bluuebunny/crossref_metadata_2025 huggingface dataset:
Alteration of Metabolites Accumulation in Maize Inbreds Leaf Tissue under Long-Term Water Deficit
Authors: Kravic Natalija , Babic Vojka , Vukadinovic Jelena , Ristic Danijela , Dragicevic Vesna , Mladenovic Drinic Snezana , Andjelkovic Violeta
Published: July 2021

Plants reconfigure their metabolic pathways to cope with water deficit. The aim of this study was to determine the status of the physiological parameters and the content of phenolic acids in the upper most ear leaf of maize inbred lines contrasting in drought tolerance in terms of improved plant productivity e.g., increased grain yield. The experiment was conducted under irrigation and rain-fed conditions. In drought-tolerant lines, the effect of water deficit was reflected through a chlorophyll and nitrogen balance index increase followed by a flavonols index decrease. The opposite trend was noticed in drought susceptible inbreds, with the exception of the anthocyanins index. Moreover, in comparison to irrigation treatment, opposite trends in the correlations between grain yield and physiological parameters found under water deficit conditions indicated the activation of different metabolic pathways in defense against water deficit stress. Concerning phenolic acid content, water deficit caused the reduction of protocatechuic, caffeic, and sinapic acid in all inbreds evaluated. However, the highly pronounced increase of ferulic and especially cinnamic acid content under water deficit conditions indicated possible crucial role of these secondary metabolites in preventing the harmful effects of water deficit stress, which, in turn, might be useful in maize breeding selection for drought tolerance.
Pathological Mechanism of a Constitutively Active Form of Stromal Interaction Molecule 1 in Skeletal Muscle
Authors: Park Ji Hee , Jeong Seung Yeon , Choi Jun Hee , Lee Eun Hui
Published: July 2021

Stromal interaction molecule 1 (STIM1) is the main protein that, along with Orai1, mediates store-operated Ca2+ entry (SOCE) in skeletal muscle. Abnormal SOCE due to mutations in STIM1 is one of the causes of human skeletal muscle diseases. STIM1-R304Q (a constitutively active form of STIM1) has been found in human patients with skeletal muscle phenotypes such as muscle weakness, myalgia, muscle stiffness, and contracture. However, the pathological mechanism(s) of STIM1-R304Q in skeletal muscle have not been well studied. To examine the pathological mechanism(s) of STIM1-R304Q in skeletal muscle, STIM1-R304Q was expressed in mouse primary skeletal myotubes, and the properties of the skeletal myotubes were examined using single-myotube Ca2+ imaging, transmission electron microscopy (TEM), and biochemical approaches. STIM1-R304Q did not interfere with the terminal differentiation of skeletal myoblasts to myotubes and retained the ability of STIM1 to attenuate dihydropyridine receptor (DHPR) activity. STIM1-R304Q induced hyper-SOCE (that exceeded the SOCE by wild-type STIM1) by affecting both the amplitude and the onset rate of SOCE. Unlike that by wild-type STIM1, hyper-SOCE by STIM1-R304Q contributed to a disturbance in Ca2+ distribution between the cytosol and the sarcoplasmic reticulum (SR) (high Ca2+ in the cytosol and low Ca2+ in the SR). Moreover, the hyper-SOCE and the high cytosolic Ca2+ level induced by STIM1-R304Q involve changes in mitochondrial shape. Therefore, a series of these cellular defects induced by STIM1-R304Q could induce deleterious skeletal muscle phenotypes in human patients carrying STIM1-R304Q.
Neutrophil Elastase and Chronic Lung Disease
Authors: Voynow Judith A. , Shinbashi Meagan
Published: July 2021

Neutrophil elastase (NE) is a major inflammatory protease released by neutrophils and is present in the airways of patients with cystic fibrosis (CF), chronic obstructive pulmonary disease, non-CF bronchiectasis, and bronchopulmonary dysplasia. Although NE facilitates leukocyte transmigration to the site of infection and is required for clearance of Gram-negative bacteria, it also activates inflammation when released into the airway milieu in chronic inflammatory airway diseases. NE exposure induces airway remodeling with increased mucin expression and secretion and impaired ciliary motility. NE interrupts epithelial repair by promoting cellular apoptosis and senescence and it activates inflammation directly by increasing cytokine expression and release, and indirectly by triggering extracellular trap release and exosome release, which magnify protease activity and inflammation in the airway. NE inhibits innate immune function by digesting opsonins and opsonin receptors, degrading innate immune proteins such as lactoferrin, and inhibiting macrophage phagocytosis. Importantly, NE-directed therapies have not yet been effective in preventing the pathologic sequelae of NE exposure, but new therapies are being developed that offer both direct antiprotease activity and multifunctional anti-inflammatory properties.
Evidence That Artificial Light at Night Induces Structure-Specific Changes in Brain Plasticity in a Diurnal Bird
Authors: Moaraf Stan , Heiblum Rachel , Okuliarová Monika , Hefetz Abraham , Scharf Inon , Zeman Michal , Barnea Anat
Published: July 2021

We recently reported that artificial light at night (ALAN), at ecologically relevant intensities (1.5, 5 lux), increases cell proliferation in the ventricular zone and recruitment of new neurons in several forebrain regions of female zebra finches (Taeniopygia guttata), along with a decrease of total neuronal densities in some of these regions (indicating possible neuronal death). In the present study, we exposed male zebra finches to the same ALAN intensities, treated them with 5′-bromo-2′-deoxyuridine, quantified cell proliferation and neuronal recruitment in several forebrain regions, and compared them to controls that were kept under dark nights. ALAN increased cell proliferation in the ventricular zone, similar to our previous findings in females. We also found, for the first time, that ALAN increased new neuronal recruitment in HVC and Area X, which are part of the song system in the brain and are male-specific. In other brain regions, such as the medial striatum, nidopallium caudale, and hippocampus, we recorded an increased neuronal recruitment only in the medial striatum (unlike our previous findings in females), and relative to the controls this increase was less prominent than in females. Moreover, the effect of ALAN duration on total neuronal densities in the studied regions varied between the sexes, supporting the suggestion that males are more resilient to ALAN than females. Suppression of nocturnal melatonin levels after ALAN exhibited a light intensity-dependent decrease in males in contrast to females, another indication that males might be less affected by ALAN. Taken together, our study emphasizes the importance of studying both sexes when considering ALAN effects on brain plasticity.
A Thermodynamic Analysis of the Binding Specificity between Four Human PDZ Domains and Eight Host, Viral and Designed Ligands
Authors: Cobos Eva S. , Sánchez Ignacio E. , Chemes Lucía B. , Martinez Jose C. , Murciano-Calles Javier
Published: July 2021

PDZ domains are binding modules mostly involved in cell signaling and cell–cell junctions. These domains are able to recognize a wide variety of natural targets and, among the PDZ partners, viruses have been discovered to interact with their host via a PDZ domain. With such an array of relevant and diverse interactions, PDZ binding specificity has been thoroughly studied and a traditional classification has grouped PDZ domains in three major specificity classes. In this work, we have selected four human PDZ domains covering the three canonical specificity-class binding mode and a set of their corresponding binders, including host/natural, viral and designed PDZ motifs. Through calorimetric techniques, we have covered the entire cross interactions between the selected PDZ domains and partners. The results indicate a rather basic specificity in each PDZ domain, with two of the domains that bind their cognate and some non-cognate ligands and the two other domains that basically bind their cognate partners. On the other hand, the host partners mostly bind their corresponding PDZ domain and, interestingly, the viral ligands are able to bind most of the studied PDZ domains, even those not previously described. Some viruses may have evolved to use of the ability of the PDZ fold to bind multiple targets, with resulting affinities for the virus–host interactions that are, in some cases, higher than for host–host interactions.
Platforms for Production of Protein-Based Vaccines: From Classical to Next-Generation Strategies
Authors: Cid Raquel , Bolívar Jorge
Published: July 2021

To date, vaccination has become one of the most effective strategies to control and reduce infectious diseases, preventing millions of deaths worldwide. The earliest vaccines were developed as live-attenuated or inactivated pathogens, and, although they still represent the most extended human vaccine types, they also face some issues, such as the potential to revert to a pathogenic form of live-attenuated formulations or the weaker immune response associated with inactivated vaccines. Advances in genetic engineering have enabled improvements in vaccine design and strategies, such as recombinant subunit vaccines, have emerged, expanding the number of diseases that can be prevented. Moreover, antigen display systems such as VLPs or those designed by nanotechnology have improved the efficacy of subunit vaccines. Platforms for the production of recombinant vaccines have also evolved from the first hosts, Escherichia coli and Saccharomyces cerevisiae, to insect or mammalian cells. Traditional bacterial and yeast systems have been improved by engineering and new systems based on plants or insect larvae have emerged as alternative, low-cost platforms. Vaccine development is still time-consuming and costly, and alternative systems that can offer cost-effective and faster processes are demanding to address infectious diseases that still do not have a treatment and to face possible future pandemics.
Heart Rate Variability Analyses in Parkinson’s Disease: A Systematic Review and Meta-Analysis
Authors: Heimrich Konstantin G. , Lehmann Thomas , Schlattmann Peter , Prell Tino
Published: July 2021

Recent evidence suggests that the vagus nerve and autonomic dysfunction play an important role in the pathogenesis of Parkinson’s disease. Using heart rate variability analysis, the autonomic modulation of cardiac activity can be investigated. This meta-analysis aims to assess if analysis of heart rate variability may indicate decreased parasympathetic tone in patients with Parkinson’s disease. The MEDLINE, EMBASE and Cochrane Central databases were searched on 31 December 2020. Studies were included if they: (1) were published in English, (2) analyzed idiopathic Parkinson’s disease and healthy adult controls, and (3) reported at least one frequency- or time-domain heart rate variability analysis parameter, which represents parasympathetic regulation. We included 47 studies with 2772 subjects. Random-effects meta-analyses revealed significantly decreased effect sizes in Parkinson patients for the high-frequency spectral component (HFms2) and the short-term measurement of the root mean square of successive normal-to-normal interval differences (RMSSD). However, heterogeneity was high, and there was evidence for publication bias regarding HFms2. There is some evidence that a more advanced disease leads to an impaired parasympathetic regulation. In conclusion, short-term measurement of RMSSD is a reliable parameter to assess parasympathetically impaired cardiac modulation in Parkinson patients. The measurement should be performed with a predefined respiratory rate.
Assessment of Knowledge, Attitudes, and Practices Regarding Dengue among Physicians: A Web-Based Cross-Sectional Survey
Authors: Koonisetty Kranthi Swaroop , Aghamohammadi Nasrin , Urmi Tamanna , Yavaşoglu Sare İlknur , Rahman Md. Shahinur , Nandy Rajesh , Haque Ubydul
Published: July 2021

Dengue fever is one of the most important viral infections transmitted by Aedes mosquitoes and a major cause of morbidity and mortality globally. Accurate identification of cases and treatment of dengue patients at the early stages can reduce medical complications and dengue mortality rate. This survey aims to determine the knowledge, attitude, and practices (KAP) among physicians in dengue diagnosis and treatment. This study was conducted among physicians in Turkey as one nonendemic country and Bangladesh, India, and Malaysia as three dengue-endemic countries. The dosing frequencies, maximum doses, and contraindications in dengue fever were examined. The results found that physicians from Bangladesh, India, and Malaysia have higher KAP scores in dengue diagnosis and treatment compared to physicians in Turkey. This may be due to a lack of physician’s exposure to a dengue patient as Turkey is considered a nonendemic country. This assessment may help establish a guideline for intervention strategies among physicians to have successful treatment outcomes and reduce dengue mortality.
Analyzing Predictors of Control Measures and Psychosocial Problems Associated with COVID-19 Pandemic: Evidence from Eight Countries
Authors: Jony Sheikh Saifur Rahman , Haque Ubydul , Webb Nathaniel J. , Spence Emily , Rahman Md. Siddikur , Aghamohammadi Nasrin , Lie Yongchan , Angulo-Molina Aracely , Ananth Sushmitha , Ren Xuelian , Kawachi Nobuyuki , Ito Hiromu , Ulvi Osman , Lubinda Jailos , Karamehic-Muratovic Ajlina , Maher Wasim , Ali Parveen , Rahman M. Sohel
Published: July 2021

COVID-19 has harshly impacted communities globally. This study provides relevant information for creating equitable policy interventions to combat the spread of COVID-19. This study aims to predict the knowledge, attitude, and practice (KAP) of the COVID-19 pandemic at a global level to determine control measures and psychosocial problems. A cross-sectional survey was conducted from July to October 2020 using an online questionnaire. Questionnaires were initially distributed to academicians worldwide. These participants distributed the survey among their social, professional, and personal groups. Responses were collected and analyzed from 67 countries, with a sample size of 3031. Finally, based on the number of respondents, eight countries, including Bangladesh, China, Japan, Malaysia, Mexico, Pakistan, the United States, and Zambia were rigorously analyzed. Specifically, questionnaire responses related to COVID-19 accessibility, behavior, knowledge, opinion, psychological health, and susceptibility were collected and analyzed. As per our analysis, age groups were found to be a primary determinant of behavior, knowledge, opinion, psychological health, and susceptibility scores. Gender was the second most influential determinant for all metrics except information about COVID-19 accessibility, for which education was the second most important determinant. Respondent profession was the third most important metric for all scores. Our findings suggest that health authorities must promote health educations, implement related policies to disseminate COVID-19-awareness that can prevent and control the spread of COVID-19 infection.
Natural History of Untreated Retinoblastoma
Authors: Zhao Junyang , Feng Zhaoxun , Gallie Brenda L.
Published: July 2021

Treatment abandonment is a leading cause of death in children with retinoblastoma worldwide. We studied children who abandoned treatment upfront at diagnosis to delineate the natural history of untreated retinoblastoma. Studied were children who received no treatment, diagnosed between 2007 and 2017 at 29 Chinese centers. Data were retrospectively collected from medical chart reviews and interviews with each patient’s family. During the study period, 44 children received no treatment after diagnosis of retinoblastoma. Clinical or radiologic evidence of orbital extension was available for 25 children, and radiologic evidence of systemic metastasis was available for 12 children. Median times from diagnosis of intraocular tumor to orbital disease was 13.7 months, orbital disease to metastasis was 2.6 months, and metastasis to death was 2.0 months. Children with brain metastasis had shorter survival than those with metastasis to other sites (median 1.0 vs. 3.1 months; p = 0.015). Overall, 36% of patients died within 12 months of diagnosis, 77% within 24 months, 95% within 36 months and 100% within 48 months. While multiple factors influence refusal of treatment, insights into the natural history of retinoblastoma derived from real-world evidence can inform clinicians and parents that retinoblastoma is life-threatening and encourage urgent treatment at diagnosis.
MicroRNAs as a Potential New Preventive Approach in the Transition from Asymptomatic to Symptomatic Multiple Myeloma Disease
Authors: Desantis Vanessa , Solimando Antonio Giovanni , Saltarella Ilaria , Sacco Antonio , Giustini Viviana , Bento Marta , Lamanuzzi Aurelia , Melaccio Assunta , Frassanito Maria Antonia , Paradiso Angelo , Montagnani Monica , Vacca Angelo , Roccaro Aldo M.
Published: July 2021

Multiple myeloma (MM) is a hematological malignancy characterised by proliferation of clonal plasma cells (PCs) within the bone marrow (BM). Myelomagenesis is a multi-step process which goes from an asymptomatic phase, defined as monoclonal gammopathy of undetermined significance (MGUS), to a smouldering myeloma (SMM) stage, to a final active MM disease, characterised by hypercalcemia, renal failure, bone lesions anemia, and higher risk of infections. Overall, microRNAs (miRNAs) have shown to significantly impact on MM tumorigenesis, as a result of miRNA-dependent modulation of genes involved in pathways known to be crucial for MM pathogenesis and disease progression. We aim to revise the literature related to the role of miRNAs as potential diagnostic and prognostic biomarkers, thus highlighting their key role as novel players within the field of MM and related premalignant conditions.
Immune Checkpoint Inhibition in Advanced Non-Clear Cell Renal Cell Carcinoma: Leveraging Success from Clear Cell Histology into New Opportunities
Authors: Zarrabi Kevin , Walzer Emily , Zibelman Matthew
Published: July 2021

Renal cell carcinoma (RCC) is a histologically heterogeneous disease with multiple subtypes. Clear cell RCC (ccRCC) represents the most common histology and has thus been easiest to study in clinical trials. Non-clear cell RCC (nccRCC) represents about 25% of RCC tumors, with fewer treatment options available, compared to ccRCC, and with poorer outcomes. Non-clear cell RCC tumors are histologically diverse, with each subtype having distinct molecular and clinical characteristics. Our understanding of nccRCC is evolving, with a gradual shift from treating nccRCC as a single entity to approaching each subtype as its own disease with unique features. Due to the scarcity of patients for study development, trials have predominantly combined all nccRCC subtypes and re-purposed drugs already approved for ccRCC, despite the decreased efficacy. We are now in the early stages of a potential paradigm shift in the treatment of nccRCC, with a rapid development of clinical studies with a focus on this subset of tumors. Investigators have launched trials focused on the molecular drivers of tumorigenesis using targeted therapies. Harboring the immunogenicity of some nccRCC subtypes, and based on promising retrospective studies, clinicians have also devised multiple trials using immune checkpoint inhibitors (ICIs), both alone or in combination with targeted therapies, for nccRCC subtypes. We highlight the promising completed and ongoing studies employing ICIs that will likely continue to improve outcomes in patients with nccRCC and propose future potential immunotherapeutic avenues.
Metastasis, an Example of Evolvability
Authors: Laruelle Annick , Manini Claudia , Iñarra Elena , López José I.
Published: July 2021

This overview focuses on two different perspectives to analyze the metastatic process taking clear cell renal cell carcinoma as a model, molecular and ecological. On the one hand, genomic analyses have demonstrated up to seven different constrained routes of tumor evolution and two different metastatic patterns. On the other hand, game theory applied to cell encounters within a tumor provides a sociological perspective of the possible behaviors of individuals (cells) in a collectivity. This combined approach provides a more comprehensive understanding of the complex rules governing a neoplasm.
Pleuropneumonectomy as Salvage Therapy in Children Suffering from Primary or Metastatic Sarcomas with Pleural Localizations
Authors: Hameury Frédéric , Marec-Berard Perrine , Eymery Mathilde , Wijnen Marc H. W. , van der Kaaij Niels , Mure Pierre-Yves , Tronc François , Chotel Franck , Libbrecht Clara , van Boven Wim Jan P. , Haveman Lianne M.
Published: July 2021

Pediatric sarcoma patients with pleuropulmonary lesions have a dismal prognosis because the impossibility to obtain local control. The aim of this study was to determine if pleuropneumonectomy (PP) could be a therapeutic option. We retrospectively reviewed nine patients who underwent salvage PP for pleuropulmonary localization of primary localized sarcoma or metastatic recurrence. Surgery and complications were analyzed, pulmonary function tests were conducted, and quality of life was determined with EORTC-QLQ-C30 questionnaire. At the time of PP age was between 9–17 years. Underlying disease included metastatic osteosarcoma (n = 5), Ewing sarcoma (two metastatic, one primary), and one primary undifferentiated sarcoma. Early complications occurred in three patients. Mean postoperative hospitalization stay was 14.5 days. Pulmonary function test showed 19–66% reduction of total lung capacity which led to mild exercise intolerance but did not affect daily life. Four patients died of multi-metastatic relapse <14 months after PP, one patient had a local recurrence, and four patients are in complete remission between 1.5 and 12 years after PP. In conclusion, in this small patient group treated with a pleuropneumonectomy for primary or metastatic lesions, outcome is variable; however, this extended surgical technique was generally quite well tolerated. Postoperative lung function seems well preserved, and it seems to lead to at least an extension of life with good quality and therefor can be considered as salvage therapy.
The Small-Molecule Inhibitor MRIA9 Reveals Novel Insights into the Cell Cycle Roles of SIK2 in Ovarian Cancer Cells
Authors: Raab Monika , Rak Marcel , Tesch Roberta , Gasimli Khayal , Becker Sven , Knapp Stefan , Strebhardt Klaus , Sanhaji Mourad
Published: July 2021

The activity of the Salt inducible kinase 2 (SIK2), a member of the AMP-activated protein kinase (AMPK)-related kinase family, has been linked to several biological processes that maintain cellular and energetic homeostasis. SIK2 is overexpressed in several cancers, including ovarian cancer, where it promotes the proliferation of metastases. Furthermore, as a centrosome kinase, SIK2 has been shown to regulate the G2/M transition, and its depletion sensitizes ovarian cancer to paclitaxel-based chemotherapy. Here, we report the consequences of SIK2 inhibition on mitosis and synergies with paclitaxel in ovarian cancer using a novel and selective inhibitor, MRIA9. We show that MRIA9-induced inhibition of SIK2 blocks the centrosome disjunction, impairs the centrosome alignment, and causes spindle mispositioning during mitosis. Furthermore, the inhibition of SIK2 using MRIA9 increases chromosomal instability, revealing the role of SIK2 in maintaining genomic stability. Finally, MRIA9 treatment enhances the sensitivity to paclitaxel in 3D-spheroids derived from ovarian cancer cell lines and ovarian cancer patients. Our study suggests selective targeting of SIK2 in ovarian cancer as a therapeutic strategy for overcoming paclitaxel resistance.
Diagnosis and Treatment of Prostate Adenocarcinoma
Authors: Kimura Shoji , Kimura Takahiro
Published: July 2021

Prostate cancer is the second most common cancer and the fifth leading cause of cancer-related death among men worldwide [...]
The Presence of Small Nerve Fibers in the Tumor Microenvironment as Predictive Biomarker of Oncological Outcome Following Partial Hepatectomy for Intrahepatic Cholangiocarcinoma
Authors: Bednarsch Jan , Tan Xiuxiang , Czigany Zoltan , Liu Dong , Lang Sven Arke , Sivakumar Shivan , Kather Jakob Nikolas , Appinger Simone , Rosin Mika , Boroojerdi Shiva , Dahl Edgar , Gaisa Nadine Therese , den Dulk Marcel , Coolsen Mariëlle , Ulmer Tom Florian , Neumann Ulf Peter , Heij Lara Rosaline
Published: July 2021

The oncological role of the density of nerve fibers (NFs) in the tumor microenvironment (TME) in intrahepatic cholangiocarcinoma (iCCA) remains to be determined. Therefore, data of 95 iCCA patients who underwent hepatectomy between 2010 and 2019 was analyzed regarding NFs and long-term outcome. Extensive group comparisons were carried out and the association of cancer-specific survival (CSS) and recurrence-free survival (RFS) with NFs were assessed using Cox regression models. Patients with iCCA and NFs showed a median CSS of 51 months (5-year-CSS = 47%) compared to 27 months (5-year-CSS = 21%) in patients without NFs (p = 0.043 log rank). Further, NFs (hazard ratio (HR) = 0.39, p = 0.002) and N-category (HR = 2.36, p = 0.010) were identified as independent predictors of CSS. Patients with NFs and without nodal metastases displayed a mean CSS of 89 months (5-year-CSS = 62%), while patients without NFs or with nodal metastases but not both showed a median CCS of 27 months (5-year-CSS = 25%) and patients with both positive lymph nodes and without NFs showed a median CCS of 10 months (5-year-CSS = 0%, p = 0.001 log rank). NFs in the TME are, therefore, a novel and important prognostic biomarker in iCCA patients. NFs alone and in combination with nodal status is suitable to identify iCCA patients at risk of poor oncological outcomes following curative-intent surgery.
Fracture Risk of Long Bone Metastases: A Review of Current and New Decision-Making Tools for Prophylactic Surgery
Authors: Nguyễn Mỹ-Vân , Carlier Christophe , Nich Christophe , Gouin François , Crenn Vincent
Published: July 2021

Long bone pathological fractures very much reflect bone metastases morbidity in many types of cancer. Bearing in mind that they not only compromise patient function but also survival, identifying impending fractures before the actual event is one of the main concerns for tumor boards. Indeed, timely prophylactic surgery has been demonstrated to increase patient quality of life as well as survival. However, early surgery for long bone metastases remains controversial as the current fracture risk assessment tools lack accuracy. This review first focuses on the gold standard Mirels rating system. It then explores other unique imaging thresholds such as axial or circumferential cortical involvement and the merits of nuclear imaging tools. To overcome the lack of specificity, other fracture prediction strategies have focused on biomechanical models based on quantitative computed tomography (CT): computed tomography rigidity analysis (CT-RA) and finite element analysis (CT-FEA). Despite their higher specificities in impending fracture assessment, their limited availability, along with a need for standardization, have limited their use in everyday practice. Currently, the prediction of long bone pathologic fractures is a multifactorial process. In this regard, machine learning could potentially be of value by taking into account clinical survival prediction as well as clinical and improved CT-RA/FEA data.
Role of Oncogenic Pathways on the Cancer Immunosuppressive Microenvironment and Its Clinical Implications in Hepatocellular Carcinoma
Authors: Nishida Naoshi
Published: July 2021

The tumor immune microenvironment, including hepatocellular carcinoma (HCC), is complex, consisting of crosstalk among tumor components such as the cancer cells, stromal cells and immune cells. It is conceivable that phenotypic changes in cancer cells by genetic and epigenetic alterations affect the cancer–stroma interaction and anti-cancer immunity through the expression of immune checkpoint molecules, growth factors, cytokines, chemokines and metabolites that may act on the immune system in tumors. Therefore, predicting the outcome of ICI therapy requires a thorough understanding of the oncogenic signaling pathways in cancer and how they affect tumor immune evasion. In this review, we have detailed how oncogenic signaling pathways can play a role in altering the condition of the cellular components of the tumor immune microenvironment such as tumor-associated macrophages, regulatory T cells and myeloid-derived suppressor cells. The RAS/MAPK, PI3K/Akt, Wnt/β-catenin and JAK/STAT pathways have all been implicated in anti-tumor immunity. We also found that factors that reflect the immune microenvironment of the tumor, including the status of oncogenic pathways such as the volume of tumor-infiltrating T cells, expression of the immune checkpoint protein PD-1 and its ligand PD-L1, and activation of the Wnt/β-catenin signaling pathway, predict a response to ICI therapy in HCC cases.
DC-Derived Exosomes for Cancer Immunotherapy
Authors: Yao Yi , Fu Chunmei , Zhou Li , Mi Qing-Sheng , Jiang Aimin
Published: July 2021

As the initiators of adaptive immune responses, DCs play a central role in regulating the balance between CD8 T cell immunity versus tolerance to tumor antigens. Exploiting their function to potentiate host anti-tumor immunity, DC-based vaccines have been one of most promising and widely used cancer immunotherapies. However, DC-based cancer vaccines have not achieved the promised success in clinical trials, with one of the major obstacles being tumor-mediated immunosuppression. A recent discovery on the critical role of type 1 conventional DCs (cDC1s) play in cross-priming tumor-specific CD8 T cells and determining the anti-tumor efficacy of cancer immunotherapies, however, has highlighted the need to further develop and refine DC-based vaccines either as monotherapies or in combination with other therapies. DC-derived exosomes (DCexos) have been heralded as a promising alternative to DC-based vaccines, as DCexos are more resistance to tumor-mediated suppression and DCexo vaccines have exhibited better anti-tumor efficacy in pre-clinical animal models. However, DCexo vaccines have only achieved limited clinical efficacy and failed to induce tumor-specific T cell responses in clinical trials. The lack of clinical efficacy might be partly due to the fact that all current clinical trials used peptide-loaded DCexos from monocyte-derived DCs. In this review, we will focus on the perspective of expanding current DCexo research to move DCexo cancer vaccines forward clinically to realize their potential in cancer immunotherapy.
Anti-Angiogenic Treatments Interact with Steroid Secretion in Inflammatory Breast Cancer Triple Negative Cell Lines
Authors: Alonso-Diez Ángela , Cáceres Sara , Peña Laura , Crespo Belén , Illera Juan Carlos
Published: July 2021

Human inflammatory breast cancer (IBC) is a highly angiogenic disease for which antiangiogenic therapy has demonstrated only a modest response, and the reason for this remains unknown. Thus, the purpose of this study was to determine the influence of different antiangiogenic therapies on in vitro and in vivo steroid hormone and angiogenic growth factor production using canine and human inflammatory breast carcinoma cell lines as well as the possible involvement of sex steroid hormones in angiogenesis. IPC-366 and SUM149 cell lines and xenotransplanted mice were treated with different concentrations of VEGF, SU5416, bevacizumab and celecoxib. Steroid hormone (progesterone, dehydroepiandrostenedione, androstenedione, testosterone, dihydrotestosterone, estrone sulphate and 17β-oestradiol), angiogenic growth factors (VEGF-A, VEGF-C and VEGF-D) and IL-8 determinations in culture media, tumour homogenate and serum samples were assayed by EIA. In vitro, progesterone- and 17β-oestradiol-induced VEGF production promoting cell proliferation and androgens are involved in the formation of vascular-like structures. In vivo, intratumoural testosterone concentrations were augmented and possibly associated with decreased metastatic rates, whereas elevated E1SO4 concentrations could promote tumour progression after antiangiogenic therapies. In conclusion, sex steroid hormones could regulate the production of angiogenic factors. The intratumoural measurement of sex steroids and growth factors may be useful to develop preventive and individualized therapeutic strategies.
The Promotor and Poison Effects of the Inorganic Elements of Kraft Lignin during Hydrotreatment over NiMoS Catalyst
Authors: Sebastian Joby , Cheah You Wayne , Bernin Diana , Creaser Derek , Olsson Louise
Published: July 2021

One-pot deoxygenation of kraft lignin to aromatics and hydrocarbons of fuel-range quality is a promising way to improve its added value. Since most of the commercially resourced kraft lignins are impure (Na, S, K, Ca, etc., present as impurities), the effect of these impurities on the deoxygenation activity of a catalyst is critical and was scrutinized in this study using a NiMoS/Al2O3 catalyst. The removal of impurities from the lignin indicated that they obstructed the depolymerization. In addition, they deposited on the catalyst during depolymerization, of which the major element was the alkali metal Na which existed in kraft lignin as Na2S and single-site ionic Na+. Conditional experiments have shown that at lower loadings of impurities on the catalyst, their promotor effect was prevalent, and at their higher loadings, a poisoning effect. The number of moles of impurities, their strength, and the synergism among the impurity elements on the catalyst were the major critical factors responsible for the catalyst’s deactivation. The promotor effects of deposited impurities on the catalyst, however, could counteract the negative effects of impurities on the depolymerization.
Role of Transglutaminase 2 in Cell Death, Survival, and Fibrosis
Authors: Tatsukawa Hideki , Hitomi Kiyotaka
Published: July 2021

Transglutaminase 2 (TG2) is a ubiquitously expressed enzyme catalyzing the crosslinking between Gln and Lys residues and involved in various pathophysiological events. Besides this crosslinking activity, TG2 functions as a deamidase, GTPase, isopeptidase, adapter/scaffold, protein disulfide isomerase, and kinase. It also plays a role in the regulation of hypusination and serotonylation. Through these activities, TG2 is involved in cell growth, differentiation, cell death, inflammation, tissue repair, and fibrosis. Depending on the cell type and stimulus, TG2 changes its subcellular localization and biological activity, leading to cell death or survival. In normal unstressed cells, intracellular TG2 exhibits a GTP-bound closed conformation, exerting prosurvival functions. However, upon cell stimulation with Ca2+ or other factors, TG2 adopts a Ca2+-bound open conformation, demonstrating a transamidase activity involved in cell death or survival. These functional discrepancies of TG2 open form might be caused by its multifunctional nature, the existence of splicing variants, the cell type and stimulus, and the genetic backgrounds and variations of the mouse models used. TG2 is also involved in the phagocytosis of dead cells by macrophages and in fibrosis during tissue repair. Here, we summarize and discuss the multifunctional and controversial roles of TG2, focusing on cell death/survival and fibrosis.
Farnesoid X Receptor as Target for Therapies to Treat Cholestasis-Induced Liver Injury
Authors: Petrescu Anca D. , DeMorrow Sharon
Published: July 2021

Recent studies on liver disease burden worldwide estimated that cirrhosis is the 11th most common cause of death globally, and there is a great need for new therapies to limit the progression of liver injuries in the early stages. Cholestasis is caused by accumulation of hydrophobic bile acids (BA) in the liver due to dysfunctional BA efflux or bile flow into the gall bladder. Therefore, strategies to increase detoxification of hydrophobic BA and downregulate genes involved in BA production are largely investigated. Farnesoid X receptor (FXR) has a central role in BA homeostasis and recent publications revealed that changes in autophagy due to BA-induced reactive oxygen species and increased anti-oxidant response via nuclear factor E2-related factor 2 (NRF2), result in dysregulation of FXR signaling. Several mechanistic studies have identified new dysfunctions of the cholestatic liver at cellular and molecular level, opening new venues for developing more performant therapies.
Plasma-Induced Hemi-Wicking on Sanded Polymer Surfaces
Authors: Chiu Po-Hsien , Wu Ching-Jung , Hsiao Chun-Ping , Liu Chih-Tung , Wu Mu-Chien , Wu Jong-Shinn
Published: July 2021

In this paper, a plasma-induced hemi-wicking phenomenon observed on hydrophobic sanded polymer surfaces, polypropylene (PP), polyethylene terephthalate (PET) and polyethylene (PE) is reported. An atmospheric-pressure argon plasma jet was used to treat a limited area of the carefully sanded polymer surfaces to induce the hemi-wicking phenomenon. Such hemi-wicking triggered by the plasma activation is different from the traditional type, which is achieved purely by the surface topography. Surface analyses by X-ray photoelectron spectroscopy (XPS) and water contact analysis (WCA) show that the combination of sanding and plasma treatment increased the oxygen-to-carbon ratio, which is highly beneficial for surface hydrophilicity. The shear stress tests show that the combination of sanding and plasma treatment can enhance the shear stress by 125%, 95%, and 296% on PP, PET, and PE, respectively. The study shows that the newly developed technique by combining the sanding and plasma processing for polymers could be a potentially useful method in future industry applications.
Research and Development of Blockchain Recordkeeping at the National Archives of Korea
Authors: Wang Hosung , Yang Dongmin
Published: July 2021

In 2019, the National Archives of Korea (NAK) developed a blockchain recordkeeping platform to conduct R&D on recordkeeping approaches. This paper introduces two types of R&D studies that have been conducted thus far. The first is the use of blockchain transaction audit trail technology to ensure the authenticity of audiovisual archives, i.e., the application of blockchain to a new system. The second uses blockchain technology to verify whether the datasets of numerous information systems built by government agencies are managed without forgery or tampering, i.e., the application of blockchain to an existing system. Government work environments globally are rapidly shifting from paper records to digital. However, the traditional recordkeeping methodology has not adequately kept up with these digital changes. Despite the importance of responding to digital changes by incorporating innovative technologies such as blockchain in recordkeeping practices, it is not easy for most archives to invest funds in experiments on future technologies. Owing to the Korean government’s policy of investing in digital transformation, NAK’s blockchain recordkeeping platform has been developed, and several R&D tasks are underway. Hopefully, the findings of this study will be shared with archivists around the world who are focusing on the future of recordkeeping.
Synergistic Strengthening Effect of Reinforcing Spark Plasma Sintered Al-Zn-TiC Nanocomposites with TiC Nanoparticles
Authors: Abdo Hany S. , Seikh Asiful H. , Fouly Ahmed , Ragab Sameh A.
Published: July 2021

In this investigation, Al-10Zn-TiC nanocomposite powders were prepared by varying the reinforcement content in wt.% via mechanical alloying in order to fabricate bulk samples via spark plasma sintering technique. The grain size exhibited in bulk samples was 17 ± 08 μm in 10 wt% TiC reinforced nanocomposites. The introduced TiC nanoparticles were improved the load carrying ability of the final product. The advanced microscopic studies such as X-ray diffraction analysis, SEM, HR-TEM along with the ring pattern were analysed to ensure the phases and their distribution of reinforced nanoparticles in the Al matrix. The XRD results revealed the formation of TiC present in the matrix, and SEM analysis conveys the uniform distribution and absence of clustering among the reinforcement particles; TEM results depicted the clear interface between the matrix and TiC nanoparticles. The mechanical properties such as hardness and compression studies were carried out in the bulk specimens. The obtained results confirmed the nanocomposites exhibit higher strength which was not only due to decrease in grain size but also due to the occurrence of different strengthening mechanisms such as grain boundary, Orowan and thermal expansion coefficient mismatch strengthening commensurate with the nanoscale TiC addition.
Operation Design of Reaction Crystallization Using Homogeneity Evaluation for the Quality Improvement of Agglomerated Crystalline Particles
Authors: Ohyama Mitsuki , Amari Shuntaro , Takiyama Hiroshi
Published: July 2021

In the quality control of crystalline particles, the uniformity of the distribution of each characteristic, such as size and shape, is important. In particular, the problem in reaction crystallization is that the comprehensive uniformity of characteristic distributions is frequently reduced by the agglomeration phenomena. In this study, we designed an operation method to improve the comprehensive uniformity in a liquid–liquid reaction crystallization by evaluating the dynamic variation in the uniformity of particle size and crystal shape using homogeneity. The homogeneity of final particles increased when the supersaturation was lowered by intermittent operation with inner seed production. Since the ratios of the uniformities of particle sizes and crystal shapes constituting homogeneity varied dynamically, the intermittent operation was designed by focusing on individual uniformities. The uniformity of particle size for the final particles was increased via modulation operation using reverse addition for the dissolution of the microparticles. In the growth stage after the reverse addition, the uniformity of the shape of the final particles was increased by raising the number of times of adding solution for decreasing the supersaturation. In addition, we proposed suitable addition methods to improve comprehensive uniformity by controlling uniformity constituting homogeneity at each stage of intermittent operation.
Optimization and Standardization of Human Saliva Collection for MALDI-TOF MS
Authors: Costa Monique Melo , Benoit Nicolas , Saby Florian , Pradines Bruno , Granjeaud Samuel , Almeras Lionel
Published: July 2021

SARS-CoV-2 outbreak led to unprecedented innovative scientific research to preclude the virus dissemination and limit its impact on life expectancy. Waiting for the collective immunity by vaccination, mass-testing, and isolation of positive cases remain essential. The development of a diagnosis method requiring a simple and non-invasive sampling with a quick and low-cost approach is on demand. We hypothesized that the combination of saliva specimens with MALDI-TOF MS profiling analyses could be the winning duo. Before characterizing MS saliva signatures associated with SARS-CoV-2 infection, optimization and standardization of sample collection, preparation and storage up to MS analyses appeared compulsory. In this view, successive experiments were performed on saliva from healthy healthcare workers. Specimen sampling with a roll cotton of Salivette® devices appeared the most appropriate collection mode. Saliva protein precipitation with organic buffers did not improved MS spectra profiles compared to a direct loading of samples mixed with acetonitrile/formic acid buffer onto MS plate. The assessment of sample storage conditions and duration revealed that saliva should be stored on ice until MS analysis, which should occur on the day of sampling. Kinetic collection of saliva highlighted reproducibility of saliva MS profiles over four successive days and also at two-week intervals. The intra-individual stability of saliva MS profiles should be a key factor in the future investigation for biomarkers associated with SARS-CoV-2 infection. However, the singularity of MS profiles between individuals will require the development of sophisticated bio-statistical analyses such as machine learning approaches. MALDI-TOF MS profiling of saliva could be a promising PCR-free tool for SARS-CoV-2 screening.
Salivary Duct Carcinoma in the External Auditory Canal Causing Ipsilateral Hearing Loss
Authors: Chen Shih-Lung , Yeh Chi-Ju , Chan Kai-Chieh
Published: July 2021

Background: Salivary duct carcinoma (SDC) is a rare aggressive tumor. Most tumors are not confined to the salivary ducts; rather, they invade the major and minor salivary glands. Only a few case reports on such tumors in other primary sites have appeared. Case presentation: A 40-year-old male complained of right hearing loss (a common condition), but we made an extremely rare diagnosis of an SDC in the external auditory canal (EAC). EAC cancers are frequently misdiagnosed. In our patient, the otoscope revealed a smooth, bulging subcutaneous lesion with a non-epithelial defect suggestive of a benign lesion. However, an SDC of the EAC was confirmed through pathological and immunohistochemical analysis. Conclusions: We suggest detailed evaluation of even smooth EAC subcutaneous lesions to avoid erroneous diagnoses. To the best of our knowledge, this is the first report of SDC in the EAC.
Moving People Tracking and False Track Removing with Infrared Thermal Imaging by a Multirotor
Authors: Yeom Seokwon
Published: July 2021

Infrared (IR) thermal imaging can detect the warm temperature of the human body regardless of the light conditions, thus small drones equipped with the IR thermal camera can be utilized to recognize human activity for smart surveillance, road safety, and search and rescue missions. However, the unpredictable motion of the drone poses more challenges than a fixed camera. This paper addresses the detection and tracking of people through IR thermal video captured by a multirotor. For object detection, each frame is first registered with a reference frame to compensate for its coordinates. Then, the objects in each frame are segmented through k-means clustering and morphological operations. Falsely detected objects are removed considering the actual size and the shape of the object. The centroid of the segmented area is considered the measured position for target tracking. The track is initialized with two-point differencing initialization, and the target states are continuously estimated by the interacting multiple model (IMM) filter. The nearest neighbor association rule assigns the measurement to the track. Tracks that move slower than the minimum speed are terminated at the proposed criteria. In the experiments, three videos were captured with a long-wave IR band thermal imaging camera mounted on a multirotor. In the first and second videos, eight pedestrians on a pavement and three hikers on a mountain on winter nights were captured, respectively. In the third video, two walking people with complex backgrounds were captured on a windy summer day. The image characteristics vary between videos depending on the climate and surrounding objects, but the proposed scheme shows the robust performance in all cases; the average root mean squared errors in position and velocity are obtained as 0.08 m and 0.53 m/s, respectively for the first video, 0.06 m and 0.58 m/s, respectively for the second video, and 0.18 m and 1.84 m/s, respectively for the third video. The proposed method reduces false tracks from 10 to 1 in the third video.