bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of FABP5 in T Cell Lipid Metabolism and Function in the Tumor Microenvironment
Authors: Jin Rong , Hao Jiaqing , Yu Jianyu , Wang Pingzhang , Sauter Edward R. , Li Bing
Published: January 2023

To evade immune surveillance, tumors develop a hostile microenvironment that inhibits anti-tumor immunity. Recent immunotherapy breakthroughs that target the reinvigoration of tumor-infiltrating T lymphocytes (TIL) have led to unprecedented success in treating some cancers that are resistant to conventional therapy, suggesting that T cells play a pivotal role in anti-tumor immunity. In the hostile tumor microenvironment (TME), activated T cells are known to mainly rely on aerobic glycolysis to facilitate their proliferation and anti-tumor function. However, TILs usually exhibit an exhausted phenotype and impaired anti-tumor activity due to the limited availability of key nutrients (e.g., glucose) in the TME. Given that different T cell subsets have unique metabolic pathways which determine their effector function, this review introduces our current understanding of T cell development, activation signals and metabolic pathways. Moreover, emerging evidence suggests that fatty acid binding protein 5 (FABP5) expression in T cells regulates T cell lipid metabolism and function. We highlight how FABP5 regulates fatty acid uptake and oxidation, thus shaping the survival and function of different T cell subsets in the TME.
Novel Computed-Tomography-Based Transformer Models for the Noninvasive Prediction of PD-1 in Pre-Operative Settings
Authors: Wei Yi , Yang Meiyi , Xu Lifeng , Liu Minghui , Zhang Feng , Xie Tianshu , Cheng Xuan , Wang Xiaomin , Che Feng , Li Qian , Xu Qing , Huang Zixing , Liu Ming
Published: January 2023

The expression status of programmed cell death protein 1 (PD-1) in patients with hepatocellular carcinoma (HCC) is associated with the checkpoint blockade treatment responses of PD-1/PD-L1. Thus, accurately and preoperatively identifying the status of PD-1 has great clinical implications for constructing personalized treatment strategies. To investigate the preoperative predictive value of the transformer-based model for identifying the status of PD-1 expression, 93 HCC patients with 75 training cohorts (2859 images) and 18 testing cohorts (670 images) were included. We propose a transformer-based network architecture, ResTransNet, that efficiently employs convolutional neural networks (CNNs) and self-attention mechanisms to automatically acquire a persuasive feature to obtain a prediction score using a nonlinear classifier. The area under the curve, receiver operating characteristic curve, and decision curves were applied to evaluate the prediction model’s performance. Then, Kaplan–Meier survival analyses were applied to evaluate the overall survival (OS) and recurrence-free survival (RFS) in PD-1-positive and PD-1-negative patients. The proposed transformer-based model obtained an accuracy of 88.2% with a sensitivity of 88.5%, a specificity of 88.9%, and an area under the curve of 91.1% in the testing cohort.
Changes in Nucleolin Expression during Malignant Transformation Leading to Ovarian High-Grade Serous Carcinoma
Authors: Paris Elizabeth A. , Bahr Janice M. , Basu Sanjib , Barua Animesh
Published: January 2023

Objective: Ovarian high-grade serous carcinoma (HGSC) is a fatal malignancy of women. Alterations in the expression of nuclear proteins are early steps in malignant transformation; nucleolin is one such protein. Changes in nucleolin expression and circulatory levels during ovarian HGSC development are unknown. The study goal was to determine if tissue and circulatory levels of nucleolin change in response to malignant transformation leading to ovarian HGSC. Methods: Sera, ovaries, and BRCA+ fimbria from healthy subjects, and sera and tumor tissues from patients (n = 10 each), and healthy hens and hens with HGSC were examined in exploratory and prospective studies for nucleolin expression by immunohistochemistry, immunoblotting, gene expression, and immunoassay, and analyzed by analysis of variance (ANOVA). Results: Compared with normal, nucleolin expression was higher in patients and hens with ovarian HGSC and in women with a risk of HGSC (P < 0.05). Compared with normal (1400 + 105 pg/mL, n = 8), serum nucleolin levels were 1.5 and 1.7-fold higher in patients with early- (n = 5) and late-stage (n = 5) HGSC, respectively. Additionally, serum nucleolin levels increased significantly (P < 0.05) prior to the formation of detectable masses. Conclusion: This pilot study concluded that tissue and serum levels of nucleolin increase in association with malignant changes in ovaries and fimbriae leading to ovarian HGSC.
IL-15 Prevents the Development of T-ALL from Aberrant Thymocytes with Impaired DNA Repair Functions and Increased NOTCH1 Activation
Authors: Nandi Madhuparna , Ghosh Amit , Akbari Sara Ali , Bobbala Diwakar , Boucher Marie-Josée , Menendez Alfredo , Hoang Trang , Ilangumaran Subburaj , Ramanathan Sheela
Published: January 2023

We previously reported that NOD.Scid mice lacking interleukin-15 (IL-15), or IL-15 receptor alpha-chain, develop T-acute lymphoblastic leukemia (T-ALL). To understand the mechanisms by which IL-15 signaling controls T-ALL development, we studied the thymocyte developmental events in IL-15-deficient Scid mice from NOD and C57BL/6 genetic backgrounds. Both kinds of mice develop T-ALL characterized by circulating TCR-negative cells expressing CD4, CD8 or both. Analyses of thymocytes in NOD.Scid.Il15−/− mice prior to T-ALL development revealed discernible changes within the CD4−CD8− double-negative (DN) thymocyte developmental stages and increased frequencies of CD4+CD8+ double-positive cells with a high proportion of TCR-negative CD4+ and CD8+ cells. The DN cells also showed elevated expressions of CXCR4 and CD117, molecules implicated in the expansion of DN thymocytes. T-ALL cell lines and primary leukemic cells from IL-15-deficient NOD.Scid and C57BL/6.Scid mice displayed increased NOTCH1 activation that was inhibited by NOTCH1 inhibitors and blockers of the PI3K/AKT pathway. Primary leukemic cells from NOD.Scid.Il15−/− mice survived and expanded when cultured with MS5 thymic stromal cells expressing Delta-like ligand 4 and supplemented with IL-7 and FLT3 ligand. These findings suggest that IL-15 signaling in the thymus controls T-ALL development from aberrant thymocytes with an impaired DNA repair capacity and increased NOTCH1 activation.
Integrating Immunotherapy into Multimodal Treatment of Head and Neck Cancer
Authors: Rao Yuan James , Goodman Joseph F. , Haroun Faysal , Bauman Julie E.
Published: January 2023

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) have a poor prognosis, with a significant risk of progression or death despite multimodal treatment with surgery, chemotherapy, and radiotherapy. Immune checkpoint inhibitors targeting the programmed death receptor-1 (PD1) have dramatically changed the treatment landscape for recurrent/metastatic disease, improving overall survival in both the first- and second-line palliative settings. This success has driven the investigation of treatment strategies incorporating immunotherapy earlier into the multimodal curative-intent or salvage treatment of both locally advanced and recurrent/metastatic HNSCC. This review encompassed the following three subjects, with a focus on recently reported and ongoing clinical trials: (1) the use of neoadjuvant immunotherapy prior to surgery for locally advanced HNSCC, (2) the use of immunochemoradiotherapy for locally advanced head and neck cancers, and (3) novel uses of immunotherapy in the salvage of recurrent/metastatic HNSCC via a combined modality, including reirradiation paradigms. The results of these studies are eagerly awaited to improve patient outcomes in this challenging disease.
A20 as a Potential New Tool in Predicting Recurrence and Patient’s Survival in Oral Squamous Cell Carcinoma
Authors: Spoerl Steffen , Erber Ramona , Gerken Michael , Taxis Juergen , Ludwig Nils , Nieberle Felix , Biermann Niklas , Geppert Carol Immanuel , Ettl Tobias , Hartmann Arndt , Beckhove Philipp , Reichert Torsten E. , Spanier Gerrit , Spoerl Silvia
Published: January 2023

A20, known as a potent inhibitor of NF-κB signaling, has been characterized in numerous clinical as well as preclinical studies. Recently, especially in various malignant diseases, the prognostic and therapeutic relevance of A20 was investigated. In oral squamous cell carcinoma (OSCC) however, the characterization of A20 is uncharted territory. We analyzed a tissue microarray (TMA) of 229 surgically-treated OSCC patients (2003–2013). Immunohistochemical (IHC) stainings were performed for A20 and CD3; additionally, standard haematoxylin-eosin staining was applied. IHC findings were correlated with a comprehensive dataset, comprising clinical and pathohistological information. A20 expression was analyzed in tumor cells as well as in tumor infiltrating lymphocytes (TILs) and correlated with the overall survival (OS) and recurrence-free survival (RFS) using uni- and multivariable Cox regression. The median follow-up time was 10.9 years and the A20 expression was significantly decreased in CD3+ TILs compared to mucosa-infiltrating lymphocytes (MILs). In the Kaplan–Meier analyses, higher A20 expression in TILs was correlated with better OS (p = 0.017) and RFS (p = 0.020). In the multivariable survival analysis, A20 overexpression correlated with improved OS (HR: 0.582; 95% CI 0.388–0.873, p = 0.009) and RFS (HR 0.605; 95% CI 0.411–0.889, p = 0.011). Our results indicate a novel prognostic role for A20 in OSCC. Due to its elevated expression in TILs, further research is highly desirable, which therefore could offer new therapeutic opportunities for patients suffering from OSCC.
Endothelial Dysfunction Syndromes after Allogeneic Stem Cell Transplantation
Authors: Vythoulkas Dionysios , Tsirigotis Panagiotis , Griniezaki Marianna , Konstantellos Ioannis , Lazana Ioanna
Published: January 2023

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only therapy with a curative potential for a variety of malignant and non-malignant diseases. The major limitation of the procedure is the significant morbidity and mortality mainly associated with the development of graft versus host disease (GVHD) as well as with a series of complications related to endothelial injury, such as sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), transplant-associated thrombotic microangiopathy (TA-TMA), etc. Endothelial cells (ECs) are key players in the maintenance of vascular homeostasis and during allo-HSCT are confronted by multiple challenges, such as the toxicity from conditioning, the administration of calcineurin inhibitors, the immunosuppression associated infections, and the donor alloreactivity against host tissues. The early diagnosis of endothelial dysfunction syndromes is of paramount importance for the development of effective prophylactic and therapeutic strategies. There is an urgent need for the better understanding of the pathogenetic mechanisms as well as for the identification of novel biomarkers for the early diagnosis of endothelial damage. This review summarizes the current knowledge on the biology of the endothelial dysfunction syndromes after allo-HSCT, along with the respective therapeutic approaches, and discusses the strengths and weaknesses of possible biomarkers of endothelial damage and dysfunction.
The Evolving Landscape of Leptomeningeal Cancer from Solid Tumors: A Systematic Review of Clinical Trials
Authors: Marenco-Hillembrand Lina , Bamimore Michael A. , Rosado-Philippi Julio , Perdikis Blake , Abarbanel David N. , Quinones-Hinojosa Alfredo , Chaichana Kaisorn L. , Sherman Wendy J.
Published: January 2023

Leptomeningeal carcinomatosis (LMC) is a fatal but uncommon complication occurring in 5–15% of patients with stage IV cancer. Current treatment options are ineffective at managing leptomeningeal spread, with a median overall survival (mOS) of 2–6 months. We aimed to conduct a systematic review of the literature to identify past and future therapies for LMC from solid tumors. Forty-three clinical trials (CTs) published between 1982–2022 were identified. Of these, 35 (81.4%) were non-randomized CTs and 8 (18.6%) were randomized CTs. The majority consisted of phase I (16.3%) and phase II CTs (65.1%). Trials enrolled patients with LMC from various primary histology (n = 23, 57.5%), with one CT evaluating LCM from melanoma (2.4%). A total of 21 trials evaluated a single modality treatment. Among CTs, 23.7% closed due to low accrual. Intraventricular (ITV)/intrathecal (IT) drug delivery was the most common route of administration (n = 22, 51.2%) vs. systemic drug delivery (n = 13, 30.3%). Two clinical trials evaluated the use of craniospinal irradiation for LMC with favorable results. LMC continues to carry a dismal prognosis, and over the years, increments in survival have remained stagnant. A paradigm shift towards targeted systemic therapy with continued standardization of efficacy endpoints will help to shed light on promising treatments.
Classification of Pancreatic Ductal Adenocarcinoma Using MALDI Mass Spectrometry Imaging Combined with Neural Networks
Authors: Kanter Frederic , Lellmann Jan , Thiele Herbert , Kalloger Steve , Schaeffer David F. , Wellmann Axel , Klein Oliver
Published: January 2023

Despite numerous diagnostic and therapeutic advances, pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate, and is the fourth leading cause of cancer death in developing countries. Besides its increasing prevalence, pancreatic malignancies are characterized by poor prognosis. Omics technologies have potential relevance for PDAC assessment but are time-intensive and relatively cost-intensive and limited by tissue heterogeneity. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can obtain spatially distinct peptide-signatures and enables tumor classification within a feasible time with relatively low cost. While MALDI-MSI data sets are inherently large, machine learning methods have the potential to greatly decrease processing time. We present a pilot study investigating the potential of MALDI-MSI in combination with neural networks, for classification of pancreatic ductal adenocarcinoma. Neural-network models were trained to distinguish between pancreatic ductal adenocarcinoma and other pancreatic cancer types. The proposed methods are able to correctly classify the PDAC types with an accuracy of up to 86% and a sensitivity of 82%. This study demonstrates that machine learning tools are able to identify different pancreatic carcinoma from complex MALDI data, enabling fast prediction of large data sets. Our results encourage a more frequent use of MALDI-MSI and machine learning in histopathological studies in the future.
Autoimmune and Metabolic Diseases and the Risk of Early-Onset Colorectal Cancer, a Nationwide Nested Case–Control Study
Authors: Lundqvist Erik , Myrberg Ida Hed , Boman Sol Erika , Saraste Deborah , Weibull Caroline E. , Landerholm Kalle , Haapaniemi Staffan , Martling Anna , Myrelid Pär , Nordenvall Caroline
Published: January 2023

Incidence of early-onset (<50 years) colorectal cancer (EOCRC) is increasing in developed countries. The aim was to investigate autoimmune and metabolic conditions as risk factors for EOCRC. In a nationwide nested case–control study, we included all EOCRC cases in Sweden diagnosed during 2007–2016, together with controls, matched for birth year, sex, and county. Information on exposure of autoimmune or metabolic disease was collected from the National Patient Register and Prescribed Drugs Registry. Hazard ratios (HR) as measures of the association between EOCRC and the exposures were estimated using conditional logistic regression. In total, 2626 EOCRC patients and 15,756 controls were included. A history of metabolic disease nearly doubled the incidence hazard of EOCRC (HR 1.82, 95% CI 1.66–1.99). A sixfold increased incidence hazard of EOCRC (HR 5.98, 95% CI 4.78–7.48) was seen in those with inflammatory bowel disease (IBD), but the risk increment decreased in presence of concomitant metabolic disease (HR 3.65, 95% CI 2.57–5.19). Non-IBD autoimmune disease was not statistically significantly associated with EOCRC. IBD and metabolic disease are risk factors for EOCRC and should be considered in screening guidelines.
Immune-Related Adverse Events of the Gastrointestinal System
Authors: Nicolaides Steven , Boussioutas Alex
Published: January 2023

Immune checkpoint inhibitors (ICI) are a form of immunotherapy that have revolutionized the treatment of a number of cancers. Specifically, they are antibodies targeted against established and emerging immune checkpoints, such as cytotoxic T-cell antigen 4 (CTLA4), programmed cell death ligand 1 (PD-L1) and programmed cell death 1 protein (PD-1) on CD8-positive T cells, which promote the destruction of tumor cells. While the immune checkpoint inhibitors are very effective in the treatment of a number of cancers, their use is limited by serious and in some cases life-threatening immune-related adverse events. While these involve many organs, one of the most prevalent serious adverse events is immune checkpoint inhibitor colitis, occurring in a significant proportion of patients treated with this therapy. In this review, we aim to broadly describe the immune-related adverse events known to occur within the gastrointestinal system and the potential role played by the intestinal microbiome.
Survival of Testicular Pure Teratoma vs. Mixed Germ Cell Tumor Patients in Primary Tumor Specimens across All Stages
Authors: Cano Garcia Cristina , Barletta Francesco , Incesu Reha-Baris , Piccinelli Mattia Luca , Tappero Stefano , Panunzio Andrea , Tian Zhe , Saad Fred , Shariat Shahrokh F. , Antonelli Alessandro , Terrone Carlo , De Cobelli Ottavio , Graefen Markus , Tilki Derya , Briganti Alberto , Wenzel Mike , Banek Severine , Kluth Luis A. , Chun Felix K. H. , Karakiewicz Pierre I.
Published: January 2023

We aimed to test for survival differences between testicular pure teratoma vs. mixed germ cell tumor (GCT) patients in a stage-specific fashion. Pure teratoma and mixed GCT in primary tumor specimens were identified within the Surveillance, Epidemiology, and End Results database (2004–2019). Kaplan–Meier curves depicted five-year overall survival (OS) and subsequently, cumulative incidence plots depicted cancer-specific mortality (CSM) and other-cause mortality (OCM) in a stage-specific fashion. Multivariable competing risks regression (CRR) models were used. Of 9049 patients, 299 (3%) had pure teratoma. In stage I, II and III, five-year OS rates differed between pure teratoma and mixed GCT (stage I: 91.6 vs. 97.2%, p < 0.001; stage II: 100 vs. 95.9%, p < 0.001; stage III: 66.8 vs. 77.8%, p = 0.021). In stage I, survival differences originated from higher OCM (6.4 vs. 1.2%; p < 0.001). Conversely in stage III, survival differences originated from higher CSM (29.4 vs. 19.0%; p = 0.03). In multivariable CRR models, pure teratoma was associated with higher OCM in stage I (Hazard Ratio (HR): 4.83; p < 0.01). Conversely, in stage III, in multivariable CRR models, pure teratoma was associated with higher CSM (HR: 1.92; p = 0.04). In pure teratoma, survival disadvantage in stage I patients relates to OCM. Survival disadvantage in stage III pure teratoma originates from higher CSM.
Prospective Epigenetic Actions of Organo-Sulfur Compounds against Cancer: Perspectives and Molecular Mechanisms
Authors: Shoaib Shoaib , Ansari Mohammad Azam , Ghazwani Mohammed , Hani Umme , Jamous Yahya F. , Alali Zahraa , Wahab Shadma , Ahmad Wasim , Weir Sydney A. , Alomary Mohammad N. , Yusuf Nabiha , Islam Najmul
Published: January 2023

Major epigenetic alterations, such as chromatin modifications, DNA methylation, and miRNA regulation, have gained greater attention and play significant roles in oncogenesis, representing a new paradigm in our understanding of cancer susceptibility. These epigenetic changes, particularly aberrant promoter hypermethylation, abnormal histone acetylation, and miRNA dysregulation, represent a set of epigenetic patterns that contribute to inappropriate gene silencing at every stage of cancer progression. Notably, the cancer epigenome possesses various HDACs and DNMTs, which participate in the histone modifications and DNA methylation. As a result, there is an unmet need for developing the epigenetic inhibitors against HDACs and DNMTs for cancer therapy. To date, several epigenetically active synthetic inhibitors of DNA methyltransferases and histone deacetylases have been developed. However, a growing body of research reports that most of these synthetic inhibitors have significant side effects and a narrow window of specificity for cancer cells. Targeting tumor epigenetics with phytocompounds that have the capacity to modulate abnormal DNA methylation, histone acetylation, and miRNAs expression is one of the evolving strategies for cancer prevention. Encouragingly, there are many bioactive phytochemicals, including organo-sulfur compounds that have been shown to alter the expression of key tumor suppressor genes, oncogenes, and oncogenic miRNAs through modulation of DNA methylation and histones in cancer. In addition to vitamins and microelements, dietary phytochemicals such as sulforaphane, PEITC, BITC, DADS, and allicin are among a growing list of naturally occurring anticancer agents that have been studied as an alternative strategy for cancer treatment and prevention. Moreover, these bioactive organo-sulfur compounds, either alone or in combination with other standard cancer drugs or phytochemicals, showed promising results against many cancers. Here, we particularly summarize and focus on the impact of specific organo-sulfur compounds on DNA methylation and histone modifications through targeting the expression of different DNMTs and HDACs that are of particular interest in cancer therapy and prevention.
Methods to Assess Proliferation of Stimulated Human Lymphocytes In Vitro: A Narrative Review
Authors: Ganesan Nirosha , Ronsmans Steven , Hoet Peter
Published: January 2023

The ability to monitor lymphocyte responses is critical for developing our understanding of the immune response in humans. In the current clinical setting, relying on the metabolic incorporation of [3H] thymidine into cellular DNA via a lymphocyte proliferation test (LPT) is the only method that is routinely performed to determine cell proliferation. However, techniques that measure DNA synthesis with a radioactive material such as [3H] thymidine are intrinsically more sensitive to the different stages of the cell cycle, which could lead to over-analyses and the subsequent inaccurate interpretation of the information provided. With cell proliferation assays, the output should preferably provide a direct and accurate measurement of the number of actively dividing cells, regardless of the stimuli properties or length of exposure. In fact, an ideal technique should have the capacity to measure lymphocyte responses on both a quantitative level, i.e., cumulative magnitude of lymphoproliferative response, and a qualitative level, i.e., phenotypical and functional characterization of stimulated immune cells. There are many LPT alternatives currently available to measure various aspects of cell proliferation. Of the nine techniques discussed, we noted that the majority of these LPT alternatives measure lymphocyte proliferation using flow cytometry. Across some of these alternatives, the covalent labelling of cells with a high fluorescence intensity and low variance with minimal cell toxicity while maximizing the number of detectable cell divisions or magnitude of proliferation was achieved. Herein, we review the performance of these different LPT alternatives and address their compatibility with the [3H] thymidine LPT so as to identify the “best” alternative to the [3H] thymidine LPT.
HGCA2.0: An RNA-Seq Based Webtool for Gene Coexpression Analysis in Homo sapiens
Authors: Zogopoulos Vasileios L. , Malatras Apostolos , Kyriakidis Konstantinos , Charalampous Chrysanthi , Makrygianni Evanthia A. , Duguez Stéphanie , Koutsi Marianna A. , Pouliou Marialena , Vasileiou Christos , Duddy William J. , Agelopoulos Marios , Chrousos George P. , Iconomidou Vassiliki A. , Michalopoulos Ioannis
Published: January 2023

Genes with similar expression patterns in a set of diverse samples may be considered coexpressed. Human Gene Coexpression Analysis 2.0 (HGCA2.0) is a webtool which studies the global coexpression landscape of human genes. The website is based on the hierarchical clustering of 55,431 Homo sapiens genes based on a large-scale coexpression analysis of 3500 GTEx bulk RNA-Seq samples of healthy individuals, which were selected as the best representative samples of each tissue type. HGCA2.0 presents subclades of coexpressed genes to a gene of interest, and performs various built-in gene term enrichment analyses on the coexpressed genes, including gene ontologies, biological pathways, protein families, and diseases, while also being unique in revealing enriched transcription factors driving coexpression. HGCA2.0 has been successful in identifying not only genes with ubiquitous expression patterns, but also tissue-specific genes. Benchmarking showed that HGCA2.0 belongs to the top performing coexpression webtools, as shown by STRING analysis. HGCA2.0 creates working hypotheses for the discovery of gene partners or common biological processes that can be experimentally validated. It offers a simple and intuitive website design and user interface, as well as an API endpoint.
Long-Term Outcome Following Liver Transplantation for Primary Hepatic Tumors—A Single Centre Observational Study over 40 Years
Authors: Leiskau Christoph , Junge Norman , Mutschler Frauke E. , Laue Tobias , Ohlendorf Johanna , Richter Nicolas , Vondran Florian W. R. , Pfister Eva-Doreen , Baumann Ulrich
Published: January 2023

The incidence of pediatric liver tumors in general has been rising over the last years and so is the number of children undergoing liver transplantation for this indication. To contribute to the ongoing improvement of pre- and post-transplant care, we aim to describe outcome and risk factors in our patient cohort. We have compared characteristics and outcome for patients transplanted for hepatoblastoma to other liver malignancies in our center between 1983 and 2022 and analysed influential factors on tumor recurrence and mortality using nominal logistic regression analysis. Of 39 children (16 f) who had transplants for liver malignancy, 31 were diagnosed with hepatoblastoma. The proportion of malignant tumors in the transplant cohort rose from 1.9% (1983–1992) to 9.1% in the current decade (p < 0.0001). Hepatoblastoma patients were transplanted at a younger age and were more likely to have tumor extent beyond the liver. Post-transplant bile flow impairment requiring intervention was significantly higher compared to our total cohort (48 vs. 24%, p > 0.0001). Hearing loss was a common side effect of ototoxic chemotherapy in hepatoblastoma patients (48%). The most common maintenance immunosuppression were mTor-inhibitors. Risk factors for tumor recurrence in patients with hepatoblastoma were higher AFP before transplant (AFPpre-LTX), a low ratio of AFPmax to AFPpre-LTX and salvage transplantation. Liver malignancies represent a rising number of indications for liver transplantation in childhood. Primary tumor resection can spare a liver transplant with all its long-term complications, but in case of tumor recurrence, transplantation might have inferior outcome. The rate of acute biopsy-proven rejections and biliary complications in comparison to our total transplant cohort needs further investigations.
Nutritional Aspects of Juvenile Idiopathic Arthritis: An A to Z for Dietitians
Authors: Grammatikopoulou Maria G. , Gkiouras Konstantinos , Syrmou Vasiliki , Vassilakou Tonia , Simopoulou Theodora , Katsiari Chistina G. , Goulis Dimitrios G. , Bogdanos Dimitrios P.
Published: January 2023

Juvenile idiopathic arthritis (JIA) represents a chronic, autoimmune, rheumatic musculoskeletal disease with a diagnosis before 16 years of age. Chronic arthritis is a common manifestation in all JIA subtypes. The nature of JIA, in combination to its therapy often results in the development of nutrition-, gastrointestinal (GI)- or metabolic-related issues. The most-common therapy-related nutritional issues involve methotrexate (MTX) and glucocorticosteroids (GCC) adverse events. MTX is a folic acid antagonist, thus supplementation with folic acid in required for improving GI side effects and correcting low serum levels. On the other hand, long-term GCC administration is often associated with hyperglycemia, insulin resistance and growth delay. This relationship is further aggravated when more joints are affected and greater doses of GCC are being administered. Apart from stature, body mass index z-scores are also suboptimal in JIA. Other signs of malnutrition include decreased phase angle and muscle mass, especially among patients with polyarthritis JIA. Evidence also points to the existence of an inverse relationship between disease activity and overweight/obesity. Specific dietary patterns, including the anti-inflammatory diet, might confer improvements in selected JIA outcomes, but the level of available research is yet insufficient to draw safe conclusions. The majority of patients exhibit suboptimal vitamin D status; hence, supplementation is recommended. Collectively, the evidence indicates that, due to the age of onset and the complexity of the disease, along with its pharmacotherapy, children with JIA are prone to the development of several nutritional problems, warranting expert monitoring. Vitamin deficiencies, oral and GI-problems limiting dietary intake, faltering growth, overweight and obesity, physical inactivity, or impaired bone health are among the many nutritional issues in JIA requiring dietitian support.
The Key Metabolites in Rice Quality Formation of Conventional japonica Varieties
Authors: Xiong Qiangqiang , Sun Changhui , Wang Runnan , Wang Ruizhi , Wang Xiaoyu , Zhang Yu , Zhu Jinyan
Published: January 2023

To understand differences in the quality of different conventional japonica rice varieties and variations in metabolites related to rice quality, the quality of three conventional japonica varieties was determined, and the metabolites of the milled rice were investigated using nontargeted metabolomics technology. The results showed that the taste value (TV) of Yangda 4Hao (YD4) was significantly higher than that of Yangda 3Hao (YD3) and Huaidao 5Hao (HD5). The protein content (PC) of HD5 was significantly higher than that of YD3 and YD4. PC was significantly negatively correlated with TV. Ninety-one differential metabolites (59 increased and 32 decreased) were identified between YD3 and HD5. A total of 144 differential metabolites (96 upregulated and 48 downregulated) were identified between YD4 and HD5. A total of 114 differential metabolites (40 increased and 74 decreased) were identified between YD3 and YD4. The metabolites with a high correlation to rice quality were mostly involved in the amino acid metabolism pathway. Amino acid metabolites play an important role in the formation of rice quality. The key metabolites in the synthesis and regulation of metabolic pathways are sucrose, levan, and amylose, which are carbohydrates, and L-glutamine, L-aspartic acid, and L-asparagine, which are amino acid metabolites. It can be seen from this study that the metabolites of sucrose, levan, amylose, L-glutamine, L-aspartic acid, and L-asparagine may be the key metabolites in the quality formation of high-quality rice varieties.
Effect of Polar Faces of SiC on the Epitaxial Growth of Graphene: Growth Mechanism and Its Implications for Structural and Electrical Properties
Authors: Pitsch Stefan A. , Sumathi R. Radhakrishnan
Published: January 2023

In this study, epitaxial graphene layers of cm2 sizes were grown on silicon carbide (SiC) substrates by high-temperature sublimation. The behavior of the two crystallographic SiC-polar faces and its effect on the growth mechanism of graphene layers and their properties were investigated. Crystallographic structural differences observed in AFM studies were shown to cause disparities in the electrical conductivity of the grown layers. On the silicon-polar (Si-polar) face of SiC, the graphene formation occurred in spike-like structures that originated orthogonally from atomic steps of the substrate and grew outwards in the form of 2D nucleation with a fairly good surface coverage over time. On the carbon-polar (C-polar) face, a hexagonal structure already formed at the beginning of the growth process. On both polar faces, the known process of step-bunching promoted the formation of nm-scale structural obstacles. Such a step-bunching effect was found to be more pronounced on the C-polar face. These 2D-obstacles account for a low probability of a complete nano-sheet formation, but favor 2D-structures, comparable to graphene nanoribbons. The resulting direction-dependent anisotropic behavior in electrical conductivity measured by four-point probe method mainly depends on the height and spacing between these structural-obstacles. The anisotropy becomes less prudent as and when more graphene layers are synthesized.
COI-Barcoding and Species Delimitation Assessment of Toad-Headed Agamas of the Genus Phrynocephalus (Agamidae, Squamata) Reveal Unrecognized Diversity in Central Eurasia
Authors: Solovyeva Evgeniya N. , Dunayev Evgeniy A. , Nazarov Roman A. , Bondarenko Dmitriy A. , Poyarkov Nikolay A.
Published: January 2023

We provide a diversity assessment of the agamid genus Phrynocephalus Kaup, 1825. We analyze COI mtDNA barcodes from 385 individuals sampled all over Phrynocephalus range. We apply the ABGD, ASAP, bGMYC, mlPTP and hsPTP species delimitation algorithms to analyze the COI gene fragment variation and assess the species diversity in Phrynocephalus. Nine species groups are revealed in Phrynocephalus in agreement with earlier studies on the phylogenetic relationships of the genus. We demonstrate that the present taxonomy likely underestimates the actual diversity of the genus. Alternative species delimitation algorithms provide a confusingly wide range of possible number of Phrynocephalus species—from 54 to 103 MOTUs (molecular operational taxonomic units). The ASAP species delimitation scheme recognizing 63 MOTUs likely most closely fits the currently recognized taxonomic framework of Phrynocephalus. We also report on 13 previously unknown Phrynocephalus lineages as unverified candidate species. We demonstrate that the ASAP and the ABGD algorithms likely most closely reflect the actual diversity of Phrynocephalus, while the mlPTP and hsPTP largely overestimate it. We argue that species delimitation in these lizards based exclusively on mtDNA markers is insufficient, and call for further integrative taxonomic studies joining the data from morphology, mtDNA and nuDNA markers to fully stabilize the taxonomy of Phrynocephalus lizards.
Multidisciplinary Study of the Rybachya Core in the North Caspian Sea during the Holocene
Authors: Berdnikova Alina , Lysenko Elena , Makshaev Radik , Zenina Maria , Yanina Tamara
Published: January 2023

Mollusk fauna is an important component of the Caspian Sea ecosystem alongside ostracods and diatoms. These faunal proxies are essential indicators of hydrological shifts reflecting global and regional climate changes. Adding lithological, geochemical, and geochronological (radiocarbon) data, we revealed paleogeographic events of different scales recorded in the sequence of the Rybachya core from the North Caspian Sea. Here, we present the reconstruction of Mangyshlak paleovalley sediments during the Holocene multi-stage Neocaspian transgression, reflecting global and regional climate changes varying in scale and direction. The determined age of paleovalley-fill sediments, 8070 ± 110 cal yr BP and 7020 ± 140 cal yr BP, suggests that sedimentation processes with extended warming and humidification started later and lasted longer than was assumed earlier. Biological proxies indicate quasi-cyclic variability and shifts from brackish to freshwater conditions throughout the studied interval. Rybachya core was obtained from the early Khvalynian deposits. The Mangyshlak flow formed the depression and eroded the late Khvalynian deposits, which we did not observe in the core structure. It possibly collapsed into paleodepression and acted as a host material for the freshwater lentic faunal association. During the Holocene, we detected a transition from a tranquil water regime to a more dynamic one during the paleovalley gradual filling, followed by marine conditions typical for the modern Caspian Sea.
A New Webbing Aberoptus Species from South Africa Provides Insight in Silk Production in Gall Mites (Eriophyoidea)
Authors: Chetverikov Philipp E. , Craemer Charnie , Gankevich Vladimir D. , Vishnyakov Andrey E. , Zhuk Anna S.
Published: January 2023

Arthropods include a high diversity of lineages adapted for silk production. Several species of microscopic phytophagous mites of the hyperdiverse superfamily Eriophyoidea spin web; however, the origin of their silk is unknown. We described a new web-spinning mite, Aberoptus schotiae n. sp., collected from leaves of Schotia brachypetala (Fabaceae) in South Africa and showed that it has a complex life cycle, including two morphotypes of adults and nymphs. Molecular phylogenetic analyses and 28S sequence comparison showed conspecificity of heteromorphic females and rejected synonymy of Aberoptus and Aceria proposed by previous authors. For the first time, we provided SEM images of the web nests and, using a set of different microscopic techniques, described the silk-producing anal secretory apparatus (ASA) of Aberoptus. It comprises two pairs of anal glands (hypertrophied in web-spinning females), three cuticular sacs and a rectal tube leading to the anal opening. This is a unique case (analogy) of anal silk secretion in Chelicerata previously reported only in Serianus (Pseudoscorpiones). Recent findings of rudimentary ASA in distant eriophyoid lineages and the results of this study transform the current paradigm of exoticism of web-spinning eriophyoid taxa into the concept of synapomorphic specialization of the hindgut for excreting the anal gland secretions in Eriophyoidea.
Effect of Various Mentha sp. Extracts on the Growth of Trichoderma viride and Chaetomium globusom on Agar Medium and Pine Wood
Authors: Betlej Izabela , Andres Bogusław , Krajewski Krzysztof , Kiełtyka-Dadasiewicz Anna , Szadkowska Dominika , Zawadzki Janusz
Published: January 2023

This paper presents the effect of water extracts from the leaves of various Mentha spp. on the growth of selected fungi causing the gray decay of wood. The study determined which of the Mentha spp. extracts used had the best effect on inhibiting the development of fungi on various substrates including pine wood. The best results in the complete inhibition of fungi growth on an agar medium were obtained for the M. × piperita ‘Almira’ extract. Biocidal properties were not achieved on wood samples, although it was noticed that at doses of extracts of 600 g/m2 and higher, the growth of fungi in the initial stages of cultivation was clearly inhibited. Chemical substances in the obtained extracts were characterized by gas chromatography. Oxygen monoterpenes were the dominant group of substances, substances belonging to sesquiterpene hydrocarbons, monoterpene hydrocarbons containing oxygen sesquiterpenes, and one substance belonging to non-terpene hydrocarbons were also identified.
Microbial Community Abundance Affects the Methane Ebullition Flux in Dahejia Reservoir of the Yellow River in the Warm Season
Authors: Wu Yi , Mao Xufeng , Xia Liang , Yu Hongyan , Yu Yao , Tang Wenjia , Xiao Feng , Ji Haichuan
Published: January 2023

Reservoirs are an integral part of the global carbon cycle and generally considered to be methane (CH4) emission hot spots. Although remarkable research achievements have been made concerning CH4 ebullition from inland waters, such as rivers, lakes, and ponds, few have been devoted to CH4 ebullition from plateau reservoirs. The present study focused on CH4 ebullition from the Dahejia Reservoir located in the upper reaches of the Yellow River. We analyzed the spatial and temporal characteristics of CH4 ebullition flux across the water-atmosphere interface between July and August 2021. We also evaluated the influence of microbes on CH4 ebullition flux. The results showed that (1) CH4 ebullition was the dominant mode of CH4 emissions in the study site, which contributed to 78.85 ± 20% of total CH4 flux. (2) The mean CH4 ebullition flux in the nighttime (0.34 ± 0.21 mg m−2 h−1) was significantly higher than that in the daytime (0.19 ± 0.21 mg m−2 h−1). The mean CH4 ebullition flux first decreased and then increased from the upstream (0.52 ± 0.57 mg m−2 h−1) to the downstream (0.43 ± 0.3 mg m−2 h−1) of the Yellow River. (3) Sediment microbes affected the CH4 ebullition flux primarily by changing the microbial community abundance. The regression analysis showed that CH4 ebullition flux had a significantly linear negative correlation with microbial abundance in sediments. The redundancy analysis further showed CH4 ebullition flux was significantly positively correlated with the abundances of Firmicutes and Actinobacteria, and negatively with that of Proteobacteria and Chloroflexi. Among abiotic variables, CH4 ebullition flux was closely related to total phosphorus, total organic carbon, pH and nitrate nitrogen.
Time-Series Analysis of Oxygen as an Important Environmental Parameter for Monitoring Diversity Hotspot Ecosystems: An Example of a River Sinking into the Karst Underground
Authors: Bhattacharyya Saptashwa , Mulec Janez , Oarga-Mulec Andreea
Published: January 2023

Predicting variations in dissolved oxygen concentration (DO) is important for management and environmental monitoring of aquatic ecosystems. Regression analyses and univariate and multivariate time-series analyses based on autoregressive methods were performed to investigate oxygen conditions in the Pivka River, Slovenia. The monitoring site was established upstream where the river sinks into the karst cave Postojnska jama, which hosts one of the richest subterranean faunas yet studied worldwide. It was found that abnormal variations of DO started to be noticeable at values of DO < 3 mg/L and became more pronounced until the ecosystem reached fully anoxic conditions. The abnormal fluctuations during the critical summer period were due to environmental conditions, organic load and resident biota. Predictions for future detection of anomalies in DO values were made from stable residuals of the measured data, and it was demonstrated that the model could be used to obtain a reliable estimate for a short period, such as one day. The example presented an analysis pipeline based on specific and established threshold DO values, and it is particularly important for ecosystems with diversity hotspots where prolonged low DO values can pose a threat to their biota.
Fire Impact on the Formation and Development of the Boreal Pine Wooded Mires
Authors: Goncharova Nadezhda , Dubrovskiy Yuri A. , Miglovets Mikhail , Kutyavin Ivan N. , Dymov Alexey
Published: January 2023

Based on the analysis of the botanical composition of the organic-mineral soil layer and peat, dendrochronological and radiocarbon datings, we performed the reconstruction of the development of six pine wooded sphagnum bogs located in the boreal zone of Russia. Most of the bogs under study followed the endogenesis patterns with the vegetation cover gradually changing, peat layer growing, substrate trophicity declining and shrub-sphagnous vegetation forming under modern conditions. Emerging pyrogenic layers and charcoals in the peat indicate that the study sites were constantly affected by fires, which periodically interrupted the endogenous development of the bogs, especially during the warmest Holocene periods.
A Prospective Study on Diabetic Retinopathy Detection Based on Modify Convolutional Neural Network Using Fundus Images at Sindh Institute of Ophthalmology & Visual Sciences
Authors: Bajwa Awais , Nosheen Neelam , Talpur Khalid Iqbal , Akram Sheeraz
Published: January 2023

Diabetic Retinopathy (DR) is the most common complication that arises due to diabetes, and it affects the retina. It is the leading cause of blindness globally, and early detection can protect patients from losing sight. However, the early detection of Diabetic Retinopathy is an difficult task that needs clinical experts’ interpretation of fundus images. In this study, a deep learning model was trained and validated on a private dataset and tested in real time at the Sindh Institute of Ophthalmology & Visual Sciences (SIOVS). The intelligent model evaluated the quality of the test images. The implemented model classified the test images into DR-Positive and DR-Negative ones. Furthermore, the results were reviewed by clinical experts to assess the model’s performance. A total number of 398 patients, including 232 male and 166 female patients, were screened for five weeks. The model achieves 93.72% accuracy, 97.30% sensitivity, and 92.90% specificity on the test data as labelled by clinical experts on Diabetic Retinopathy.
The Diagnostic Role of FGF 21 in Endometrial Cancer and Other Pathologies of the Uterine Corpus
Authors: Jagodzińska Anna , Chudecka-Głaz Anita , Michalczyk Kaja , Pius-Sadowska Ewa , Wieder-Huszla Sylwia , Jurczak Anna , Machaliński Bogusław
Published: January 2023

Endometrial cancer is becoming an increasing problem. Taking into account its pathomechanisms, we aimed to investigate whether FGF 21, an important metabolism regulator, could be used as a biomarker for endometrial cancer. The study included 233 patients who were classified into five subgroups depending on the result of the histological examination: endometrial carcinomas, sarcomas, endometrial polyps, fibroids, and normal endometrium. Statistically significantly higher FGF 21 levels were found in patients diagnosed with malignant lesions (p < 0.001). FGF 21 concentration correlated with the degree of cellular differentiation (p = 0.020) and the presence of lymph node metastases (p = 0.009). The diagnostic performance characteristics of FGF 21 as an EC diagnostic marker demonstrated an AUC of 0.677. Of all of the assessed biomarkers, FGF 21 had the highest specificity (90%), yet limited sensitivity (41%). Additionally, HE4 and CA 125 were confirmed to have roles as EC biomarkers, with a higher accuracy for HE4 (79% vs. 72%).
Diagnosing Pain in Individuals with Intellectual and Developmental Disabilities: Current State and Novel Technological Solutions
Authors: Lotan Meir , Icht Michal
Published: January 2023

Pain assessment poses a challenge in several groups of clients, yet specific barriers arise when it comes to pain assessment of individuals with intellectual and developmental disabilities (IDD), due mostly to communication challenges preventing valid and reliable self-reports. Despite increased interest in pain assessment of those diagnosed with IDD within recent years, little is known about pain behavior in this group. The present article overviews the current state of pain diagnosis for individuals with IDD, focusing on existing pain assessment scales. In addition, it suggests technological developments offering new ways to diagnose existence of pain in this population, such as a Smartphone App for caregivers based on unique acoustic characteristics of pain-related vocal responses, or the use of smart wearable shirts that enable continuous surveillance of vital physiological signs. Such novel technological solutions may improve diagnosis of pain in the IDD population, as well as in other individuals with complex communication needs, to provide better pain treatment and enhance overall quality of life.