bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic analysis of glucosidase II beta subunit (GluIIß) knockout A549 cells reveals its roles in regulation of cell adhesion molecules (CAMs) and anti-tumor immunity
Authors: Khaodee Worapong , Xiyuan Guo , Han Moe Thi Thi , Tayapiwatana Chatchai , Chiampanichayakul Sawitree , Anuchapreeda Songyot , Cressey Ratchada
Published: January 2024

Glucosidase II beta subunit (GluIIß), encoded from PRKCSH, is a subunit of the glucosidase II enzyme responsible for quality control of N-linked glycoprotein folding and suppression of GluIIß led to inhibitory effect of the receptor tyrosine kinase (RTKs) activities known to be critical for survival and development of cancer. In this study, we investigated the effect of GluIIß knockout on the global gene expression of cancer cells and its impact on functions of immune cells. GluIIß knockout lung adenocarcinoma A549 cell line was generated using CRISPR/Cas9-based genome editing system and subjected to transcriptomic analysis. Among 23,502 expressed transcripts, 1068 genes were significantly up-regulated and 807 genes greatly down-regulated. The KEGG enrichment analysis showed significant down-regulation of genes related extracellular matrix (ECM), ECM-receptor interaction, cytokine-cytokine receptor interaction and cell adhesion molecules (CAMs) in GluIIß knockout cells. Of 9 CAMs encoded DEG identified by KEGG enrichment analysis, real time RT-PCR confirmed 8 genes to be significantly down-regulated in all 3 different GluIIß knockout clones, which includes cadherin 4 (CDH4), cadherin 2 (CDH2), versican (VCAN), integrin subunit alpha 4 (ITGA4), endothelial cell-selective adhesion molecule (ESAM), CD274 (program death ligand-1 (PD-L1)), Cell Adhesion Molecule 1 (CADM1), and Nectin Cell Adhesion Molecule 3 (NECTIN3). Whereas PTPRF (Protein Tyrosine Phosphatase Receptor Type F) was significantly decreased only in 1 out of 3 knockout clones. Microscopic analysis revealed distinctively different cell morphology of GluIIβ knockout cells with lesser cytoplasmic and cell surface area compared to parental A549 cells and non-targeted transfected cells.

Further investigations revealed that Jurkat E6.1 T cells or human peripheral blood mononuclear cells (PBMCs) co-cultured with GluIIß knockout A549 exhibited significantly increased viability and tumor cell killing activity compared to those co-cultured with non-target transfected cells. Analysis of cytokine released from Jurkat E6.1 T cells co-cultured with GluIIß knockout A549 cells showed significant increased level of angiogenin and significant decreased level of ENA-78. In conclusion, knockout of GluIIß from cancer cells induced altered gene expression profile that improved anti-tumor activities of co-cultured T lymphocytes and PBMCs thus suppression of GluIIß may represent a novel approach of boosting anti-tumor immunity.
Computational dissection of genetic variation modulating the response of multiple photosynthetic phenotypes to the light environment
Authors: Gong Huiying , Zhou Ziyang , Bu Chenhao , Zhang Deqiang , Fang Qing , Zhang Xiao-Yu , Song Yuepeng
Published: January 2024

Background

The expression of biological traits is modulated by genetics as well as the environment, and the level of influence exerted by the latter may vary across characteristics. Photosynthetic traits in plants are complex quantitative traits that are regulated by both endogenous genetic factors and external environmental factors such as light intensity and CO2 concentration. The specific processes impacted occur dynamically and continuously as the growth of plants changes. Although studies have been conducted to explore the genetic regulatory mechanisms of individual photosynthetic traits or to evaluate the effects of certain environmental variables on photosynthetic traits, the systematic impact of environmental variables on the dynamic process of integrated plant growth and development has not been fully elucidated.

Results

In this paper, we proposed a research framework to investigate the genetic mechanism of high-dimensional complex photosynthetic traits in response to the light environment at the genome level. We established a set of high-dimensional equations incorporating environmental regulators to integrate functional mapping and dynamic screening of gene‒environment complex systems to elucidate the process and pattern of intrinsic genetic regulatory mechanisms of three types of photosynthetic phenotypes of Populus simonii that varied with light intensity. Furthermore, a network structure was established to elucidate the crosstalk among significant QTLs that regulate photosynthetic phenotypic systems. Additionally, the detection of key QTLs governing the response of multiple phenotypes to the light environment, coupled with the intrinsic differences in genotype expression, provides valuable insights into the regulatory mechanisms that drive the transition of photosynthetic activity and photoprotection in the face of varying light intensity gradients.

Conclusions

This paper offers a comprehensive approach to unraveling the genetic architecture of multidimensional variations in photosynthetic phenotypes, considering the combined impact of integrated environmental factors from multiple perspectives.
Development and validation of a long-read metabarcoding platform for the detection of filarial worm pathogens of animals and humans
Authors: Huggins Lucas G. , Atapattu Ushani , Young Neil D. , Traub Rebecca J. , Colella Vito
Published: January 2024

Background

Filarial worms are important vector-borne pathogens of a large range of animal hosts, including humans, and are responsible for numerous debilitating neglected tropical diseases such as, lymphatic filariasis caused by Wuchereria bancrofti and Brugia spp., as well as loiasis caused by Loa loa. Moreover, some emerging or difficult-to-eliminate filarioid pathogens are zoonotic using animals like canines as reservoir hosts, for example Dirofilaria sp. ‘hongkongensis’. Diagnosis of filariasis through commonly available methods, like microscopy, can be challenging as microfilaremia may wane below the limit of detection. In contrast, conventional PCR methods are more sensitive and specific but may show limited ability to detect coinfections as well as emerging and/or novel pathogens. Use of deep-sequencing technologies obviate these challenges, providing sensitive detection of entire parasite communities, whilst also being better suited for the characterisation of rare or novel pathogens. Therefore, we developed a novel long-read metabarcoding assay for deep-sequencing the filarial nematode cytochrome c oxidase subunit I gene on Oxford Nanopore Technologies’ (ONT) MinION™ sequencer. We assessed the overall performance of our assay using kappa statistics to compare it to commonly used diagnostic methods for filarial worm detection, such as conventional PCR (cPCR) with Sanger sequencing and the microscopy-based modified Knott’s test (MKT).

Results

We confirmed our metabarcoding assay can characterise filarial parasites from a diverse range of genera, including, Breinlia, Brugia, Cercopithifilaria, Dipetalonema, Dirofilaria, Onchocerca, Setaria, Stephanofilaria and Wuchereria. We demonstrated proof-of-concept for this assay by using blood samples from Sri Lankan dogs, whereby we identified infections with the filarioids Acanthocheilonema reconditum, Brugia sp. Sri Lanka genotype and zoonotic Dirofilaria sp. ‘hongkongensis’. When compared to traditionally used diagnostics, such as the MKT and cPCR with Sanger sequencing, we identified an additional filarioid species and over 15% more mono- and coinfections.

Conclusions

Our developed metabarcoding assay may show broad applicability for the metabarcoding and diagnosis of the full spectrum of filarioids from a wide range of animal hosts, including mammals and vectors, whilst the utilisation of ONT’ small and portable MinION™ means that such methods could be deployed for field use.
Clinical characteristics of congenital heart defects in mild congenital anorectal malformation: single-centre experience
Authors: Feng Wei , Zhang Minjie , Hou Jinping , Die Xiaohong , Wang Yi , Liu Rong
Published: January 2024

Objective

To analyze the clinical characteristics and types of congenital heart defect (CHD) in mild congenital anorectal malformation (CARM), namely the rectoperineal and rectovestibular fistulas.

Methods

The retrospective study of 183 patients with mild CARM was conducted with assessments of demographic information, color Doppler echocardiography results, and follow-up data. We performed an analysis of the clinical characteristics of CHD, grouping them based on sex and type of mild CARM.

Results

Of the 183 patients, rectoperineal fistula occurred in 133 patients (72.7%), while the frequency of CHD was 79.8% (146/183). Ventricular septal defects (VSDs) occur more frequently in patients with rectoperineal fistula compared to those with rectovestibular fistula (1.5% vs. 10%), while the opposite trend was observed for patent ductus arteriosus (PDAs) (39.8% vs. 22.0%). Additionally, males presented higher frequency of PDA (42.7% vs. 26.4%) and self-healing (6 months: 87.2% vs. 42.6%; 12 months: 91.0% vs. 63.2%) than females. However, males had a lower rate of undergoing cardiac surgery (6.4% vs. 17.6%) and a younger median diagnosis age (1 day vs. 9 days).

Conclusion

Our study indicates that there is a necessity for meticulous cardiac assessment and follow-up in neonates diagnosed with mild CARM.
The impact of China's universal two-child policy on total, preterm, and multiple births: a nationwide interrupted time-series analysis
Authors: Geng Yuehang , Zhuo Lin , Zhang Rui , Zhao Houyu , Hou Xinlin , Chen Hu , Liu Lili
Published: January 2024

Background

Although years have passed since the implementation of China’s universal two-child policy, the effectiveness of this policy remains unclear. To address this knowledge gap, we, here, assessed the impact of the two-child policy on total live births, preterm births, and multiple live births.

Methods

Data identifying pregnancies resulting in at least one live birth between April 1 2013 and December 31 2018 were collected from the Hospital Quality Monitoring System database. Using an interrupted time-series analysis, we estimated immediate level changes and long-term trends in total, preterm (birth before 37 weeks’ gestation), and multiple live births that had occurred after July 2016, when the universal two-child policy had taken effect.

Results

A total of 8,273,622 live births were reported during the study time frame. The number of live births (p = 0.277), preterm births (p = 0.052), and multiple births (p = 0.856) per month slightly increased immediately after July 2016, but these increases did not meet statistical significance. Further, all three outcomes showed a significant downward trend that lasted until the end of 2018 (p < 0.0001 for all). Among all live births, the percentage of preterm births remained stable (p = 0.101), while the percentage of multiple live births that were preterm significantly increased (trend change = 0.21% per month, 95% CI 0.14 to 0.28, p < 0.0001). The percentage of live multiple births among all live births significantly decreased (p for trend = 0.0039).

Conclusions

Overall, our data reveal a transient baby boom, as well as an increase in the proportion of live multiple births that were preterm, after China’s two-child policy took effect. The latter should be noted by healthcare professionals due to the high risk of complications and special medical care required by preterm babies.
Reducing risk for chronic disease: evaluation of a collective community approach to sustainable evidence-based health programming
Authors: Oestman Katherine , Rechis Ruth , Williams Pamela A. , Brown Jill A. , Treiman Katherine , Zulkiewicz Brittany , Walsh Michael T. , Basen-Engquist Karen , Rodriguez Trina , Chennisi Catherine , Macneish Amber , Neff Alise , Pomeroy Mike , Bhojani Faiyaz A. , Hawk Ernest
Published: January 2024

Background

Community initiatives can shape health behaviors, such as physical activity and dietary habits, across a population and help reduce the risk of developing chronic disease. To achieve this goal and impact health outcomes, Pasadena Vibrant Community aimed to engage communities in an ongoing dialogue about the importance of healthy behaviors, implement and advance community-based strategies to promote health, and improve diet and physical activity behaviors. The initiative was centered around a collaboration between a backbone organization, steering committee, and 7 collaborating organizations funded to implement multicomponent, evidence-based programs.. The common agenda was detailed in a community action plan, which included 19 interventions targeting healthy eating and active living among adults and youth in Pasadena, Texas.

Methods

A mixed methods evaluation of the initiative was conducted over 4 years. Data sources included document reviews of quarterly progress reports (n = 86) and supplemental data reports (n = 16) provided by collaborating organizations, annual Steering Committee surveys (n = 4), and interviews conducted with staff from a subset of Collaborating Organizations (n = 4).

Results

The initiative reached over 50,000 community members per year through 19 evidence-based interventions and impacted health outcomes, including knowledge and adoption of healthy eating practices and increased physical activity. Thirty-one systems-level changes were implemented during the initiative, including 16 environmental changes. Steering Committee meetings and shared goals enabled connections, communication, and cooperation, which allowed Collaborating Organizations to address challenges and combine resources to deliver their programs.

Conclusions

Community initiatives can effectively permeate the community by reaching individuals, improving physical activity and dietary habits, and ensuring sustainability. Based on the experience reported here, the success of a community initiative can be facilitated if collaborating organizations come together to implement evidence-based interventions and tailor them to the community, and if they are empowered by significant leadership and supportive collaboration and aligned by a common agenda.
Validity across four common street-crossing distraction indicators to predict pedestrian safety
Authors: Ning Peishan , Xie Cifu , Cheng Peixia , Li Li , Schwebel David C. , Yang Yang , He Jieyi , Li Jie , Hu Guoqing
Published: January 2024

Background

Multiple distraction indicators have been applied to measure street-crossing distraction but their validities in predicting pedestrian safety are poorly understood.

Methods

Based on a video-based observational study, we compared the validity of four commonly used distraction indicators (total duration of distraction while crossing a street, proportion of distracted time over total street-crossing time, duration of the longest distraction time, and total number of distractions) in predicting three pedestrian safety outcomes (near-crash incidence, frequency of looking left and right, and speed crossing the street) across three types of distraction (mobile phone use, talking to other pedestrians, eating/drinking/smoking). Change in Harrell’s C statistic was calculated to assess the validity of each distraction indicator based on multivariable regression models including only covariates and including both covariates and the distraction indicator.

Results

Heterogeneous capacities in predicting the three safety outcomes across the four distraction indicators were observed: 1) duration of the longest distraction time was most predictive for the occurrence of near-crashes and looks left and right among pedestrians with all three types of distraction combined and talking with other pedestrians (Harrell’s C statistic changes ranged from 0.0310 to 0.0335, P < 0.05), and for the occurrence of near-crashes for pedestrians involving mobile phone use (Harrell’s C statistic change: 0.0053); 2) total duration of distraction was most predictive for speed crossing the street among pedestrians with the combination and each of the three types of distraction (Harrell’s C statistic changes ranged from 0.0037 to 0.0111, P < 0.05), frequency of looking left and right among pedestrians distracted by mobile phone use (Harrell’s C statistic change: 0.0115), and the occurrence of near-crash among pedestrians eating, drinking, or smoking (Harrell’s C statistic change: 0.0119); and 3) the total number of distractions was the most predictive indicator of frequency of looking left and right among pedestrians eating, drinking, or smoking (Harrell’s C statistic change: 0.0013). Sensitivity analyses showed the results were robust to change in grouping criteria of the four distraction indicators.

Conclusions

Future research should consider the pedestrian safety outcomes and type of distractions to select the best distraction indicator.
Effect of lower limb alignment on outcome after lateral unicompartmental knee arthroplasty: a retrospective study
Authors: Zheng Tong , Liu Dehua , Chu Ziyue , Luo Yange , Lu Qunshan , Zhang Baoqing , Liu Peilai
Published: January 2024

Purpose

The objective of this study was to investigate the correlation between lower limb alignment and patient outcomes after lateral unicompartmental knee arthroplasty (LUKA).

Methods

In this retrospective study, the information of 51 patients who underwent lateral UKA was collected after an average of 27months of follow-up (13 to 60 months). Evaluation indicators include the AKS and WOMAC score. The Kellgren-Lawrence grade is used to evaluate the severity of osteoarthritis, while the hip-knee-ankle (HKA) angle is utilized to measure the valgus angle of lower limb alignment.

Result

Patients with postoperative valgus (≥ 3°) alignment had the best outcomes, while those with varus (≤-3°) alignment had the worst outcomes (p < 0.001). Furthermore, it was noted that patients with preoperative mild valgus (≤ 4°) alignment had worse postoperative outcomes than those with severe valgus (≥ 7°) alignment (p < 0.05). The study also revealed a positive correlation between postoperative valgus and WOMAC scores (p < 0.001), whereas a negative correlation was observed between the change in valgus angle and WOMAC scores (p = 0.005).

Conclusion

During follow-ups, we found that lower limb alignment seems to be an independent predictor of postoperative outcomes. It is recommended that more than 3° of valgus alignment should be maintained after LUKA. Surgeons performing lateral UKA should be cautious of overcorrecting alignment, particularly in patients with preoperative mild valgus alignment.
No-ozone cold plasma induces apoptosis in human neuroblastoma cell line via increased intracellular reactive oxygen species (ROS)
Authors: Lee Jung-Han , Jaiswal M Shriya , Jang Yoon-Seo , Choi Jeong-Hae , Kim Gyoo-Cheon , Hong Jin-Woo , Hwang Dae-Seok
Published: January 2024

Background

This study aimed to evaluate the effect of argon-based No-ozone Cold Plasma (NCP) on neuroblastoma cancer cell apoptosis.

Methods

Experiments were performed with SK-N-SH and HS 68. Cell cultures were treated with NCP for 1, 3, and 5 min. NCP was applied using three different strategies: direct NCP application to cell cultures, to only media, and to only cells. Evaluation of cell viability and the level of the reactive oxygen species (ROS) was performed. N-acetyl-L-cysteine (NAC) was also used to antagonize intracellular ROS. Cleaved caspase 3, PARP, aquaporin (AQP) 3 and 8 were detected.

Results

NCP induced a gradual decrease in the SK-N-SH cell viability. In contrast, the viability of HS 68 cells did not change. SK-N-SH cells viability was reduced the most when the only media-NCP application strategy was employed. Intracellular ROS levels were significantly increased with time. Cleaved caspase 3 and PARP were increased at 6 h after NCP application. SK-N-SH cells remained viable with NAC after NCP application. AQP 3 and 8 were over-expressed in SK-N-SH cells.

Conclusion

These findings demonstrate the anti-cancer effect of NCP on neuroblastoma cells. NCP enhanced the selective apoptosis of neuroblastoma cells due to the increased intracellular ROS.
From master’s thesis to research publication: a mixed-methods study of medical student publishing and experiences with the publishing process
Authors: Björklund Maria , Massoumi Ramin , Ohlsson Bodil
Published: January 2024

Background

Medical student master’s theses are often carried out as research projects, and some are published as research papers in journals. We investigated the percentage of master’s theses conducted by 5th -year students at the Medical Degree Program at Lund University, Sweden, that subsequently served as the basis for research publications. In addition, we explored both student and supervisor experiences with the publishing process.

Methods

A cohort of four semesters of student data covering the period from 2019 to 2020 (n = 446) was searched in PubMed, Embase and the Web of Science to assess whether they had been published as research papers. Surveys were sent to students (n = 121) and supervisors (n = 77) to explore their experiences with the publishing process.

Results

We found that 33% (149 of 446) of the students in the 2019–2020 cohort subsequently published their theses, and 50% of these students were listed as first authors. Most students published original research. Students (n = 21) and supervisors (n = 44) reported that the publishing process was time-consuming and that students needed multilevel support from supervisors to achieve successful publication. The publishing process was reported by 79% of the students to have led to additional learning. Most of the papers (126 of 149, 85%) had a clinical or patient-oriented focus.

Conclusion

A high percentage of the student publications in which students are listed as first authors require engagement from both students and supervisors. Supervisors play an essential role in supporting students in a successful publication process. Most of the published papers were either clinical or patient-oriented research.
Oncology nurses’ experiences of providing emotional support for cancer patients: a qualitative study
Authors: Lyu Xiao-Chen , Jiang Hai-Jiao , Lee Li-Hung , Yang Cheng-I. , Sun Xiang-Yun
Published: January 2024

Background

A high percentage of cancer patients may experience emotional distress. Oncology nurses are expected to play an important role in recognizing emotional distress and planning and delivering care that meets the individual needs of each patient. However, few studies have focused on the experiences of clinical nurses in such cases. This study adopted a qualitative research method to gain an in-depth understanding of the experience of nursing staff in caring for cancer patients with emotional distress.

Methods

A qualitative descriptive design and semi-structured interviews were used in this study. Twenty-one oncology nurses were interviewed, and the qualitative content analysis suggested by Graneheim & Lundman (2004) was used to interpret the data.

Results

Six themes were identified, as follows: (1) dictating the abnormality of emotion, (2) soothing and comforting patients, (3) a lack of psychology knowledge and communication skills, (4) negative impacts of a lack of time, (5) managing emotional labor, and (6) reflecting on the experiences.

Conclusion

Hospital administrators should arrange pre-employment education and training as well as on-the-job education to help nurses in caring for cancer patients with emotional distress. They should also focus attention on the personal emotional states of nursing staff in a timely manner and provide psychological support and emotional counseling as necessary.
Inactivation of pentraxin 3 suppresses M2-like macrophage activity and immunosuppression in colon cancer
Authors: Chen Feng-Wei , Wu Yung-Ling , Cheng Chao-Chun , Hsiao Yu-Wei , Chi Jhih-Ying , Hung Liang-Yi , Chang Chih-Peng , Lai Ming-Derg , Wang Ju-Ming
Published: January 2024

Background

The tumor microenvironment is characterized by inflammation-like and immunosuppression situations. Although cancer-associated fibroblasts (CAFs) are among the major stromal cell types in various solid cancers, including colon cancer, the interactions between CAFs and immune cells remains largely uncharacterized. Pentraxin 3 (PTX3) is responsive to proinflammatory cytokines and modulates immunity and tissue remodeling, but its involvement in tumor progression appears to be context-dependent and is unclear.

Methods

Open-access databases were utilized to examine the association of PTX3 expression and the fibroblast signature in colon cancer. Loss-of-function assays, including studies in tamoxifen-induced Ptx3 knockout mice and treatment with an anti-PTX3 neutralizing antibody (WHC-001), were conducted to assess the involvement of PTX3 in colon cancer progression as well as its immunosuppressive effect. Finally, bioinformatic analyses and in vitro assays were performed to reveal the downstream effectors and decipher the involvement of the CREB1/CEBPB axis in response to PTX3 and PTX3-induced promotion of M2 macrophage polarization.

Results

Clinically, higher PTX3 expression was positively correlated with fibroblasts and inflammatory response signatures and associated with a poor survival outcome in colon cancer patients. Blockade of PTX3 significantly reduced stromal cell-mediated tumor development. The decrease of the M2 macrophage population and an increase of the cytotoxic CD8+ T-cell population were observed following PTX3 inactivation in allografted colon tumors. We further revealed that activation of cyclic AMP-responsive element-binding protein 1 (CREB1) mediated the PTX3-induced promotion of M2 macrophage polarization.

Conclusions

PTX3 contributes to stromal cell-mediated protumor immunity by increasing M2-like macrophage polarization, and inhibition of PTX3 with WHC-001 is a potential therapeutic strategy for colon cancer.
Circulating palmitoyl sphingomyelin levels predict the 10-year increased risk of cardiovascular disease death in Chinese adults: findings from the Da Qing Diabetes Study
Authors: Qian Xin , Jia Hongmei , Wang Jinping , He Siyao , Yu Meng , Feng Xinxing , Gong Qiuhong , An Yali , Wang Xuan , Shi Na , Li Hui , Zou Zhongmei , Li Guangwei , Chen Yanyan
Published: January 2024

Background

Higher levels of palmitoyl sphingomyelin (PSM, synonymous with sphingomyelin 16:0) are associated with an increased risk of cardiovascular disease (CVD) in people with diabetes. Whether circulating PSM levels can practically predict the long-term risk of CVD and all-cause death remains unclear. This study aimed to investigate whether circulating PSM is a real predictor of CVD death in Chinese adults with or without diabetes.

Methods

A total of 286 and 219 individuals with and without diabetes, respectively, from the original Da Qing Diabetes Study were enrolled. Blood samples collected in 2009 were used as a baseline to assess circulating PSM levels. The outcomes of CVD and all-cause death were followed up from 2009 to 2020, and 178 participants died, including 87 deaths due to CVD. Cox proportional hazards regression was used to estimate HRs and their 95% CIs for the outcomes.

Results

Fractional polynomial regression analysis showed a linear association between baseline circulating PSM concentration (log-2 transformed) and the risk of all-cause and CVD death (p < 0.001), but not non-CVD death (p > 0.05), in all participants after adjustment for confounders. When the participants were stratified by PSM-tertile, the highest tertile, regardless of diabetes, had a higher incidence of CVD death (41.5 vs. 14.7 and 22.2 vs. 2.9 per 1000 person-years in patients with and without diabetes, respectively, all log-rank p < 0.01). Individuals with diabetes in the highest tertile group had a higher risk of CVD death than those in the lowest tertile (HR = 2.73; 95%CI, 1.20–6.22).

Conclusions

Elevated PSM levels are significantly associated with a higher 10-year risk of CVD death, but not non-CVD death, in Chinese adults with diabetes. These findings suggest that PSM is a potentially useful long-term predictor of CVD death in individuals with diabetes.
Transforming growth factor-induced gene TGFBI is correlated with the prognosis and immune infiltrations of breast cancer
Authors: Wang Haiwei , Wang Xinrui , Xu Liangpu
Published: January 2024

Background

Transforming growth factor β (TGFβ) is a critical regulator of lung metastasis of breast cancer and is correlated with the prognosis of breast cancer. However, not all TGFβ stimulated genes were functional and prognostic in breast cancer lung metastatic progress. In this study, we tried to determine the prognosis of TGFβ stimulated genes in breast cancer.

Methods

TGFβ stimulated genes in MDA-MB-231 cells and lung metastasis-associated genes in LM2-4175 cells were identified through gene expression microarray. The prognosis of the induced gene (TGFBI) in breast cancer was determined through bioinformatics analysis and validated using tissue microarray. The immune infiltrations of breast cancer were determined through “ESTIMATE” and “TIMER”.

Results

TGFBI was up-regulated by TGFβ treatment and over-expressed in LM2-4175 cells. Through bioinformatics analysis, we found that higher expression of TGFBI was associated with shorted lung metastasis-free survival, relapse-free survival, disease-free survival, and overall survival of breast cancer. Moreover, the prognosis of TGFBI was validated in 139 Chinese breast cancer patients. Chinese breast cancer patients with higher TGFBI expression had lower overall survival. Correspondingly, breast cancer patients with higher TGFBI methylation had higher overall survival. TGFBI was correlated with the score of the TGFβ signaling pathway and multiple immune-related signaling pathways in breast cancer. The stromal score, immune score, and the infiltrations of immune cells were also correlated with TGFBI expression in breast cancer.

Conclusions

TGFβ-induced gene TGFBI was correlated with the prognosis and immune infiltrations of breast cancer.
An efficient grafting method for phytoplasma transmission in Catharanthus roseus
Authors: Chang Ho-Chun , Chen Jen-Chih
Published: January 2024

Background

Phytoplasmas are parasitic plant pathogens that reside intracellularly within the sieve tube cells. Phytoplasmas induce various symptoms, including floral virescence, phyllody, leaf yellowing, and witches’-broom. Currently, it is challenging to culture phytoplasma in vitro. In the laboratory, phytoplasmas are generally maintained in alternative host plants, such as Catharanthus roseus. Grafting is used to transmit phytoplasmas among the alternative hosts. During the experiment, scions from infected plants are grafted onto healthy plants using a side grafting method. However, the practice has certain limitations, including its inability to be applied to small plants and its irregular disease incidence.

Results

Here, we demonstrate a new approach, penetration grafting, to overcome the limitations of side grafting. This grafting method allows phytoplasma to be efficiently and uniformly transmitted into the inoculated plants. No significant difference was observed in phytoplasma accumulation between both grafting techniques. However, penetration grafting allows rapid symptom development, saving waiting time and reducing space usage.

Conclusions

This study provides a reliable and stable method for experiments that require grafting transmission.
Finite element analysis of the effect of residual lateral wall volume on postoperative stability in intertrochanteric fractures
Authors: Zhang Yachun , Zhao Enzhe , Zhu Jian , Wu Dou , Fu Yujie , Zhang Xingyu , Zhang Xiaolun , Song Xubin
Published: January 2024

Background

Lateral wall fractures represent crucial risk factors for postoperative internal fixation failure in intertrochanteric femoral fractures. However, no consensus exists on the type of lateral wall fracture requiring interventional management. This study aimed to investigate the effect of residual lateral wall volume on the postoperative stability of intertrochanteric femur fractures with associated lateral wall fractures, providing valuable reference for the clinical management of the lateral wall.

Methods

Eleven bone defect models of intertrochanteric femur fractures with varying residual lateral wall volumes were constructed using finite element analysis. These models were fixed with proximal femoral nail antirotation (PFNA). Simulations of von Mises stress and displacement distribution of the PFNA and femur during normal walking were conducted. Statistical analysis was performed to assess the correlation between volume and the maximum von Mises stresses and displacements of the PFNA and femur.

Results

In all 11 models, the maximum von Mises stress and displacement of the helical blade, intramedullary nail, and femur occurred at the same locations. As residual lateral wall volume increased, the maximum von Mises stress and displacement of the helical blade, intramedullary nail, and maximum femoral displacement gradually decreased. However, the overall trend of the maximum femoral von Mises stress gradually decreased. At 70% retention of the residual lateral wall volume, there was a more pronounced change in the value of the maximum stress change of the helical blade and the intramedullary nail. Statistical analysis, including the Shapiro–Wilk test and Pearson correlation analysis, demonstrated a significant negative correlation between volume and the maximum von Mises stress and displacement of the helical blade, intramedullary nail, and femur. Linear regression analysis further confirmed this significant negative correlation.

Conclusion

Finite element analysis of the residual lateral wall revealed a significant correlation between volume and the postoperative stability of intertrochanteric femur fractures. A volume of 70% may serve as the threshold for stabilizing the residual lateral wall. Volume emerges as a novel index for evaluating the strength of the residual lateral walls.
High and selective cytotoxicity of ex vivo expanded allogeneic human natural killer cells from peripheral blood against bladder cancer: implications for natural killer cell instillation after transurethral resection of bladder tumor
Authors: Wang Fangming , Zhang Gang , Xu Tianli , Ma Jianlin , Wang Jing , Liu Shuai , Tang Yuzhe , Jin Song , Li Jianxing , Xing Nianzeng
Published: January 2024

Background

Non-muscle-invasive bladder cancer (NMIBC) is treated with transurethral resection of bladder tumor (TURBT) followed by intravesical instillation of chemotherapy or Bacillus Calmette–Guérin therapy. However, these treatments have a high recurrence rate and side effects, emphasizing the need for alternative instillations. Previously, we revealed that expanded allogeneic human natural killer (NK) cells from peripheral blood are a promising cellular therapy for prostate cancer. However, whether NK cells exhibit a similar killing effect in bladder cancer (BCa) remains unknown.

Methods

Expansion, activation, and cryopreservation of allogeneic human NK cells obtained from peripheral blood were performed as we previously described. In vitro cytotoxicity was evaluated using the cell counting kit-8. The levels of perforin, granzyme B, interferon-γ, tumor necrosis factor-α, and chemokines (C-C-motif ligand [CCL]1, CCL2, CCL20, CCL3L1, and CCL4; C-X-C-motif ligand [CXCL]1, CXCL16, CXCL2, CXCL3, and CXCL8; and X-motif ligand 1 and 2) were determined using enzyme-linked immunosorbent assay. The expression of CD107a, major histocompatibility complex class I (MHC-I), MHC-I polypeptide-related sequences A and B (MICA/B), cytomegalovirus UL16-binding protein-2/5/6 (ULBP-2/5/6), B7-H6, CD56, CD69, CD25, killer cell Ig-like receptors (KIR)2DL1, KIRD3DL1, NKG2D, NKp30, NKp46, and CD16 of NK cells or BCa and normal urothelial cells were detected using flow cytometry. Cytotoxicity was evaluated using lactate dehydrogenase assay in patient-derived organoid models. BCa growth was monitored in vivo using calipers in male NOD-scid IL2rg−/− mice subcutaneously injected with 5637 and NK cells. Differential gene expressions were investigated using RNA sequence analysis. The chemotaxis of T cells was evaluated using transwell migration assays.

Results

We revealed that the NK cells possess higher cytotoxicity against BCa lines with more production of cytokines than normal urothelial cells counterparts in vitro, demonstrated by upregulation of degranulation marker CD107a and increased interferon-γ secretion, by MICA/B/NKG2D and B7H6/NKp30-mediated activation. Furthermore, NK cells demonstrated antitumor effects against BCa in patient-derived organoids and BCa xenograft mouse models. NK cells secreted chemokines, including CCL1/2/20, to induce T-cell chemotaxis when encountering BCa cells.

Conclusions

The expanded NK cells exhibit potent cytotoxicity against BCa cells, with few toxic side effects on normal urothelial cells. In addition, NK cells recruit T cells by secreting a panel of chemokines, which supports the translational application of NK cell intravesical instillation after TURBT from bench to bedside for NMIBC treatment.
Study protocol for a randomised cross-over trial of Neurally adjusted ventilatory Assist for Neonates with Congenital diaphragmatic hernias: the NAN-C study
Authors: Poole Grace , Harris Christopher , Shetty Sandeep , Dassios Theodore , Jenkinson Allan , Greenough Anne
Published: January 2024

Background

Neurally adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation that delivers oxygen pressures in proportion to electrical signals of the diaphragm. The proportional assistance can be adjusted by the clinician to reduce the patient’s work of breathing. Several case series of infants with congenital diaphragmatic hernias (CDH) have shown that NAVA may reduce oxygenation index and mean airway pressures. To date, no clinical trial has compared NAVA to standard methods of mechanical ventilation for babies with CDH.

Methods

The aim of this dual-centre randomised cross-over trial is to compare post-operative NAVA with assist control ventilation (ACV) for infants with CDH. If eligible, infants will be enrolled for a ventilatory support tolerance trial (VSTT) to assess their suitability for randomisation. If clinically stable during the VSTT, infants will be randomised to receive either NAVA or ACV first in a 1:1 ratio for a 4-h period. The oxygenation index, respiratory severity score and cumulative sedative medication use will be measured.

Discussion

Retrospective studies comparing NAVA to ACV in neonates with congenital diaphragmatic hernia have shown the ventilatory mode may improve respiratory parameters and benefit neonates. To our knowledge, this is the first prospective cross-over trial comparing NAVA to ACV.

Trial registration

NAN-C was prospectively registered on ClinicalTrials.govNCT05839340 Registered on May 2023
Potential role of RhoA GTPase regulation in type interferon signaling in systemic lupus erythematosus
Authors: Fan Wei , Wei Bo , Chen Xuyan , Zhang Yi , Xiao Pingping , Li Kaiyan , Zhang Yi qin , Huang Jinmei , Leng Lin , Bucala Richard
Published: January 2024

Objective

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal activation of the type I interferon (IFN) pathway, which results in tissue inflammation and organ damage. We explored the role of the RhoA GTPase in the type I IFN activation pathway to provide a potential basis for targeting GTPase signaling for the treatment of SLE.

Methods

Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls, and the mRNA expression levels of RhoA and IFN-stimulated genes were measured by SYBR Green quantitative reverse transcriptase-polymerase chain reaction. IFN-a-stimulated response element (ISRE)-luciferase reporter gene assays and Western blotting were conducted to assess the biologic function of RhoA. An enzyme-linked immunoassay (ELISA) measured C-X-C motif chemokine ligand 10 (CXCL10) protein expression.

Results

Our studies demonstrate that the expression of RhoA in the PBMCs of SLE subjects was significantly higher than in healthy controls and positively correlated with type I IFN scores and type I IFN-stimulated gene (ISGs) expression levels. SiRNA-mediated knockdown of RhoA and the RhoA/ROCK inhibitor Y27632 reduced the activity of the type I IFN-induced ISRE, the signal transducer and activator of transcription 1 (STAT-1) phosphorylation, and the expression of CXCL10 and 2′-5′-oligoadenylate synthetase 1 (OAS1). Finally, we verified that Y27632 could significantly down-regulate the OAS1 and CXCL10 expression levels in the PBMCs of SLE patients.

Conclusion

Our study shows that RhoA positively regulates the activation of the type I IFN response pathway. Reducing the expression level of RhoA inhibits the abnormal activation of the type I IFN system, and the RhoA/ROCK inhibitor Y27632 decreases aberrant type I IFN signaling in SLE PBMCs, suggesting the possibility of targeting the RhoA GTPase for the treatment of SLE.
A systematic review of the relationship between muscle oxygen dynamics and energy rich phosphates. Can NIRS help?
Authors: Maliszewski Kevin , Feldmann Andri , McCully Kevin K. , Julian Ross
Published: January 2024

Background

Phosphocreatine dynamics provide the gold standard evaluation of in-vivo mitochondrial function and is tightly coupled with oxygen availability. Low mitochondrial oxidative capacity has been associated with health issues and low exercise performance.

Methods

To evaluate the relationship between near-infrared spectroscopy-based muscle oxygen dynamics and magnetic resonance spectroscopy-based energy-rich phosphates, a systematic review of the literature related to muscle oxygen dynamics and energy-rich phosphates was conducted. PRISMA guidelines were followed to perform a comprehensive and systematic search of four databases on 02-11-2021 (PubMed, MEDLINE, Scopus and Web of Science). Beforehand pre-registration with the Open Science Framework was performed. Studies had to include healthy humans aged 18–55, measures related to NIRS-based muscle oxygen measures in combination with energy-rich phosphates. Exclusion criteria were clinical populations, laboratory animals, acutely injured subjects, data that only assessed oxygen dynamics or energy-rich phosphates, or grey literature. The Effective Public Health Practice Project Quality Assessment Tool was used to assess methodological quality, and data extraction was presented in a table.

Results

Out of 1483 records, 28 were eligible. All included studies were rated moderate. The studies suggest muscle oxygen dynamics could indicate energy-rich phosphates under appropriate protocol settings.

Conclusion

Arterial occlusion and exercise intensity might be important factors to control if NIRS application should be used to examine energetics. However, more research needs to be conducted without arterial occlusion and with high-intensity exercises to support the applicability of NIRS and provide an agreement level in the concurrent course of muscle oxygen kinetics and muscle energetics.

Trial registration

https://osf.io/py32n/.

Key points

1. NIRS derived measures of muscle oxygenation agree with gold-standard measures of high energy phosphates when assessed in an appropriate protocol setting.

2. At rest when applying the AO protocol, in the absence of muscle activity, an initial disjunction between the NIRS signal and high energy phosphates can been seen, suggesting a cascading relationship.

3. During exercise and recovery a disruption of oxygen delivery is required to provide the appropriate setting for evaluation through either an AO protocol or high intensity contractions.
Indigenous art-themed personalised theatre caps improve patient perioperative experience and perceived staff communication in the operating theatre: a quality improvement project at Royal Darwin Hospital in Australia
Authors: Peake Benjamin , Smirk Alexander , Debelak Guy
Published: January 2024

Background

Personalised theatre caps have been shown to improve staff communication in the operating theatre. The impact of these caps on the patient perioperative experience, particularly in Indigenous Australian patients, has not been well established.

Methodology

Surgical patients and operating theatre staff at Royal Darwin Hospital in Australia were surveyed before and after the introduction of Indigenous art-themed personalised (name and role) theatre caps in October 2021 and January 2022. Staff name and role visibility in operating theatres was also audited.

Results

A total of 223 staff and patients completed surveys. Most patients reported the theatre caps to be helpful (90%, 95% confidence interval [CI] 81–99) and felt more comfortable because staff were wearing them (91%, 95% CI 82–100). These results were consistent across Indigenous and non-Indigenous patients. The majority of staff agreed that personalised name and role theatre caps improved staff communication (89%, 95% CI 81–97), improved the staff-patient interaction (77%, 95% CI 67–87), and made it easier to use staff names (100%). Staff name and role visibility increased from 8 to 51% (p < 0.001) after the introduction of personalised theatre caps.

Conclusions

The introduction of Indigenous art-themed personalised theatre caps for operating theatre staff at Royal Darwin Hospital improved perceived staff communication and the patient perioperative experience.
Integrative analysis identifies gene signatures mediating the effect of DNA methylation on asthma severity and lung function
Authors: Dessie Eskezeia Y. , Ding Lili , Mersha Tesfaye B.
Published: January 2024

DNA methylation (DNAm) changes play a key role in regulating gene expression in asthma. To investigate the role of epigenetics and transcriptomics change in asthma, we used publicly available DNAm (asthmatics, n = 96 and controls, n = 46) and gene expression (asthmatics, n = 79 and controls, n = 39) data derived from bronchial epithelial cells (BECs). We performed differential methylation/expression and weighted co-methylation/co-expression network analyses to identify co-methylated and co-expressed modules associated with asthma severity and lung function. For subjects with both DNAm and gene expression data (asthmatics, n = 79 and controls, n = 39), machine-learning technique was used to prioritize CpGs and differentially expressed genes (DEGs) for asthma risk prediction, and mediation analysis was used to uncover DEGs that mediate the effect of DNAm on asthma severity and lung function in BECs. Finally, we validated CpGs and their associated DEGs and the asthma risk prediction model in airway epithelial cells (AECs) dataset. The asthma risk prediction model based on 18 CpGs and 28 DEGs showed high accuracy in both the discovery BEC dataset with area under the receiver operating characteristic curve (AUC) = 0.99 and the validation AEC dataset (AUC = 0.82). Genes in the three co-methylated and six co-expressed modules were enriched in multiple pathways including WNT/beta-catenin signaling and notch signaling. Moreover, we identified 35 CpGs correlated with DEGs in BECs, of which 17 CpGs including cg01975495 (SERPINE1), cg10528482 (SLC9A3), cg25477769 (HNF1A) and cg26639146 (CD9), cg17945560 (TINAGL1) and cg10290200 (FLNC) were replicated in AECs. These DEGs mediate the association between DNAm and asthma severity and lung function. Overall, our study investigated the role of DNAm and gene expression change in asthma and provided an insight into the mechanisms underlying the effects of DNA methylation on asthma, asthma severity and lung function.