bluuebunny/crossref_metadata_2025 huggingface dataset:
Procedural Risk of Bleeding: Does the Management of Thrombocytopenia in Chronic Liver Disease Patients Make a Difference? A Debate
Authors: Ryan Liz
Published: November 2022

Prof Nezam Afdhal provided a background to thrombocytopenia (TCP) in chronic liver disease (CLD). He explored the causes of TCP and discussed what are considered acceptable platelet levels. He described the delicate balance between thrombosis risk and bleeding risk that puts CLD patients with TCP at risk of complications, particularly when they require invasive procedures.

Through a series of case studies, the faculty highlighted current management dilemmas and novel approaches to TCP management. Prof Edoardo Giannini presented the case of a patient with hepatocellular carcinoma (HCC) (platelet count of <50×109/L) who was given a platelet transfusion prior to radiofrequency thermal ablation (RFTA). The patient’s increase in platelet count was not clinically significant; therefore, the procedure was cancelled. Prof Giannini noted that radiology guidelines state that for procedures with a moderate risk of bleeding (such as RFTA), platelet transfusion is recommended for counts <50×109/L.

Prof Mark Thursz presented a case of a nonalcoholic steatohepatitis and refractory ascites, in which the patient had a number of large-volume paracentesis procedures. He then presented paracentesis studies highlighting that bleeding events are often unrelated to patients’ platelet levels. Prof Giannini described a study in patients with acute-on-chronic liver failure (AoCLF) who underwent paracentesis and in whom the bleeding rate was 3%.

Following these case presentations, Prof Markus Peck-Radosavljevic discussed the role of thrombopoietin (TPO) in TCP in CLD. He then examined the pivotal trials of various TPO-receptor (TPO-R) agonists which have been studied in CLD patients with TCP undergoing invasive procedures. Clinical studies of the TPO-R agonist lusutrombopag included a large proportion of high-risk bleeding patients and therapy with this agent has been shown to elevate platelet count levels for up to 2 weeks, allowing a window in which to schedule invasive procedures.
Overlap Syndrome with Autoimmune Hepatitis and Primary Sclerosing Cholangitis
Authors: Nayagam Jeremy S. , Miquel Rosa , Joshi Deepak
Published: November 2022

Patients with autoimmune liver disease frequently fit diagnostic criteria for more than one condition. Up to 12.5% of autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) cohorts have a label of AIH/PSC overlap. There can be an interval of many years between the diagnoses of the two conditions, and the sequence in which they are made is unpredictable. Issues exist with the use of diagnostic criteria validated for AIH in patients with AIH/PSC overlap. There are no agreed criteria for the diagnosis of AIH/PSC overlap, it is based on a combination of biochemistry, autoantibody profile, cholangiogram, and liver histology. A positive diagnosis of AIH/PSC overlap impacts therapeutic options and prognosis. There is a beneficial role for immunosuppression, albeit with a higher relapse rate and evidence of progressive liver disease despite immunosuppression in some cases. Liver related outcomes sit somewhere between the constituent diseases, with better outcomes than PSC but poorer outcomes than AIH. There is an increasing body of data for patients with AIH/PSC overlap undergoing liver transplantation for end-stage disease.

Nearly half of patients with autoantibody positive liver disease in childhood have autoimmune sclerosing cholangitis (ASC). ASC patients are differentiated from those with AIH by having abnormal cholangiograms. Histological analysis shows chronic hepatitis in <50% of ASC cases. The biochemical response to immunosuppression in ASC patients is less than that seen in AIH patients, and cholangiograms commonly show progressive disease. Transplant-free survival of the ASC population is poorer than in AIH.
Primary Hepatic Angiosarcoma: A Brief Review of the Literature
Authors: Chen Nelson , (Jia Sheng) Yu Aidan , Jung Jihye
Published: November 2022

Primary hepatic angiosarcoma (HAS) is a liver tumour of endothelial cell origin. It is the most common malignant mesenchymal tumour of the liver, but is nonetheless rare, accounting for approximately 0.1–2.0% of all primary liver malignancies. Historically, 25% of HAS cases were associated with occupational or medicinal exposure, but most cases are now considered idiopathic. Patients present with vague signs and symptoms of liver disease, often resulting in late diagnoses; patients may present with acute liver failure or spontaneous rupture of the tumour, but this is rare. Preoperative diagnosis of HAS is difficult because laboratory and radiological findings are often non-specific or unable to discern malignant masses from benign growths. Obtaining a biopsy for histopathological diagnosis of HAS is also difficult because of its vascular and haemorrhagic nature, and reports of death from closed biopsies have been noted. Prognosis is poor because of the disease’s diagnostic challenges and the tumour’s rapidly progressive and early metastatic nature. The reported median survival is approximately 6 months, with only 3% of patients living >2 years. This paper will review and summarise new and existing publications in the English language literature to provide a better understanding of the challenges posed by HAS.
Factors of Entrepreneurial Intentions: the Case of Sports Science Students in Novi Sad
Authors: Janković Uglješa , Matić Radenko M. , Milovanović Ivana M. , Vuković Jovan , Imbronjev Milka
Published: November 2022

Background. The concept of sports entrepreneurship is increasingly explored, both in the world and in Serbia. This paper aims to examine which factors influence the entrepreneurial intentions of sports science students at the Faculty in Novi Sad and describe their influence on entrepreneurial intentions in more detail.
Methods. For research, a survey questionnaire was conducted, which consisted of 114 respondents, that is, 40 female students and 74 male final-year students of the Faculty of Sports and Physical Education in Novi Sad. The questionnaire consists of 33 questions related to several factors: entrepreneurial skills, entrepreneurial culture, attitude toward behavior, subjective norms, and perceived behavioral control.
Results. During data analysis, descriptive indicators and factor analysis were used.
Conclusion. It was observed that the mentioned factors significantly influenced students’ entrepreneurial intentions, and their mutual connection was proven.
Keywords: entrepreneurial intentions, sports science, students, entrepreneurship.
Cell morphogenesis in desmids (Zygnematophyceae, Desmidiaceae): taxonomic significance of their shape
Authors: Anissimova Olga V. , Yarutich Irina A.
Published: November 2022

The article deals with the problems of taxonomy of desmid algae (Desmidiaceae). An analysis of the literature devoted to studies of cell morphogenesis and the role of cellular structures in the formation of daughter semicells was carried out. It is shown that the traits of desmidian algae cells, such as the length and number of processes, the degree of expression of lobes, and other morphological structures, are quite variable at the species level and depend on many factors. However, at the generic level, cell shape is generally stable.
Word and World: Bodily Perception in the Narrative Non-fiction of Kathleen Jamie and Nan Shepherd
Authors: Bell Kirsteen
Published: November 2022

In a tradition of nature and mountain writing in which the solitary male intellectual has long dominated, Kathleen Jamie and Nan Shepherd stood out as offering a new way of writing about the natural world. Inherent in their writing is a repositioning of humanity that neither separates the human from the living world, nor determines anything that is perceived there. Instead, both Jamie and Shepherd focus on their sensed experience of the world, on their bodily perception, as a means by which to interpret that world and to express their part of it. I will draw primarily on the non-fiction prose of both writers to establish this privileging of the senses of the body, and to consider then the relationship that language has with the body and the role that it can play in what Shepherd calls the ‘interpenetration’ of place and mind. 1 I will then consider how Jamie's and Shepherd's perspective shapes the writing of their texts, the journey from sensed experience of the living landscape, through its transformation into language, to the text formed by the writer, and the subsequent implications for the way in which nature writing connects with the living world from which it came.
Second Language (L2) Training Effects on the Cognitive Control of Greek Preschool Children
Authors: Vassiliu Chrysoula , Hendriks Henriette , Leong Victoria
Published: November 2022

Bilingualism’s role in Executive Function (EF) improvement has generated significant discussion but few conclusive results. Researchers have drawn an artificial dichotomy between monolinguals and bilinguals. Studies primarily include young adults with ceiling performances and use very few tasks, failing to capture EF complexity. To assess the effects of emerging bilingualism on cognitive control, we employed a longitudinal design, evaluating the influence of seven months of L2 learning in preschool children. We used multiple tasks for Inhibition, Working Memory (WM) and Cognitive Flexibility (CF). We tested 78 Greek-speaking children from Athens, with no prior L2 experience. Half (n = 40) received L2 training in school. Results showed that children learning an L2 improved significantly more than controls in areas of CF related to rule learning and adapting to change, and in spatial WM. Our longitudinal design and rich task battery allowed us to reliably detect language-related influences on EF.
Women at heart: Introducing gender cardio-oncology
Authors: Canale Maria Laura , Bisceglia Irma , Gallucci Giuseppina , Russo Giulia , Camerini Andrea , Di Fusco Stefania Angela , Paccone Andrea , Camilli Massimiliano , Fiscella Damiana , Lestuzzi Chiara , Turazza Fabio Maria , Gulizia Michele Massimo , Pavan Daniela , Maurea Nicola , Gabrielli Domenico , Oliva Fabrizio , Colivicchi Furio
Published: November 2022

As cardio-oncology imposed itself as the reference specialty for a comprehensive cardiovascular approach to all patients with cancer, a more specific and careful cardiac evaluation of women entering their journey into cancer care is needed. Gender medicine refers to the study of how sex-based biological and gender-based socioeconomic and cultural differences influence people’s health. Gender-related aspects could account for differences in the development, progression, and clinical signs of diseases as well as in the treatment of adverse events. Gender also accounts for major differences in access to healthcare. As for medicine and healthcare in general, gender-related characteristics have gained significance in cardio-oncology and should no longer be neglected in both clinical practice and research. We aimed to review the most relevant cardiovascular issues in women related to the cardio-oncology approach to offer a specific gender-related point of view for clinicians involved in the care process for both cancer and cardiovascular disease.
The diagnostic value of salivary cortisol and salivary cortisone in patients with suspected hypercortisolism
Authors: Berndt Vendela , Dahlqvist Per , de Verdier Jennie , Ryberg Henrik , Ragnarsson Oskar
Published: November 2022

Background

Diagnosing endogenous hypercortisolism remains a challenge, partly due to a lack of biochemical tests with good diagnostic accuracy.

Objectives

To evaluate the diagnostic value of salivary cortisol and cortisone in patients with suspected hypercortisolism.

Methods

Retrospective study including 155 patients with adrenal incidentaloma, and 54 patients with suspected Cushing´s syndrome (CS). Salivary samples were collected at home, at 11 p.m., and at 8 a.m. following an over-night dexamethasone suppression test (DST). Salivary cortisol and cortisone were measured with liquid chromatography-tandem mass spectrometry.

Results

Ten of 155 patients with adrenal incidentaloma were considered to have autonomous cortisol secretion (ACS). Using previously established cut-offs, all patients with ACS had elevated plasma-cortisol (>50 nmol/L) following DST, 9/10 had elevated late-night salivary cortisone (>15 nmol/L) whereas only 4/10 had elevated late-night salivary cortisol (LNSC; >3 nmol/L) compared to 35%, 9% and 8%, respectively, of the 145 patients with non-functioning adrenal incidentaloma. Six (60%) patents with ACS had elevated salivary cortisol and cortisone at 8 a.m. following DST compared to 9% and 8%, respectively, of patients with non-functioning adrenal incidentaloma. One of 6 patients with overt CS had a normal LNSC and one had normal late-night salivary cortisone, while all had increased salivary cortisol and cortisone following DST.

Conclusion

LNSC is not sufficiently sensitive or specific to be used for screening patients with suspected hypercortisolism. Instead, late-night salivary cortisone seems to be a promising alternative in patients with adrenal incidentaloma and salivary cortisone at 8 a.m. following DST in patients with suspected CS. Larger studies are needed to confirm these findings.
LASSO-based machine learning models for the prediction of central lymph node metastasis in clinically negative patients with papillary thyroid carcinoma
Authors: Feng Jia-Wei , Ye Jing , Qi Gao-Feng , Hong Li-Zhao , Wang Fei , Liu Sheng-Yong , Jiang Yong
Published: November 2022

Background

The presence of central lymph node metastasis (CLNM) is crucial for surgical decision-making in clinical N0 (cN0) papillary thyroid carcinoma (PTC) patients. We aimed to develop and validate machine learning (ML) algorithms-based models for predicting the risk of CLNM in cN0 patients.

Methods

A total of 1099 PTC patients with cN0 central neck from July 2019 to March 2022 at our institution were retrospectively analyzed. All patients were randomly split into the training dataset (70%) and the validation dataset (30%). Eight ML algorithms, including the Logistic Regression, Gradient Boosting Machine, Extreme Gradient Boosting (XGB), Random Forest (RF), Decision Tree, Neural Network, Support Vector Machine and Bayesian Network were used to evaluate the risk of CLNM. The performance of ML models was evaluated by the area under curve (AUC), sensitivity, specificity, and decision curve analysis (DCA).

Results

We firstly used the LASSO Logistic regression method to select the most relevant factors for predicting CLNM. The AUC of XGB was slightly higher than RF (0.907 and 0.902, respectively). According to DCA, RF model significantly outperformed XGB model at most threshold points and was therefore used to develop the predictive model. The diagnostic performance of RF algorithm was dependent on the following nine top-rank variables: size, margin, extrathyroidal extension, sex, echogenic foci, shape, number, lateral lymph node metastasis and chronic lymphocytic thyroiditis.

Conclusion

By incorporating clinicopathological and sonographic characteristics, we developed ML-based models, suggesting that this non-invasive method can be applied to facilitate individualized prediction of occult CLNM in cN0 central neck PTC patients.
The anticancer effects of Metformin in the male germ tumor SEM-1 cell line are mediated by HMGA1
Authors: Salatino Alessandro , Mirabelli Maria , Chiefari Eusebio , Greco Marta , Di Vito Anna , Bonapace Giuseppe , Brunetti Francesco S. , Crocerossa Fabio , Epstein Alan L. , Foti Daniela P. , Brunetti Antonio
Published: November 2022

Introduction

Germ cell tumors (GCTs) are the most common type of cancer in young men. These tumors usually originate from the testis, but they can occasionally develop from extragonadal sites probably due to primordial germ cells (PGCs) migration errors. Cisplatin-based chemotherapy is usually effective for male GCTs, but the risk of toxicity is high and new therapeutic strategies are needed. Although Metformin (Met) has been widely studied as a potential cancer treatment over the past decades, there is limited evidence to support its use in treating male GCTs. Additionally, the mechanism by which it acts on tumor cells is still not entirely understood.

Methods

SEM-1 cells, a newly established human cell line of extragonadal origin, were treated with Met. Cell viability was studied by MTT assay, while cell migration and invasion were studied by the wound healing assay and the transwell assay, respectively. The effect of Met on 3D spheroid formation was determined by seeding SEM-1 cells in appropriate cell suspension culture conditions, and cell cycle was characterized by flow cytometry. Factors involved in PGCs migration and GCT invasion, such as IGFBP1, IGF1R, MMP-11 and c-Kit, together with cyclin D1 (a key regulator of cell cycle progression), and the upstream factor, HMGA1, were determined by immunoblots.

Results

Treatment of SEM-1 cells with Met resulted in a potent and dose-dependent reduction of cell proliferation, as evidenced by decreased nuclear abundance of cyclin D1 and cell cycle arrest in G1 phase. Also, Met prevented the formation of 3D spheroids, and blocked cell migration and invasion by reducing the expression of IGFBP1, IGF1R and MMP-11. Both, IGFBP1 and MMP-11 are under control of HMGA1, a chromatin-associated protein that is involved in the regulation of important oncogenic, metabolic and embryological processes. Intriguingly, an early reduction in the nuclear abundance of HMGA1 occurred in SEM-1 cells treated with Met.

Conclusions

Our results document the antiproliferative and antimigratory effects of Met in SEM-1 cells, providing new insights into the potential treatments for male GCTs. The anticancer properties of Met in SEM-1 cells are likely related to its ability to interfere with HMGA1 and downstream targets, including cyclin D1, the IGFs system, and MMP-11.
Efficacy of low-dose hCG on FET cycle in patients with recurrent implantation failure
Authors: Zhai Xinyu , Shu Mingming , Guo Yiming , Yao Shun , Wang Yiran , Han Shujie , Song Chunlan , Chuai Yunhai , Wang Qihang , Ma Fu , Chen Fu , Zhou Ming , Shang Wei
Published: November 2022

Objective

To study patients’ new treatment methods and mechanisms of repeated implantation failure.

Design

A retrospective study.

Setting

In vitro fertilization (IVF) unit in a Three-A hospital.

Patient(s)

Ninety-three patients with repeated implantation failure in IVF and embryo transfer.

Intervention(s)

the luteal phase support.

Main outcome measure(s)

According to whether human chorionic gonadotropin(HCG) was added, the two groups were divided into an observation group and a control group, and the clinical outcomes of the two groups were compared. Furthermore, 20 patients were selected for whole exome sequencing to investigate the mechanism.

Results

The observation group’s clinical pregnancy rate and live birth rate were significantly higher than those in the control group (P=0.004). Functional enrichment analysis showed that these genes were significantly enriched in embryo implantation or endometrial receptivity processes, such as microtubule-based movement, NABA CORE MATRISOME, superoxide anion generation, protein localization to vacuole, extracellular matrix organization, fertilization, microtubule-based transport, cell junction organization, microtubule cytoskeleton organization. Furthermore, variants detected in these pathway genes were missense mutations that affect the protein’s biological activity but do not effectuate its inactivation.

Conclusions

Adding HCG in the luteal phase might improve the clinical pregnancy and live birth rates in RIF patients. The potential pathogenesis of RIF genetic level may be caused by microtubule-based movement, extracellular matrix organization, and the Superoxide Anion generation pathway.
China’s urban-rural expansion and natural habitat loss since the 1980s: Retrospective analysis and future suggestions
Authors: Han Lijian , Zhang Lumiao , Zhou Weiqi , Li Weifeng , Qian Yuguo
Published: November 2022

Natural habitats transformed to city or countryside with human activities of different intensities have reshaped regional and global landscapes, especially in those rapid developed low- and mid-income countries, like China. China’s rapid shift in urban and rural expansion, which are greater than and equal to, and below county-level’s artificial land expansion, and reduction in farmland and ecological land are important for determining future urban and rural development under the conservation and protection of farmland and ecosystems; however, such an understanding is still inadequate. Here, we show that both urban and rural expansions have encroached on farmland and ecological land since 1980; rural areas, with 1.33 km2 × 105 km2 in 2020, remain larger than urban areas, with 0.97 km2 × 105 km2 in 2020. However, urban areas (1857.5 km2/year) increased faster than rural areas (695.0 km2/year) during 1980–2020, rural expansion primarily occurred in the 1980s and 1990s, and urban expansion primarily occurred after 2000 especially 2000s. Farmland is the major land cover that has been occupied by urban and rural expansion for 53.7 and 39.1 thousand km2, especially in East China’s densely populated areas. And, both farmland and ecological land were primarily encroached during 2000s. Our results demonstrate imbalanced urban and rural expansion and encroachment on farmland and ecological land; thus, both forms of encroachment should be optimized at the regional scale based on the socioeconomic needs and natural conditions, and diverse policies can be designed to support local sustainable development.
Effects of China’s land-intensive use on carbon emission reduction: A new perspective of industrial structure upgrading
Authors: Wu Haiyang , Qiu Yige , Yin Li , Liu Shanshan , Zhao Dongxue , Zhang Mei
Published: November 2022

The rapid and disorderly expansion of urban construction land has resulted in massive carbon emissions, intensifying the contradiction between land use and low-carbon development. As an essential tool to increase land use efficiency, whether land-intensive use can balance economic and environmental benefits has emerged as a topical issue. This paper investigates the influence of land-intensive use on carbon emissions and its role mechanism under the perspective of industrial structure upgrading by using a two-way fixed-effects model with provincial panel data from 2008 to 2020 in China. The statistical results reveal that land-intensive use not only reduces carbon emissions but also boosts carbon emission efficiency, which achieves carbon emission reduction from both quantity and quality aspects. The carbon emission reduction effect of land-intensive use is mainly manifested in energy, capital, science, and education factors of land-intensive use. The carbon emission reduction benefits obtained through land-intensive use are more noticeable in regions with higher economic development levels. Land-intensive utilization is mainly responsible for carbon emission reduction through promoting industrial structure advanced quality. Our findings suggest that policy makers shall expedite land intensive use development, appropriately synchronize land use levels across regions, and adequately leverage the role mechanisms of advanced industrial structure as a potent measure to promote carbon emission reduction.
Development and validation of a chromatin regulator prognostic signature in colon adenocarcinoma
Authors: Yang Wenlong , Luo Chenhua , Chen Shan
Published: November 2022

Aberrant expression of chromatin regulators (CRs) could lead to the development of various diseases including cancer. However, the biological function and prognosis role of CRs in colon adenocarcinoma (COAD) remains unclear. We performed the clustering analyses for expression profiling of COAD downloaded from The Cancer Genome Atlas. We developed a chromatin regulator prognostic model, which was validated in an independent cohort data. Time-intendent receiver operating characteristics curve was used to evaluate predict ability of model. Univariate and multivariate cox regression were used to assess independence of risk score. Nomogram was established to assess individual risk. Gene ontology, and Kyoto Encyclopedia of genes and genomes, gene set variation analysis and gene set enrichment analysis were performed to explore the function of CRs. Immune infiltration and drug sensitivity were also performed to assess effect of CRs on treatment in COAD. COAD can be separated into two subtypes with different clinical characteristics and prognosis. The C2 had elevated immune infiltration levels and low tumor purity. Using 12 chromatin regulators, we developed and validated a prognostic model that can predict the overall survival of COAD patients. We built a risk score that can be an independent prognosis predictor of COAD. The nomogram score system achieved the best predict ability and were also confirmed by decision curve analysis. There were significantly different function and pathway enrichment, immune infiltration levels, and tumor mutation burden between high-risk and low-risk group. The external validation data also indicated that high-risk group had higher stable disease/progressive disease response rate and poorer prognosis than low-risk group. Besides, the signature genes included in the model could cause chemotherapy sensitivity to some small molecular compounds. Our integrative analyses for chromatin regulators could provide new insights for the risk management and individualized treatment in COAD.
A vasculogenic mimicry prognostic signature associated with immune signature in human gastric cancer
Authors: Wang Jie , Xia Wei , Huang Yujie , Li Haoran , Tang Yuchen , Li Ye , Yi Bin , Zhang Zixiang , Yang Jian , Cao Zhifei , Zhou Jian
Published: November 2022

Background

Gastric cancer (GC) is one of the most lethal malignant tumors worldwide with poor outcomes. Vascular mimicry (VM) is an alternative blood supply to tumors that is independent of endothelial cells or angiogenesis. Previous studies have shown that VM was associated with poor prognosis in patients with GC, but the underlying mechanisms and the relationship between VM and immune infiltration of GC have not been well studied.

Methods

In this study, expression profiles from VM-related genes were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Cox regression was performed to identify key VM-related genes for survival. Subsequently, a novel risk score model in GC named VM index and a nomogram was constructed. In addition, the expression of one key VM-related gene (serpin family F member 1, SERPINF1) was validated in 33 GC tissues and 23 paracancer tissues using immunohistochemistry staining.

Results

Univariate and multivariate Cox regression suggested that SERPINF1 and tissue factor pathway inhibitor 2 (TFPI2) were independent risk factors for the prognosis of patients with GC. The AUC (> 0.7) indicated the satisfactory discriminative ability of the nomogram. SsGESA and ESTIMATE showed that higher expression of SERPINF1 and TFPI2 is associated with immune infiltration of GC. Immunohistochemistry staining confirmed that the expression of SERPINF1 protein was significantly higher in GC tissues than that in paracancer tissues.

Conclusion

A VM index and a nomogram were constructed and showed satisfactory predictive performance. In addition, VM was confirmed to be widely involved in immune infiltration, suggesting that VM could be a promising target in guiding immunotherapy. Taken together, we identified SERPINF1 and TFPI2 as immunologic and prognostic biomarkers related to VM in GC.
Combinatory local ablation and immunotherapies for hepatocellular carcinoma: Rationale, efficacy, and perspective
Authors: Chen Shuling , Zeng Xuezhen , Su Tianhong , Xiao Han , Lin Manxia , Peng Zhenwei , Peng Sui , Kuang Ming
Published: November 2022

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. Local ablation, such as radiofrequency ablation, microwave ablation, cryoablation and irreversible electroporation, etc., are well established in elimination and control of HCC. However, high recurrence rate after local ablation remains the biggest challenge for HCC management. Novel and effective therapeutic strategies to improve long-term survival are urgently needed. Accumulating studies have reported the role of ablation in modulating the tumor signaling pathway and the immune microenvironment to both eliminate residual/metastatic tumor and promote tumor progression. Ablation has been shown to elicit tumor-specific immune responses by inducing massive cell death and releasing tumor antigen. Immunotherapies that unleash the immune system have the potential to enhance the anti-tumor immunity induced by ablation. Multiple combinatory strategies have been explored in preclinical and clinical studies. In this review, we comprehensively summarize the latest progress on different mechanisms underlying the effects of ablation on tumor cells and tumor microenvironment. We further analyze the clinical trials testing the combination of ablation and immunotherapies, and discuss the possible role of immunomodulation to boost the anti-tumor effects of ablation and prevent HCC recurrence.
Hemoglobin induces inflammation through NF-kB signaling pathway and causes cell oxidative damage in grass carp (Ctenopharyngodon idella)
Authors: Tang Ying , Yang Shiyi , Yao Minshan , Yang Minxuan , Wei Lixiang , Chen Hong , Lin Junyan , Huang Yao , Lin Li , Qin Zhendong
Published: November 2022

Hemolytic disease in grass carp (C. idella) leads to hemolysis in vivo, releasing damage-related molecular patterns (DAMPs) hemoglobin (Hb; which is rapidly oxidized to Hb-Fe3+ and Hb-Fe4+) and generating a high level of reactive oxygen species (ROS) that cause oxidative damage. However, the effect of cell-free Hb on tissue cells of grass carp has yet to be elucidated. In this study, western blotting (WB) and immunofluorescence analysis (IFA) results showed that PHZ-induced hemolysis caused Hb and iron accumulation, increased the production of ROS and resulted in apoptosis in head kidney and middle kidney of the grass carp. Quantitative real-time PCR (qRT-PCR), WB, and IFA revealed that PHZ-induced hemolysis significantly upregulated the expression of inflammation-related genes through activation of the NF-κB signaling pathway. To further explore the effect of Hb, three forms of Hb (Hb, MetHb, and FerrylHb) were prepared. The incubation with the different forms of Hb and heme markedly upregulated the expression of cytokine genes through NF-κB signaling pathway, which was further confirmed by a specific inhibitor (caffeic acid phenethyl ester, CAPE). Flow cytometry analysis data showed that the stimulation of different forms of Hb and heme increased the production of ROS, and resulted in apoptosis. In summary, our data suggest that the excess cell-free Hb released during hemolysis modulates the inflammatory response through activation of the NF-κB signaling pathway and causes cell oxidative damage and apoptosis.
Humoral and cellular immune responses to Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine in adolescents with liver transplantation: Single center experience
Authors: Sánchez-Zapardiel Elena , Alós María , Nozal Pilar , González-Muñoz Miguel , Frauca-Remacha Esteban , Gavilán Lucía Blanca , Quiles María José , Hierro Loreto , López-Granados Eduardo
Published: November 2022

Background

Immune responses to vaccines against severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 are variable. In the absence of disease, youngsters are expected to better react to vaccines than adults. Nevertheless, chronic immunosuppression in transplant recipients may impair their capability to generate protection. We aim to explore immune responses after BNT162b2 SARS-CoV-2 vaccination in our cohort of young liver-transplanted patients.

Methods

A prospective study of adolescent liver-transplanted patients (n=33) in the long-term follow-up was performed. Immune responses after receiving Pfizer-BioNTech BNT162b2 vaccine were analyzed at two time-points: baseline and 30 days after the second dose. Humoral responses were measured by fluoroenzyme-immunoassay and T-cell responses by interferon-γ-release assay. Post-vaccine coronavirus disease (COVID-19) events were recorded by a survey.

Results

Pre-vaccine SARS-CoV-2-specific antibodies were undetectable in 27/32 (84.4%), negative/indeterminate in 3/32 (9.4%) and positive in 2/32 (6.3%) patients. Cellular responses at baseline were negative in 12/18 (66.6%), positive in 3/18 (16.6%) and indeterminate in 3/18 (16.6%) recipients. None of the baseline positives recalled any symptoms. Post-vaccine antibodies were detected in all patients and 92.6% showed levels >816 BAU/mL. Twenty (71.4%) recipients had positive T-cell responses. Regarding post-vaccine SARS-Cov-2 infection, 10 (30.3%) patients reported COVID-19 without hospitalization and 21 (63.6%) did not notify any infection. Negative and positive cell-response groups after vaccination showed statistically significant differences regarding COVID-19 cases (62.5% vs 22.2%, respectively; p=0.046).

Conclusions

Adolescents and young adults with liver transplantation responded to SARS-Cov-2 vaccine, generating both humoral and cellular responses. Recipients developing cellular responses after vaccination had a lower incidence of COVID-19.
Cytokine and chemokine multiplex analysis-based exploration for potential treatment and prognostic prediction in large-vessel vasculitis: A preliminary observational study
Authors: Abe Nobuya , Kono Michihiro , Kono Michihito , Katsuyama Takayuki , Ohmura Kazumasa , Sato Taiki , Karino Kohei , Fujieda Yuichiro , Kato Masaru , Hasebe Rie , Murakami Masaaki , Atsumi Tatsuya
Published: November 2022

Large-vessel vasculitis (LVV) is subclassified into two phenotypes; Takayasu arteritis and giant cell arteritis. Although the pathogenesis of LVV is not fully established, IL-6−IL-17 axis and IL-12−IFN-γ axis play critical roles in the disease development. We aimed to clarify the association between the disease state and cytokine/chemokine levels, to assess disease course as prognosis and to predict regulators in patients with LVV using the blood profiles of multiple cytokines/chemokines. This retrospective analysis comprised 35 LVV patients whose blood were collected, and multiplex cytokine/chemokine analysis with 28 analytes was performed. The differences of cytokines/chemokines corresponding disease status, upstream regulator analysis, pathway analysis and cluster analysis were conducted using the cytokines/chemokines profile. Relapse-free survival rate was calculated with Kaplan-Meier analysis in the classified clusters. In the robust analysis, IL-4, CCL2/MCP-1, TNFSF13/APRIL, TNFSF13B/BAFF, CHI3L1 and VEGF-A levels were significantly changed after treatment. Untreated LVV patients demonstrated activation of NFκB-related molecules and these patients are potentially treated with JAK/STAT inhibitors, anti-TNF-α inhibitors and IL-6 inhibitors. Cluster analysis in active LVV patients revealed two clusters including one with high blood levels of IL-1β, IL-6, IL-17, IL-23 and CCL20/MIP-3. A subgroup of the LVV patients showed activated IL-17 signature with high relapse frequency, and JAK/TyK2 inhibitors and IFN-γ inhibitors were detected as potentially upstream inhibitors. Blood cytokine/chemokine profiles would be useful for prediction of relapse and potentially contributes to establish therapeutic strategy as precision medicine in LVV patients.
Biofilms as potential reservoirs of stony coral tissue loss disease
Authors: Evans James S. , Paul Valerie J. , Kellogg Christina A.
Published: November 2022

Since 2014, corals throughout Florida’s Coral Reef have been plagued by an epizootic of unknown etiology, colloquially termed stony coral tissue loss disease (SCTLD). Although in Florida the movement of this waterborne coral disease has been consistent with natural transport via water currents, outbreaks in the Caribbean have been more sporadic, with infections occurring in locations inconsistent with spread via natural means. Often Caribbean outbreaks have been clustered near ports, potentially implicating ships as mediators of SCTLD into new regions. Biofilms attached to ship hulls, ballast tank walls, or other surfaces could represent a possible vector for the disease. We investigated whether bacteria shed by healthy and SCTLD-diseased corals would form distinct biofilms, and whether a SCTLD signal would be detectable within biofilm bacterial communities. Stainless steel plates serving as proxies for ship hulls, ballast tank walls, and other colonizable surfaces were incubated for three days in filtered seawater mesocosms containing healthy or SCTLD-infected corals. Resulting biofilm bacterial communities were characterized through sequencing of the V4 region of the 16S rRNA gene. We determined that bacteria shed by healthy and diseased corals formed significantly different biofilms consisting of highly diverse taxa. Comparison with 16S data from previous SCTLD investigations spanning different coral species, collection locations, years, and source material revealed the presence of numerous genetically identical sequences within the biofilm bacterial communities formed during exposure to SCTLD-infected corals, including several previously identified as possible SCTLD bioindicators. These results suggest ship-associated biofilms may have the potential to be vectors for the transmission of SCTLD into new regions.
A study on green technology efficiency of China’s marine ship industry chain based on meta-frontier framework and three-stage EBM model
Authors: Guan Hongjun , Wang Yu , Zhao Aiwu
Published: November 2022

Under strict resource and environmental constraints, improving the overall green efficiency of the industrial chain is crucial to the sustainable development of the marine ship industry. Based on the data of 40 listed companies in the industry chain from 2015 to 2019, the meta-frontier framework and three-stage epsilon based measure (EBM) model are employed to study the green technical efficiency (GTE) in each link of the industry chain and the technical gap between each link. The impact of the external environment on GTE, the main reasons hindering the development of GTE, and the ways to improve GTE are also discussed for policy reference. The results show that: (1) under the meta-frontier, the GTEs of the whole industry chain and the composed links are all high and rising year by year. (2) There are obvious green technological development gaps among the links of the industry chain. The GTEs are ranked as the upstream>the downstream>the midstream. (3) The inefficiencies of green technology (GTEI) in the upstream and downstream of the industry chain come from endogenous hindrance, while the GTEI of the midstream is due to exogenous hindrance. (4) The external environment has a significant influence on the development of GTE in the industrial chain. Highly open and innovative external environment can effectively reduce the input redundancy. (5) After eliminating the external influencing factors and random interferences, the actual GTE of the industrial chain is only 0.4 or so, with more serious imbalance among the three links. Therefore, it is important for the marine ship industry chain to optimize the allocation of innovation resources and cultivate an open and shared innovation environment.
Influence of prepreg parameters on the interlaminar consolidation of fiber reinforced thermoplastic laminates manufactured by vacuum-bag-only process
Authors: Saffar Florence , Beauchêne Pierre , Sonnenfeld Camille , Park Chung Hae
Published: November 2022

To better understand the influence of the prepreg parameters such as surface roughness, fibres/matrix distribution (e.g. presence or absence of pure matrix layer on the prepreg surface) and initial matrix crystallinity, two different carbon fibres/Poly-Ether-Ketone-Ketone prepregs are used to fabricate unidirectional laminate by Vacuum-Bag-Only (VBO) process. By an in-situ monitoring set-up, the laminate thickness and the temperature difference along the thickness direction are measured throughout the consolidation cycle. The quality of laminate is assessed in terms of interlaminar shear strength and void content. A finite element model has been developed to describe the intimate contact establishment by the deformation of surface roughness between the glass transition temperature and the melting temperature of the matrix. In particular, the model takes into account the real profilometer data and the variable Young’s modulus of matrix in terms of temperature and crystallinity. Finally, the high influence of the matrix crystallinity degree and the surface roughness on the intimate contact phenomenon is highlighted.
Is student mentoring career-defining in surgical disciplines? A comparative survey among medical schools and medical students for mentoring programs
Authors: Hertling Stefan Ferdinand , Back David Alexander , Wildemann Britt , Schleußner Ekkehard , Kaiser Mario , Graul Isabel
Published: November 2022

Objective

Facing a shortage of young surgeons, this study aimed to examine the availability of mentoring programs and if this can counteract this lack.

Summary background data

Medical mentoring programs have proven to be decisive to influence students’ later career decisions. Since their structure may depend on the medical school and the effort of single disciplines, the offers are often very heterogeneous.

Methods

Anonymous online-questionnaires were developed and distributed among medical students in Germany and the dean for teaching of the medical schools from July 2019 to January 2020 in Germany. Data of the availability of mentoring programs, their structure and the impact of surgery were collected.

Results

Forty three medical schools participated, with 65% offering mentoring programs. 18 of medical schools had no additional funding available for this. Surgical subjects participated in these programs in only 30%. Additionally, 1,516 medical students participated in the second survey. A total of 70% had already participated in a mentoring program with a significantly higher proportion of men. Of these, 94% stated that this was helpful and had an impact on their career planning, without any gender differences. 95% would participate in structured surgical mentoring programs and 95% agreed that this could have an impact on their career planning.

Conclusion

Mentoring programs may be able to influence career planning, nevertheless participation by surgical specialties has been low. Becoming more active in providing mentoring programs with a special focus on women and offering more surgical content can be a way to counteract the lack of surgical trainees.
Secondary myoadenylate deaminase deficiency is not a common feature of inflammatory myopathies: A descriptive study
Authors: Wilkinson Michael , Cash Kathy , Gutschmidt Bernice , Otto Sophia , Limaye Vidya
Published: November 2022

Background

Myoadenylate deaminase (MAD) deficiency is a form of metabolic myopathy, which generally causes only mild symptoms in the primary inherited form. Inflammatory myopathies are a group of autoimmune diseases which result in skeletal muscle weakness. In addition to inflammatory pathology, it has been speculated that non-inflammatory mechanisms, and possibly secondary MAD-deficiency, may potentially contribute to weakness in these conditions.

Methods

We investigated for an association between these two myopathic processes through two complementary methods. Firstly, muscle biopsy records in South Australia over a 17-year period were retrospectively reviewed for diagnosis of myositis or MAD-deficiency, as well as associated clinical features. Secondly, a prospective arm histochemically tested all incident biopsy specimens over a 12-month period for MAD-deficiency.

Results

In the retrospective arm, 30 MAD-deficient cases were identified (1.3% of all biopsies), with no significant difference observed in overall rates of myositis diagnosis between patients with intact and deficient MAD activity (21.3% vs 26.7%, P = 0.47). No cases of MAD-deficiency were detected in the prospective arm, despite 39 cases of myositis being identified over this period.

Conclusion

Secondary MAD deficiency is unlikely to be a major driver of symptoms in inflammatory myopathies.
Impact of unplanned peritoneal dialysis start on patients' outcomes—A multicenter cohort study
Authors: Hangai Kellen Thayanne , Pecoits-Filho Roberto , Blake Peter G. , da Silva Daniela Peruzzo , Barretti Pasqual , de Moraes Thyago Proença
Published: November 2022

Background

Patients with end-stage kidney disease (ESKD) who start unplanned dialysis therapy are more likely to be treated with hemodialysis (HD) using a central venous catheter, which has been associated with a greater risk of infections and other complications, as well as with a higher long-term risk of death. Urgent-start PD is an alternative that has been suggested as an option for starting dialysis in these cases, with potentially better patient outcomes. However, the definition of urgent-start PD is not homogeneous, and no study, to our knowledge, has compared clinical outcomes among urgent start, early start, and conventional start of PD. In this study, we aimed to compare these types of initiation of dialysis therapy in terms of a composite outcome of patient survival and technique failure.

Methods

This is a retrospective, multicenter, cohort study, involving data from 122 PD clinics in Brazil. We used the following: Urgent-start groups refer to patients who initiated PD within 72 h after the PD catheter insertion; early-start groups are those starting PD from 72 h to 2 weeks after the catheter insertion; and conventional-start groups are those who used the PD catheter after 2 weeks from its insertion. We analyzed the composite endpoint of all causes of patient's mortality and technique failure (within the initial 90 days of PD therapy) using the following three different statistical models: multivariate Cox, Fine and Gay competing risk, and a multilevel model.

Results

We included 509 patients with valid data across 68 PD clinics. There were 38 primary outcomes, comprising 25 deaths and 13 technique failures, with a total follow-up time of 1,393.3 months. Urgent-start PD had no association with the composite endpoint in all three models.

Conclusion

Unplanned PD seems to be a safe and feasible option for treatment for patients with non-dialysis ESKD in urgent need of dialysis.
Yap1-mediated Flr1 expression reveals crosstalk between oxidative stress signaling and caffeine resistance in Saccharomyces cerevisiae
Authors: Choi Ji Eun , Heo Seo-Hee , Chung Woo-Hyun
Published: November 2022

Caffeine, a methylxanthine derivative, affects various physiological conditions such as cell growth, proliferation, and energy metabolism. A genome-wide screening for genes required for caffeine resistance in Schizosaccharomyces pombe revealed several candidates, including Pap1 and downstream target genes involved in caffeine efflux. We found that Yap1, a budding yeast AP-1 homolog required for oxidative stress response, has a caffeine tolerance function. Although the Yap1 mutant is not sensitive to caffeine, overexpression of Yap1 renders cells resistant to high concentrations of caffeine. Caffeine sensitivity of mutants lacking two multidrug transporters, Pdr5 or Snq2, is completely recovered by Yap1 overexpression. Among Yap1-dependent target genes, FLR1, a fluconazole-resistant gene, is necessary but not sufficient for caffeine tolerance. Low concentrations of hydrogen peroxide induce Yap1 activation, which restores cell viability against caffeine toxicity. Intriguingly, oxidative stress-mediated cellular adaptation to caffeine toxicity requires Yap1, but not Flr1. Moreover, caffeine is involved in reduction of intracellular reactive oxygen species (ROS), as well as mutation rate and Rad52 foci formation. Altogether, we identified novel reciprocal crosstalk between ROS signaling and caffeine resistance.