bluuebunny/crossref_metadata_2025 huggingface dataset:
Merkel Cell Carcinoma of the Head and Neck: Epidemiology, Pathogenesis, Current State of Treatment and Future Directions
Authors: Yusuf Mehran Behruj , McKenzie Grant , Rattani Abbas , Tennant Paul , Bumpous Jeffrey , Miller Donald , Dunlap Neal
Published: July 2021

Merkel cell carcinoma (MCC) is a rare, cutaneous neuroendocrine malignancy with increasing incidence. The skin of the head and neck is a common subsite for MCC with distinctions in management from other anatomic areas. Given the rapid pace of developments regarding MCC pathogenesis (Merkel cell polyoma virus (MCPyV)-positive or virus-negative, cell of origin), diagnosis, staging and treatment, and up to date recommendations are critical for optimizing outcomes. This review aims to summarize currently available literature for MCC of the head and neck. The authors reviewed current literature, including international guidelines regarding MCC pathogenesis, epidemiology, diagnosis, staging, and treatment. Subsequently recommendations were derived including the importance of baseline imaging, MCPyV serology testing, primary site surgery, nodal evaluation, radiotherapy, and the increasing role of immune modulating agents in MCC. MCPyV serology testing is increasingly important with potential distinctions in treatment response and surveillance between virus-positive and virus-negative MCC. Surgical management continues to balance optimizing local control with minimal morbidity. Similarly, radiotherapy continues to have importance in the adjuvant, definitive, and palliative setting for MCC of the head and neck. Immunotherapy has changed the paradigm for advanced MCC, with increasing work focusing on optimizing outcomes for non-responders and high-risk patients, including those with immunosuppression.
Real-World Evidence on Palliative Gemcitabine and Oxaliplatin (GemOx) Combination Chemotherapy in Advanced Biliary Tract Cancer
Authors: Lagenfelt Hanna , Blomstrand Hakon , Elander Nils O.
Published: July 2021

Background: Gemcitabine and oxaliplatin (GemOx) is a standard combination regimen in advanced biliary tract cancer (BTC). There is limited evidence on its efficacy and safety in real life. Methods: A retrospective multicentre cohort study in the South East Region of Sweden, covering nine years (2011–2020) and three hospitals where GemOx was treatment of choice, was designed. Clinicopathological prognostic parameters were explored. Results: One hundred and twenty-one patients with advanced BTC were identified. Median overall and progression-free survival (OS and PFS) were 8.9 (95% CI = 7.2–10.6) and 5.3 (95% CI = 3.8–6.7) months. Performance status according to Eastern Cooperative Oncology Group (PS according to ECOG) 1–2 and primary gallbladder carcinoma were independent predictors for poor OS. PS and derived neutrophil/lymphocyte ratio were predictive for PFS. The most common severe type of myelosuppresion was grade 3 neutropenia that was recorded in 8%. Fifty-three (43.8%) experienced at least one episode of unplanned hospitalisation. One hundred and seventeen (97%) received oxaliplatin with lower dosage than was utilized in previous phase III trials (80–85 vs. 100 mg/m2) and a majority received further dose reductions of oxaliplatin and/or gemcitabine. Conclusion: The outcome of GemOx in advanced BTC appears comparable in controlled trials and real-world contexts. A lower dose of oxaliplatin seems more tolerable without compromising the outcome.
Fluorescence-Guided Surgery in the Surgical Treatment of Gliomas: Past, Present and Future
Authors: Sun Rosa , Cuthbert Hadleigh , Watts Colin
Published: July 2021

Gliomas are central nervous systems tumours which are diffusely infiltrative and difficult to treat. The extent of surgical resection is correlated with improved outcomes, including survival and disease-free progression. Cancerous tissue can be directly visualised intra-operatively under fluorescence by administration of 5-aminolevulinic acid to the patient. The adoption of this technique has allowed surgeons worldwide to achieve greater extents of resection, with implications for improved prognosis. However, there are practical limitations to use of 5-aminolevulinic acid. New adjuncts in the field of fluorescence-guided surgery aim to improve recognition of the interface between tumour and brain with the objective of improving resection and patient outcomes.
Serum Cartilage Oligomeric Matrix Protein and Golgi Protein-73: New Diagnostic and Predictive Tools for Liver Fibrosis and Hepatocellular Cancer?
Authors: Gatselis Nikolaos K. , Zachou Kalliopi , Giannoulis George , Gabeta Stella , Norman Gary L. , Dalekos George N.
Published: July 2021

The cartilage oligomeric matrix protein (COMP) and Golgi-protein-73 (GP73) have been proposed as markers of liver fibrosis and hepatocellular carcinoma (HCC). Our aim was to assess the performance of the combination of these markers in diagnosing cirrhosis and predicting HCC development. Sera from 288 consecutive patients with chronic liver diseases were investigated by using COMP and GP73-ELISAs. Dual positivity for COMP (>15 U/L) and GP73 (>20 units) was observed in 24 (8.3%) patients, while 30 (10.4%) were GP73(+)/COMP(−), 37/288 (12.8%) GP73(−)/COMP(+), and 197 (68.5%) GP73(−)/COMP(−). Positivity for both markers was associated with cirrhosis [23/24 (95.8%) for GP73(+)/COMP(+) vs. 22/30 (73.3%) for GP73(+)/COMP(−) vs. 25/37 (67.6%) for GP73(−)/COMP(+) vs. 46/197 (23.4%) for GP73(−)/COMP(−); P < 0.001]. The combination of GP73, COMP, the aspartate aminotransferase/platelets ratio index, and the Fibrosis-4 score had even higher diagnostic accuracy to detect the presence of cirrhosis [AUC (95% CI): 0.916 (0.878–0.946)] or significant liver fibrosis (METAVIR ≥ F2) [AUC (95% CI): 0.832 (0.768–0.883)] than each marker alone. Kaplan-Meier analysis showed that positivity for both GP73 and COMP was associated with higher rates of HCC development (P < 0.001) and liver-related deaths (P < 0.001) during follow-up. In conclusion, the combination of GP73 and COMP seems efficient to detect cirrhosis and predict worse outcomes and the development of HCC in patients with chronic liver diseases.
Expression of Retroelements in Cervical Cancer and Their Interplay with HPV Infection and Host Gene Expression
Authors: Curty Gislaine , Menezes Albert N. , Brant Ayslan C. , de Mulder Rougvie Miguel , Moreira Miguel Ângelo M. , Soares Marcelo A.
Published: July 2021

Retroelements are expressed in diverse types of cancer and are related to tumorigenesis and to cancer progression. We characterized the expression of retroelements in cervical cancer and explored their interplay with HPV infection and their association with expression of neighboring genes. Forty biopsies of invasive cervical carcinoma (squamous cell carcinomas and adenocarcinomas) with genotyped HPV were selected and analyzed for human endogenous retrovirus (HERV) and long interspersed nuclear element 1 (L1) expression through RNA-seq data. We found 8060 retroelements expressed in the samples and a negative correlation of DNA methyltransferase 1 expression with the two most expressed L1 elements. A total of 103 retroelements were found differentially expressed between tumor histological types and between HPV types, including several HERV families (HERV-K, HERV-H, HERV-E, HERV-I and HERV-L). The comparison between HPV mono- and co-infections showed the highest proportion of differentially expressed L1 elements. The location of retroelements affected neighboring gene expression, such as shown for the interleukin-20 gene family. Three HERVs and seven L1 were located close to this gene family and two L1 showed a positive association with IL20RB expression. This study describes the expression of retroelements in cervical cancer and shows their association with HPV status and host gene expression.
Management of Patients with Pancreatic Ductal Adenocarcinoma in the Real-Life Setting: Lessons from the French National Hospital Database
Authors: de la Fouchardière Christelle , Adham Mustapha , Marion-Audibert Anne-Marie , Duclos Antoine , Darcha Claude , Berthelet Olivier , Hervieu Valérie , Artru Pascal , Labrosse Hélène , Fayet Yohan , Ferroud-Plattet Bruno , Aublet-Cuvellier Bruno , Chambon Georges , Baconnier Mathieu , Rebischung Christine , Farsi Fadila , Ray-Coquard Isabelle , Mastier Charles , Ternamian Pierre-Jean , Williet Nicolas , Buc Emmanuel , Walter Thomas , Herr Andrée-Laure
Published: July 2021

Pancreatic ductal adenocarcinoma (PDAC) remains a major public health challenge, and faces disparities and delays in the diagnosis and access to care. Our purposes were to describe the medical path of PDAC patients in the real-life setting and evaluate the overall survival at 1 year. We used the national hospital discharge summaries database system to analyze the management of patients with newly diagnosed PDAC over the year 2016 in Auvergne-Rhône-Alpes region (AuRA) (France). A total of 1872 patients met inclusion criteria corresponding to an incidence of 22.6 per 100,000 person-year. Within the follow-up period, 353 (18.9%) were operated with a curative intent, 743 (39.7%) underwent chemo- and/or radiotherapy, and 776 (41.4%) did not receive any of these treatments. Less than half of patients were operated in a high-volume center, defined by more than 20 PDAC resections performed annually, mainly university hospitals. The 1-year survival rate was 47% in the overall population. This study highlights that a significant number of patients with PDAC are still operated in low-volume centers or do not receive any specific oncological treatment. A detailed analysis of the medical pathways is necessary in order to identify the medical and territorial determinants and their impact on the patient’s outcome.
Targeting PI3K/AKT/mTOR Signaling Pathway in Breast Cancer
Authors: Li Huayi , Prever Lorenzo , Hirsch Emilio , Gulluni Federico
Published: July 2021

Breast cancer is the most frequently diagnosed cancer and the primary cause of cancer death in women worldwide. Although early diagnosis and cancer growth inhibition has significantly improved breast cancer survival rate over the years, there is a current need to develop more effective systemic treatments to prevent metastasis. One of the most commonly altered pathways driving breast cancer cell growth, survival, and motility is the PI3K/AKT/mTOR signaling cascade. In the past 30 years, a great surge of inhibitors targeting these key players has been developed at a rapid pace, leading to effective preclinical studies for cancer therapeutics. However, the central role of PI3K/AKT/mTOR signaling varies among diverse biological processes, suggesting the need for more specific and sophisticated strategies for their use in cancer therapy. In this review, we provide a perspective on the role of the PI3K signaling pathway and the most recently developed PI3K-targeting breast cancer therapies.
HGF/MET Axis Induces Tumor Secretion of Tenascin-C and Promotes Stromal Rewiring in Pancreatic Cancer
Authors: Modica Chiara , Olivero Martina , Zuppini Francesca , Milan Melissa , Basilico Cristina , Vigna Elisa
Published: July 2021

Pancreatic ductal adenocarcinoma is an aggressive tumor characterized by the presence of an abundant stromal compartment contributing significantly to the malignant phenotype. Pancreatic stellate cells are peculiar fibroblasts present in the stroma and represent the predominant source of extracellular matrix proteins, pro-inflammatory cytokines, and growth factors, including hepatocyte growth factor (HGF). Exploiting a co-culture system of human pancreatic stellate cells and cancer cells, we demonstrated that fibroblast activation was reduced upon HGF/MET axis inhibition. To unveil the signaling pathways sustaining stroma modulation orchestrated by MET activation in the tumor, we analyzed the gene expression profile in pancreatic cancer cells stimulated with HGF and treated with HGF/MET inhibitors. Transcriptome analysis showed that, among all the genes modulated by HGF, a subset of 125 genes was restored to the basal level following treatment with the inhibitors. By examining these genes via ingenuity pathway analysis, tenascin C emerged as a promising candidate linking MET signaling and tumor microenvironment. MET-dependent tenascin C modulation in pancreatic cancer cells was validated at RNA and protein levels both in vitro and in vivo. In conclusion, this work identifies tenascin C as a gene modulated by MET activation, suggesting a role in MET-mediated tumor-stroma interplay occurring during pancreatic tumor progression.
Assessment and Prediction of Response to Neoadjuvant Chemotherapy in Breast Cancer: A Comparison of Imaging Modalities and Future Perspectives
Authors: Romeo Valeria , Accardo Giuseppe , Perillo Teresa , Basso Luca , Garbino Nunzia , Nicolai Emanuele , Maurea Simone , Salvatore Marco
Published: July 2021

Neoadjuvant chemotherapy (NAC) is becoming the standard of care for locally advanced breast cancer, aiming to reduce tumor size before surgery. Unfortunately, less than 30% of patients generally achieve a pathological complete response and approximately 5% of patients show disease progression while receiving NAC. Accurate assessment of the response to NAC is crucial for subsequent surgical planning. Furthermore, early prediction of tumor response could avoid patients being overtreated with useless chemotherapy sections, which are not free from side effects and psychological implications. In this review, we first analyze and compare the accuracy of conventional and advanced imaging techniques as well as discuss the application of artificial intelligence tools in the assessment of tumor response after NAC. Thereafter, the role of advanced imaging techniques, such as MRI, nuclear medicine, and new hybrid PET/MRI imaging in the prediction of the response to NAC is described in the second part of the review. Finally, future perspectives in NAC response prediction, represented by AI applications, are discussed.
Resectable Colorectal Cancer: Current Perceptions on the Correlation of Recurrence Risk, Microbiota and Detection of Genetic Mutations in Liquid Biopsies
Authors: Koulouris Andreas , Tsagkaris Christos , Messaritakis Ippokratis , Gouvas Nikolaos , Sfakianaki Maria , Trypaki Maria , Spyrou Vasiliki , Christodoulakis Manousos , Athanasakis Elias , Xynos Evangelos , Tzardi Maria , Mavroudis Dimitrios , Souglakos John
Published: July 2021

Metastatic colorectal cancer (mCRC) remains a highly lethal malignancy, although considerable progress has resulted from molecular alterations in guiding optimal use of available treatments. CRC recurrence remains a great barrier in the disease management. Hence, the spotlight turns to newly mapped fields concerning recurrence risk factors in patients with resectable CRC with a focus on genetic mutations, microbiota remodeling and liquid biopsies. There is an urgent need for novel biomarkers to address disease recurrence since specific genetic signatures can identify a higher or lower recurrence risk (RR) and, thus, be used both as biomarkers and treatment targets. To a large extent, CRC is mediated by the immune and inflammatory interplay of microbiota, through intestinal dysbiosis. Clarification of these mechanisms will yield new opportunities, leading not only to the appropriate stratification policies, but also to more precise, personalized monitoring and treatment navigation. Under this perspective, early detection of post-operative CRC recurrence is of utmost importance. Ongoing trials, focusing on circulating tumor cells (CTCs) and, even more, circulating tumor DNA (ctDNA), seem to pave the way to a promising, minimally invasive but accurate and life-saving monitoring, not only supporting personalized treatment but favoring patients’ quality of life, as well.
Identification and Characterization of Multiple Myeloma Stem Cell-Like Cells
Authors: Guo Wancheng , Wang Haiqin , Chen Peng , Shen Xiaokai , Zhang Boxin , Liu Jing , Peng Hongling , Xiao Xiaojuan
Published: July 2021

Multiple myeloma (MM) is a B-cell tumor of the blood system with high incidence and poor prognosis. With a further understanding of the pathogenesis of MM and the bone marrow microenvironment, a variety of adjuvant cell therapies and new drugs have been developed. However, the drug resistance and high relapse rate of MM have not been fundamentally resolved. Studies have shown that, in patients with MM, there is a type of poorly differentiated progenitor cell (MM stem cell-like cells, MMSCs). Although there is no recognized standard for identification and classification, it is confirmed that they are closely related to the drug resistance and relapse of MM. This article therefore systematically summarizes the latest developments in MMSCs with possible markers of MMSCs, introduces the mechanism of how MMSCs work in MM resistance and recurrence, and discusses the active pathways that related to stemness of MM.
Targeting Immune Modulators in Glioma While Avoiding Autoimmune Conditions
Authors: Bitar Lynn , Schumann Ulrike , König Renate , Zipp Frauke , Schmidt Mirko H. H.
Published: July 2021

Communication signals and signaling pathways are often studied in different physiological systems. However, it has become abundantly clear that the immune system is not self-regulated, but functions in close association with the nervous system. The neural–immune interface is complex; its balance determines cancer progression, as well as autoimmune disorders. Immunotherapy remains a promising approach in the context of glioblastoma multiforme (GBM). The primary obstacle to finding effective therapies is the potent immunosuppression induced by GBM. Anti-inflammatory cytokines, induction of regulatory T cells, and the expression of immune checkpoint molecules are the key mediators for immunosuppression in the tumor microenvironment. Immune checkpoint molecules are ligand–receptor pairs that exert inhibitory or stimulatory effects on immune responses. In the past decade, they have been extensively studied in preclinical and clinical trials in diseases such as cancer or autoimmune diseases in which the immune system has failed to maintain homeostasis. In this review, we will discuss promising immune-modulatory targets that are in the focus of current clinical research in glioblastoma, but are also in the precarious position of potentially becoming starting points for the development of autoimmune diseases like multiple sclerosis.
Predictive and Prognostic Biomarker Identification in a Large Cohort of Androgen Receptor-Positive Salivary Duct Carcinoma Patients Scheduled for Combined Androgen Blockade
Authors: Lassche Gerben , Tada Yuichiro , van Herpen Carla M. L. , Jonker Marianne A. , Nagao Toshitaka , Saotome Takashi , Hirai Hideaki , Saigusa Natsuki , Takahashi Hideaki , Ojiri Hiroya , van Engen-Van Grunsven Adriana C. H. , Schalken Jack A. , Fushimi Chihiro , Verhaegh Gerald W.
Published: July 2021

Patients suffering from recurrent or metastatic (R/M) salivary duct carcinoma (SDC) are often treated with combined androgen blockade (CAB). However, CAB frequently fails, resulting in a worse prognosis. Therefore, biomarkers that can predict treatment failure are urgently needed. mRNA from 76 R/M androgen receptor (AR)-positive SDC patients treated with leuprorelin acetate combined with bicalutamide was extracted from pre-treatment tumor specimens. AR, Notch, MAPK, TGFβ, estrogen receptor (ER), Hedgehog (HH), and PI3K signaling pathway activity scores (PAS) were determined based on the expression levels of target genes. Additionally, 5-alpha reductase type 1 (SRD5A1) expression was determined. These markers were related to clinical benefit (complete/partial response or stable disease ≥6 months) and progression-free and overall survival (PFS/OS). SRD5A1 expression had the highest general predictive value for clinical benefit and positive predictive value (PPV: 85.7%). AR PAS had the highest negative predictive value (NPV: 93.3%). The fitting of a multivariable model led to the identification of SRD5A1, TGFβ, and Notch PAS as the most predictive combination. High AR, high Notch, high ER, low HH PAS, and high SRD5A1 expression were also of prognostic importance regarding PFS and SRD5A1 expression levels for OS. AR, Notch PAS, and SRD5A1 expression have the potential to predict the clinical benefit of CAB treatment in SDC patients. SRD5A1 expression can identify patients that will and AR PAS patients that will not experience clinical benefit (85.7% and 93.3% for PPV and NPV, respectively). The predictive potential of SRD5A1 expression forms a rational basis for including SRD5A1-inhibitors in SDC patients’ treatment.
Pursuing Precision: Receptor Tyrosine Kinase Inhibitors for Treatment of Pediatric Solid Tumors
Authors: Bellantoni Andrew J. , Wagner Lars M.
Published: July 2021

Receptor tyrosine kinases are critical for the growth and proliferation of many different cancers and therefore represent a potential vulnerability that can be therapeutically exploited with small molecule inhibitors. Over forty small molecule inhibitors are currently approved for the treatment of adult solid tumors. Their use has been more limited in pediatric solid tumors, although an increasing number of single-agent and combination studies are now being performed. These agents have been quite successful in certain clinical contexts, such as the treatment of pediatric tumors driven by kinase fusions or activating mutations. By contrast, only modest activity has been observed when inhibitors are used as single agents for solid tumors that do not have genetically defined alterations in the target genes. The absence of predictive biomarkers has limited the wider applicability of these drugs and much work remains to define the appropriate patient population and clinical situation in which receptor tyrosine kinase inhibitors are most beneficial. In this manuscript, we discuss these issues by highlighting past trials and identifying future strategies that may help add precision to the use of these agents for pediatric extracranial solid tumors.
Deregulation of Transcriptional Enhancers in Cancer
Authors: Mirzadeh Azad Fatemeh , Atlasi Yaser
Published: July 2021

Epigenetic regulations can shape a cell’s identity by reversible modifications of the chromatin that ultimately control gene expression in response to internal and external cues. In this review, we first discuss the concept of cell plasticity in cancer, a process that is directly controlled by epigenetic mechanisms, with a particular focus on transcriptional enhancers as the cornerstone of epigenetic regulation. In the second part, we discuss mechanisms of enhancer deregulation in adult stem cells and epithelial-to-mesenchymal transition (EMT), as two paradigms of cell plasticity that are dependent on epigenetic regulation and serve as major sources of tumour heterogeneity. Finally, we review how genetic variations at enhancers and their epigenetic modifiers contribute to tumourigenesis, and we highlight examples of cancer drugs that target epigenetic modifications at enhancers.
Elucidating Synergistic Effects of Different Metal Ratios in Bimetallic Fe/Co-N-C Catalysts for Oxygen Reduction Reaction
Authors: Gollasch Marius , Müller-Hülstede Julia , Schmies Henrike , Schonvogel Dana , Wagner Peter , Dyck Alexander , Wark Michael
Published: July 2021

Lowering or eliminating the noble-metal content in oxygen reduction fuel cell catalysts could propel the large-scale introduction of commercial fuel cell systems. Several noble-metal free catalysts are already under investigation with the metal-nitrogen-carbon (Me-N-C) system being one of the most promising. In this study, a systematic approach to investigate the influence of metal ratios in bimetallic Me-N-C fuel cells oxygen reduction reaction (ORR) catalysts has been taken. Different catalysts with varying ratios of Fe and Co have been synthesized and characterized both physically and electrochemically in terms of activity, selectivity and stability with the addition of an accelerated stress test (AST). The catalysts show different electrochemical properties depending on the metal ratio such as a high electrochemical mass activity with increasing Fe ratio. Properties do not change linearly with the metal ratio, with a Fe/Co ratio of 5:3 showing a higher mass activity with simultaneous higher stability. Selectivity indicators plateau for catalysts with a Co content of 50% metal ratio and less, showing the same values as a monometallic Co catalyst. These findings indicate a deeper relationship between the ratio of different metals and physical and electrochemical properties in bimetallic Me-N-C catalysts.
Effect of Textural Properties and Presence of Co-Cation on NH3-SCR Activity of Cu-Exchanged ZSM-5
Authors: Jabłońska Magdalena , Góra-Marek Kinga , Grilc Miha , Bruzzese Paolo Cleto , Poppitz David , Pyra Kamila , Liebau Michael , Pöppl Andreas , Likozar Blaž , Gläser Roger
Published: July 2021

Comparative studies over micro-/mesoporous Cu-containing zeolites ZSM-5 prepared by top-down treatment involving NaOH, TPAOH or mixture of NaOH/TPAOH (tetrapropylammonium hydroxide) were conducted. The results of the catalytic data revealed the highest activity of the Cu-ZSM-5 catalyst both in the absence and presence of water vapor. The physico-chemical characterization (diffuse reflectance UV-Vis (DR UV-Vis), Fourier transform infrared (FT-IR) spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, temperature-programmed desorption of NOx (TPD-NOx), and microkinetic modeling) results indicated that the microporous structure of ZSM-5 effectively stabilized isolated Cu ion monomers. Besides the attempts targeted to the modification of the textural properties of the parent ZSM-5, in the next approach, we studied the effect of the co-presence of sodium and copper cations in the microporous H-ZSM-5. The presence of co-cation promoted the evolution of [Cu–O–Cu]2+ dimers that bind NOx strongly with the desorption energy barrier of least 80 kJ mol−1. Water presence in the gas phase significantly decreases the rate of ammonia oxidation, while the reaction rates and activation energies of NH3-SCR remain unaffected.
Adsorption Followed by Plasma Assisted Catalytic Conversion of Toluene into CO2 on Hopcalite in an Air Stream
Authors: Sonar Shilpa , Giraudon Jean-Marc , Veerapandian Savita Kaliya Perumal , Lamonier Jean-François , Morent Rino , Löfberg Axel , De Geyter Nathalie
Published: July 2021

The abatement of toluene was studied in a sequential adsorption-plasma catalysis (APC) process. Within this process, Hopcalite was used as bifunctional material: as adsorbent (storage stage) and as catalyst via the oxidation of adsorbed toluene (discharge stage). It was observed that the desorption and oxidation activity of the adsorbed toluene was significantly affected the process variables. In addition, the adsorption time influenced the CO2 selectivity and CO2 yield by changing the interaction between the catalyst and the plasma generated species. At least four APC sequences were performed for each examined condition suggesting that Hopcalite is very stable under plasma exposure during all the sequences. Consequently, these results could contribute to advance the plasma–catalyst system with an optimal VOC oxidation efficiency. The catalytic activity, amount of toluene adsorbed, amount of toluene desorbed and product formation have been quantified by FT-IR. Moreover, the catalyst was characterized by XRD, H2-TPR, N2 adsorption–desorption analysis and XPS. Hopcalite shows a good CO2 selectivity and CO2 yield when the APC process is performed with an adsorption time of 20 min and a plasma treatment with a discharge power of 46 W which leads to a low energy cost of 11.6 kWh·m−3 and energy yields of toluene and CO2 of 0.18 (±0.01) g·kWh−1 and 0.48 (±0.06) g·kWh−1 respectively.
Effect of Temperature, Syngas Space Velocity and Catalyst Stability of Co-Mn/CNT Bimetallic Catalyst on Fischer Tropsch Synthesis Performance
Authors: Akbarzadeh Omid , Alshahateet Solhe F. , Mohd Zabidi Noor Asmawati , Moosavi Seyedehmaryam , Kordijazi Amir , Babadi Arman Amani , Hamizi Nor Aliya , Wahab Yasmin Abdul , Chowdhury Zaira Zaman , Sagadevan Suresh
Published: July 2021

The effect of reaction temperature, syngas space velocity, and catalyst stability on Fischer-Tropsch reaction was investigated using a fixed-bed microreactor. Cobalt and Manganese bimetallic catalysts on carbon nanotubes (CNT) support (Co-Mn/CNT) were synthesized via the strong electrostatic adsorption (SEA) method. For testing the performance of the catalyst, Co-Mn/CNT catalysts with four different manganese percentages (0, 5, 10, 15, and 20%) were synthesized. Synthesized catalysts were then analyzed by TEM, FESEM, atomic absorption spectrometry (AAS), and zeta potential sizer. In this study, the temperature was varied from 200 to 280 °C and syngas space velocity was varied from 0.5 to 4.5 L/g.h. Results showed an increasing reaction temperature from 200 °C to 280 °C with reaction pressure of 20 atm, the Space velocity of 2.5 L/h.g and H2/CO ratio of 2, lead to the rise of CO % conversion from 59.5% to 88.2% and an increase for C5+ selectivity from 83.2% to 85.8%. When compared to the other catalyst formulation, the catalyst sample with 95% cobalt and 5% manganese on CNT support (95Co5Mn/CNT) performed more stable for 48 h on stream.
Renin–Angiotensin–Aldosterone System and Immunomodulation: A State-of-the-Art Review
Authors: Laghlam Driss , Jozwiak Mathieu , Nguyen Lee S.
Published: July 2021

The renin–angiotensin system (RAS) has long been described in the field of cardiovascular physiology as the main player in blood pressure homeostasis. However, other effects have since been described, and include proliferation, fibrosis, and inflammation. To illustrate the immunomodulatory properties of the RAS, we chose three distinct fields in which RAS may play a critical role and be the subject of specific treatments. In oncology, RAS hyperactivation has been associated with tumor migration, survival, cell proliferation, and angiogenesis; preliminary data showed promise of the benefit of RAS blockers in patients treated for certain types of cancer. In intensive care medicine, vasoplegic shock has been associated with severe macro- and microcirculatory imbalance. A relative insufficiency in angiotensin II (AngII) was associated to lethal outcomes and synthetic AngII has been suggested as a specific treatment in these cases. Finally, in solid organ transplantation, both AngI and AngII have been associated with increased rejection events, with a regional specificity in the RAS activity. These elements emphasize the complexity of the direct and indirect interactions of RAS with immunomodulatory pathways and warrant further research in the field.
The Vascular Circadian Clock in Chronic Kidney Disease
Authors: Egstrand Søren , Mace Maria L. , Olgaard Klaus , Lewin Ewa
Published: July 2021

Chronic kidney disease is associated with extremely high cardiovascular mortality. The circadian rhythms (CR) have an impact on vascular function. The disruption of CR causes serious health problems and contributes to the development of cardiovascular diseases. Uremia may affect the master pacemaker of CR in the hypothalamus. A molecular circadian clock is also expressed in peripheral tissues, including the vasculature, where it regulates the different aspects of both vascular physiology and pathophysiology. Here, we address the impact of CKD on the intrinsic circadian clock in the vasculature. The expression of the core circadian clock genes in the aorta is disrupted in CKD. We propose a novel concept of the disruption of the circadian clock system in the vasculature of importance for the pathology of the uremic vasculopathy.
Potential Therapies Targeting Metabolic Pathways in Cancer Stem Cells
Authors: Shen Yao-An , Chen Chang-Cyuan , Chen Bo-Jung , Wu Yu-Ting , Juan Jiun-Ru , Chen Liang-Yun , Teng Yueh-Chun , Wei Yau-Huei
Published: July 2021

Cancer stem cells (CSCs) are heterogeneous cells with stem cell-like properties that are responsible for therapeutic resistance, recurrence, and metastasis, and are the major cause for cancer treatment failure. Since CSCs have distinct metabolic characteristics that plays an important role in cancer development and progression, targeting metabolic pathways of CSCs appears to be a promising therapeutic approach for cancer treatment. Here we classify and discuss the unique metabolisms that CSCs rely on for energy production and survival, including mitochondrial respiration, glycolysis, glutaminolysis, and fatty acid metabolism. Because of metabolic plasticity, CSCs can switch between these metabolisms to acquire energy for tumor progression in different microenvironments compare to the rest of tumor bulk. Thus, we highlight the specific conditions and factors that promote or suppress CSCs properties to portray distinct metabolic phenotypes that attribute to CSCs in common cancers. Identification and characterization of the features in these metabolisms can offer new anticancer opportunities and improve the prognosis of cancer. However, the therapeutic window of metabolic inhibitors used alone or in combination may be rather narrow due to cytotoxicity to normal cells. In this review, we present current findings of potential targets in these four metabolic pathways for the development of more effective and alternative strategies to eradicate CSCs and treat cancer more effectively in the future.
Immune Cells Profiling in ANCA-Associated Vasculitis Patients—Relation to Disease Activity
Authors: Żabińska Marcelina , Kościelska-Kasprzak Katarzyna , Krajewska Joanna , Bartoszek Dorota , Augustyniak-Bartosik Hanna , Krajewska Magdalena
Published: July 2021

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of necrotizing multiorgan autoimmune vasculitides that predominantly affect small blood vessels and are associated with the presence of ANCAs. The aim was to assess regulatory and effector cell populations accompanied by the suPAR biomarker level and link the so-defined immune state to the AAV disease activity. The research involved a multicomponent description of an immune state encompassing a range of B and T cell subsets such as transitional/regulatory B cells (CD19+CD24++CD38++), naïve B cells (CD19+CD24INTCD38INT), Th17 cells, T regulatory cells (CD4+CD25+FoxP3+) and cytotoxic CD4+CD28− cells by flow cytometry. The suPAR plasma level was measured by ELISA. The results indicate that AAV is associated with an increased suPAR plasma level and immune fingerprint characterized by an expansion of Th17 cells and T cells lacking the costimulatory molecule CD28, accompanied by a decrease of regulatory populations (Tregs and transitional B cells) and NK cells. Decreased numbers of regulatory T cells and transitional B cells were shown to be linked to activation of the AAV disease while the increased suPAR plasma level—to AAV-related deterioration of kidney function. The observed immune fingerprint might be a reflection of peripheral tolerance failure responsible for development and progression of ANCA-associated vasculitides.
β-(1→4)-Mannobiose Acts as an Immunostimulatory Molecule in Murine Dendritic Cells by Binding the TLR4/MD-2 Complex
Authors: Cheng Ting-Yu , Lin Yen-Ju , Saburi Wataru , Vieths Stefan , Scheurer Stephan , Schülke Stefan , Toda Masako
Published: July 2021

Some β-mannans, including those in coffee bean and soy, contain a mannose backbone with β-(1→4) bonds. Such mannooligosaccharides could have immunological functions involving direct interaction with immune cells, in addition to acting as prebiotics. This study aimed at assessing the immunological function of mannooligosaccharides with β-(1→4) bond, and elucidating their mechanism of action using bone marrow-derived murine dendritic cells (BMDCs). When BMDCs were stimulated with the mannooligosaccharides, only β-Man-(1→4)-Man significantly induced production of cytokines that included IL-6, IL-10, TNF-α, and IFN-β, and enhanced CD4+ T-cell stimulatory capacity. Use of putative receptor inhibitors revealed the binding of β-Man-(1→4)-Man to TLR4/MD2 complex and involvement with the complement C3a receptor (C3aR) for BMDC activation. Interestingly, β-Man-(1→4)-Man prolonged the production of pro-inflammatory cytokines (IL-6 and TNF-α), but not of the IL-10 anti-inflammatory cytokine during extended culture of BMDCs, associated with high glucose consumption. The results suggest that β-Man-(1→4)-Man is an immunostimulatory molecule, and that the promotion of glycolysis could be involved in the production of pro-inflammatory cytokine in β-Man-(1→4)-Man-stimulated BMDCs. This study could contribute to development of immune-boosting functional foods and a novel vaccine adjuvant.
Butyrate and the Intestinal Epithelium: Modulation of Proliferation and Inflammation in Homeostasis and Disease
Authors: Salvi Pooja S. , Cowles Robert A.
Published: July 2021

The microbial metabolite butyrate serves as a link between the intestinal microbiome and epithelium. The monocarboxylate transporters MCT1 and SMCT1 are the predominant means of butyrate transport from the intestinal lumen to epithelial cytoplasm, where the molecule undergoes rapid β-oxidation to generate cellular fuel. However, not all epithelial cells metabolize butyrate equally. Undifferentiated colonocytes, including neoplastic cells and intestinal stem cells at the epithelial crypt base preferentially utilize glucose over butyrate for cellular fuel. This divergent metabolic conditioning is central to the phenomenon known as “butyrate paradox”, in which butyrate induces contradictory effects on epithelial proliferation in undifferentiated and differentiated colonocytes. There is evidence that accumulation of butyrate in epithelial cells results in histone modification and altered transcriptional activation that halts cell cycle progression. This manifests in the apparent protective effect of butyrate against colonic neoplasia. A corollary to this process is butyrate-induced inhibition of intestinal stem cells. Yet, emerging research has illustrated that the evolution of the crypt, along with butyrate-producing bacteria in the intestine, serve to protect crypt base stem cells from butyrate’s anti-proliferative effects. Butyrate also regulates epithelial inflammation and tolerance to antigens, through production of anti-inflammatory cytokines and induction of tolerogenic dendritic cells. The role of butyrate in the pathogenesis and treatment of intestinal neoplasia, inflammatory bowel disease and malabsorptive states is evolving, and holds promise for the potential translation of butyrate’s cellular function into clinical therapies.
Short-Term Evaluation of Cellular Fate in an Ovine Bone Formation Model
Authors: Markides Hareklea , Foster Nicola C. , McLaren Jane S. , Hopkins Timothy , Black Cameron , Oreffo Richard O. C. , Scammell Brigitte E. , Echevarria Iria , White Lisa J. , El Haj Alicia J.
Published: July 2021

The ovine critical-sized defect model provides a robust preclinical model for testing tissue-engineered constructs for use in the treatment of non-union bone fractures and severe trauma. A critical question in cell-based therapies is understanding the optimal therapeutic cell dose. Key to defining the dose and ensuring successful outcomes is understanding the fate of implanted cells, e.g., viability, bio-distribution and exogenous infiltration post-implantation. This study evaluates such parameters in an ovine critical-sized defect model 2 and 7 days post-implantation. The fate of cell dose and behaviour post-implantation when combined with nanomedicine approaches for multi-model tracking and remote control using external magnetic fields is also addressed. Autologous STRO-4 selected mesenchymal stromal cells (MSCs) were labelled with a fluorescent lipophilic dye (CM-Dil), functionalised magnetic nanoparticles (MNPs) and delivered to the site within a naturally derived bone extracellular matrix (ECM) gel. Encapsulated cells were implanted within a critical-sized defect in an ovine medial femoral condyle and exposed to dynamic gradients of external magnetic fields for 1 h per day. Sheep were sacrificed at 2 and 7 days post-initial surgery where ECM was harvested. STRO-4-positive (STRO-4+) stromal cells expressed osteocalcin and survived within the harvested gels at day 2 and day 7 with a 50% loss at day 2 and a further 45% loss at 7 days. CD45-positive leucocytes were also observed in addition to endogenous stromal cells. No elevation in serum C-reactive protein (CRP) or non-haem iron levels was observed following implantation in groups containing MNPs with or without magnetic field gradients. The current study demonstrates how numbers of therapeutic cells reduce substantially after implantation in the repair site. Cell death is accompanied by enhanced leucocyte invasion, but not by inflammatory blood marker levels. Crucially, a proportion of implanted STRO-4+ stromal cells expressed osteocalcin, which is indicative of osteogenic differentiation. Furthermore, MNP labelling did not alter cell number or result in a further deleterious impact on stromal cells following implantation.
KIR Receptors as Key Regulators of NK Cells Activity in Health and Disease
Authors: Dębska-Zielkowska Joanna , Moszkowska Grażyna , Zieliński Maciej , Zielińska Hanna , Dukat-Mazurek Anna , Trzonkowski Piotr , Stefańska Katarzyna
Published: July 2021

Natural killer (NK) cells are part of the cellular immune response. They target mainly cancer and virally infected cells. To a high extent cytotoxic activity of NK cells is regulated inter alia by signals from killer immunoglobulin-like receptors (KIR). The major histocompatibility complex (MHC) class I molecules are important ligands for KIR receptors. Binding of ligands (such as MHC I) to the KIR receptors has the important role in solid organ or hematopoietic cell transplantation. Of note, the understanding of the relationship between KIR and MHC receptors may contribute to the improvement of transplant results. Donor-recipient matching, which also includes the KIR typing, may improve monitoring, individualize the treatment and allow for predicting possible effects after transplantation, such as the graft-versus-leukemia effect (GvL) or viral re-infection. There are also less evident implications of KIR/MHC matching, such as with pregnancy and cancer. In this review, we present the most relevant literature reports on the importance of the KIR/MHC relationship on NK cell activity and hematopoietic stem cell transplantation (HSCT)/solid organ transplantation (SOT) effects, the risk of allograft rejection, protection against post-transplant cytomegalovirus (CMV) infection, pregnancy complications, cancer and adoptive therapy with NK cells.
The Interactome of the VAP Family of Proteins: An Overview
Authors: James Christina , Kehlenbach Ralph H.
Published: July 2021

Membrane contact sites (MCS) are sites of close apposition of two organelles that help in lipid transport and synthesis, calcium homeostasis and several other biological processes. The VAMP-associated proteins (VAPs) VAPA, VAPB, MOSPD2 and the recently described MOSPD1 and MOSPD3 are tether proteins of MCSs that are mainly found at the endoplasmic reticulum (ER). VAPs interact with various proteins with a motif called FFAT (two phenylalanines in an acidic tract), recruiting the associated organelle to the ER. In addition to the conventional FFAT motif, the recently described FFNT (two phenylalanines in a neutral tract) and phospho-FFAT motifs contribute to the interaction with VAPs. In this review, we summarize and compare the recent interactome studies described for VAPs, including in silico and proximity labeling methods. Collectively, the interaction repertoire of VAPs is very diverse and highlights the complexity of interactions mediated by the different FFAT motifs to the VAPs.
Development of a High-Throughput Low-Cost Approach for Fabricating Fully Drawn Paper-Based Analytical Devices Using Commercial Writing Tools
Authors: Pagkali Varvara , Stavra Eleftheria , Soulis Dionysios , Economou Anastasios
Published: July 2021

This work reports the development and optimization of a rapid and low-cost pen-on-paper plotting approach for the fabrication of paper-based analytical devices (PADs) using commercial writing stationery. The desired fluidic patterns were drawn on the paper substrate with commercial marker pens using an inexpensive computer-controlled x–y plotter. For the fabrication of electrochemical PADs, electrodes were further deposited on the devices using a second x–y plotting step with commercial writing pencils. The effect of the fabrication parameters (type of paper, type of marker pen, type of pencil, plotting speed, number of passes, single- vs. double-sided plotting), the chemical resistance of the plotted devices to different solvents and the structural rigidity to multiple loading cycles were assessed. The analytical utility of these devices is demonstrated through application in optical sensing of total phenols using reflectance calorimetry and in electrochemical sensing of paracetamol and ascorbic acid. The proposed manufacturing approach is simple, low cost, flexible, rapid and fit-for-purpose and enables the fabrication of sub-“one-dollar” PADs with satisfactory mechanical and chemical resistance and good analytical performance.
Strategies for Improving the Sensing Performance of Semiconductor Gas Sensors for High-Performance Formaldehyde Detection: A Review
Authors: Yuan Zhenyu , Yang Chang , Meng Fanli
Published: July 2021

Formaldehyde is a poisonous and harmful gas, which is ubiquitous in our daily life. Long-term exposure to formaldehyde harms human body functions; therefore, it is urgent to fabricate sensors for the real-time monitoring of formaldehyde concentrations. Metal oxide semiconductor (MOS) gas sensors is favored by researchers as a result of their low cost, simple operation and portability. In this paper, the mechanism of formaldehyde detection by gas sensors is introduced, and then the ways of ameliorating the response of gas sensors for formaldehyde detection in recent years are summarized. These methods include the control of the microstructure and morphology of sensing materials, the doping modification of matrix materials, the development of new semiconductor sensing materials, the outfield control strategy and the construction of the filter membrane. These five methods will provide a good prerequisite for the preparation of better performing formaldehyde gas sensors.