bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and validation of a novel survival prediction model based on the T-cell phenotype in the tumor immune microenvironment and peripheral blood for gastric cancer prognosis
Authors: Ma Jing , Li Jianhui , He Nan , Qian Meirui , Lu Yuanyuan , Wang Xin , Wu Kaichun
Published: February 2023

Background

The correlation and difference in T-cell phenotypes between peripheral blood lymphocytes (PBLs) and the tumor immune microenvironment (TIME) in patients with gastric cancer (GC) is not clear. We aimed to characterize the phenotypes of CD8+ T cells in tumor infiltrating lymphocytes (TILs) and PBLs in patients with different outcomes and to establish a useful survival prediction model.

Methods

Multiplex immunofluorescence staining and flow cytometry were used to detect the expression of inhibitory molecules (IMs) and active markers (AMs) in CD8+TILs and PBLs, respectively. The role of these parameters in the 3-year prognosis was assessed by receiver operating characteristic analysis. Then, we divided patients into two TIME clusters (TIME-A/B) and two PBL clusters (PBL-A/B) by unsupervised hierarchical clustering based on the results of multivariate analysis, and used the Kaplan–Meier method to analyze the difference in prognosis between each group. Finally, we constructed and compared three survival prediction models based on Cox regression analysis, and further validated the efficiency and accuracy in the internal and external cohorts.

Results

The percentage of PD-1+CD8+TILs, TIM-3+CD8+TILs, PD-L1+CD8+TILs, and PD-L1+CD8+PBLs and the density of PD-L1+CD8+TILs were independent risk factors, while the percentage of TIM-3+CD8+PBLs was an independent protective factor. The patients in the TIME-B group showed a worse 3-year overall survival (OS) (HR: 3.256, 95% CI 1.318–8.043, P = 0.006), with a higher density of PD-L1+CD8+TILs (P < 0.001) and percentage of PD-1+CD8+TILs (P = 0.017) and PD-L1+CD8+TILs (P < 0.001) compared to the TIME-A group. The patients in the PBL-B group showed higher positivity for PD-L1+CD8+PBLs (P = 0.042), LAG-3+CD8+PBLs (P < 0.001), TIM-3+CD8+PBLs (P = 0.003), PD-L1+CD4+PBLs (P = 0.001), and LAG-3+CD4+PBLs (P < 0.001) and poorer 3-year OS (HR: 0.124, 95% CI 0.017–0.929, P = 0.015) than those in the PBL-A group. In our three survival prediction models, Model 3, which was based on the percentage of TIM-3+CD8+PBLs, PD-L1+CD8+TILs and PD-1+CD8+TILs, showed the best sensitivity (0.950, 0.914), specificity (0.852, 0.857) and accuracy (κ = 0.787, P < 0.001; κ = 0.771, P < 0.001) in the internal and external cohorts, respectively.

Conclusion

We established a comprehensive and robust survival prediction model based on the T-cell phenotype in the TIME and PBLs for GC prognosis.
VEGF-A enhances the cytotoxic function of CD4+ cytotoxic T cells via the VEGF-receptor 1/VEGF-receptor 2/AKT/mTOR pathway
Authors: Chen Ziyi , Zhang Meng , Liu Yufeng , Chen Zhe , Wang Ling , Wang Wenjuan , Wang Jincheng , He Mingqian , Shi Bingyin , Wang Yue
Published: February 2023

Background

CD4+ cytotoxic T cells (CD4 CTLs) are CD4+ T cells with major histocompatibility complex-II-restricted cytotoxic function. Under pathologic conditions, CD4 CTLs hasten the development of autoimmune disease or viral infection by enhancing cytotoxicity. However, the regulators of the cytotoxicity of CD4 CTLs are not fully understood.

Methods

To explore the potential regulators of the cytotoxicity of CD4 CTLs, bulk RNA and single-cell RNA sequencing (scRNA-seq), enzyme-linked immunosorbent assay, flow cytometry, quantitative PCR, and in-vitro stimulation and inhibition assays were performed.

Results

In this study, we found that VEGF-A promoted the cytotoxicity of CD4 CTLs through scRNA-seq and flow cytometry. Regarding the specific VEGF receptor (R) involved, VEGF-R1/R2 signaling was activated in CD4 CTLs with increased cytotoxicity, and the VEGF-A effects were inhibited when anti-VEGF-R1/R2 neutralizing antibodies were applied. Mechanistically, VEGF-A treatment activated the AKT/mTOR pathway in CD4 CTLs, and the increases of cytotoxic molecules induced by VEGF-A were significantly reduced when the AKT/mTOR pathway was inhibited.

Conclusion

In conclusion, VEGF-A enhances the cytotoxicity of CD4 CTLs through the VEGF-R1/VEGF-R2/AKT/mTOR pathway, providing insights for the development of novel treatments for disorders associated with CD4 CTLs.
Hydrogen attenuates postoperative pain through Trx1/ASK1/MMP9 signaling pathway
Authors: Li Juan , Ruan Shirong , Jia Jinhui , Li Qian , Jia Rumeng , Wan Li , Yang Xing , Teng Peng , Peng Qilin , Shi Ya-dan , Yu Pan , Pan Yinbing , Duan Man-lin , Liu Wen-Tao , Zhang Li , Hu Liang
Published: February 2023

Background

Postoperative pain is a serious clinical problem with a poorly understood mechanism, and lacks effective treatment. Hydrogen (H2) can reduce neuroinflammation; therefore, we hypothesize that H2 may alleviate postoperative pain, and aimed to investigate the underlying mechanism.

Methods

Mice were used to establish a postoperative pain model using plantar incision surgery. Mechanical allodynia was measured using the von Frey test. Cell signaling was assayed using gelatin zymography, western blotting, immunohistochemistry, and immunofluorescence staining. Animals or BV-2 cells were received with/without ASK1 and Trx1 inhibitors to investigate the effects of H2 on microglia.

Results

Plantar incision surgery increased MMP-9 activity and ASK1 phosphorylation in the spinal cord of mice. MMP-9 knockout and the ASK1 inhibitor, NQDI-1, attenuated postoperative pain. H2 increased the expression of Trx1 in the spinal cord and in BV-2 cells. H2 treatment mimicked NQDI1 in decreasing the phosphorylation of ASK1, p38 and JNK. It also reduced MMP-9 activity, downregulated pro-IL-1β maturation and IBA-1 expression in the spinal cord of mice, and ameliorated postoperative pain. The protective effects of H2 were abolished by the Trx1 inhibitor, PX12. In vitro, in BV-2 cells, H2 also mimicked NQDI1 in inhibiting the phosphorylation of ASK1, p38, and JNK, and also reduced MMP-9 activity and decreased IBA-1 expression induced by LPS. The Trx1 inhibitor, PX12, abolished the protective effects of H2 in BV-2 cells.

Conclusions

For the first time, the results of our study confirm that H2 can be used as a therapeutic agent to alleviate postoperative pain through the Trx1/ASK1/MMP9 signaling pathway. MMP-9 and ASK1 may be the target molecules for relieving postoperative pain.
Blood tissue Plasminogen Activator (tPA) of liver origin contributes to neurovascular coupling involving brain endothelial N-Methyl-D-Aspartate (NMDA) receptors
Authors: Furon Jonathane , Yetim Mervé , Pouettre Elsa , Martinez de Lizarrondo Sara , Maubert Eric , Hommet Yannick , Lebouvier Laurent , Zheng Ze , Ali Carine , Vivien Denis
Published: February 2023

Background

Regulation of cerebral blood flow (CBF) directly influence brain functions and dysfunctions and involves complex mechanisms, including neurovascular coupling (NVC). It was suggested that the serine protease tissue-type plasminogen activator (tPA) could control CNV induced by whisker stimulation in rodents, through its action on N-methyl-d-Aspartate receptors (NMDARs). However, the origin of tPA and the location and mechanism of its action on NMDARs in relation to CNV remained debated.

Methods

Here, we answered these issues using tPANull mice, conditional deletions of either endothelial tPA (VECad-CreΔtPA) or endothelial GluN1 subunit of NMDARs (VECad-CreΔGluN1), parabioses between wild-type and tPANull mice, hydrodynamic transfection-induced deletion of liver tPA, hepatectomy and pharmacological approaches.

Results

We thus demonstrate that physiological concentrations of vascular tPA, achieved by the bradykinin type 2 receptors-dependent production and release of tPA from liver endothelial cells, promote NVC, through a mechanism dependent on brain endothelial NMDARs.

Conclusions

These data highlight a new mechanism of regulation of NVC involving both endothelial tPA and NMDARs.
An interpersonal neurobiology perspective on the mind and mental health: personal, public, and planetary well-being
Authors: Siegel Daniel J. , Drulis Chloe
Published: February 2023

This article outlines an Interpersonal Neurobiology (IPNB) perspective on the fundamental components that comprise mental health and promote well-being. The central aim of this paper is to answer essential but often overlooked questions related to the field of mental health, such as: What is the mind? What is the basis of well-being? What is the self and how does it develop? We will offer scientific support for the IPNB position that the mind is relational and embodied and that integration is the basis of mental health. It will also describe how the self extends beyond the individual, arising from and inextricably connected to the social, cultural and planetary systems in which we exist. IPNB is not a form of therapy; rather, it is a framework that focuses on deepening our understanding of the mind and human development across the lifespan. Drawing from interdisciplinary principles from a range of fields including physics, mathematics, neuroscience, and psychology, we will provide a practical view of the underlying basis of mental suffering and the scientific mechanisms of change to improve mental well-being. These core principles are building blocks of clinical evaluation and treatment that can be applied across multiple theoretical orientations and client populations. The special emphasis in this article is on the issue of psychache as an underlying cause of suicide and its relationship to personal, public and planetary health.
Primary extranodal soft tissue Lennert lymphoma (lymphoepithelioid variant of peripheral T-cell lymphoma, unspecified): a case report and review of the literature
Authors: Yin Ying , Liu Huaipu , Luo Minghua , Yu Guangyin , Yin Weihua , Li Ping
Published: February 2023

Lennert lymphoma (LeL) is a rare variant of peripheral T-cell lymphoma, not otherwise specified (PTCL/NOS) that is rich in epithelioid histiocytes. LeL may pose great diagnostic and therapeutic challenges to the pathologist and clinician. Primary extranodal soft tissue LeL is even rarer and has not been reported. Herein, we report a case of LeL arising from soft tissue.

A 65-year-old male presented for evaluation of a painless mass in the subcutaneous soft tissue of the left forehead. There was no invasion of the bone and no ulceration on the surface of the skin. The surrounding skin was erythematous and swollen. Grossly, the tumor was gray-red and 30 mm × 20 mm × 10 mm in size.

Microscopically, the demarcation between the lesion and surrounding tissues was unclear without a capsule. The tumor invaded the surrounding striated muscle and adipose tissue. The tumor had a diffuse proliferation of small-sized atypical lymphocytes and numerous large clusters of epithelioid histiocytes. Plasma cells, eosinophils, and Hodgkin-Reed-Sternberg (HRS) cells were not identified. Rare multinucleated histiocytes were noted, and well-formed granulomas were not present. Rare mitotic figures were noted, but no necrosis. The immunophenotypic features in this case were as follows: CD2+/CD3+/CD5low+/CD7+/CD4low+/ CD8+/CD30−/CD56− in neoplastic lymphocytes; CD163+/CD31+/CK(pan)− in epithelioid histiocytes; and CD20−/CD30−/TdT−/CD5−/ALK−/S-100−/CD1α−/CD21 + 23−/SSTR2− in neoplastic lymphocytes and epithelioid histiocytes. Epstein-Barr virus (EBV)-encoded RNA in situ hybridization (EBER-ISH) was negative. The Ki-67 index was elevated to 60%. PCR showed a polyclonal pattern for IgH and a monoclonal TCR γ-chain rearrangement.

The final diagnosis was PTCL/NOS, lymphoepithelioid cell variant (LeL), which arose from soft tissue and had a rare double-positive CD4low+/CD8+ immunophenotype. The patient received four cycles of cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone tablets (CHOP) and was followed for 20 months. Overall treatment efficacy was achieved without lymphadenopathy, and no other discomfort or illnesses were reported.
Effects of whole-brain radiation therapy on the blood–brain barrier in immunocompetent and immunocompromised mouse models
Authors: Blethen K. E. , Sprowls S. A. , Arsiwala T. A. , Wolford C. P. , Panchal D. M. , Fladeland R. A. , Glass M. J. , Dykstra L. P. , Kielkowski B. N. , Blackburn J. R. , Andrick C. J. , Lockman P. R.
Published: February 2023

Background

Approximately 20% of all cancer patients will develop brain metastases in their lifespan. The standard of care for patients with multiple brain metastases is whole-brain radiation therapy, which disrupts the blood–brain barrier. Previous studies have shown inflammatory mediators play a role in the radiation-mediated increase in permeability. Our goal was to determine if differential permeability post-radiation occurs between immunocompetent and immunocompromised mice.

Methods

We utilized a commissioned preclinical irradiator to irradiate brains of C57Bl/6J wild-type and athymic nude mice. Acute (3–24 h) effects on blood–brain barrier integrity were evaluated with our in-situ brain perfusion technique and quantitative fluorescent and phosphorescent microscopy. The presence of inflammatory mediators in the brain and serum was determined with a proinflammatory cytokine panel.

Results

Blood–brain barrier integrity and efflux transporter activity were altered in the immunocompetent mice 12 h following irradiation without similar observations in the immunocompromised mice. We observed increased TNF-α concentrations in the serum of wild-type mice immediately post-radiation and nude mice 12 h post-radiation. The brain concentration of CXCL1 was also increased in both mouse strains at the 12-h time point.

Conclusions

The immune response plays a role in the magnitude of blood–brain barrier disruption following irradiation in a time- and size-dependent manner.
Virulence gene detection and antimicrobial resistance analysis of Enterococcus faecium in captive giant pandas (Ailuropoda melanoleuca) in China
Authors: Liu Hai-Feng , Huang Xiao-Yao , Li Zhe-Meng , Zhou Zi-Yao , Zhong Zhi-Jun , Peng Guang-Neng
Published: February 2023

Background

The emergence of multidrug resistance among enterococci makes effective treatment of enterococcal infections more challenging. Giant pandas (Ailuropoda melanoleuca) are vulnerable to oral trauma and lesions as they feast on bamboo. Enterococci may contaminate such oral lesions and cause infection necessitating treatment with antibiotics. However, few studies have focused on the virulence and drug resistance of oral-derived enterococci, including Enterococcus faecium, in giant pandas. In this study, we analyzed the prevalence of 8 virulence genes and 14 drug resistance genes in E. faecium isolates isolated from saliva samples of giant pandas held in captivity in China and examined the antimicrobial drug susceptibility patterns of the E. faecium isolates.

Results

Twenty-eight isolates of E. faecium were successfully isolated from the saliva samples. Four virulence genes were detected, with the acm gene showing the highest prevalence (89%). The cylA, cpd, esp, and hyl genes were not detected. The isolated E. faecium isolates possessed strong resistance to a variety of drugs; however, they were sensitive to high concentrations of aminoglycosides. The resistance rates to vancomycin, linezolid, and nitrofurantoin were higher than those previously revealed by similar studies in China and other countries.

Conclusions

The findings of the present study indicate the drugs of choice for treatment of oral E. faecium infection in the giant panda.
Plasma extracellular vesicle messenger RNA profiling identifies prognostic EV signature for non-invasive risk stratification for survival prediction of patients with pancreatic ductal adenocarcinoma
Authors: Han Yi , Drobisch Pascal , Krüger Alexander , William Doreen , Grützmann Konrad , Böthig Lukas , Polster Heike , Seifert Lena , Seifert Adrian M. , Distler Marius , Pecqueux Mathieu , Riediger Carina , Plodeck Verena , Nebelung Heiner , Weber Georg F. , Pilarsky Christian , Kahlert Ulf , Hinz Ulf , Roth Susanne , Hackert Thilo , Weitz Jürgen , Wong Fang Cheng , Kahlert Christoph
Published: February 2023

Background

The prognosis of pancreatic ductal adenocarcinoma (PDAC) is one of the most dismal of all cancers and the median survival of PDAC patients is only 6–8 months after diagnosis. While decades of research effort have been focused on early diagnosis and understanding of molecular mechanisms, few clinically useful markers have been universally applied. To improve the treatment and management of PDAC, it is equally relevant to identify prognostic factors for optimal therapeutic decision-making and patient survival. Compelling evidence have suggested the potential use of extracellular vesicles (EVs) as non-invasive biomarkers for PDAC. The aim of this study was thus to identify non-invasive plasma-based EV biomarkers for the prediction of PDAC patient survival after surgery.

Methods

Plasma EVs were isolated from a total of 258 PDAC patients divided into three independent cohorts (discovery, training and validation). RNA sequencing was first employed to identify differentially-expressed EV mRNA candidates from the discovery cohort (n = 65) by DESeq2 tool. The candidates were tested in a training cohort (n = 91) by digital droplet polymerase chain reaction (ddPCR). Cox regression models and Kaplan–Meier analyses were used to build an EV signature which was subsequently validated on a multicenter cohort (n = 83) by ddPCR.

Results

Transcriptomic profiling of plasma EVs revealed differentially-expressed mRNAs between long-term and short-term PDAC survivors, which led to 10 of the top-ranked candidate EV mRNAs being tested on an independent training cohort with ddPCR. The results of ddPCR enabled an establishment of a novel prognostic EV mRNA signature consisting of PPP1R12A, SCN7A and SGCD for risk stratification of PDAC patients. Based on the EV mRNA signature, PDAC patients with high risk displayed reduced overall survival (OS) rates compared to those with low risk in the training cohort (p = 0.014), which was successfully validated on another independent cohort (p = 0.024). Interestingly, the combination of our signature and tumour stage yielded a superior prognostic performance (p = 0.008) over the signature (p = 0.022) or tumour stage (p = 0.016) alone. It is noteworthy that the EV mRNA signature was demonstrated to be an independent unfavourable predictor for PDAC prognosis.

Conclusion

This study provides a novel and non-invasive prognostic EV mRNA signature for risk stratification and survival prediction of PDAC patients.
MiR-455-5p suppresses PDZK1IP1 to promote the motility of oral squamous cell carcinoma and accelerate clinical cancer invasion by regulating partial epithelial-to-mesenchymal transition
Authors: Hsiao Sheng-Yen , Weng Shang-Mei , Hsiao Jenn-Ren , Wu Yi-Ying , Wu Jia-En , Tung Chia-Hao , Shen Wan-Lin , Sun Shu-Fang , Huang Wen-Tsung , Lin Cheng-Yao , Chen Shang-Hung , Hong Tse-Ming , Chen Yuh-Ling , Chang Jang-Yang
Published: February 2023

Background

Lymph node and distant metastasis contribute to poor outcomes in patients with oral squamous cell carcinoma (OSCC). The mechanisms regulating cancer migration and invasion play a key role in OSCC.

Methods

We determined migration and invasion ability of OSCC by wound-healing assay, two-chamber transwell invasion assay and cell mobility tracking and evaluated tumor metastasis in vivo. Western blot (WB), qRT-PCR, RNA-seq, dual-luciferase reporter assays and nuclear/cytoplasmic fractionation were performed to investigate the potential mechanism. Immunohistochimical (IHC) staining determined vimentin and PDZK1IP1 expression in OSCC tissues.

Results and conclusion

In this study, we determined that miR-455-5p was associated with lymph node metastasis and clinical invasion, leading to poor outcomes in patients with OSCC. MiR-455-5p promoted oral cancer cell migration and invasion and induced epithelial-to-mesenchymal transition (EMT). We also identified a new biomarker, PDZK1IP1 (MAP17), that was targeted by miR-455-5p. PDZK1IP1 knockdown led to migration, metastasis, EMT, and increased transforming growth factor-β signaling in OSCC. In addition, miR-455-5p overexpression and PDZK1IP1 inhibition promoted collective OSCC cell migration. According to data from the Cancer Genome Atlas database and the NCKU-OrCA-40TN data set, miR-455-5p and PDZK1IP1 are positively and negatively correlated, respectively, with partial EMT score. High miR-455-5p expression was associated with high vimentin levels and low MAP17 H-scores. The patients with low MAP17 expression had higher rates of disease recurrence than did patients with high MAP17 expression, especially for patients with clinical invasion risk factors and low MAP17 expression. These results suggest that miR-455-5p suppresses PDZK1IP1 expression and mediates OSCC progression. MiR-455-5p and PDZK1IP1 may therefore serve as key biomarkers and be involved in regulating partial EMT in OSCC cells. PDZK1IP1 expression may also serve as an independent factor that impacts outcomes in patients with clinical risk factors for recurrence.
A post-market cluster randomized controlled trial of the effect of the TENA SmartCare Change Indicator™ on urinary continence care efficiency and skin health in older nursing home residents
Authors: Omotunde Muyibat , Agholme Fredrik , Böhling Arne , Huige Nicole , Schweigel Hardy , Hayder-Beichel Daniela , Reidy Robert , Wagg Adrian
Published: February 2023

Background

Urinary continence care for residents of nursing homes who are unable to communicate their toileting needs usually involves care aides manually checking continence products (pads) to determine the level of urine saturation prior to changing. The TENA SmartCare Change Indicator is a medical device which estimates urine saturation and notifies caregivers of the optimal time for pad changes. This study will seek to examine the effect of the TENA SmartCare Change Indicator on urinary continence care efficiency and skin health, in comparison to usual care.

Methods

This cluster randomized controlled trial (NCT05247047) involving older nursing home residents with urinary incontinence unable to consistently indicate their toileting needs, and their care aides, will compare technology-based and usual continence care over a period of 8 weeks. Co-primary endpoints of superiority in continence care efficiency and non-inferiority in the maintenance of skin health will be assessed. Secondary outcomes will examine the resident quality of life, sleep quality, responsive behaviours, changes in pad use and leakage episodes outside the pad. Change in care aide work engagement, job satisfaction and rushed tasks will be assessed. Benefits and challenges with the use of the device for continence care will be identified from the perspectives of the care staff.

Discussion

Urinary continence assessment and care in nursing homes is reported as suboptimal and threatening to dignity. Data on the utility and effect of technological solutions for improving urinary continence care are few and conflicting. If shown effective, this technological solution has the potential to improve the care for older residents and improve the working lives of caregiving staff who look after this most vulnerable section of the population.

Trial registration

ClinicalTrials.gov NCT05247047. Registration date is Feb 18, 2022
Radiomics-based analysis of CT imaging for the preoperative prediction of invasiveness in pure ground-glass nodule lung adenocarcinomas
Authors: Feng Hui , Shi Gaofeng , Xu Qian , Ren Jialiang , Wang Lijia , Cai Xiaojia
Published: February 2023

Objective

The purpose of the study is to investigate the performance of radiomics-based analysis in prediction of pure ground-glass nodule (pGGN) lung adenocarcinomas invasiveness using thin-section computed tomography images.

Methods

A total of 382 patients surgically resected single pGGN and pathologically confirmed were enrolled in the retrospective study. The pGGN cases were divided into two groups: the noninvasive group and the invasive adenocarcinoma (IAC) group. 330 patients were randomly assigned to the training and testing cohorts with a ratio of 7:3 (245 noninvasive lesions, 85 IAC lesions), while 52 patients (30 noninvasive lesions, 22 IAC lesions) were assigned to the external validation cohort. A model, radiomics model, and combined clinical-radiographic-radiomic model were built using the LASSO and multivariate backward stepwise regression analysis on the basis of the selected and radiomics features. The area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate and compare the model performance for invasiveness discrimination among the three cohorts.

Results

Three clinical-radiographic features (including age, gender and the mean CT value) and three radiomics features were selected for model building. The combined model and radiomics model performed better than the clinical-radiographic model. The AUCs of the combined model in the training, testing, and validation cohorts were 0.856, 0.859, and 0.765, respectively. The DCA demonstrated the radiomics signatures incorporating clinical-radiographic feature was clinically useful in predicting pGGN invasiveness.

Conclusions

The proposed radiomics-based analysis incorporating the clinical-radiographic feature could accurately predict pGGN invasiveness, providing a noninvasive biomarker for the individualized and precise medical treatment of patients.
Artificial intelligence education for radiographers, an evaluation of a UK postgraduate educational intervention using participatory action research: a pilot study
Authors: van de Venter Riaan , Skelton Emily , Matthew Jacqueline , Woznitza Nick , Tarroni Giacomo , Hirani Shashivadan P. , Kumar Amrita , Malik Rizwan , Malamateniou Christina
Published: February 2023

Background

Artificial intelligence (AI)-enabled applications are increasingly being used in providing healthcare services, such as medical imaging support. Sufficient and appropriate education for medical imaging professionals is required for successful AI adoption. Although, currently, there are AI training programmes for radiologists, formal AI education for radiographers is lacking. Therefore, this study aimed to evaluate and discuss a postgraduate-level module on AI developed in the UK for radiographers.

Methodology

A participatory action research methodology was applied, with participants recruited from the first cohort of students enrolled in this module and faculty members. Data were collected using online, semi-structured, individual interviews and focus group discussions. Textual data were processed using data-driven thematic analysis.

Results

Seven students and six faculty members participated in this evaluation. Results can be summarised in the following four themes: a. participants’ professional and educational backgrounds influenced their experiences, b. participants found the learning experience meaningful concerning module design, organisation, and pedagogical approaches, c. some module design and delivery aspects were identified as barriers to learning, and d. participants suggested how the ideal AI course could look like based on their experiences.

Conclusions

The findings of our work show that an AI module can assist educators/academics in developing similar AI education provisions for radiographers and other medical imaging and radiation sciences professionals. A blended learning delivery format, combined with customisable and contextualised content, using an interprofessional faculty approach is recommended for future similar courses.
Mifepristone induced liver injury in a patient with Cushing syndrome: a case report and review of the literature
Authors: Ault Taylor A. , Braxton David R. , Watson Rebecca A. , Marcus Alan O. , Fong Tse-Ling
Published: February 2023

Background

Mifepristone, also known as RU-486, is an anti-progestational steroid with similar chemical structure to anabolic steroids. Given as a single dose in conjunction with misoprostol, mifepristone is used to induce medical abortion. Mifepristone administered chronically at a higher dose is also approved for the management of hypercortisolism. There have been only 2 reported cases of mifepristone associated liver injury, in both cases, in the setting of Cushing syndrome. We report a third patient with Cushing syndrome with mifepristone induced liver injury with unique histological findings that provide insight to the pathophysiology of liver injury in mifepristone and anabolic steroids.

Case presentation

Patient is a 63-year-old Caucasian female Cushing disease with no prior history of liver disease. She was started on mifepristone and semaglutide. Ninety days after initiating mifepristone, she developed deep jaundice, severe pruritus, fatigue, and nausea. Liver tests revealed a mixed hepatocellular/cholestatic pattern. Viral and autoimmune serologies were negative and there was no biliary dilatation on imaging. Liver biopsy showed severe cholestasis but no bile duct injury. Focal endothelialitis was present within a central venule. Cholestatic symptoms persisted for one month after presentation before slowly subsiding. Four months after stopping mifepristone, the patient’s symptoms completely resolved, and liver tests became normal. Compilation of Roussell Uclaf Causality Assessment Method score indicated probable causality.

Conclusions

Mifepristone shares a similar chemical structure as synthetic anabolic/androgenic steroids and there are many similarities in the clinical presentation of liver injury. This case and the 2 other reported cases share similar clinical characteristics. The observation of endothelialitis in our patient may provide a mechanistic link between mifepristone, or anabolic steroids in general, and the development of vascular complications such as peliosis.
Adipose-derived stem cell spheroid-laden microbial transglutaminase cross-linked gelatin hydrogel for treating diabetic periodontal wounds and craniofacial defects
Authors: Tu Che-Chang , Cheng Nai-Chen , Yu Jiashing , Pan Yi-Xuan , Tai Wei-Chiu , Chen Yin-Chuan , Chang Po-Chun
Published: February 2023

Background

Diabetes mellitus deteriorates the destruction and impairs the healing of periodontal wounds and craniofacial defects. This study is to evaluate the potential of self-assembled adipose-derived stem cell spheroids (ADsp) in microbial transglutaminase cross-linked gelatin hydrogel (mTG) for treating diabetic periodontal wounds and craniofacial defects.

Methods

Human adipose-derived stem cells (ADSCs) were isolated by lipoaspiration, pluripotent genes and trilineage differentiation were examined, and the maintenance of ADsp properties in mTG was verified. Oral mucosal wounds and calvarial osseous defects were created in diabetic rats. Gross observation, histologic evaluation, and immunohistochemistry for proliferating cells and keratinization were conducted in the mucosal wounds within 4–28 days. Micro-CT imaging, histologic evaluation, and immunohistochemistry for proliferating cells and osteogenic differentiation were conducted in the osseous defects at 7 and 28 days.

Results

ADSCs expressed pluripotent genes and were capable of trilineage differentiation. ADsp retained morphology and stemness in mTG. In diabetic mucosal wounds, wound closure, epithelization, and keratinization were accelerated in those with ADsp and ADsp-mTG. In diabetic osseous defects, osteogenic differentiation markers were evidently expressed, cell proliferation was promoted from day 7, and bone formation was significantly promoted at day 28 in those with osteogenically pretreated ADsp-mTG.

Conclusions

ADsp-mTG accelerated diabetic oral mucosal wound healing, and osteogenically pretreated ADsp-mTG promoted diabetic osseous defect regeneration, proving that ADsp-mTG facilitated diabetic periodontal wound healing and craniofacial osseous defect regeneration.
CD24+CD44+CD54+EpCAM+ gastric cancer stem cells predict tumor progression and metastasis: clinical and experimental evidence
Authors: Gómez-Gallegos Angel A. , Ramírez-Vidal Lizbeth , Becerril-Rico Jared , Pérez-Islas Elizabeth , Hernandez-Peralta Zuly J. , Toledo-Guzmán Mariel E. , García-Carrancá Alejandro , Langley Elizabeth , Hernández-Guerrero Angélica , López-Casillas Fernando , Herrera-Goepfert Roberto , Oñate-Ocaña Luis F. , Ortiz-Sánchez Elizabeth
Published: February 2023

Background

Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. Specific and thorough identification of cancer cell subsets with higher tumorigenicity and chemoresistance, such as cancer stem cells (CSCs), could lead to the development of new and promising therapeutic targets. For better CSC identification, a complete or extended surface marker phenotype is needed to provide increased specificity for new cell targeting approaches. Our goal is to identify and characterize a putative extended phenotype for CSCs derived from patients with GC before treatment, as well as to evaluate its clinical value. In addition, we aim to ensure that cells with this phenotype have stemness and self-renewal capabilities.

Methods

This is a cohort study including 127 treatment-naïve patients with GC who attended the Instituto Nacional de Cancerología. Multiparametric flow cytometry analysis was performed to determine the extended phenotype of cells derived from gastric biopsies. The tumorigenic capability of cells identified in patients was assessed in a zebrafish model.

Results

CD24+CD44+CD54+EpCAM+ cells were present in all treatment-naïve patients included, with a median abundance of 1.16% (0.57–1.89%). The percentage of CD24+CD44+CD54+EpCAM+ cells was categorized as high or low using 1.19% as the cutoff for the CD24+CD44+CD54+EpCAM+ cell subset. Additionally, a higher TNM stage correlated with a higher percentage of CD24+CD44+CD54+EpCAM+ cells (Rho coefficient 0.369; p < 0.0001). We also demonstrated that a higher percentage of CD24+CD44+CD54+EpCAM+ cells was positively associated with metastasis. The metastatic potential of these cells was confirmed in a zebrafish model. Ultimately, under our conditions, we conclude that CD24+CD44+CD54+EpCAM+ cells are true gastric cancer stem cells (GCSCs).

Conclusion

The CD24+CD44+CD54+EpCAM+ cells present in tissue samples from patients are true GCSCs. This extended phenotype results in better and more specific characterization of these highly tumorigenic cells. The relative quantification of CD24+CD44+CD54+EpCAM+ cells has potential clinical value, as these cells are associated with metastatic disease, making their presence an additional prognostic marker and possibly a target for the design of new antineoplastic treatments in the era of precision oncology. Overall, the extended CD24+CD44+CD54+EpCAM+ phenotype of GCSCs could support their isolation for the study of their stemness mechanisms, leading to the identification of better molecular targets for the development of both new therapeutic approaches such as oncoimmunotherapy and new diagnostic and clinical prognostic strategies for GC.
Two years of explicit CiTO annotations
Authors: Willighagen Egon
Published: February 2023

Citations are an essential aspect of research communication and have become the basis of many evaluation metrics in the academic world. Some see citation counts as a mark of scientific impact or even quality, but in reality the reasons for citing other work are manifold which makes the interpretation more complicated than a single citation count can reflect. Two years ago, the Journal of Cheminformatics proposed the CiTO Pilot for the adoption of a practice of annotating citations with their citation intentions. Basically, when you cite a journal article or dataset (or any other source), you also explain why specifically you cite that source. Particularly, the agreement and disagreement and reuse of methods and data are of interest. This article explores what happened after the launch of the pilot. We summarize how authors in the Journal of Cheminformatics used the pilot, shows citation annotations are distributed with Wikidata, visualized with Scholia, discusses adoption outside BMC, and finally present some thoughts on what needs to happen next.
Association of metformin exposure with low risks of frailty and adverse outcomes in patients with diabetes
Authors: Liu Pan , Pan Yiming , Song Yu , Zhou Yaru , Zhang Wanshu , Li Xiaojun , Li Jiatong , Li Yun , Ma Lina
Published: February 2023

Background

Diabetes is an independent risk factor of frailty, which increases adverse outcomes in patients with diabetes. Metformin is a common antidiabetic drug in clinical practice. Insulin resistance and chronic inflammation are the two common mechanisms of diabetes and frailty, as well as the main targets of metformin. Research suggested that metformin has anti-aging potential. However, few studies focus on the relationship between metformin and frailty. Thus, we aimed to explore whether metformin was associated with a low risk of frailty and other adverse outcomes in diabetic patients.

Methods

A total of 422 patients (≥ 40 years old) with type 2 diabetes were recruited. Frailty was defined by the Fried phenotype. General information and metformin exposure data were collected, and comprehensive geriatric assessment and laboratory tests were performed. Follow-up was conducted after 4.5 years. The primary outcome was the combined endpoint of cardiovascular events, cerebrovascular events, readmission, and death. Binary logistic regression analysis was used to analyze the association of metformin with frailty. Survival analysis was performed using Cox proportional hazards models.

Results

The total prevalence of frailty was 19.4% among the participants with diabetes. 13.1% of patients in the metformin group and 28.2% in the non-metformin group had frailty. Metformin was inversely associated with frailty after adjusting for age, sex, duration, blood glucose levels, target organ damage, comorbidities, and polypharmacy. Further longitudinal analysis showed that metformin was also independently associated with a low risk of combined primary outcomes after adjusting for multiple covariables, while frailty was related to an increased risk of the combined primary outcomes. In the non-frail group, metformin was associated with a decreased risk of combined primary outcomes after adjustment for age and sex. However, the protective effect of metformin on adverse outcomes was not found in frail participants with diabetes.

Conclusions

Metformin use is associated with a reduced risk of frailty. In addition, frailty may attenuate the protective effects of metformin on adverse outcomes in diabetic patients. The early identification and prevention of frailty progression may help enhance the benefits of metformin in patients with diabetes.
Isorhamnetin protects porcine oocytes from zearalenone-induced reproductive toxicity through the PI3K/Akt signaling pathway
Authors: Li Xiaoya , Duan Jiaxin , Wang Shiyou , Cheng Jianyong , Chen Huali , Zhang Zelin , Yang Li , Hua Rongmao , Li Qingwang
Published: February 2023

Background

Zearalenone (ZEA) widely exists in moldy grains, which seriously destroys the fertility of females. Isorhamnetin, a natural flavonoid, has extensive of pharmacological activities. However, the beneficial effect and the underlying molecular mechanism of isorhamnetin involvement in ZEA-induced porcine oocyte damage have not been investigated.

Methods

Oocytes were treated with different concentrations of ZEA (3, 5, 8 and 10 μmol/L) and isorhamnetin (5, 10, 20 and 30 μmol/L) for 44 h at 39 ℃. ZEA (5 μmol/L) and isorhamnetin (10 μmol/L) were selected for subsequent studies. Polar body exclusion rate, apoptosis rate and apoptosis related proteins, ROS levels and SOD2 protein, mitochondrial membrane potential and distribution, endoplasmic reticulum distribution and proteins expression, and PI3K, Akt and p-Akt proteins expression of oocytes were detected. In addition, the effect of PI3K antagonist (LY294002) on oocyte nuclear maturation and apoptosis were used to determine the involvement of PI3K/Akt signaling pathway.

Results

Our findings showed that ZEA exposure damaged oocytes and isorhamnetin therapy restored the developmental capability of porcine oocytes. Isorhamnetin promoted polar body extrusion rate to rescue ZEA-induced meiotic arrest in porcine oocytes. Isorhamnetin alleviated ZEA-induced oxidative stress by stimulating SOD2 protein expression and inhibiting ROS production. Moreover, isorhamnetin enhanced normal mitochondrial distribution and mitochondrial membrane potential to prevent mitochondrial dysfunction induced by ZEA. Changing the expression of endoplasmic reticulum stress-related marker proteins (CHOP, GRP78) and the distribution rate of normal endoplasmic reticulum showed that isorhamnetin relieved ZEA-caused endoplasmic reticulum stress. Mechanistically, isorhamnetin decreased Bax/Bcl-2 protein expression and inhibited ZEA-induced apoptosis through PI3K/Akt signaling pathway.

Conclusions

Collectively, these results suggest that isorhamnetin protects oocytes from ZEA-caused damage through PI3K/Akt signaling pathway, which enhances meiotic maturation and mitochondrial function, and inhibits early apoptosis, oxidative stress and endoplasmic reticulum stress in porcine oocytes. Our study provides a new strategy for solving the reproductive toxicity induced by ZEA and treating woman infertility.

Graphical Abstract

A possible mechanism by which isorhamnetin protected porcine oocytes from ZEA-induced damage. Isorhamnetin inhibited meiosis arrest and apoptosis of porcine oocytes induced by ZEA through the PI3K/Akt signaling pathway. Moreover, isorhamnetin repaired ZEA-induced oocyte damage by alleviating oxidative stress, mitochondrial dysfunction and ER stress.
RNA-seq analysis reveals the critical role of the novel lncRNA BIANCR in intramuscular adipogenesis through the ERK1/2 signaling pathway
Authors: Ma Xinhao , Yang Xinran , Zhang Dianqi , Zhang Wenzhen , Wang Xiaoyu , Xie Kuncheng , He Jie , Mei Chugang , Zan Linsen
Published: February 2023

Background

Long non-coding RNAs (lncRNAs) regulate numerous biological processes, including adipogenesis. Research on adipogenesis will assist in the treatment of human metabolic diseases and improve meat quality in livestock, such as the content of intramuscular fat (IMF). However, the significance of lncRNAs in intramuscular adipogenesis remains unclear. This research aimed to reveal the lncRNAs transcriptomic profiles in the process of bovine intramuscular adipogenesis and to identify the lncRNAs involved in the adipogenesis of bovine intramuscular adipocytes.

Results

In this research, a landscape of lncRNAs was identified with RNA-seq in bovine intramuscular adipocytes at four adipogenesis stages (0 d, 3 d, 6 d, and 9 d after differentiation). A total of 7035 lncRNAs were detected, including 3396 novel lncRNAs. Based on the results of differential analysis, co-expression analysis, and functional prediction, we focused on the bovine intramuscular adipogenesis-associated long non-coding RNA (BIANCR), a novel lncRNA that may have an important regulatory function. The knockdown of BIANCR inhibited proliferation and promoted apoptosis of intramuscular preadipocytes. Moreover, BIANCR knockdown inhibited intramuscular adipogenesis by regulating the ERK1/2 signaling pathway.

Conclusion

This study obtained the landscape of lncRNAs during adipogenesis in bovine intramuscular adipocytes. BIANCR plays a crucial role in adipogenesis through the ERK1/2 signaling pathway. The results are noteworthy for improving beef meat quality, molecular breeding, and metabolic disease research.

Graphical Abstract
The effect of the combined self-talk and mental imagery program on the badminton motor skills and self-confidence of youth beginner student-athletes
Authors: Hidayat Yusuf , Yudiana Yunyun , Hambali Burhan , Sultoni Kuston , Ustun Umit Dogan , Singnoy Chatkamon
Published: February 2023

Background

The psychological strategies of self-talk (S.T.) and mental imagery (MI) have an essential role in training and sports performance, but their implementation, particularly in combination, is still limited. This study aimed to examine badminton motor skills (BMS) and self-confidence (S.C.) mastery after a psychological strategy intervention of S.T. and MI, which were integrated into the BMS training process in both independent and interactive functions. The S.T. strategy consisted of instructional (I-S.T.) and motivational (M-S.T.) functions, while the MI consisted of cognitive (C-MI) and motivational (M-MI) aspects.

Methods

Eighty youth beginner badminton student-athletes aged 10–12 years (male = 40, female = 40) were divided through a disproportional stratified sampling into four experimental groups (EG: 2-function S.T. × 2-function MI) and one control group (CG). The intervention program lasted eight weeks (three meetings a week for a total of 24 meetings). The participants completed a fidelity check at each session. At the end of the intervention, they took a BMS test and completed a self-confidence scale.

Results

The S.T. and MI strategies had a significant effect on BMS and S.C. mastery (independent and interaction functions) in multivariate and univariate ways; however, independently, they had no significant effect on S.C. The effect of I-S.T. > M-S.T. and the effect of C-MI > M-MI on BMS, but there was no difference in S.C. In the I-S.T. condition, the C-MI and M-MI strategies did not have a different interaction effect on BMS mastery, but the effect of M-MI > C-MI on S.C. In the M-S.T. condition, the effect of C-MI > M-MI on the BMS and S.C. mastery. In the C-MI condition, the I-S.T. and M-S.T. strategies did not have a different interaction effect on BMS mastery, but the effect of M-S.T. > I-ST on S.C. In the M-MI condition, the effect of I-S.T. > M-S.T. on the BMS and S.C. mastery.

Conclusion

The results of this study contribute to the existing evidence on the effectiveness of S.T. and MI strategies in the motor skill mastery and psychological skill development of beginner student-athletes. Thus, S.T. and MI strategies can be adapted as psychological strategies that coaches and physical educators can use to improve beginner student-athlete learning, sports performance, and psychological skills.