bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomal ERBB2IP contributes to tumor growth via elevating PSAT1 expression in non‐small cell lung carcinoma
Authors: Peng Xijuan , Zhao Lanfu , Yao Linong , Dong Jingzhi , Wu Wei , Luo Tao 
Published: May 2023

AbstractBackgroundBoth exosomes and circular RNAs (circRNAs) are involved in tumor growth. Hsa_circ_0001492 (circERBB2IP) has been reported to be overexpressed in plasma exosomes from patients with lung adenocarcinoma, but the biological role of exosomal circERBB2IP in non‐small cell lung carcinoma (NSCLC) is indistinct.MethodsExosomes isolated from serums and medium samples were validated by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. Relative expression of circERBB2IP was detected by RT‐qPCR. Loss‐of‐function was done to determine the effect of circERBB2IP on NSCLC cell proliferation and migration. Molecular mechanisms associated with circERBB2IP were predicted by bioinformatic analysis and validated by dual‐luciferase reporter, RIP, and RNA pulldown assays. In vivo experiments were performed to identify the function of circERBB2IP in NSCLC.ResultsWe discovered that circERBB2IP expression was correlated with TNM grade, lymph node metastasis and tumor size of NSCLC patients. Upregulation of circERBB2IP was observed in exosomes derived from NSCLC patient's serum and circERBB2IP might be a potential diagnostic biomarker for NSCLC. CircERBB2IP was transmitted between carcinoma cells through exosomes. Knockdown of circERBB2IP lowered cell growth in mouse models and restrained NSCLC cell proliferation and migration. CircERBB2IP could mediate PSAT1 expression via sponging miR‐5195‐3p.ConclusionIn conclusion, circERBB2IP may drive NSCLC growth by the miR‐5195‐3p/PSAT1 axis in NSCLC, shedding light on a diagnostic biomarker and therapeutic target for NSCLC.
Circ_0069094 regulates malignant phenotype and paclitaxel resistance in breast cancer cells via targeting the miR‐136‐5p/YWHAZ axis
Authors: Kong Zhihua , Han Qi , Zhu Bisheng , Wan Long , Feng Enrong 
Published: May 2023

AbstractBackgroundBreast cancer is one of the most malignant cancers. Increasing evidence suggests that circular RNAs (circRNAs) are involved in breast cancer progression through sponging microRNA (miRNA). However, the underlying molecular mechanisms of circ_0069094 in breast cancer are unclear. This study aimed to reveal the effect of the circ_0069094/miR‐136‐5p/tyrosine 3‐monooxygenase/tryptophan 5‐monooxygenase activation protein zeta (YWHAZ) pathway on the malignant progression of breast cancer.MethodsThe quantitative real‐time polymerase chain reaction and western blot were used to assess the expression of circRNA/miRNA/mRNA. The functional effects of circ_0069094 on the cell processes of breast cancer were investigated by cell counting kit‐8, colony‐forming assay, 5‐ethynyl‐2′‐deoxyuridine (EdU) assay, flow cytometry, and transwell invasion assay. The interactions among circ_0069094, miR‐136‐5p, and YWHAZ were assessed by dual‐luciferase reporter assay. A xenograft experiment was performed to determine the effects of circ_0069094 on tumor formation.ResultsCirc_0069094 was overexpressed in paclitaxel (PTX)‐resistant breast cancer tissues and cells, and the silencing of circ_0069094 decreased tumor growth, cell proliferation and cell invasion while increasing PTX sensitivity and cell apoptosis in PTX‐resistant cells. In addition, miR‐136‐5p was a target of circ_0069094, and miR‐136‐5p inhibition abolished circ_0069094 knockdown‐induced effects in PTX‐resistant cells. MiR‐136‐5p expression was decreased in PTX‐resistant breast cancer tissues and cells, and the overexpression of miR‐136‐5p suppressed the malignant behaviors of breast cancer cells by targeting YWHAZ. Importantly, circ_0069094 regulated YWHAZ expression in breast cancer by targeting miR‐136‐5p.ConclusionCirc_0069094 silencing improved PTX sensitivity in breast cancer progression through competitively sponging miR‐136‐5p.
CEO career concerns in early tenure and corporate social responsibility reporting
Authors: Chen Long , Liao Chih‐Hsien , Tsang Albert , Yu Li 
Published: May 2023

AbstractThe literature on corporate social responsibility (CSR) disclosure focuses on its economic consequences, but little is known about motivations—especially CEO personal incentives—behind such disclosure. Using an array of CSR reporting measures, we find that career concerns of CEOs early in their tenure motivate them to use voluntary CSR reporting as a signaling mechanism. The negative association between CEO tenure and CSR reporting is more pronounced in firms with stronger information intermediaries—that is, a higher level of socially responsible investors, a higher number of analysts following, and a higher level of media coverage. We also find that CEOs early in their tenure receive more personal benefits after voluntary CSR reporting, in terms of higher total compensation, better reputation, and less turnover, than CEOs later in their tenure. Taken together, the findings of our study lend support to the conjecture that CEO career concerns early in their tenure can be an important determinant of firms' voluntary CSR reporting.
Natural progression of deep pelvic endometriosis in women who opt for expectant management
Authors: Knez Jure , Bean Elisabeth , Nijjar Simrit , Tellum Tina , Chaggar Prubpreet , Jurkovic Davor 
Published: May 2023

AbstractIntroductionThe natural history of endometriosis is poorly understood, and despite numerous studies, the rate of the disease progression and optimal treatment planning in women who are asymptomatic or experience mild symptoms not requiring treatment are unknown. The aim of this study was to assess the behavior of deep endometriosis in women who are managed expectantly without any medical or surgical intervention.Material and methodsA retrospective cohort study of women diagnosed with deep endometriosis on transvaginal ultrasound scan at the Department of Gynecology, University College London Hospitals and The Gynecology Ultrasound Centre, London, UK, from April 2007 to April 2022. All women attended for at least two ultrasound scans which were carried out by a single expert ultrasound examiner and at least 6 months apart. The number and position of endometriotic nodules were recorded, and the mean diameter of each nodule was calculated from measurements taken in three orthogonal planes.ResultsDuring the study period, 1922 women were found to have moderate or severe deep endometriosis on pelvic ultrasound examination. A total of 135 premenopausal women who were managed expectantly fitted the inclusion criteria. The median number of endometriotic nodules per woman at the initial visit was 2 (range: 0–7), and the median follow‐up time was 666 days (181–2984). In the follow‐up period, 50/135 women (37%, 95% CI: 29–46) developed additional nodules or experienced an increase in nodule size, and 17/135 women (13%, 95% CI: 8–19) had a regression in the number or size of the nodules. In the remaining 68/135 women (50%, 95% CI: 42–59) the disease remained static during the follow‐up. The median change in mean diameter of nodules during the study period per woman was +0.13 mm (−11.67 − +5.83), with an annual growth rate of +0.09 mm/year (−6.65 − +6.45).ConclusionsIn our study we found evidence of deep endometriosis progression in just over a third of women. In view of this, asymptomatic or mildly symptomatic women diagnosed with deep endometriosis could be reassured that their disease is unlikely to worsen with time.
Urinary angiotensinogen is associated with albuminuria in adults with sickle cell anaemia
Authors: Elsherif Laila , Kanthakumar Praghalathan , Afolabi Jeremiah , Stratton Ashley F. , Ogu Ugochi , Nelson Marquita , Mukhopadhyay Ayesha , Smeltzer Matthew P. , Adebiyi Adebowale , Ataga Kenneth I. 
Published: May 2023

SummaryWe explored the association of novel urinary biomarkers with albumin‐creatinine ratio (ACR) in adults with sickle cell anaemia. Of 37 participants, 13 (35.2%) had persistent albuminuria (PA). Urinary levels of clusterin (p = 0.002), retinol‐binding protein 4 (p = 0.008), alpha‐1 microglobulin (p = 0.002) and angiotensinogen (p = 0.006) were significantly higher in participants with PA than in those without PA. Although univariate analysis showed significant associations between both alpha‐1 microglobulin (p = 0.035) and angiotensinogen (p = 0.0021) with ACR, only angiotensinogen was associated with ACR in multivariable analysis (p = 0.04). Our results suggest that urinary angiotensinogen may identify sickle cell anaemia patients at risk for kidney disease.
Emerging strategies for cancer therapy by ATR inhibitors
Authors: Yano Kimiyoshi , Shiotani Bunsyo 
Published: May 2023

AbstractDNA replication stress (RS) causes genomic instability and vulnerability in cancer cells. To counteract RS, cells have evolved various mechanisms involving the ATR kinase signaling pathway, which regulates origin firing, cell cycle checkpoints, and fork stabilization to secure the fidelity of replication. However, ATR signaling also alleviates RS to support cell survival by driving RS tolerance, thereby contributing to therapeutic resistance. Cancer cells harboring genetic mutations and other changes that disrupt normal DNA replication increase the risk of DNA damage and the levels of RS, conferring addiction to ATR activity for sustainable replication and susceptibility to therapeutic approaches using ATR inhibitors (ATRis). Therefore, clinical trials are currently being conducted to evaluate the efficacy of ATRis as monotherapies or in combination with other drugs and biomarkers. In this review, we discuss recent advances in the elucidation of the mechanisms by which ATR functions in the RS response and its therapeutic relevance when utilizing ATRis.
The SHH‐GLI1 pathway is required in skin expansion and angiogenesis
Authors: Zhang Xinling , Chen Yujie , Ding Pengbing , Lin Zhiyu , Sun Zhixuan , Jin Mengying , Li Chong , Zhao Zhenmin , Bi Hongsen 
Published: May 2023

AbstractTo investigate the role of GLI1 on skin proliferation and neovascularization during skin expansion in mice. We constructed GLI1‐cre/R26‐Tdtomato and GLI1‐cre/R26‐mtmg gene‐tagged skin expansion mouse models. Using a two‐photon in vivo imaging instrument to observe the changes in the number and distribution of GLI1(+) cells during the expansion process and to clarify the spatial relationship between GLI1(+) cells and blood vessels during the expansion process. In vitro proliferation assays were performed to further validate the effects of SHH (sonic hedgehog) and its downstream component GLI1 on cell proliferation viability. Finally, qRT‐PCR was used to verify the changes in proliferation, angiogenesis‐related factors, SHH signalling pathway‐related factors, and the role of GLI1 cells in the process of skin expansion in mice. The number of GLI1(+) cells increased during dilation and were attached to the outer membrane of the vessel. The epidermis was thickened and the dermis thinned after the dilated skin was taken, while the epidermal thickening was suppressed and the dermis became thinner after the GLI1 cells were inhibited. The non‐inhibited group showed a significant increase in PCNA positivity with prolonged dilation compared to the GANT61(GLI specificity inhibitor) inhibited group; CD31 immunofluorescence showed a significant increase in the number of dilated skin vessels and a significant decrease in the number of vessels after treatment with GANT61 inhibitor. In vitro proliferation results showed that SHH signalling activator significantly increased the proliferation viability of GLI1(+) hair follicle mesenchymal stem cells, while GNAT61 significantly inhibited the proliferation viability of GLI1(+) hair follicle mesenchymal stem cells. GLI1 is necessary for proliferation and neovascularization in expansion skin of mice through activation of the SHH signalling pathway.
Tocilizumab increases regulatory T cells, reduces natural killer cells and delays graft‐versus‐host disease development in humanized mice treated with post‐transplant cyclophosphamide
Authors: Sligar Chloe , Cuthbertson Peter , Miles Nicole A , Adhikary Sam R , Elhage Amal , Zhang Geoff , Alexander Stephen I , Sluyter Ronald , Watson Debbie 
Published: May 2023

AbstractGraft‐versus‐host disease (GVHD) is a life‐threatening complication following donor hematopoietic stem cell transplantation, where donor T cells damage host tissues. This study investigated the effect of tocilizumab (TOC) combined with post‐transplant cyclophosphamide (PTCy) on immune cell engraftment and GVHD development in a humanized mouse model. NOD‐scid‐IL2Rγnull (NSG) mice were injected intraperitoneally with 2 × 107 human (h) peripheral blood mononuclear cells and cyclophosphamide (33 mg kg−1) or saline on days 3 and 4, then TOC or control antibody (0.5 mg mouse−1) twice weekly for 28 days. Mice were monitored for clinical signs of GVHD for either 28 or 70 days. Spleens and livers were assessed for human leukocyte subsets, and serum cytokines and tissue histology were analyzed. In the short‐term model (day 28), liver and lung damage were reduced in PTCy + TOC compared with control mice. All groups showed similar splenic hCD45+ leukocyte engraftment (55–60%); however, PTCy + TOC mice demonstrated significantly increased (1.5–2‐fold) splenic regulatory T cells. Serum human interferon gamma was significantly reduced in PTCy + TOC compared with control mice. Long‐term (day 70), prolonged survival was similar in PTCy + TOC (median survival time, > 70 days) and PTCy mice (median survival time, 56 days). GVHD onset was significantly delayed in PTCy + TOC, compared with TOC or control mice. Notably, natural killer cells were reduced (77.5%) in TOC and PTCy + TOC mice. Overall, combining PTCy with TOC increases regulatory T cells and reduces clinical signs of early GVHD, but does not improve long‐term survival compared with PTCy alone.
Insights into phenotypic and functional CD8+ TRM heterogeneity
Authors: Heeg Maximilian , Goldrath Ananda W. 
Published: May 2023

SummaryCytotoxic CD8+ T cells recognize and eliminate infected or cancerous cells. A subset of CD8+ memory T cells called tissue‐resident memory T cells (TRM) resides in peripheral tissues, monitors the periphery for pathogen invasion, and offers a rapid and potent first line of defense at potential sites of re‐infection. TRM cells are found in almost all tissues and are transcriptionally and epigenetically distinct from circulating memory populations, which shows their ability to acclimate to the tissue environment to allow for long‐term survival. Recent work and the broader availability of single‐cell profiling have highlighted TRM heterogeneity among different tissues, as well as identified specialized subsets within individual tissues, that are time and infection dependent. TRM cell phenotypic and transcriptional heterogeneity has implications for understanding TRM function and longevity. This review aims to summarize and discuss the latest findings on CD8+ TRM heterogeneity using single‐cell molecular profiling and explore the potential implications for immune protection and the design of immune therapies.
INTRAPLEURAL UROKINASE IN THE MANAGEMENT OF PARAPNEUMONIC EMPYEMA: A RANDOMISED CONTROLLED TRIAL
Authors: Tuncozgur B , Ustunsoy H , Sivrikoz MC , Dikensoy O , Topal M , Sanli M , Elbeyli L 
Published: May 2023

SUMMARYWe compared the effectiveness of intrapleural urokinase versus normal saline via a thoracostomy tube in the treatment of parapneumonic empyema in a randomised controlled study. Forty‐nine patients with parapneumonic empyema were randomly assigned to receive either intrapleural urokinase or normal saline treatment. The daily volume instilled through a chest tube was 100 ml in both groups. Urokinase (100,000 IU/day) was diluted in normal saline before instillation. The mean duration for defervescence was shorter (7 ± 3 vs 13 ± 5 days, p<0.01) and the mean volume of drained fluid during the five‐day treatment period was significantly greater in the urokinase group (1.8 ± 1.5 vs 0.8 ± 0.8 litres, p<0.001) than in the control group. The subsequent decortication rate was 60% and 29.1%, respectively (p<0.001). The duration of hospitalisation was also shorter in the urokinase group (14 ± 4 vs 21 ±4 days, p<0.001) than in the saline group. We conclude that intrapleural instillation of urokinase in the management of parapneumonic empyema provides a better outcome and reduces the need for decortication.
A COMPARISON OF CARDIOVASCULAR RISK FACTORS AMONG INDO‐ASIAN AND CAUCASIAN PATIENTS ADMITTED WITH ACUTE MYOCARDIAL INFARCTION IN KUALA LUMPUR, MALAYSIA AND BIRMINGHAM, ENGLAND
Authors: Dhanjal TS , Lal M , Haynes R , Lip GYH 
Published: May 2023

SUMMARYIndo‐Asians in the UK are at an increased risk of coronary artery disease (CAD); this may be a reflection of their cardiovascular risk factor profile as well as of a more sedentary lifestyle. We hypothesised that Indo‐Asians in Malaysia and the UK may exhibit a similar cardiovascular risk factor and physical activity profile, which would be more adverse compared with caucasians. We studied 70 consecutive Indo‐Asian patients admitted to hospitals in Kuala Lumpur, Malaysia (n=42; 35 males; mean age 60.6 years, SD 11.8); and Birmingham, England (n=28; 20 males; mean age 60.8 years, SD 12.9). Both groups of Indo‐Asian patients were compared with 20 caucasian patients (13 males; mean age 62.7 years, SD 9.4) admitted with myocardial infarction from Birmingham. There was a higher prevalence of diabetes among Indo‐Asians in both countries than among caucasians (p=0.0225). By contrast, caucasians had a higher prevalence of hypercholesterolaemia (p=0.0113), peripheral vascular disease (p=0.0008), regular alcohol consumption (p<0.0001) and family history of CAD (p=0.0041). There were no significant differences in mean age, body mass index or blood pressures. There was a significantly lower leisure activity score (p=0.001) and total physical activity score (p=0.003) among Indo‐Asians in both countries than among caucasians. This survey has demonstrated differences in cardiovascular risk factors among Indo‐Asian and caucasian patients. The high prevalence of diabetes, as well as the lower physical activity and sedentary lifestyles among Indo‐Asians, in both Malaysia and the UK, may in part contribute to the high incidence of CAD in this ethnic group.
AUDITING FIRST EPISODE PSYCHOSIS: GIVING MEANING TO CLINICAL GOVERNANCE
Authors: Rowlands RP 
Published: May 2023

SUMMARYPeople in a first episode of psychosis are receiving increasing attention. This study describes the demographic and clinical diagnostic features of a cohort of 84 cases of first episode psychosis presenting in North Derbyshire from October 1999 to October 2000. Forty‐two cases falling within the schizophrenia spectrum diagnosis were identified, an incidence rate of 0.17 per 1000 population. The rate for all psychoses, including drug‐induced psychoses, was 0.35 per 1000 population aged 15–64. More than 50% of the cases were from the main urban centre, which contains around one third of the population. There were high rates of substance misuse in all diagnostic groups. The majority of patients (73%) presented via their general practitioners, but 18% presented via accident and emergency (13%) or the police (5%). The median duration of untreated psychosis for the whole group was two months. Within the schizophrenia spectrum group, however, there was a wide distribution, with duration of untreated psychosis of up to 10 years. The median duration of unteated psychosis in the schizophrenia spectrum group was three months. About half the cases in this cohort were aged more than 35 (all diagnostic categories). Further work exploring the outcome in this cohort is currently under way. As the configuration of mental health services is set to change rapidly in the next few years, there is a crucial need to develop further observational studies assessing how services deliver care to people with severe mental illness.
7. MANAGEMENT OF ADVANCED BREAST CANCER
Authors: Rubens RD 
Published: May 2023

SUMMARYApproximately half the patients with breast cancer relapse with locally recurrent or metastatic disease. This disease is incurable but can often be controlled, sometimes for many years. Careful clinical evaluation and restaging provides a baseline reference against which response can be judged. Investigations are selected but may include biochemical screens, blood counts, chest X‐ray, isotopic bone scan and radiographs of abnormal regions. Selection of systemic treatment is based on three key factors: the extent, pattern and aggressiveness of the disease; hormone sensitivity; and menstrual status. Chemotherapy is used for rapidly progressing visceral disease such as lymphangitis carcinomatosa or hepatic metastases with deranged liver biochemistry where death ensues rapidly unless disease progression can be reversed. With less aggressive disease, treatment is planned around the oestrogen and progesterone status of the tumour. Those with low tumour receptor levels are unlikely to respond to endocrine treatment and chemotherapy should be considered. For patients with steroid receptor‐positive tumours, endocrine treatment is used before chemotherapy is needed and consideration of menstrual status can assist in the selection of the precise approach.
AIR TRAVEL AND THROMBOSIS
Authors: Giangrande PLF 
Published: May 2023

SUMMARYIt is now generally accepted that there is a link between long haul air travel and venous thromboembolism. A similar risk is also recognised with other modes of transport including long coach and car journeys, and the term ‘traveller's thrombosis’ is to be encouraged instead of ‘economy class syndrome’. More research is required to quantify the precise risk, but the risk does appear to be small and largely confined to those with recognised risk factors, which include previous episode of thrombosis, hormonal therapy, recent surgery, malignancy and pregnancy. In addition, haematological abnormalities can predispose to thrombosis. Such thrombophilic disorders include the factor V Leiden mutation and deficiencies of natural anticoagulants such as antithrombin, protein C and protein S. General measures which can be taken to reduce the risk include leg exercises while seated. In addition, there is evidence to support the use of elasticated stockings, but evidence relating to the use of aspirin is less convincing.
LIFE‐THREATENING HAEMOPTYSIS PRESENTING AS A LATE COMPLICATION OF AN OVARIAN TUMOUR
Authors: Riha RL , Tubby J , Duhig EE , Clarke BE , Haug G , Bell SC 
Published: May 2023

SUMMARYMassive haemoptysis may arise as a result of lung malignancy. This case represents the first report of an ovarian granulosa cell tumour metastasising many years after initial tumour resection to the lung causing life‐threatening haemoptysis. The management and subsequent clinical course of the patient are discussed as well as the natural history of granulosa‐theca cell tumours.