bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating perceptions and attitude toward telenursing among undergraduate nursing students for the future of nursing education: a cross-sectional study
Authors: Mun Minji , Choi Subin , Woo Kyungmi
Published: April 2024

Background

Telenursing is poised to emerge as a novel healthcare delivery system in the digital age. Hence, understanding nursing students' perspectives and readiness is pivotal for its effective implementation. This study investigated nursing students' perceptions regarding, and attitudes toward, telenursing and the factors that influenced their attitudes based on the technology acceptance model.

Methods

This study used a cross-sectional descriptive approach. The participants consisted of 188 nursing students (first to fourth year) enrolled in the College of Nursing in Korea. Differences in attitudes toward telenursing were analyzed using independent t-test and one-way analysis of variance. Pearson’s correlation coefficient was used to examine the correlations between the main variables. Factors that influenced attitudes toward telenursing were analyzed using multiple regression.

Results

Of the participants, 65.4% lacked substantial awareness of telenursing and 19.1% had prior telenursing experience. Although prospects on telenursing indicated that 90.4% had an optimistic view, face-to-face nursing was heavily preferred for both satisfactory and favored healthcare delivery. Many cited the Internet as their source of knowledge, and only 18.6% had received telenursing education. Attitude toward telenursing was significantly more positive among those with experience of telenursing, telenursing observation in clinical practice, and telenursing education exposure. The regression model was statistically significant (F = 67.445, p < .000). Factors, such as perceived usefulness, social influence, innovativeness, and self-efficacy, influenced attitudes toward telenursing.

Conclusions

Nursing students exhibited a lack of substantial awareness of telenursing; however, they simultaneously displayed a positive outlook. This lack of comprehensive understanding could stem from the absence of formal education in telenursing. Understanding and utilizing the potential of telenursing could be significantly aided by nursing students' education and knowledge. Thus, it is necessary to include telenursing education in the nursing curriculum. The skills and knowledge required for telenursing clinical practice can be developed through telenursing education. Such preparedness will affect nurses’ attitudes and intentions and the quality of telenursing offered to patients in the future.
Transformational nurse leadership attributes in German hospitals pursuing organization-wide change via Magnet® or Pathway® principles: results from a qualitative study
Authors: Kleine Joan , Köppen Julia , Gurisch Carolin , Maier Claudia B.
Published: April 2024

Background

Budget constraints, staff shortages and high workloads pose challenges for German hospitals. Magnet® and Pathway® are concepts for implementing organization-wide change and redesigning work environments. There is limited research on the key elements that characterize nurse leaders driving the implementation of Magnet®/Pathway® principles outside the U.S. We explored the key attributes of nurse leaders driving organization-wide change through Magnet®/Pathway® principles in German hospitals.

Methods

Using a qualitative study design, semi-structured interviews (n = 18) were conducted with nurse leaders, managers, and clinicians, in five German hospitals known as having started implementing Magnet® or Pathway® principles. The interviews were recorded and transcribed verbatim. Data were analyzed in Atlas.ti using content analysis. For the analysis, a category system was created using a deductive-inductive approach.

Results

Five leadership attributes and eleven sub-attributes were identified as main themes and sub-themes: Visionary leaders who possess and communicate a strong vision and serve as role models to inspire change. Strategic leaders who focus on strategic planning and securing top management support. Supportive leaders who empower, emphasizing employee motivation, individualized support, and team collaboration. Stamina highlights courage, assertiveness, and resilience in the face of challenges. Finally, agility which addresses a leader’s presence, accessibility, and rapid responsiveness, fostering adaptability.

Conclusions

The study demonstrates leadership attributes explicitly focusing on instigating and driving organization-wide change through Magnet®/Pathway® principles in five German hospitals. The findings suggest a need for comprehensive preparation and ongoing development of nurse leaders aimed at establishing and sustaining a positive hospital work environment.
Characterization of a pleiotropic regulator MtrA in Streptomyces avermitilis controlling avermectin production and morphological differentiation
Authors: Tian Jinpin , Li Yue , Zhang Chuanbo , Su Jianyu , Lu Wenyu
Published: April 2024

Background

The macrolide antibiotic avermectin, a natural product derived from Streptomyces avermitilis, finds extensive applications in agriculture, animal husbandry and medicine. The mtrA (sav_5063) gene functions as a transcriptional regulator belonging to the OmpR family. As a pleiotropic regulator, mtrA not only influences the growth, development, and morphological differentiation of strains but also modulates genes associated with primary metabolism. However, the regulatory role of MtrA in avermectin biosynthesis remains to be elucidated.

Results

In this study, we demonstrated that MtrA, a novel OmpR-family transcriptional regulator in S. avermitilis, exerts global regulator effects by negatively regulating avermectin biosynthesis and cell growth while positively controlling morphological differentiation. The deletion of the mtrA gene resulted in an increase in avermectin production, accompanied by a reduction in biomass and a delay in the formation of aerial hyphae and spores. The Electrophoretic Mobility Shift Assay (EMSA) revealed that MtrA exhibited binding affinity towards the upstream region of aveR, the intergenic region between aveA1 and aveA2 genes, as well as the upstream region of aveBVIII in vitro. These findings suggest that MtrA exerts a negative regulatory effect on avermectin biosynthesis by modulating the expression of avermectin biosynthesis cluster genes. Transcriptome sequencing and fluorescence quantitative PCR analysis showed that mtrA deletion increased the transcript levels of the cluster genes aveR, aveA1, aveA2, aveC, aveE, aveA4 and orf-1, which explains the observed increase in avermectin production in the knockout strain. Furthermore, our findings demonstrate that MtrA positively regulates the cell division and differentiation genes bldM and ssgC, while exerting a negative regulatory effect on bldD, thereby modulating the primary metabolic processes associated with cell division, differentiation and growth in S. avermitilis, consequently impacting avermectin biosynthesis.

Conclusions

In this study, we investigated the negative regulatory effect of the global regulator MtrA on avermectin biosynthesis and its effects on morphological differentiation and cell growth, and elucidated its transcriptional regulatory mechanism. Our findings indicate that MtrA plays crucial roles not only in the biosynthesis of avermectin but also in coordinating intricate physiological processes in S. avermitilis. These findings provide insights into the synthesis of avermectin and shed light on the primary and secondary metabolism of S. avermitilis mediated by OmpR-family regulators.
Anti-EGFR ScFv functionalized exosomes delivering LPCAT1 specific siRNAs for inhibition of lung cancer brain metastases
Authors: Jiang Jun , Lu Yuan , Chu Jie , Zhang Xiao , Xu Chao , Liu Shaojie , Wan Zhuo , Wang Jiawei , Zhang Lu , Liu Kui , Liu Zhenhua , Yang Angang , Ren Xinling , Zhang Rui
Published: April 2024

Brain metastasis (BM) is one of the leading causes of cancer-related deaths in patients with advanced non-small cell lung cancer (NSCLC). However, limited treatments are available due to the presence of the blood-brain barrier (BBB). Upregulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) in NSCLC has been found to promote BM. Conversely, downregulating LPCAT1 significantly suppresses the proliferation and metastasis of lung cancer cells. In this study, we firstly confirmed significant upregulation of LPCAT1 in BM sites compared to primary lung cancer by analyzing scRNA dataset. We then designed a delivery system based on a single-chain variable fragment (scFv) targeting the epidermal growth factor receptor (EGFR) and exosomes derived from HEK293T cells to enhance cell-targeting capabilities and increase permeability. Next, we loaded LPCAT1 siRNA (siLPCAT1) into these engineered exosomes (exoscFv). This novel scFv-mounted exosome successfully crossed the BBB in an animal model and delivered siLPCAT1 to the BM site. Silencing LPCAT1 efficiently arrested tumor growth and inhibited malignant progression of BM in vivo without detectable toxicity. Overall, we provided a potential platform based on exosomes for RNA interference (RNAi) therapy in lung cancer BM.
Comprehensive HIV knowledge and associated factors among reproductive-age women: analysis of the Gambia Demographic and Health Survey 2019/2020
Authors: Tsegaw Menen , Mulat Bezawit , Shitu Kegnie , Barrow Amadou
Published: April 2024

Introduction

Globally, there are 37.7 million people living with human immunodeficiency virus (HIV). So far, there is no study done in Gambia which assessed comprehensive HIV knowledge and its associated factors. Therefore, this study aims to assess comprehensive HIV knowledge and its associated factors among reproductive-age women in Gambia.

Objective

To assess the prevalence of comprehensive HIV knowledge and its associated factors among reproductive-age women in Gambia.

Methods

The study used the Gambian Demographic and Health Survey, which was conducted from 21 November 2019 to 30 March 2020 in Gambia. The survey employed a stratified two-stage cluster sampling technique to recruit study participants. Logistic regression analysis was used to identify factors associated with HIV comprehensive knowledge. Statistical significance was declared at a P value of less than 0.05 with a 95% confidence interval (CI).

Results

The overall prevalence of comprehensive HIV knowledge was 27.1% (25.1–36.2%). Older age [adjusted odds ratio (AOR) of 1.20 (95% CI 1.16–1.26)], using contraceptive [AOR of 1.15 (95% CI 1.01–1.31)], higher education [AOR of 4.73 (95% CI 3.86–5.81)], rich wealth quintile [AOR of 1.61 (95% CI 1.37–1.87)], media exposure [AOR of 1.76 (95% CI 1.39–2.23)], ever tested for HIV [AOR of 1.55 (95% CI 1.42–1.74)], visited health facility within the last 12 months [AOR of 1.26 (95% CI 1.12–1.41)] and decision-making autonomy [AOR of 1.42 (95% CI 1.27–1.60)] were positively associated with comprehensive HIV knowledge. However, being married [AOR of 0.72 (95% CI 0.62–0.82)] was negatively associated with comprehensive HIV knowledge.

Conclusions

The prevalence of comprehensive HIV knowledge was low in Gambia. Educational interventions that focused mainly on awareness creation about HIV/AIDS should be designed especially for married women and lower socio-economic status. An effort has to be made to address those disparities at the national level.
The protein composition of exosomes released by prostate cancer cells is distinctly regulated by androgen receptor-antagonists and -agonist to stimulate growth of target cells
Authors: Atri Roozbahani Golnaz , Kokal-Ribaudo Miriam , Heidari Horestani Mehdi , Pungsrinont Thanakorn , Baniahmad Aria
Published: April 2024

Background

Prostate cancer (PCa) is a prevalent malignancy in men worldwide, ranking as the second leading cause of cancer-related death in Western countries. Various PCa hormone therapies, such as androgen receptor (AR)-antagonists or supraphysiological androgen level (SAL) reduce cancer cell proliferation. However, treated cells may influence the growth of neighboring cells through secreted exosomes in the tumor microenvironment (TME). Here, the change of protein content of exosomes secreted from PCa cells through treatment with different AR-antagonists or SAL has been analyzed.

Methods

Isolation of exosomes via ultracentrifugation of treated human PCa LNCaP cells with AR-agonist and various AR-antagonists; analysis of cellular senescence by detection of senescence associated beta galactosidase activity (SA β-Gal); Western blotting and immunofluorescence staining; Mass spectrometry (MS-spec) of exosomes and bioinformatic analyses to identify ligand-specific exosomal proteins. Growth assays to analyze influence of exosomes on non-treated cells.

Results

MS-spec analysis identified ligand-specific proteins in exosomes. One thousand seventy proteins were up- and 52 proteins downregulated by SAL whereas enzalutamide upregulated 151 proteins and downregulated 42 exosomal proteins. The bioinformatic prediction indicates an up-regulation of pro-proliferative pathways. AR ligands augment hub factors in exosomes that include AKT1, CALM1, PAK2 and CTNND1. Accordingly, functional assays confirmed that the isolated exosomes from AR-ligand treated cells promote growth of untreated PCa cells.

Conclusion

The data suggest that the cargo of exosomes is controlled by AR-agonist and -antagonists and distinct among the AR-antagonists. Further, exosomes promote growth that might influence the TME. This finding sheds light into the complex interplay between AR signaling and exosome-mediated communication between PCa cells.
Melanocytes in regenerative medicine applications and disease modeling
Authors: Coutant Kelly , Magne Brice , Ferland Karel , Fuentes-Rodriguez Aurélie , Chancy Olivier , Mitchell Andrew , Germain Lucie , Landreville Solange
Published: April 2024

Melanocytes are dendritic cells localized in skin, eyes, hair follicles, ears, heart and central nervous system. They are characterized by the presence of melanosomes enriched in melanin which are responsible for skin, eye and hair pigmentation. They also have different functions in photoprotection, immunity and sound perception. Melanocyte dysfunction can cause pigmentary disorders, hearing and vision impairments or increased cancer susceptibility. This review focuses on the role of melanocytes in homeostasis and disease, before discussing their potential in regenerative medicine applications, such as for disease modeling, drug testing or therapy development using stem cell technologies, tissue engineering and extracellular vesicles.
Provider assessment of the temporomandibular joint in Juvenile idiopathic arthritis: a retrospective analysis from the CARRA database
Authors: Costello Anna , Twilt Marinka , Lerman Melissa A. ,   for the CARRA Registry Investigators
Published: April 2024

Background

Temporomandibular joint (TMJ) involvement is an often underrecognized complication of juvenile idiopathic arthritis (JIA) that can cause decreased mandibular growth, altered facial morphology, and orofacial pain. It is estimated that the TMJ is affected in 30–45% of children with JIA. Standardized physical examination and imaging evaluations are important in accurately assessing active TMJ arthritis and sequalae. Little is known about the rate at which providers evaluate TMJ involvement in their clinical practice.

Methods

Data were obtained from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Data fields related to assessment for TMJ arthritis were added in 2019. Patients were included in the study if they had a diagnosis of JIA and had data recorded between January 2020 and August 2021. Standard descriptive statistics were used to describe demographic and clinical features.

Results

A total of 17,761 visits were reviewed for a total of 7473 patients with JIA. A total of 52.7% of patients had maximal mouth opening (MMO) recorded as finger breadths or total incisal distance (TID). Only 8% had TID measured. A total of 5.0% had MRI with contrast performed. A total of 939 patients had a diagnosis of TMJ arthritis. Of these, 28.5% had an MRI documented, 83% had an MMO documented, and 40% had TID measured. Few patient-level characteristics were statistically related to having MMO assessed. MRI was more likely to be obtained in older and in female patients. MMO was recorded at a given visit > 80% of the time at 17 sites, and it was recorded < 1% of the time at 8 sites. MRIs were infrequently performed at all sites, with 27 sites having no MRIs obtained and only 7 sites having an MRI obtained at > 10% of visits.

Conclusions

MMO is not consistently measured in patients with JIA, and it is rarely measured quantitatively. Similarly, TMJ MRIs are rarely obtained in patients with JIA. Site of care is more associated with TMJ assessments than patient-level characteristics. These data suggest that provider education is needed to improve the assessment of the TMJ in patients with JIA to enable earlier recognition and prevent long-term complications.
Synergistic efficacy of repetitive peripheral magnetic stimulation on central intermittent theta burst stimulation for upper limb function in patients with stroke: a double-blinded, randomized controlled trial
Authors: Chang Chi-Shou , Chen Chia-Ling , Chen Rou-Shayn , Chen Hsieh-Ching , Chen Chung-Yao , Chung Chia-Ying , Wu Katie Pei-Hsuan , Wu Ching-Yi , Lin Keh-chung
Published: April 2024

Background

Non-invasive techniques such as central intermittent theta burst stimulation (iTBS) and repetitive peripheral magnetic stimulation (rPMS) have shown promise in improving motor function for patients with stroke. However, the combined efficacy of rPMS and central iTBS has not been extensively studied. This randomized controlled trial aimed to investigate the synergistic effects of rPMS and central iTBS in patients with stroke.

Method

In this study, 28 stroke patients were randomly allocated to receive either 1200 pulses of real or sham rPMS on the radial nerve of the affected limb, followed by 1200 pulses of central iTBS on the ipsilesional hemisphere. The patients received the intervention for 10 sessions over two weeks. The primary outcome measures were the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and the Action Research Arm Test (ARAT). Secondary outcomes for activities and participation included the Functional Independence Measure-Selfcare (FIM-Selfcare) and the Stroke Impact Scale (SIS). The outcome measures were assessed before and after the intervention.

Results

Both groups showed significant improvement in FMA-UE and FIM-Selfcare after the intervention (p < 0.05). Only the rPMS + iTBS group had significant improvement in ARAT-Grasp and SIS-Strength and activity of daily living (p < 0.05). However, the change scores in all outcome measures did not differ between two groups.

Conclusions

Overall, the study’s findings suggest that rPMS may have a synergistic effect on central iTBS to improve grasp function and participation. In conclusion, these findings highlight the potential of rPMS as an adjuvant therapy for central iTBS in stroke rehabilitation. Further large-scale studies are needed to fully explore the synergistic effects of rPMS on central iTBS.

Trial registration

This trial was registered under ClinicalTrials.gov ID No.NCT04265365, retrospectively registered, on February 11, 2020.
Multilevel modeling analysis of bottle feeding and its determinants among children 0–23 months in East Africa: evidence from recent DHS data (2015–2022)
Authors: Terefe Bewuketu , Habtie Adane , Chekole Bogale
Published: April 2024

Background

Despite breastfeeding recommendations, the prevalence and length of breast milk feeding in developing nations is rapidly decreasing, with bottle feeding taking its place. This reduces the effectiveness of breastfeeding and is associated with diarrheal disease mortality and morbidity. The purpose of this study was to determine the prevalence, distribution, and determinants of bottle feeding among under-two-year-old children in the region.

Methods

The ten East African countries’ Demographic and Health Surveys (DHS) recent data from 2015 to 2022 was used. The data were weighted using sample weights for probability sampling and nonresponse. The study used 43,150 weighted children. A multi-level logistic regression model was used, and P - values of ≤ 0.2 and < 0.05 were used to declare candidate variables in the binary, and multivariable to declare significant variables, respectively.

Results

The prevalence of bottle feeding among children under-two-years-old in East Africa was 10.08% (95% CI 9.79, 10.36), ranging from 4.04% (95% CI 3.56, 4.53) in Tanzania to 33.40% (95% CI 32.72, 34.08) in Kenya. High antenatal care communities (AOR 1.22; 95% CI 1.11, 1.35), mothers aged 25–34 years (AOR 1.17; 95% CI 1.06, 1.28), high wealth index communities (AOR 1.12; 95% CI 1.02,1.25), women who had at least one types mass media exposure (AOR 1.64; 95% CI 1.53, 1.77), women from communities with high level mass media exposure (AOR 1.36; 95% CI 1.23, 1.52), given first birth after teenage years (AOR 1.17; 95% CI 1.09, 1.26), having more than one health visit in the year (AOR 1.37; 95% CI 1.27,1.47), multiple children (AOR 1.46; 95% CI 1.22, 1.75) were associated with higher rates of bottle feeding. Whereas a primary education (AOR 0.51; 95% CI 0.47, 0.54), having 3–5 living children (AOR 0.86; 95% CI 0.79, 0.95), a rural setting (AOR 0.53; 95% CI 0.49, 0.58), and a long distance from health facilities (AOR 0.84; 95% CI, 0.78, 0.91) were associated with lower rates of bottle feeding.

Conclusions

The overall prevalence of bottle feeding was moderate in East African countries. Improving the availability and accessibility of health facilities to mothers, utilizing maternal healthcare, and media exposure will contribute to a significant decrease in the inappropriate bottle feeding of children in East Africa.
Is fracture management merely a physical process? Exploring the psychological effects of internal and external fixation
Authors: Jia Qiyu , Peng Zhenlei , Huang Anqi , Jiang Shijie , Zhao Wen , Xie Zengru , Ma Chuang
Published: April 2024

Background

Internal and external fixation are common surgical procedures for treating fractures. However, the impact of different surgical approaches (including internal and external fixations) on patients’ psychological status and Quality of Life (QoL) is rarely examined. Herein, we aimed to investigate the effects of internal and external fixation on anxiety, depression, insomnia, and overall mental and physical health in Distal Radius Fractures (DRF) patients.

Methods

We performed a retrospective study on 96 fracture patients who underwent internal fixation (57 patients) or external fixation (39 patients). The Visual Analog Scale (VAS), the Hospital Anxiety and Depression Scale (HADS), the Athens Insomnia Scale (AIS), and the Medical Outcomes Study Short Form 36 (SF-36) questionnaire were used to assess the patients’ pain, anxiety, depression, sleep, and QoL before surgery and at seven days, one month, and three months post-surgery.

Results

The VAS scores were significantly lower in the Internal Fixation Group (IFG) than in the External Fixation Group (EFG) on the seventh day and one month postoperatively (P < 0.05). Although both groups showed no significant anxiety, depression, or insomnia before surgery (P > 0.05), the EFG showed significantly higher HADS-A, HADS-D, and AIS scores than the IFG at seven days and one and three months postoperatively (P < 0.05). Additionally, changes in HADS-A, HADS-D, and AIS scores were most significant at day seven post-surgery in the EFG (P < 0.05). Furthermore, no significant difference was found between the two groups in the average Physical Component Summary (PCS) and Mental Component Summary (MCS) scores before surgery (P > 0.05). However, both groups showed positive changes in PCS and MCS scores at postoperative day seven and one and three months postoperatively, with the IFG having significantly higher average PCS and MCS scores compared to the EFG (P < 0.05).

Conclusion

Compared to external fixation, internal fixation did not significantly impact patients’ emotions regarding anxiety and depression in the early postoperative period, and physical and mental health recovery was better during the postoperative rehabilitation period. Furthermore, when there are no absolute indications, the impact on patients’ psychological well-being should be considered as one of the key factors in the treatment plan during surgical approach selection.
SP1 transcriptionally activates HTR2B to aggravate traumatic spinal cord injury by shifting microglial M1/M2 polarization
Authors: Xu Qifei , Kong Fanguo , Zhao Guanghui , Jin Junwei , Feng Shengkai , Li Ming
Published: April 2024

Background

Spinal cord injury (SCI) can result in structural and functional damage to the spinal cord, which may lead to loss of limb movement and sensation, loss of bowel and bladder control, and other complications. Previous studies have revealed the critical influence of trans-acting transcription factor 1 (SP1) in neurological pathologies, however, its role and mechanism in SCI have not been fully studied.

Methods

The study was performed using mouse microglia BV2 stimulated using lipopolysaccharide (LPS) and male adult mice subjected to spinal hitting. Western blotting was performed to detect protein expression of SP1, 5-hydroxytryptamine (serotonin) receptor 2B (HTR2B), BCL2-associated x protein (Bax), B-cell lymphoma-2 (Bcl-2), inducible nitric oxide synthase (iNOS), clusters of differentiation 86 (CD86), Arginase 1 (Arg-1) and clusters of differentiation 206 (CD206). Cell viability and apoptosis were analyzed by MTT assay and TUNEL assay. mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4) and tumor necrosis factor-β (TNF-β) were quantified by quantitative real-time polymerase chain reaction. The association of SP1 and HTR2B was identified by chromatin immunoprecipitation assay and dual-luciferase reporter assay. HE staining assay was performed to analyze the pathological conditions of spinal cord tissues.

Results

LPS treatment induced cell apoptosis and inhibited microglia polarization from M1 to M2 phenotype, accompanied by an increase of Bax protein expression and a decrease of Bcl-2 protein expression, however, these effects were relieved after SP1 silencing. Mechanism assays revealed that SP1 transcriptionally activated HTR2B in BV2 cells, and HTR2B knockdown rescued LPS-induced effects on BV2 cell apoptosis and microglial M1/M2 polarization. Moreover, SP1 absence inhibited BV2 cell apoptosis and promoted microglia polarization from M1 to M2 phenotype by decreasing HTR2B expression. SCI mouse model assay further showed that SP1 downregulation could attenuate spinal hitting-induced promoting effects on cell apoptosis of spinal cord tissues and microglial M1 polarization.

Conclusion

SP1 transcriptionally activated HTR2B to aggravate traumatic SCI by shifting microglial M1/M2 polarization.
Aspiration of thrombus for intermediate-risk subacute pulmonary embolism
Authors: He Jiahao , Liu Chunli
Published: April 2024

Pulmonary embolism is the most common cardiovascular disease after myocardial infarction and stroke. Konstantinides (Eur Heart J 41(4):543–603, 2020) Current guidelines categorize patients with PE as being at low, intermediate, and high risk of early death, with the intermediate-risk group experiencing the greatest uncertainty regarding treatment recommendations. Rapid reduction of the thrombus load by thrombolysis significantly reduces symptoms and decreases mortality, but is accompanied by a high risk of bleeding. Meyer (N Engl J Med 370(15):1402-11, 2014) Mechanical thrombectomy (CDTE) have been proven safe and efficient, yet current ESC guidelines suggest the utilization of catheter interventions only for hypotensive patients with high bleeding risk, failed systemic thrombolysis, and cardiogenic shock or if a patient does not respond to conservative therapy Konstantinides (Eur Heart J 41(4):543–603, 2020). Here, we report a case of an intermediate-risk patient with pulmonary embolism who underwent thrombus aspiration and showed significant improvement in symptoms after treatment.
Experience with aortic arch inclusion technique using artificial blood vessel for type A aortic dissection: an application study
Authors: Li Qingfeng , Li Bin , Xi Shuqiang , Li Zhaobin , Zhu Zhe , Jin Zeyue , Yang Fan , Liu Lei
Published: April 2024

Background

This study aimed to elucidate the methodology and assess the efficacy of the aortic arch inclusion technique using an artificial blood vessel in managing acute type A aortic dissection (ATAAD).

Methods

We conducted a retrospective review of 18 patients (11 males and 7 females, average age: 56.2 ± 8.6 years) diagnosed with ATAAD who underwent total aortic arch replacement (TAAR) using an artificial vascular “inclusion” between June 2020 and October 2022. During the operation, deep hypothermic circulatory arrest (DHCA) and selective antegrade cerebral perfusion (ACP) of the right axillary artery were employed for brain protection. The ‘inclusion’ total aortic arch replacement and stented elephant trunk (SET) surgery were performed.

Results

Four patients underwent the Bentall procedure during the study, with one additional patient requiring coronary artery bypass grafting (CABG) due to significant involvement of the right coronary orifice. Three patients died during postoperative hospitalization. Other notable complications included two cases of postoperative renal failure necessitating continuous renal replacement therapy (CRRT), one case of postoperative double lower limb paraplegia, and one case of cerebral infarction resulting in unilateral impairment of the left upper limb. Eleven patients underwent computed tomography angiography (CTA) examinations of the aorta three months to one-year post-operation. The CTA results revealed thrombosis in the false lumen surrounding the aortic arch stent in seven patients and complete thrombosis of the false lumen around the descending aortic stent in eight patients. One patient had partial thrombosis of the false lumen around the descending aortic stent, and another patient’s false lumen in the thoracic and abdominal aorta completely resolved after one year of follow-up.

Conclusions

Incorporating vascular graft in aortic arch replacement simplifies the procedure and yields promising short-term outcomes. It achieves the aim of total arch replacement using a four-branch prosthetic graft. However, extensive sampling and thorough, prolonged follow-up observations are essential to fully evaluate the long-term results.
Oleuropein alleviates myocardial ischemia–reperfusion injury by suppressing oxidative stress and excessive autophagy via TLR4/MAPK signaling pathway
Authors: He Jia , Huang Liting , Sun Kaili , Li Jilang , Han Shan , Gao Xiang , Wang Qin-Qin , Yang Shilin , Sun Wen , Gao Hongwei
Published: April 2024

Background

Myocardial ischemia/reperfusion injury (MIRI) is an important complication of reperfusion therapy, and has a lack of effective prevention and treatment methods. Oleuropein (OP) is a natural strong antioxidant with many protective effects on cardiovascular diseases, but its protective effect on MIRI has not yet been studied in depth.

Methods

Tert-Butyl hydroperoxide (tBHP) was used to establish an in vitro oxidative stress model. Cell viability was detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and lactate dehydrogenase (LDH). Flow cytometry and fluorescence assays were performed for evaluating the ROS levels and mitochondrial membrane potential (MMP). Immunofluorescence analysis detected the NRF2 nuclear translocation and autophagy indicators. Further, Western blotting and quantitative real-time PCR were performed to evaluate the expression levels of proteins and mRNAs. Molecular docking, CETSA, and molecular interaction analysis explored the binding between OP and TLR4. The protective effects of OP in vivo were determined using a preclinical MIRI rat model.

Results

OP protected against tBHP-treated injury, reduced ROS levels and reversed the damaged MMP. Mechanistically, OP activated NRF2-related antioxidant pathways, inhibited autophagy and attenuated the TLR4/MAPK signaling pathway in tBHP-treated H9C2 cells with a high binding affinity to TLR4 (KD = 37.5 µM). The TLR4 inhibitor TAK242 showed a similar effect as OP. In vivo, OP could alleviate cardiac ischemia/reperfusion injury and it ameliorated adverse cardiac remodeling. Consistent with in vitro studies, OP inhibited TLR4/MAPK and autophagy pathway and activated NRF2-dependent antioxidant pathways in vivo.

Conclusion

This study shows that OP binds to TLR4 to regulate oxidative stress and autophagy for protecting damaged cardiomyocytes, supporting that OP can be a potential therapeutic agent for MIRI.
NBR1-p62-Nrf2 mediates the anti-pulmonary fibrosis effects of protodioscin
Authors: Zeng Qian , Wen Bin-bin , Liu Xin , Luo Yong-yu , Hu Zhen-gang , Huang Lei , Zhang Xiao-hua , Huang Xiao-ting , Zhou Ting-ting , Sang Xiao-xue , Luo Yu-yang , Xiong Da-yan , Luo Zi-qiang , Liu Wei , Tang Si-yuan
Published: April 2024

Background

Idiopathic pulmonary fibrosis is a persistent disease of the lung interstitium for which there is no efficacious pharmacological therapy. Protodioscin, a steroidal saponin, possesses diverse pharmacological properties; however, its function in pulmonary fibrosis is yet to be established. Hence, in this investigation, it was attempted to figure out the anti-pulmonary fibrosis influences of protodioscin and its pharmacological properties related to oxidative stress.

Methods

A mouse lung fibrosis model was generated using tracheal injections of bleomycin, followed by intraperitoneal injection of different concentrations of protodioscin, and the levels of oxidative stress and fibrosis were detected in the lungs. Multiple fibroblasts were treated with TGF-β to induce their transition to myofibroblasts. It was attempted to quantify myofibroblast markers’ expression levels and reactive oxygen species levels as well as Nrf2 activation after co-incubation of TGF-β with fibroblasts and different concentrations of protodioscin. The influence of protodioscin on the expression and phosphorylation of p62, which is associated with Nrf2 activation, were detected, and p62 related genes were predicted by STRING database. The effects of Nrf2 inhibitor or silencing of the Nrf2, p62 and NBR1 genes, respectively, on the activation of Nrf2 by protodioscin were examined. The associations between p62, NBR1, and Keap1 in the activation of Nrf2 by protodioscin was demonstrated using a co-IP assay. Nrf2 inhibitor were used when protodioscin was treated in mice with pulmonary fibrosis and lung tissue fibrosis and oxidative stress levels were detected.

Results

In vivo, protodioscin decreased the levels of fibrosis markers and oxidative stress markers and activated Nrf2 in mice with pulmonary fibrosis, and these effects were inhibited by Nrf2 inhibitor. In vitro, protodioscin decreased the levels of myofibroblast markers and oxidative stress markers during myofibroblast transition and promoted Nrf2 downstream gene expression, with reversal of these effects after Nrf2, p62 and NBR1 genes were silenced or Nrf2 inhibitors were used, respectively. Protodioscin promoted the binding of NBR1 to p62 and Keap1, thereby reducing Keap1-Nrf2 binding.

Conclusion

The NBR1-p62-Nrf2 axis is targeted by protodioscin to reduce oxidative stress and inhibit pulmonary fibrosis.

Graphical Abstract
Molecular and phenotypic characteristics of Bardet-Biedl syndrome in Chinese patients
Authors: Gao Shiyang , Zhang Qianwen , Ding Yu , Wang Libo , Li Zhiying , Hu Feihan , Yao Ru-en , Yu Tingting , Chang Guoying , Wang Xiumin
Published: April 2024

Background

Bardet-Biedl syndrome (BBS) is a type of non-motile ciliopathy. To date, 26 genes have been reported to be associated with BBS. However, BBS is genetically heterogeneous, with significant clinical overlap with other ciliopathies, which complicates diagnosis. Disability and mortality rates are high in BBS patients; therefore, it is urgent to improve our understanding of BBS. Thus, our study aimed to describe the genotypic and phenotypic spectra of BBS in China and to elucidate genotype–phenotype correlations.

Methods

Twenty Chinese patients diagnosed with BBS were enrolled in this study. We compared the phenotypes of Chinese BBS patients in this study with those from other countries to analyze the phenotypic differences across patients worldwide. In addition, genotype–phenotype correlations were described for our cohort. We also summarized all previously reported cases of BBS in Chinese patients (71 patients) and identified common and specific genetic variants in the Chinese population.

Results

Twenty-eight variants, of which 10 are novel, in 5 different BBS-associated genes were identified in 20 Chinese BBS patients. By comparing the phenotypes of BBSome-coding genes (BBS2,7,9) with those of chaperonin-coding genes (BBS10,12), we found that patients with mutations in BBS10 and 12 had an earlier age of onset (1.10 Vs. 2.20, p < 0.01) and diagnosis (4.64 Vs. 13.17, p < 0.01), whereas patients with mutations in BBS2, 7, and 9 had a higher body mass index (28.35 Vs. 24.21, p < 0.05) and more vision problems (p < 0.05). Furthermore, in 91 Chinese BBS patients, mutations were predominant in BBS2 (28.89%) and BBS7 (15.56%), and the most frequent variants were in BBS2: c.534 + 1G > T (10/182 alleles) and BBS7: c.1002delT (7/182 alleles), marking a difference from the genotypic spectra of BBS reported abroad.

Conclusions

We recruited 20 Chinese patients with BBS for genetic and phenotypic analyses, and identified common clinical manifestations, pathogenic genes, and variants. We also described the phenotypic differences across patients worldwide and among different BBS-associated genes. This study involved the largest cohort of Chinese patients with BBS, and provides new insights into the distinctive clinical features of specific pathogenic variants.
The concept of resilience to Alzheimer’s Disease: current definitions and cellular and molecular mechanisms
Authors: de Vries Luuk E. , Huitinga Inge , Kessels Helmut W. , Swaab Dick F. , Verhaagen Joost
Published: April 2024

Some individuals are able to maintain their cognitive abilities despite the presence of significant Alzheimer’s Disease (AD) neuropathological changes. This discrepancy between cognition and pathology has been labeled as resilience and has evolved into a widely debated concept. External factors such as cognitive stimulation are associated with resilience to AD, but the exact cellular and molecular underpinnings are not completely understood. In this review, we discuss the current definitions used in the field, highlight the translational approaches used to investigate resilience to AD and summarize the underlying cellular and molecular substrates of resilience that have been derived from human and animal studies, which have received more and more attention in the last few years. From these studies the picture emerges that resilient individuals are different from AD patients in terms of specific pathological species and their cellular reaction to AD pathology, which possibly helps to maintain cognition up to a certain tipping point. Studying these rare resilient individuals can be of great importance as it could pave the way to novel therapeutic avenues for AD.
Role of viscoelasticity in the appearance of low-Reynolds turbulence: considerations for modelling
Authors: Pajic-Lijakovic Ivana , Milivojevic Milan , McClintock Peter V. E.
Published: April 2024

Inertial effects caused by perturbations of dynamical equilibrium during the flow of soft matter constitute a hallmark of turbulence. Such perturbations are attributable to an imbalance between energy storage and energy dissipation. During the flow of Newtonian fluids, kinetic energy can be both stored and dissipated, while the flow of viscoelastic soft matter systems, such as polymer fluids, induces the accumulation of both kinetic and elastic energies. The accumulation of elastic energy causes local stiffening of stretched polymer chains, which can destabilise the flow. Migrating multicellular systems are hugely complex and are capable of self-regulating their viscoelasticity and mechanical stress generation, as well as controlling their energy storage and energy dissipation. Since the flow perturbation of viscoelastic systems is caused by the inhomogeneous accumulation of elastic energy, rather than of kinetic energy, turbulence can occur at low Reynolds numbers.

This theoretical review is focused on clarifying the role of viscoelasticity in the appearance of low-Reynolds turbulence. Three types of system are considered and compared: (1) high-Reynolds turbulent flow of Newtonian fluids, (2) low and moderate-Reynolds flow of polymer solutions, and (3) migration of epithelial collectives, discussed in terms of two model systems. The models considered involve the fusion of two epithelial aggregates, and the free expansion of epithelial monolayers on a substrate matrix.
Mosaic derivative chromosomes at chorionic villi (CV) sampling are expression of genomic instability and precursors of cryptic disease-causing rearrangements: report of further four cases
Authors: Vitetta Giulia , Desiderio Laura , Baccolini Ilaria , Uliana Vera , Lanzoni Giulia , Ghi Tullio , Pilu Gianluigi , Ambrosini Enrico , Caggiati Patrizia , Barili Valeria , Trotta Anna Carmela , Liuti Maria Rosaria , Malpezzi Elisabetta , Pittalis Maria Carla , Percesepe Antonio
Published: April 2024

Mosaic chromosomal anomalies arising in the product of conception and the final fetal chromosomal arrangement are expression of complex biological mechanisms. The rescue of unbalanced chromosome with selection of the most viable cell line/s in the embryo and the unfavourable imbalances in placental tissues was documented in our previous paper and in the literature. We report four additional cases with mosaic derivative chromosomes in different feto-placental tissues, further showing the instability of an intermediate gross imbalance as a frequent mechanism of de novo cryptic deletions and duplications. In conclusion we underline how the extensive remodeling of unbalanced chromosomes in placental tissues represents the ‘backstage’ of de novo structural rearrangements, as the early phases of a long selection process that the genome undergo during embryogenesis.
Perioperative versus adjuvant S-1 plus oxaliplatin chemotherapy for stage II/III resectable gastric cancer (RESONANCE): a randomized, open-label, phase 3 trial
Authors: Wang Xinxin , Lu Canrong , Wei Bo , Li Shuo , Li Ziyu , Xue Yingwei , Ye Yingjiang , Zhang Zhongtao , Sun Yihong , Liang Han , Li Kai , Zhu Linghua , Zheng Zhichao , Zhou Yanbing , He Yulong , Li Fei , Wang Xin , Liang Pin , Huang Hua , Li Guoli , Shen Xian , Ji Jiafu , Tang Yun , Xu Zekuan , Chen Lin ,   on behalf of RESONANCE study group
Published: April 2024

Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p < 0.0001). There was no difference between two arms in surgical outcomes or postoperative complications. Safety-related data were like the known safety profile. In conclusion, from a clinical perspective, this trial indicated a trend towards higher three-year disease-free survival rate with perioperative SOX in stage II/III resectable gastric cancer with well-tolerated toxicity compared to adjuvant SOX, which might provide a theoretical basis for applying perioperative SOX in advanced gastric cancer patients. (ClinicalTrials.gov NCT01583361)
HSPA4 upregulation induces immune evasion via ALKBH5/CD58 axis in gastric cancer
Authors: Suo Daqin , Gao Xiaoling , Chen Qingyun , Zeng Tingting , Zhan Jiarong , Li Guanghui , Zheng Yinli , Zhu Senlin , Yun Jingping , Guan Xin-Yuan , Li Yan
Published: April 2024

Introduction

Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Recently, targeted therapies including PD1 (programmed cell death 1) antibodies have been used in advanced GC patients. However, identifying new biomarker for immunotherapy is still urgently needed. The objective of this study is to unveil the immune evasion mechanism of GC cells and identify new biomarkers for immune checkpoint blockade therapy in patients with GC.

Methods

Coimmunoprecipitation and meRIP were performed to investigate the mechanism of immune evasion of GC cells. Cocuture system was established to evaluate the cytotoxicity of cocultured CD8+ T cells. The clinical significance of HSPA4 upregulation was analyzed by multiplex fluorescent immunohistochemistry staining in GC tumor tissues.

Results

Histone acetylation causes HSPA4 upregulation in GC tumor tissues. HSPA4 upregulation increases the protein stability of m6A demethylase ALKBH5. ALKBH5 decreases CD58 in GC cells through m6A methylation regulation. The cytotoxicity of CD8+ T cells are impaired and PD1/PDL1 axis is activated when CD8+ T cells are cocultured with HSPA4 overexpressed GC cells. HSPA4 upregulation is associated with worse 5-year overall survival of GC patients receiving only surgery. It is an independent prognosis factor for worse survival of GC patients. In GC patients receiving the combined chemotherapy with anti-PD1 immunotherapy, HSPA4 upregulation is observed in responders compared with non-responders.

Conclusion

HSPA4 upregulation causes the decrease of CD58 in GC cells via HSPA4/ALKBH5/CD58 axis, followed by PD1/PDL1 activation and impairment of CD8+ T cell’s cytotoxicity, finally induces immune evasion of GC cells. HSPA4 upregulation is associated with worse overall survival of GC patients with only surgery. Meanwhile, HSPA4 upregulation predicts for better response in GC patients receiving the combined immunotherapy.