanced fitness and functionality for bioproduction applications
Authors: Cheng Bingjie , Yu Keyang , Weng Xing , Liu Zhaojun , Huang Xuewu , Jiang Yuhong , Zhang Shuai , Wu Shuyan , Wang Xiaoyuan , Hu Xiaoqing
Published: February 2024

Background

Pichia pastoris is a widely utilized host for heterologous protein expression and biotransformation. Despite the numerous strategies developed to optimize the chassis host GS115, the potential impact of changes in cell wall polysaccharides on the fitness and performance of P. pastoris remains largely unexplored. This study aims to investigate how alterations in cell wall polysaccharides affect the fitness and function of P. pastoris, contributing to a better understanding of its overall capabilities.

Results

Two novel mutants of GS115 chassis, H001 and H002, were established by inactivating the PAS_chr1-3_0225 and PAS_chr1-3_0661 genes involved in β-glucan biosynthesis. In comparison to GS115, both modified hosts exhibited a looser cell surface and larger cell size, accompanied by faster growth rates and higher carbon-to-biomass conversion ratios. When utilizing glucose, glycerol, and methanol as exclusive carbon sources, the carbon-to-biomass conversion rates of H001 surpassed GS115 by 10.00%, 9.23%, and 33.33%, respectively. Similarly, H002 exhibited even higher increases of 32.50%, 12.31%, and 53.33% in carbon-to-biomass conversion compared to GS115 under the same carbon sources. Both chassis displayed elevated expression levels of green fluorescent protein (GFP) and human epidermal growth factor (hegf). Compared to GS115/pGAPZ A-gfp, H002/pGAPZ A-gfp showed a 57.64% higher GFP expression, while H002/pPICZα A-hegf produced 66.76% more hegf. Additionally, both mutant hosts exhibited enhanced biosynthesis efficiencies of S-adenosyl-L-methionine and ergothioneine. H001/pGAPZ A-sam2 synthesized 21.28% more SAM at 1.14 g/L compared to GS115/pGAPZ A-sam2, and H001/pGAPZ A-egt1E obtained 45.41% more ERG at 75.85 mg/L. The improved performance of H001 and H002 was likely attributed to increased supplies of NADPH and ATP. Specifically, H001 and H002 exhibited 5.00-fold and 1.55-fold higher ATP levels under glycerol, and 6.64- and 1.47-times higher ATP levels under methanol, respectively, compared to GS115. Comparative lipidomic analysis also indicated that the mutations generated richer unsaturated lipids on cell wall, leading to resilience to oxidative damage.

Conclusions

Two novel P. pastoris chassis hosts with impaired β-1,3-D-glucan biosynthesis were developed, showcasing enhanced performances in terms of growth rate, protein expression, and catalytic capabilities. These hosts exhibit the potential to serve as attractive alternatives to P. pastoris GS115 for various bioproduction applications.
TRP channels associated with macrophages as targets for the treatment of obese asthma
Authors: Zhu Wenzhao , Bai Dinxi , Ji Wenting , Gao Jing
Published: February 2024

Globally, obesity and asthma pose significant health challenges, with obesity being a key factor influencing asthma. Despite this, effective treatments for obese asthma, a distinct phenotype, remain elusive. Since the discovery of transient receptor potential (TRP) channels in 1969, their value as therapeutic targets for various diseases has been acknowledged. TRP channels, present in adipose tissue cells, influence fat cell heat production and the secretion of adipokines and cytokines, which are closely associated with asthma and obesity. This paper aims to investigate the mechanisms by which obesity exacerbates asthma-related inflammation and suggests that targeting TRP channels in adipose tissue could potentially suppress obese asthma and offer novel insights into its treatment.
Phosphorylation: new star of pathogenesis and treatment in steatotic liver disease
Authors: Lv Tiansu , Lou Yan , Yan Qianhua , Nie Lijuan , Cheng Zhe , Zhou Xiqiao
Published: February 2024

Steatotic liver disease poses a serious threat to human health and has emerged as one of the most significant burdens of chronic liver disease worldwide. Currently, the research mechanism is not clear, and there is no specific targeted drug for direct treatment. Phosphorylation is widely regarded as the most common type of protein modification, closely linked to steatotic liver disease in previous studies. However, there is no systematic review to clarify the relationship and investigate from the perspective of phosphorylation. Phosphorylation has been found to mainly regulate molecule stability, affect localization, transform molecular function, and cooperate with other protein modifications. Among them, adenosine 5’-monophosphate-activated protein kinase (AMPK), serine/threonine kinase (AKT), and nuclear factor kappa-B (NF-kB) are considered the core mechanisms in steatotic liver disease. As to treatment, lifestyle changes, prescription drugs, and herbal ingredients can alleviate symptoms by influencing phosphorylation. It demonstrates the significant role of phosphorylation as a mechanism occurrence and a therapeutic target in steatotic liver disease, which could be a new star for future exploration.
The war on drugs is a war on us: young people who use drugs and the fight for harm reduction in the Global South
Authors: Stowe M-J , Gatonye Rita , Maharjan Ishwor , Kehinde Seyi , Arya Sidarth , Valderrábano Jorge Herrera , Mcbride Angela , Scheibein Florian , Igonya Emmy Kageha , Fast Danya
Published: February 2024

In the Global South, young people who use drugs (YPWUD) are exposed to multiple interconnected social and health harms, with many low- and middle-income countries enforcing racist, prohibitionist-based drug policies that generate physical and structural violence. While harm reduction coverage for YPWUD is suboptimal globally, in low- and middle-income countries youth-focused harm reduction programs are particularly lacking. Those that do exist are often powerfully shaped by global health funding regimes that restrict progressive approaches and reach. In this commentary we highlight the efforts of young people, activists, allies, and organisations across some Global South settings to enact programs such as those focused on peer-to-peer information sharing and advocacy, overdose monitoring and response, and drug checking. We draw on our experiential knowledge and expertise to identify and discuss key challenges, opportunities, and recommendations for youth harm reduction movements, programs and practices in low- to middle-income countries and beyond, focusing on the need for youth-driven interventions. We conclude this commentary with several calls to action to advance harm reduction for YPWUD within and across Global South settings.
Understanding immune microenvironment alterations in the brain to improve the diagnosis and treatment of diverse brain diseases
Authors: Xu Xiaotong , Han Yi , Zhang Binlong , Ren Quanzhong , Ma Juan , Liu Sijin
Published: February 2024

Abnormal inflammatory states in the brain are associated with a variety of brain diseases. The dynamic changes in the number and function of immune cells in cerebrospinal fluid (CSF) are advantageous for the early prediction and diagnosis of immune diseases affecting the brain. The aggregated factors and cells in inflamed CSF may represent candidate targets for therapy. The physiological barriers in the brain, such as the blood‒brain barrier (BBB), establish a stable environment for the distribution of resident immune cells. However, the underlying mechanism by which peripheral immune cells migrate into the brain and their role in maintaining immune homeostasis in CSF are still unclear. To advance our understanding of the causal link between brain diseases and immune cell status, we investigated the characteristics of immune cell changes in CSF and the molecular mechanisms involved in common brain diseases. Furthermore, we summarized the diagnostic and treatment methods for brain diseases in which immune cells and related cytokines in CSF are used as targets. Further investigations of the new immune cell subtypes and their contributions to the development of brain diseases are needed to improve diagnostic specificity and therapy.
Engineered bone marrow mesenchymal stem cell-derived exosomes loaded with miR302 through the cardiomyocyte specific peptide can reduce myocardial ischemia and reperfusion (I/R) injury
Authors: Gu Jianjun , You Jia , Liang Hao , Zhan Jiacai , Gu Xiang , Zhu Ye
Published: February 2024

Background

MicroRNA (miRNA)-based therapies have shown great potential in myocardial repair following myocardial infarction (MI). MicroRNA-302 (miR302) has been reported to exert a protective effect on MI. However, miRNAs are easily degraded and ineffective in penetrating cells, which limit their clinical applications. Exosomes, which are small bioactive molecules, have been considered as an ideal vehicle for miRNAs delivery due to their cell penetration, low immunogenicity and excellent stability potential. Herein, we explored cardiomyocyte-targeting exosomes as vehicles for delivery of miR302 into cardiomyocyte to potentially treat MI.

Methods

To generate an efficient exosomal delivery system that can target cardiomyocytes, we engineered exosomes with cardiomyocyte specific peptide (CMP, WLSEAGPVVTVRALRGTGSW). Afterwards, the engineered exosomes were characterized and identified using transmission electron microscope (TEM) and Nanoparticle Tracking Analysis (NTA). Later on, the miR302 mimics were loaded into the engineered exosomes via electroporation technique. Subsequently, the effect of the engineered exosomes on myocardial ischemia and reperfusion (I/R) injury was evaluated in vitro and in vivo, including MTT, ELISA, real-time quantitative polymerase chain reaction (PCR), western blot, TUNNEL staining, echocardiogram and hematoxylin and eosin (HE) staining.

Results

Results of in vitro experimentation showed that DSPE-PEG-CMP-EXO could be more efficiently internalized by H9C2 cells than unmodified exosomes (blank‐exosomes). Importantly, compared with the DSPE-PEG-CMP-EXO group, DSPE-PEG-CMP-miR302-EXO significantly upregulated the expression of miR302, while exosomes loaded with miR302 could enhance proliferation of H9C2 cells. Western blot results showed that the DSPE-PEG-CMP-miR302-EXO significantly increased the protein level of Ki67 and Yap, which suggests that DSPE-PEG-CMP-miR302-EXO enhanced the activity of Yap, the principal downstream effector of Hippo pathway. In vivo, DSPE-PEG-CMP-miR302-EXO improved cardiac function, attenuated myocardial apoptosis and inflammatory response, as well as reduced infarct size significantly.

Conclusion

In conclusion, our findings suggest that CMP-engineered exosomes loaded with miR302 was internalized by H9C2 cells, an in vitro model for cardiomyocytes coupled with potential enhancement of the therapeutic effects on myocardial I/R injury.
Combination protein biomarkers predict multiple sclerosis diagnosis and outcomes
Authors: Kodosaki Eleftheria , Watkins W. John , Loveless Sam , Kreft Karim L. , Richards Aidan , Anderson Valerie , Hurler Lisa , Robertson Neil P. , Zelek Wioleta M. , Tallantyre Emma C.
Published: February 2024

Establishing biomarkers to predict multiple sclerosis diagnosis and prognosis has been challenging using a single biomarker approach. We hypothesised that a combination of biomarkers would increase the accuracy of prediction models to differentiate multiple sclerosis from other neurological disorders and enhance prognostication for people with multiple sclerosis. We measured 24 fluid biomarkers in the blood and cerebrospinal fluid of 77 people with multiple sclerosis and 80 people with other neurological disorders, using ELISA or Single Molecule Array assays. Primary outcomes were multiple sclerosis versus any other diagnosis, time to first relapse, and time to disability milestone (Expanded Disability Status Scale 6), adjusted for age and sex. Multivariate prediction models were calculated using the area under the curve value for diagnostic prediction, and concordance statistics (the percentage of each pair of events that are correctly ordered in time for each of the Cox regression models) for prognostic predictions. Predictions using combinations of biomarkers were considerably better than single biomarker predictions. The combination of cerebrospinal fluid [chitinase-3-like-1 + TNF-receptor-1 + CD27] and serum [osteopontin + MCP-1] had an area under the curve of 0.97 for diagnosis of multiple sclerosis, compared to the best discriminative single marker in blood (osteopontin: area under the curve 0.84) and in cerebrospinal fluid (chitinase-3-like-1 area under the curve 0.84). Prediction for time to next relapse was optimal with a combination of cerebrospinal fluid[vitamin D binding protein + Factor I + C1inhibitor] + serum[Factor B + Interleukin-4 + C1inhibitor] (concordance 0.80), and time to Expanded Disability Status Scale 6 with cerebrospinal fluid [C9 + Neurofilament-light] + serum[chitinase-3-like-1 + CCL27 + vitamin D binding protein + C1inhibitor] (concordance 0.98). A combination of fluid biomarkers has a higher accuracy to differentiate multiple sclerosis from other neurological disorders and significantly improved the prediction of the development of sustained disability in multiple sclerosis. Serum models rivalled those of cerebrospinal fluid, holding promise for a non-invasive approach. The utility of our biomarker models can only be established by robust validation in different and varied cohorts.
Effective density of inhaled environmental and engineered nanoparticles and its impact on the lung deposition and dosimetry
Authors: Lizonova Denisa , Nagarkar Amogh , Demokritou Philip , Kelesidis Georgios A.
Published: February 2024

Background

Airborne environmental and engineered nanoparticles (NPs) are inhaled and deposited in the respiratory system. The inhaled dose of such NPs and their deposition location in the lung determines their impact on health. When calculating NP deposition using particle inhalation models, a common approach is to use the bulk material density, ρb, rather than the effective density, ρeff. This neglects though the porous agglomerate structure of NPs and may result in a significant error of their lung-deposited dose and location.

Results

Here, the deposition of various environmental NPs (aircraft and diesel black carbon, wood smoke) and engineered NPs (silica, zirconia) in the respiratory system of humans and mice is calculated using the Multiple-Path Particle Dosimetry model accounting for their realistic structure and effective density. This is done by measuring the NP ρeff which was found to be up to one order of magnitude smaller than ρb. Accounting for the realistic ρeff of NPs reduces their deposited mass in the pulmonary region of the respiratory system up to a factor of two in both human and mouse models. Neglecting the ρeff of NPs does not alter significantly the distribution of the deposited mass fractions in the human or mouse respiratory tract that are obtained by normalizing the mass deposited at the head, tracheobronchial and pulmonary regions by the total deposited mass. Finally, the total deposited mass fraction derived this way is in excellent agreement with those measured in human studies for diesel black carbon.

Conclusions

The doses of inhaled NPs are overestimated by inhalation particle deposition models when the ρb is used instead of the real-world effective density which can vary significantly due to the porous agglomerate structure of NPs. So the use of realistic ρeff, which can be measured as described here, is essential to determine the lung deposition and dosimetry of inhaled NPs and their impact on public health.

Graphical abstract
The efficacy and safety of corticotomy and periodontally accelerated osteogenic orthodontic interventions in tooth movement: an updated meta-analysis
Authors: Zhou Huan , Zhang Yi-Fan , Qi Yan-Xin , Zhang Qian-Qian , Liu Na , Chen Yue
Published: February 2024

Background

The surgically facilitated orthodontic strategy has been a promising strategy for orthodontic treatment recently. Therefore, the present meta-analysis was conducted to assess the available scientific evidence regarding the clinical outcomes, including the potential detrimental effects associated with these surgical procedures, with the aim of providing much more evidence-based information for clinical practice.

Methods

An electronic search of three databases (PubMed, Cochrane, and Embase) and a manual search of relevant articles published up to May 2023 were carried out. Clinical trials (≥ 10 subjects) that utilized surgically facilitated orthodontic strategies with clinical and/or radiographic outcomes were included. Meta-analyses and sub-group analyses were performed to analyze the standardized mean difference (SMD) or weighted mean difference (WMD), and confidence interval (CI) for the recorded variables.

Results

Nineteen studies published from Oct 2012 to May 2023 met the inclusion criteria. Based on the analysis outcomes, corticotomy treatment significantly decreased the alignment duration (WMD: -1.08 months; 95% CI = -1.65, -0.51 months, P = 0.0002), and accelerated the canine movement (WMD: 0.72 mm; 95% CI = 0.63, 0.81 mm, P < 0.00001) compared to the traditional orthodontic group. The periodontally accelerated osteogenic orthodontic (PAOO) strategy markedly reduced the total treatment duration (SMD: -1.98; 95% CI = -2.59, -1.37, P < 0.00001) and increased the bone thickness (SMD:1.07; 95% CI = 0.74, 1.41, P < 0.00001) compared to traditional orthodontic treatment.

Conclusion

The present study suggests that facilitated orthodontic treatment in terms of corticotomy and PAOO strategy may represent attractive and effective therapeutic strategy for orthodontic patients.
Reliability of landmark identification for analysis of the temporomandibular joint in real-time MRI
Authors: Mouchoux Jérémy , Meyer-Marcotty Philipp , Sojka Florian , Dechent Peter , Klenke Daniela , Wiechens Bernhard , Quast Anja
Published: February 2024

Background

Real-time magnetic resonance imaging (rtMRI) is essential for diagnosing and comprehending temporomandibular joint (TMJ) movements. Current methods for tracking and analysis require manual landmark placement on each acquisition frame. Therefore, our study aimed to assess the inter- and intra-rater reliability of placing cephalometric landmarks in frames from a dynamic real-time TMJ MRI.

Material and methods

Four real-time MRIs of the right TMJ were taken during mandibular movement at ten frames per second. Seven dentists identified ten landmarks on two frames (intercuspal position—ICP—and maximum mouth opening—MMO) twice at a two-week interval, yielding 112 tracings. Six typical cephalometric measurements (angles and distances) were derived from these landmarks. The reliabilities of landmarks and measurements were evaluated using distance-based (dbICC), linear mixed effect model intraclass correlation (lmeICC), and standard ICC.

Results

The average inter-rater reliability for the landmarks stood at 0.92 (dbICC) and 0.93 (lmeICC). The intra-rater reliability scores were 0.97 and 0.98. Over 80% of the landmarks showed an ICC greater than 0.98 (inter-rater) and over 0.99 (intra-rater). The lowest landmark ICC was observed for the orbitale and the oblique ridge of the mandibular ramus. However, the cephalometric angle and distance measurements derived from these landmarks showed only moderate to good reliability, whereas the reliability in the frames with ICP was better than those with MMO. Measurements performed in the ICP frame were more reliable than measurements in the MMO frame.

Conclusion

While dentists reliably localize isolated landmarks in real-time MRIs, the cephalometric measurements derived from them remain inconsistent. The better results in ICP than MMO are probably due to a more familiar jaw position. The higher error rate of the TMJ measurements in MMO could be associated with a lack of training in real-time MRI analysis in dentistry.
Plasma N-terminal containing tau fragments (NTA-tau): a biomarker of tau deposition in Alzheimer’s Disease
Authors: Lantero-Rodriguez Juan , Salvadó Gemma , Snellman Anniina , Montoliu-Gaya Laia , Brum Wagner S. , Benedet Andrea L. , Mattsson-Carlgren Niklas , Tideman Pontus , Janelidze Shorena , Palmqvist Sebastian , Stomrud Erik , Ashton Nicholas J. , Zetterberg Henrik , Blennow Kaj , Hansson Oskar
Published: February 2024

Background

Novel phosphorylated-tau (p-tau) blood biomarkers (e.g., p-tau181, p-tau217 or p-tau231), are highly specific for Alzheimer’s disease (AD), and can track amyloid-β (Aβ) and tau pathology. However, because these biomarkers are strongly associated with the emergence of Aβ pathology, it is difficult to determine the contribution of insoluble tau aggregates to the plasma p-tau signal in blood. Therefore, there remains a need for a biomarker capable of specifically tracking insoluble tau accumulation in brain.

Methods

NTA is a novel ultrasensitive assay targeting N-terminal containing tau fragments (NTA-tau) in cerebrospinal fluid (CSF) and plasma, which is elevated in AD. Using two well-characterized research cohorts (BioFINDER-2, n = 1,294, and BioFINDER-1, n = 932), we investigated the association between plasma NTA-tau levels and disease progression in AD, including tau accumulation, brain atrophy and cognitive decline.

Results

We demonstrate that plasma NTA-tau increases across the AD continuum¸ especially during late stages, and displays a moderate-to-strong association with tau-PET (β = 0.54, p < 0.001) in Aβ-positive participants, while weak with Aβ-PET (β = 0.28, p < 0.001). Unlike plasma p-tau181, GFAP, NfL and t-tau, tau pathology determined with tau-PET is the most prominent contributor to NTA-tau variance (52.5% of total R2), while having very low contribution from Aβ pathology measured with CSF Aβ42/40 (4.3%). High baseline NTA-tau levels are predictive of tau-PET accumulation (R2 = 0.27), steeper atrophy (R2 ≥ 0.18) and steeper cognitive decline (R2 ≥ 0.27) in participants within the AD continuum. Plasma NTA-tau levels significantly increase over time in Aβ positive cognitively unimpaired (βstd = 0.16) and impaired (βstd = 0.18) at baseline compared to their Aβ negative counterparts. Finally, longitudinal increases in plasma NTA-tau levels were associated with steeper longitudinal decreases in cortical thickness (R2 = 0.21) and cognition (R2 = 0.20).

Conclusion

Our results indicate that plasma NTA-tau levels increase across the AD continuum, especially during mid-to-late AD stages, and it is closely associated with in vivo tau tangle deposition in AD and its downstream effects. Moreover, this novel biomarker has potential as a cost-effective and easily accessible tool for monitoring disease progression and cognitive decline in clinical settings, and as an outcome measure in clinical trials which also need to assess the downstream effects of successful Aβ removal.
A simple and reliable method for claustrum localization across age in mice
Authors: Shaker Tarek , Dagpa Gwyneth J. , Cattaud Vanessa , Marriott Brian A. , Sultan Mariam , Almokdad Mohammed , Jackson Jesse
Published: February 2024

The anatomical organization of the rodent claustrum remains obscure due to lack of clear borders that distinguish it from neighboring forebrain structures. Defining what constitutes the claustrum is imperative for elucidating its functions. Methods based on gene/protein expression or transgenic mice have been used to spatially outline the claustrum but often report incomplete labeling and/or lack of specificity during certain neurodevelopmental timepoints. To reliably identify claustrum projection cells in mice, we propose a simple immunolabelling method that juxtaposes the expression pattern of claustrum-enriched and cortical-enriched markers. We determined that claustrum cells immunoreactive for the claustrum-enriched markers Nurr1 and Nr2f2 are devoid of the cortical marker Tle4, which allowed us to differentiate the claustrum from adjoining cortical cells. Using retrograde tracing, we verified that nearly all claustrum projection neurons lack Tle4 but expressed Nurr1/Nr2f2 markers to different degrees. At neonatal stages between 7 and 21 days, claustrum projection neurons were identified by their Nurr1-postive/Tle4-negative expression profile, a time-period when other immunolabelling techniques used to localize the claustrum in adult mice are ineffective. Finally, exposure to environmental novelty enhanced the expression of the neuronal activation marker c-Fos in the claustrum region. Notably, c-Fos labeling was mainly restricted to Nurr1-positive cells and nearly absent from Tle4-positive cells, thus corroborating previous work reporting novelty-induced claustrum activation. Taken together, this method will aid in studying the claustrum during postnatal development and may improve histological and functional studies where other approaches are not amenable.
Ketamine versus etomidate as an induction agent for tracheal intubation in critically ill adults: a Bayesian meta-analysis
Authors: Koroki Takatoshi , Kotani Yuki , Yaguchi Takahiko , Shibata Taisuke , Fujii Motoki , Fresilli Stefano , Tonai Mayuko , Karumai Toshiyuki , Lee Todd C. , Landoni Giovanni , Hayashi Yoshiro
Published: February 2024

Background

Tracheal intubation is a high-risk intervention commonly performed in critically ill patients. Due to its favorable cardiovascular profile, ketamine is considered less likely to compromise clinical outcomes. This meta-analysis aimed to assess whether ketamine, compared with other agents, reduces mortality in critically ill patients undergoing intubation.

Methods

We searched MEDLINE, Embase, and the Cochrane Library from inception until April 27, 2023, for randomized controlled trials and matched observational studies comparing ketamine with any control in critically ill patients as an induction agent. The primary outcome was mortality at the longest follow-up available, and the secondary outcomes included Sequential Organ Failure Assessment score, ventilator-free days at day 28, vasopressor-free days at day 28, post-induction mean arterial pressure, and successful intubation on the first attempt. For the primary outcome, we used a Bayesian random-effects meta-analysis on the risk ratio (RR) scale with a weakly informative neutral prior corresponding to a mean estimate of no difference with 95% probability; the estimated effect size will fall between a relative risk of 0.25 and 4. The RR and 95% credible interval (CrI) were used to estimate the probability of mortality reduction (RR < 1). The secondary outcomes were assessed with a frequentist random-effects model. We registered this study in Open Science Framework (https://osf.io/2vf79/).

Results

We included seven randomized trials and one propensity-matched study totaling 2978 patients. Etomidate was the comparator in all the identified studies. The probability that ketamine reduced mortality was 83.2% (376/1475 [25%] vs. 411/1503 [27%]; RR, 0.93; 95% CrI, 0.79–1.08), which was confirmed by a subgroup analysis excluding studies with a high risk of bias. No significant difference was observed in any secondary outcomes.

Conclusions

All of the included studies evaluated ketamine versus etomidate among critically ill adults requiring tracheal intubation. This meta-analysis showed a moderate probability that induction with ketamine is associated with a reduced risk of mortality.

Graphical abstract