bluuebunny/crossref_metadata_2025 huggingface dataset:
Light Shelf Development Using Folding Technology and Photovoltaic Modules to Increase Energy Efficiency in Building
Authors: Lee Heangwoo , Han Sowon , Seo Janghoo
Published: January 2022

Some recent research in the area of light shelves has been focused on applying photovoltaic modules to light shelves to save building energy. However, due to the modules installed on the light shelf reflectors, most such light shelves have failed to improve both daylighting and generation efficiency. This study proposes a folding technology to improve light shelves’ daylighting and generation efficiency that uses photovoltaic modules and validates their performance using a testbed. The major obtained findings are as follows: (1) The proposed folding technology has a structure in which reflectors and photovoltaic modules fold alternately by modularizing the light shelf. The reflector and photovoltaic modules are controlled by adjusting the degree of folding. (2) Because light shelf angles for improving daylighting and generation differed depending on the application of the photovoltaic module, the optimal light shelf specifications differed. (3) Compared to previous light shelf technologies, the light shelf with folding technology and a photovoltaic module reduced energy use by 31.3% to 38.2%. This demonstrates the efficacy of the proposed system. (4) Applying a photovoltaic module can lower the indoor uniformity ratio, which means that the daylighting performance of the light shelf is degraded due to the reduction of the area occupied by the reflector.
cT1N0M0 Esophageal Squamous Cell Carcinoma Invades the Muscularis Mucosa or Submucosa: Comparison of the Results of Endoscopic Submucosal Dissection and Esophagectomy
Authors: Wang Ching-Ya , Chen Bo-Huan , Lee Cheng-Han , Le Puo-Hsien , Tsou Yung-Kuan , Lin Cheng-Hui
Published: January 2022

Background: Endoscopic submucosal dissection (ESD) combined with selective adjuvant chemoradiotherapy may be a new treatment option for cT1N0M0 esophageal squamous cell carcinoma (ESCC) invading muscularis mucosa or submucosa (pT1a-M3/pT1b). We aim to report the effectiveness of this treatment by comparing the results of esophagectomy. Methods: This retrospective single-center study included 72 patients with pT1a-M3/pT1b ESCC who received ESD combined with selective adjuvant chemoradiotherapy (n = 40) and esophagectomy (n = 32). The main outcome comparison was overall survival (OS). The secondary outcomes were treatment-related events, including operation time, complication rate, and length of hospital stay. Disease-specific survival (DSS) and progression-free survival (PFS) were also evaluated. Results: There were no significant differences in the rates of OS, DSS, and PFS between the two groups (median follow-up time: 49.2 months vs. 50.9 months); these were also the same in the subgroup analysis of pT1b ESCC patients. In the ESD group, the procedure time, overall complication rates, and length of hospital stay were significantly reduced. However, the metachronous recurrence rate was significantly higher. In a multivariate analysis, tumor depth and R0 resection were the independent factors associated with OS. Conclusions: ESD combined with selective adjuvant chemoradiotherapy can be an alternative treatment to esophagectomy for cT1N0M0 ESCC invading muscularis mucosa or submucosa.
Bacterial-Viral Interactions in Human Orodigestive and Female Genital Tract Cancers: A Summary of Epidemiologic and Laboratory Evidence
Authors: Kato Ikuko , Zhang Jilei , Sun Jun
Published: January 2022

Infectious agents, including viruses, bacteria, fungi, and parasites, have been linked to pathogenesis of human cancers, whereas viruses and bacteria account for more than 99% of infection associated cancers. The human microbiome consists of not only bacteria, but also viruses and fungi. The microbiome co-residing in specific anatomic niches may modulate oncologic potentials of infectious agents in carcinogenesis. In this review, we focused on interactions between viruses and bacteria for cancers arising from the orodigestive tract and the female genital tract. We examined the interactions of these two different biological entities in the context of human carcinogenesis in the following three fashions: (1) direct interactions, (2) indirect interactions, and (3) no interaction between the two groups, but both acting on the same host carcinogenic pathways, yielding synergistic or additive effects in human cancers, e.g., head and neck cancer, liver cancer, colon cancer, gastric cancer, and cervical cancer. We discuss the progress in the current literature and summarize the mechanisms of host-viral-bacterial interactions in various human cancers. Our goal was to evaluate existing evidence and identify gaps in the knowledge for future directions in infection and cancer.
Blinatumomab in Children and Adolescents with Relapsed/Refractory B Cell Precursor Acute Lymphoblastic Leukemia: A Real-Life Multicenter Retrospective Study in Seven AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) Centers
Authors: Beneduce Giuliana , De Matteo Antonia , Stellato Pio , Testi Anna M. , Bertorello Nicoletta , Colombini Antonella , Putti Maria C. , Rizzari Carmelo , Cesaro Simone , Cellini Monica , Barisone Elena , Petruzziello Fara , Menna Giuseppe , Parasole Rosanna
Published: January 2022

Five-year event-free survival in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) currently exceeds 80–85%. However, 15–20% of patients still experience a relapsed/refractory disease. From 1 January 2015 to 31 December 2020, thirty-nine patients, 0–21 years old with r/r BCP-ALL were treated with blinatumomab with the aim of inducing remission (n = 13) or reducing MRD levels (n = 26) in the frame of different multiagent chemotherapy schedules, in seven AIEOP centers. Patients were treated in compassionate and/or off-label settings and were not enrolled in any controlled clinical trials. Treatment was well tolerated; 22 (56.4%) patients reported adverse events (AE) on a total of 46 events registered, of which 27 (58.7%) were ≤2 grade according to CTCAE. Neurological AEs were 18 (39.1%); only two patients required transient blinatumomab discontinuation. Complete remission (CR) rate was 46% for the 13 patients treated with ≥5% blasts and 81% PCR/FC MRD negativity in the 26 patients with blasts < 5%. Median relapse-free survival was 33.4 months (95% CI; 7.5–59.3); median overall survival was not reached over a mean follow-up of 16 months. In our study, as in other real-life experiences, blinatumomab proved to be effective and well-tolerated, able to induce a high rate of CR and MRD negativity.
Modern Management of Esophageal Cancer: Radio-Oncology in Neoadjuvancy, Adjuvancy and Palliation
Authors: Cellini Francesco , Manfrida Stefania , Casà Calogero , Romano Angela , Arcelli Alessandra , Zamagni Alice , De Luca Viola , Colloca Giuseppe Ferdinando , D’Aviero Andrea , Fuccio Lorenzo , Lancellotta Valentina , Tagliaferri Luca , Boldrini Luca , Mattiucci Gian Carlo , Gambacorta Maria Antonietta , Morganti Alessio Giuseppe , Valentini Vincenzo
Published: January 2022

The modern management of esophageal cancer is crucially based on a multidisciplinary and multimodal approach. Radiotherapy is involved in neoadjuvant and adjuvant settings; moreover, it includes radical and palliative treatment intention (with a focus on the use of a stent and its potential integration with radiotherapy). In this review, the above-mentioned settings and approaches will be described. Referring to available international guidelines, the background evidence bases will be reviewed, and the ongoing, more relevant trials will be outlined. Target definitions and radiotherapy doses to administer will be mentioned. Peculiar applications such as brachytherapy (interventional radiation oncology), and data regarding innovative approaches including MRI-guided-RT and radiomic analysis will be reported. A focus on the avoidance of surgery for major clinical responses (particularly for SCC) is detailed.
Clinical Impact of Prospective Whole Genome Sequencing in Sarcoma Patients
Authors: Schipper Luuk J. , Monkhorst Kim , Samsom Kris G. , Bosch Linda J.W. , Snaebjornsson Petur , van Boven Hester , Roepman Paul , van der Kolk Lizet E. , van Houdt Winan J. , van der Graaf Winette T.A. , Meijer Gerrit A. , Voest Emile E.
Published: January 2022

With more than 70 different histological sarcoma subtypes, accurate classification can be challenging. Although characteristic genetic events can largely facilitate pathological assessment, large-scale molecular profiling generally is not part of regular diagnostic workflows for sarcoma patients. We hypothesized that whole genome sequencing (WGS) optimizes clinical care of sarcoma patients by detection of diagnostic and actionable genomic characteristics, and of underlying hereditary conditions. WGS of tumor and germline DNA was incorporated in the diagnostic work-up of 83 patients with a (presumed) sarcomas in a tertiary referral center. Clinical follow-up data were collected prospectively to assess impact of WGS on clinical decision making. In 12/83 patients (14%), the genomic profile led to revision of cancer diagnosis, with change of treatment plan in eight. All twelve patients had undergone multiple tissue retrieval procedures and immunohistopathological assessments by regional and expert pathologists prior to WGS analysis. Actionable biomarkers with therapeutic potential were identified for 30/83 patients. Pathogenic germline variants were present in seven patients. In conclusion, unbiased genomic characterization with WGS identifies genomic biomarkers with direct clinical implications for sarcoma patients. Given the diagnostic complexity and high unmet need for new treatment opportunities in sarcoma patients, WGS can be an important extension of the diagnostic arsenal of pathologists.
Macrophages as a Therapeutic Target in Metastatic Prostate Cancer: A Way to Overcome Immunotherapy Resistance?
Authors: Martori Clara , Sanchez-Moral Lidia , Paul Tony , Pardo Juan Carlos , Font Albert , Ruiz de Porras Vicenç , Sarrias Maria-Rosa
Published: January 2022

Prostate cancer (PC) is the most common malignancy and the fifth cause of cancer death in men. The treatment for localized or locally advanced stages offers a high probability of cure. Even though the therapeutic landscape has significantly improved over the last decade, metastatic PC (mPC) still has a poor prognosis mainly due to the development of therapy resistance. In this context, the use of immunotherapy alone or in combination with other drugs has been explored in recent years. However, T-cell directed immune checkpoint inhibitors (ICIs) have shown limited activity with inconclusive results in mPC patients, most likely due to the highly immunosuppressive PC tumor microenvironment (TME). In this scenario, targeting macrophages, a highly abundant immunosuppressive cell type in the TME, could offer a new therapeutic strategy to improve immunotherapy efficacy. In this review, we summarize the growing field of macrophage-directed immunotherapies and discuss how these could be applied in the treatment of mPC, focusing on their combination with ICIs.
Tumor Cell Infiltration into the Brain in Glioblastoma: From Mechanisms to Clinical Perspectives
Authors: Seker-Polat Fidan , Pinarbasi Degirmenci Nareg , Solaroglu Ihsan , Bagci-Onder Tugba
Published: January 2022

Glioblastoma is the most common and malignant primary brain tumor, defined by its highly aggressive nature. Despite the advances in diagnostic and surgical techniques, and the development of novel therapies in the last decade, the prognosis for glioblastoma is still extremely poor. One major factor for the failure of existing therapeutic approaches is the highly invasive nature of glioblastomas. The extreme infiltrating capacity of tumor cells into the brain parenchyma makes complete surgical removal difficult; glioblastomas almost inevitably recur in a more therapy-resistant state, sometimes at distant sites in the brain. Therefore, there are major efforts to understand the molecular mechanisms underpinning glioblastoma invasion; however, there is no approved therapy directed against the invasive phenotype as of now. Here, we review the major molecular mechanisms of glioblastoma cell invasion, including the routes followed by glioblastoma cells, the interaction of tumor cells within the brain environment and the extracellular matrix components, and the roles of tumor cell adhesion and extracellular matrix remodeling. We also include a perspective of high-throughput approaches utilized to discover novel players for invasion and clinical targeting of invasive glioblastoma cells.
Identification of Tumor Antigens and Immune Subtypes for the Development of mRNA Vaccines and Individualized Immunotherapy in Soft Tissue Sarcoma
Authors: Wu Changwu , Duan Yingjuan , Gong Siming , Osterhoff Georg , Kallendrusch Sonja , Schopow Nikolas
Published: January 2022

Soft tissue sarcomas (STS) are a rare disease with high recurrence rates and poor prognosis. Missing therapy options together with the high heterogeneity of this tumor type gives impetus to the development of individualized treatment approaches. This study identifies potential tumor antigens for the development of mRNA tumor vaccines for STS and explores potential immune subtypes, stratifying patients for immunotherapy. RNA-sequencing data and clinical information were extracted from 189 STS samples from The Cancer Genome Atlas (TCGA) and microarray data were extracted from 103 STS samples from the Gene Expression Omnibus (GEO). Potential tumor antigens were identified using cBioportal, the Oncomine database, and prognostic analyses. Consensus clustering was used to define immune subtypes and immune gene modules, and graph learning-based dimensionality reduction analysis was used to depict the immune landscape. Finally, four potential tumor antigens were identified, each related to prognosis and antigen-presenting cell infiltration in STS: HLTF, ITGA10, PLCG1, and TTC3. Six immune subtypes and six gene modules were defined and validated in an independent cohort. The different immune subtypes have different molecular, cellular, and clinical characteristics. The immune landscape of STS reveals the immunity-related distribution of patients and intra-cluster heterogeneity of immune subtypes. This study provides a theoretical framework for STS mRNA vaccine development and the selection of patients for vaccination, and provides a reference for promoting individualized immunotherapy.
Intra-Arterial Infusion Chemotherapy in Advanced Pancreatic Cancer: A Comprehensive Review
Authors: Laface Carmelo , Laforgia Mariarita , Molinari Pasquale , Foti Caterina , Ambrogio Francesca , Gadaleta Cosmo Damiano , Ranieri Girolamo
Published: January 2022

Advanced pancreatic cancer (PC) has a very poor prognosis due to its chemoresistant nature. Nowadays, only a few therapeutic options are available for PC, and the most effective ones are characterized by low response rates (RRs), short progression-free survival and overall survival, and severe toxicity. To improve clinical results, small series studies have evaluated loco-regional chemotherapy as a treatment option for PC, demonstrating its dose-dependent sensitivity towards the tumor. In fact, pancreatic arterial infusion (PAI) chemotherapy allows higher local concentrations of chemotherapeutic agents, sparing healthy tissues with a lower rate of adverse events compared to systemic chemotherapy. This therapeutic approach has already been evaluated in different types of tumors, especially in primary and metastatic liver cancers, with favourable results. With regard to advanced PC, a few clinical studies have investigated the safety and efficacy of PAI with promising results, especially in terms of RRs compared to systemic chemotherapy. However, clear evidence about its efficacy has not been established yet nor have the underlying mechanisms leading to its success. In this review, we aim to summarize the literature data on the clinical approaches to pancreatic arterial drug administration in terms of techniques, drug pharmacokinetics, and clinical outcomes for advanced PC.
A Model of Catalytic Cracking: Catalyst Deactivation Induced by Feedstock and Process Variables
Authors: Nazarova Galina Y. , Ivashkina Elena N. , Ivanchina Emiliya D. , Mezhova Maria Y.
Published: January 2022

Changes in the quality of the feedstocks generated by involving various petroleum fractions in catalytic cracking significantly affect catalyst deactivation, which stems from coke formed on the catalyst surface. By conducting experimental studies on feedstocks and catalysts, as well as using industrial data, we studied how the content of saturates, aromatics and resins (SAR) in feedstock and the main process variables, including temperature, consumptions of the feedstock, catalyst and slops, influence the formation of catalytic coke. We also determined catalyst deactivation patterns using TG-DTA, N2 adsorption and TPD, which were further used as a basis for a kinetic model of catalytic cracking. This model helps predict the changes in reactions rates caused by coke formation and, also, evaluates quantitatively how group characteristics of the feedstock, the catalyst-to-oil ratio and slop flow influence the coke content on the catalyst and the degree of catalyst deactivation. We defined that a total loss of acidity changes from 8.6 to 30.4 wt% for spent catalysts, and this depends on SAR content in feedstock and process variables. The results show that despite enriching the feedstock by saturates, the highest coke yields (4.6–5.2 wt%) may be produced due to the high content of resins (2.1–3.5 wt%).
Fabrication and Characterization of a Marine Wet Solar Cell with Titanium Dioxide and Copper Oxides Electrodes
Authors: Wunn Htoo Nay , Motoda Shinichi , Morita Motoaki
Published: January 2022

One of the effective ways of utilizing marine environments is to generate energy, power, and hydrogen via the effect of photocatalysts in the seawater. Since the ocean is vast, we are able to use its large area, but the power generation system must be of low cost and have high durability against both force and corrosion. In order to meet those requirements, this study focuses on the fabrication of a novel marine wet solar cell composed of a titanium dioxide photoanode and a copper oxide photocathode. These electrodes were deposited on type 329J4L stainless steel, which possesses relative durability in marine environments. This study focuses on the characterization of the photocatalytic properties of electrodes in seawater. Low-cost manufacturing processes of screen-printing and vacuum vapor deposition were applied to produce the titanium dioxide and copper oxides electrodes, respectively. We investigated the photopotential of the electrodes, along with the electrochemical properties and cell voltage properties of the cell. X-ray diffraction spectroscopy (XRD) of the copper oxides electrode was analyzed in association with the loss of photocatalytic effect in the copper oxides electrode. Although the conversion efficiency of the wet cell was less than 1%, it showed promising potential for use in marine environments with low-cost production. Electrochemical impedance spectroscopy (EIS) of the cell was also conducted, from which impedance values regarding the electrical properties of electrodes and their interfaces of charge-transfer processes were obtained. This study focuses on the early phase of the marine wet solar cell, which should be further studied for long-term stability and in actual marine environmental applications.
Thermal Stability of Potassium-Promoted Cobalt Molybdenum Nitride Catalysts for Ammonia Synthesis
Authors: Adamski Paweł , Czerwonko Wojciech , Moszyński Dariusz
Published: January 2022

The application of cobalt molybdenum nitrides as ammonia synthesis catalysts requires further development of the optimal promoter system, which enhances not only the activity but also the stability of the catalysts. To do so, elucidating the influence of the addition of alkali metals on the structural properties of the catalysts is essential. In this study, potassium-promoted cobalt molybdenum nitrides were synthesized by impregnation of the precursor CoMoO4·3/4H2O with aqueous KNO3 solution followed by ammonolysis. The catalysts were characterized with the use of XRD and BET methods, under two conditions: as obtained and after the thermal stability test. The catalytic activity in the synthesis of ammonia was examined at 450 °C, under 10 MPa. The thermal stability test was carried out by heating at 650 °C in the same apparatus. As a result of ammonolysis, mixtures of two phases: Co3Mo3N and Co2Mo3N were obtained. The phase concentrations were affected by potassium admixture. The catalytical activity increased for the most active catalyst by approximately 50% compared to non-promoted cobalt molybdenum nitrides. The thermal stability test resulted in a loss of activity, on average, of 30%. Deactivation was caused by the collapse of the porous structure, which is attributed to the conversion of the Co2Mo3N phase to the Co3Mo3N phase.
Island-Type Hybrid Catalysts Applied for Anion Exchange Membrane Water Electrolysis
Authors: Chen Hsueh-Yu , Chen Guan-Cheng , Liao Kuo-Wei , Wei Wen-Hui , Huang Hsin-Chih , Wang Chen-Hao
Published: January 2022

A rapid, productive, and efficient process was invented to produce hybrid catalysts for transition metal oxide water electrolysis. The microwave-assisted hydrothermal method was applied to synthesize transition metal oxide catalysts by controlling the amount of cobalt and iron. This work solves the cracking problem for the catalytic layer during the water electrolysis. It uses Fe2O3 as the support and covers a catalytic layer outside it and a nanoscale gap between each catalyst, which can help to remove the gas and fill up the water. The unique structure of the catalysts can prevent them from accumulating gas and increasing their efficiency for long-term water electrolysis. By using unique catalysts in the water electrolyzer, the current density reaches higher than 200 mA cm−2 at 2.0 V and does not show a significant decay even after 200 h.
Catalytic Conversion of Glycerol to Methyl Lactate over Au-CuO/Sn-Beta: The Roles of Sn-Beta
Authors: Duan Ying , Luo Qianqian , Nie Renfeng , Wang Jianshe , Zhang Yongsheng , Lu Tianliang , Xu Chunbao
Published: January 2022

The production of methyl lactate as a degradable polymer monomer from biomass was an important topic for a sustainable society. In this manuscript, glycerol was oxidated to methyl lactate catalyzed by the combination of Au-CuO and Sn-Beta. The influence of Sn content, Sn source, and the preparation conditions for Sn-β was studied. The Au content in Au/CuO was also investigated by varying the Au content in Au/CuO. The catalysts were characterized by XRD, FTIR spectroscopy of pyridine adsorption, and TEM to study the role of Sn and the influence of different parameters for catalyst preparation. After the optimization of reaction parameters, the yield of methyl lactate from glycerol reached 59% at 363 K after reacting in 1.6 MPa of O2 for 6 h.
Role of Mitochondrial Cytochrome P450 2E1 in Healthy and Diseased Liver
Authors: Massart Julie , Begriche Karima , Hartman Jessica H. , Fromenty Bernard
Published: January 2022

Cytochrome P450 2E1 (CYP2E1) is pivotal in hepatotoxicity induced by alcohol abuse and different xenobiotics. In this setting, CYP2E1 generates reactive metabolites inducing oxidative stress, mitochondrial dysfunction and cell death. In addition, this enzyme appears to play a role in the progression of obesity-related fatty liver to nonalcoholic steatohepatitis. Indeed, increased CYP2E1 activity in nonalcoholic fatty liver disease (NAFLD) is deemed to induce reactive oxygen species overproduction, which in turn triggers oxidative stress, necroinflammation and fibrosis. In 1997, Avadhani’s group reported for the first time the presence of CYP2E1 in rat liver mitochondria, and subsequent investigations by other groups confirmed that mitochondrial CYP2E1 (mtCYP2E1) could be found in different experimental models. In this review, we first recall the main features of CYP2E1 including its role in the biotransformation of endogenous and exogenous molecules, the regulation of its expression and activity and its involvement in different liver diseases. Then, we present the current knowledge on the physiological role of mtCYP2E1, its contribution to xenobiotic biotransformation as well as the mechanism and regulation of CYP2E1 targeting to mitochondria. Finally, we discuss experimental investigations suggesting that mtCYP2E1 could have a role in alcohol-associated liver disease, xenobiotic-induced hepatotoxicity and NAFLD.
The Electrostatic Basis of Diacylglycerol Pyrophosphate—Protein Interaction
Authors: Graber Zachary , Owusu Kwarteng Desmond , Lange Shannon , Koukounas Yannis , Khalifa Hady , Mutambuze Jean , Kooijman Edgar
Published: January 2022

Diacylglycerol pyrophosphate (DGPP) is an anionic phospholipid formed in plants, yeast, and parasites under multiple stress stimuli. It is synthesized by the phosphorylation action of phosphatidic acid (PA) kinase on phosphatidic acid, a signaling lipid with multifunctional properties. PA functions in the membrane through the interaction of its negatively charged phosphomonoester headgroup with positively charged proteins and ions. DGPP, like PA, can interact electrostatically via the electrostatic-hydrogen bond switch mechanism but differs from PA in its overall charge and shape. The formation of DGPP from PA alters the physicochemical properties as well as the structural dynamics of the membrane. This potentially impacts the molecular and ionic binding of cationic proteins and ions with the DGPP enriched membrane. However, the results of these important interactions in the stress response and in DGPP’s overall intracellular function is unknown. Here, using 31P MAS NMR, we analyze the effect of the interaction of low DGPP concentrations in model membranes with the peptides KALP23 and WALP23, which are flanked by positively charged Lysine and neutral Tryptophan residues, respectively. Our results show a significant effect of KALP23 on the charge of DGPP as compared to WALP23. There was, however, no significant effect on the charge of the phosphomonoester of DGPP due to the interaction with positively charged lipids, dioleoyl trimethylammonium propane (DOTAP) and dioleoyl ethyl-phosphatidylcholine (EtPC). Divalent calcium and magnesium cations induce deprotonation of the DGPP headgroup but showed no noticeable differences on DGPP’s charge. Our results lead to a novel model for DGPP—protein interaction.
Identification of the Cysteine Protease Legumain as a Potential Chronic Hypoxia-Specific Multiple Myeloma Target Gene
Authors: Clees Ada-Sophia , Stolp Verena , Häupl Björn , Fuhrmann Dominik C. , Wempe Frank , Seibert Marcel , Weber Sarah , Banning Antje , Tikkanen Ritva , Williams Richard , Brüne Bernhard , Serve Hubert , Schnütgen Frank , von Metzler Ivana , Kurrle Nina
Published: January 2022

Multiple myeloma (MM) is the second most common hematologic malignancy, which is characterized by clonal proliferation of neoplastic plasma cells in the bone marrow. This microenvironment is characterized by low oxygen levels (1–6% O2), known as hypoxia. For MM cells, hypoxia is a physiologic feature that has been described to promote an aggressive phenotype and to confer drug resistance. However, studies on hypoxia are scarce and show little conformity. Here, we analyzed the mRNA expression of previously determined hypoxia markers to define the temporal adaptation of MM cells to chronic hypoxia. Subsequent analyses of the global proteome in MM cells and the stromal cell line HS-5 revealed hypoxia-dependent regulation of proteins, which directly or indirectly upregulate glycolysis. In addition, chronic hypoxia led to MM-specific regulation of nine distinct proteins. One of these proteins is the cysteine protease legumain (LGMN), the depletion of which led to a significant growth disadvantage of MM cell lines that is enhanced under hypoxia. Thus, herein, we report a methodologic strategy to examine MM cells under physiologic hypoxic conditions in vitro and to decipher and study previously masked hypoxia-specific therapeutic targets such as the cysteine protease LGMN.
RNA Molecular Signature Profiling in PBMCs of Sporadic ALS Patients: HSP70 Overexpression Is Associated with Nuclear SOD1
Authors: Garofalo Maria , Pandini Cecilia , Bordoni Matteo , Jacchetti Emanuela , Diamanti Luca , Carelli Stephana , Raimondi Manuela Teresa , Sproviero Daisy , Crippa Valeria , Carra Serena , Poletti Angelo , Pansarasa Orietta , Gagliardi Stella , Cereda Cristina
Published: January 2022

Superoxide dismutase 1 (SOD1) is one of the causative genes associated with amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder. SOD1 aggregation contributes to ALS pathogenesis. A fraction of the protein is localized in the nucleus (nSOD1), where it seems to be involved in the regulation of genes participating in the oxidative stress response and DNA repair. Peripheral blood mononuclear cells (PBMCs) were collected from sporadic ALS (sALS) patients (n = 18) and healthy controls (n = 12) to perform RNA-sequencing experiments and differential expression analysis. Patients were stratified into groups with “high” and “low” levels of nSOD1. We obtained different gene expression patterns for high- and low-nSOD1 patients. Differentially expressed genes in high nSOD1 form a cluster similar to controls compared to the low-nSOD1 group. The pathways activated in high-nSOD1 patients are related to the upregulation of HSP70 molecular chaperones. We demonstrated that, in this condition, the DNA damage is reduced, even under oxidative stress conditions. Our findings highlight the importance of the nuclear localization of SOD1 as a protective mechanism in sALS patients.
Long-Term High-Fat Diet Consumption Depletes Glial Cells and Tyrosine Hydroxylase–Containing Neurons in the Brain of Middle-Aged Rats
Authors: Chou Mei-Chuan , Lee Hsiang-Chun , Liu Yen-Chin , Yen Patrick Szu-Ying , Liu Ching-Kuan , Chen Chu-Huang , Hsieh Tzu-Han , Chen Shiou-Lan
Published: January 2022

Epidemiologic studies have indicated that dyslipidemia may facilitate the progression of neuronal degeneration. However, the effects of chronic dyslipidemia on brain function, especially in older individuals, remain unclear. In this study, middle-aged 37-week-old male Wistar-Kyoto rats were fed a normal diet (ND) or a 45% high-fat diet (HFD) for 30 weeks (i.e., until 67 weeks of age). To study the effects of chronic dyslipidemia on the brain, we analyzed spontaneous locomotor activity, cognitive function, and brain tissues in both groups of rats after 30 weeks. Compared with age-matched rats fed a ND, Wistar-Kyoto rats fed a HFD had dyslipidemia and showed decreased movement but normal recognition of a novel object. In our brain analyses, we observed a significant decrease in astrocytes and tyrosine hydroxylase–containing neurons in the substantia nigra and locus coeruleus of rats fed a HFD compared with rats fed a ND. However, hippocampal pyramidal neurons were not affected. Our findings indicate that the long-term consumption of a HFD may cause lipid metabolism overload in the brain and damage to glial cells. The decrease in astrocytes may lead to reduced protection of the brain and affect the survival of tyrosine hydroxylase–containing neurons but not pyramidal neurons of the hippocampus.
Developing Digital Photomicroscopy
Authors: Micklem Kingsley
Published: January 2022

(1) The need for efficient ways of recording and presenting multicolour immunohistochemistry images in a pioneering laboratory developing new techniques motivated a move away from photography to electronic and ultimately digital photomicroscopy. (2) Initially broadcast quality analogue cameras were used in the absence of practical digital cameras. This allowed the development of digital image processing, storage and presentation. (3) As early adopters of digital cameras, their advantages and limitations were recognised in implementation. (4) The adoption of immunofluorescence for multiprobe detection prompted further developments, particularly a critical approach to probe colocalization. (5) Subsequently, whole-slide scanning was implemented, greatly enhancing histology for diagnosis, research and teaching.
A Defective Viral Particle Approach to COVID-19
Authors: Kalamvoki Maria , Norris Vic
Published: January 2022

The novel coronavirus SARS-CoV-2 has caused a pandemic resulting in millions of deaths worldwide. While multiple vaccines have been developed, insufficient vaccination combined with adaptive mutations create uncertainty for the future. Here, we discuss novel strategies to control COVID-19 relying on Defective Interfering Particles (DIPs) and related particles that arise naturally during an infection. Our intention is to encourage and to provide the basis for the implementation of such strategies by multi-disciplinary teams. We therefore provide an overview of SARS-CoV-2 for a multi-disciplinary readership that is specifically tailored to these strategies, we identify potential targets based on the current knowledge of the properties and functions of coronaviruses, and we propose specific strategies to engineer DIPs and other interfering or therapeutic nanoparticles.
Endolysosomal Cation Channels and Lung Disease
Authors: Spix Barbara , Jeridi Aicha , Ansari Meshal , Yildirim Ali Önder , Schiller Herbert B. , Grimm Christian
Published: January 2022

Endolysosomal cation channels are emerging as key players of endolysosomal function such as endolysosomal trafficking, fusion/fission, lysosomal pH regulation, autophagy, lysosomal exocytosis, and endocytosis. Diseases comprise lysosomal storage disorders (LSDs) and neurodegenerative diseases, metabolic diseases, pigmentation defects, cancer, immune disorders, autophagy related diseases, infectious diseases and many more. Involvement in lung diseases has not been a focus of attention so far but recent developments in the field suggest critical functions in lung physiology and pathophysiology. Thus, loss of TRPML3 was discovered to exacerbate emphysema formation and cigarette smoke induced COPD due to dysregulated matrix metalloproteinase 12 (MMP-12) levels in the extracellular matrix of the lung, a known risk factor for emphysema/COPD. While direct lung function measurements with the exception of TRPML3 are missing for other endolysosomal cation channels or channels expressed in lysosome related organelles (LRO) in the lung, links between those channels and important roles in lung physiology have been established such as the role of P2X4 in surfactant release from alveolar epithelial Type II cells. Other channels with demonstrated functions and disease relevance in the lung such as TRPM2, TRPV2, or TRPA1 may mediate their effects due to plasma membrane expression but evidence accumulates that these channels might also be expressed in endolysosomes, suggesting additional and/or dual roles of these channels in cell and intracellular membranes. We will discuss here the current knowledge on cation channels residing in endolysosomes or LROs with respect to their emerging roles in lung disease.
A Special Network Comprised of Macrophages, Epithelial Cells, and Gut Microbiota for Gut Homeostasis
Authors: Chen Wei , Liu Dan , Ren Changhao , Su Xiaomin , Wong Chun-Kwok , Yang Rongcun
Published: January 2022

A number of gut epithelial cells derived immunological factors such as cytokines and chemokines, which are stimulated by the gut microbiota, can regulate host immune responses to maintain a well-balance between gut microbes and host immune system. Multiple specialized immune cell populations, such as macrophages, dendritic cells (DCs), innate lymphoid cells, and T regulatory (Treg) cells, can communicate with intestinal epithelial cells (IEC) and/or the gut microbiota bi-directionally. The gut microbiota contributes to the differentiation and function of resident macrophages. Situated at the interface between the gut commensals and macrophages, the gut epithelium is crucial for gut homeostasis in microbial recognition, signaling transformation, and immune interactions, apart from being a physical barrier. Thus, three distinct but interactive components—macrophages, microbiota, and IEC—can form a network for the delicate and dynamic regulation of intestinal homeostasis. In this review, we will discuss the crucial features of gut microbiota, macrophages, and IEC. We will also summarize recent advances in understanding the cooperative and dynamic interactions among the gut microbiota, gut macrophages, and IEC, which constitute a special network for gut homeostasis.
Fibrosis Is a Basement Membrane-Related Disease in the Cornea: Injury and Defective Regeneration of Basement Membranes May Underlie Fibrosis in Other Organs
Authors: Wilson Steven E.
Published: January 2022

Every organ develops fibrosis that compromises functions in response to infections, injuries, or diseases. The cornea is a relatively simple, avascular organ that offers an exceptional model to better understand the pathophysiology of the fibrosis response. Injury and defective regeneration of the epithelial basement membrane (EBM) or the endothelial Descemet’s basement membrane (DBM) triggers the development of myofibroblasts from resident corneal fibroblasts and bone marrow-derived blood borne fibrocytes due to the increased entry of TGF beta-1/-2 into the stroma from the epithelium and tears or residual corneal endothelium and aqueous humor. The myofibroblasts, and disordered extracellular matrix these cells produce, persist until the source of injury is removed, the EBM and/or DBM are regenerated, or replaced surgically, resulting in decreased stromal TGF beta requisite for myofibroblast survival. A similar BM injury-related pathophysiology can underly the development of fibrosis in other organs such as skin and lung. The normal liver does not contain traditional BMs but develops sinusoidal endothelial BMs in many fibrotic diseases and models. However, normal hepatic stellate cells produce collagen type IV and perlecan that can modulate TGF beta localization and cognate receptor binding in the space of Dissé. BM-related fibrosis is deserving of more investigation in all organs.
A Bioorthogonal Double Fluorogenic Probe to Visualize Protein–DNA Interaction
Authors: Kormos Attila , Egyed Alexandra , Olvany Jasmine M. , Szatmári Ágnes , Biró Adrienn , Csorba Zsóka , Kele Péter , Németh Krisztina
Published: January 2022

Two sets of bioorthogonally applicable, double fluorogenic probes, capable of sensing DNA–protein interactions, were prepared by installing an azide or tetrazine motif onto structurally fluorogenic, DNA sensitive frames. Installation of these bioorthogonal functions onto DNA intercalating dyes furnished these scaffolds with reactivity based fluorogenicity, rendering these probes double-fluorogenic, AND-type logic switches that require the simultaneous occurrence of a bioorthogonal reaction and interaction with DNA to trigger high intensity fluorescence. The probes were evaluated for double fluorogenic behavior in the presence/absence of DNA and a complementary bioorthogonal function. Our studies revealed that azide and tetrazine appending thiazole orange frames show remarkable double fluorogenic features. One of these probes, a membrane permeable tetrazine modified thiazole orange derivative was further tested in live cell labeling studies. Cells expressing bioorthogonalized DNA-binding proteins showed intensive fluorescence characteristics of the localization of the proteins upon treatment with our double fluorogenic probe. On the contrary, labeling similarly bioorthogonalized cytosolic proteins did not result in the appearance of the fluorescence signal. These studies suggest that such double-fluorogenic probes are indeed capable of sensing DNA–protein interactions in cells.
The Social Networks and Social Support of Siblings of Children with Cancer
Authors: Wawrzynski Sarah E. , Alderfer Melissa A. , Kvistad Whitney , Linder Lauri , Reblin Maija , Guo Jia-Wen , Cloyes Kristin G.
Published: January 2022

Siblings of children with cancer need support to ameliorate the challenges they encounter; however, little is known about what types and sources of support exist for siblings. This study addresses this gap in our understanding of the social networks and sources of support for adolescents with a brother or sister who has cancer. Additionally, we describe how the support siblings receive addresses what they feel are the hardest aspects of being a sibling of a child with cancer. During semi-structured interviews, siblings (ages 12–17) constructed ecomaps describing their support networks. Data were coded for support type (emotional, instrumental, informational, validation, companionship) and support provider (e.g., mother, teacher, friend). Network characteristics and patterns of support were explored. Support network size ranged from 3 to 10 individuals (M = 6 ± 1.9); siblings most frequently reported mothers as sources of support (n = 22, 91.7%), followed by fathers (n = 19, 79.2%), close friends (n = 19, 79.2%) and siblings (with or without cancer) (n = 17, 70.8%). Friends and brothers or sisters most often provided validation and companionship while instrumental and informational supports came from parents. This study provides foundational knowledge about siblings’ support networks, which can be utilized to design interventions that improve support for siblings of children with cancer.
Sugar Content and Sources in Commercial Infant Cereals in Spain
Authors: Garro-Mellado Liliana , Guerra-Hernández Eduardo , García-Villanova Belén
Published: January 2022

Instant infant cereals reconstituted with infant formula are the first complementary food for most Spanish infants. The main aim is to provide information on sugars in the formulation of infant cereals. Product information was collected from department stores, supermarkets, and pharmacies and completed with data from brand websites. A portion of the samples was selected for total sugars determination using the HPLC and Luff-Schoorl methods. The information regarding a total of 120 milk-free instant infant cereals marketed in Spain from 12 companies was summarized. The mean of total sugars was 23 ± 9 g/100 g (25–42%), providing 24% of the calories. Most of porridges are prepared with partially hydrolyzed flours providing free sugars (glucose and maltose). The most commonly added sugar is sucrose. A total of 43.3% of products contain added sucrose, and 16.7% contain fruits. Infant cereals analyzed with added sugars can have a sugar content similar to that found in products without added sugars. Consistent differences were found in sugars content between assayed methods and this label information. Although the European legislation of infant cereals establishes values for added sugars, the labeling reflects the content of total sugars, but not that of added sugars.
Improving Body Representation and Motor Skills with a Preschool Education Program: A Preliminary Study
Authors: Patriau Ambre , Cojan Juliette , Gauduel Thomas , Lopez-Vilain Jessica , Pavon Gaelle , Gomez Alice
Published: January 2022

Background: Body representation is described as a fundamental ability to build efficient motor skills. However, no structured and evidence-based program on body representation currently exists. This study assesses the effectiveness of a school-based body representation program (ENCOR: EN for ‘Enfant’ and COR for ‘Corps’ in French) on body representation abilities and motor skills in preschool children. ENCOR focus on body representation abilities as a foundational ability for motor skills. It was designed with teachers and occupational therapists to be autonomously achieved by teachers. Methods: Twenty-three children aged 5–6 years were included and provided with education interventions (control versus ENCOR). Results: Body representation accuracy and precision in localization increased by about 20% and 37%, respectively, in the intervention program compared to the control intervention. In the body part naming task, participants performed fewer of the most frequent errors (i.e., from 198 to 116 left-right discrimination errors). As expected, performance in the body representation tasks and the motor skills tasks were correlated at baseline. We show that motor skills improved after the ENCOR training. Conclusions: Given the need for evidence-based programs in schools, this program could efficiently help implementing body representation education on a large scale. Future studies should evaluate the effectiveness of the program on other cognitive abilities and academic outcomes.
Modeling Carbon Release of Brazilian Highest Economic Pole and Major Urban Emitter: Comparing Classical Methods and Artificial Neural Networks
Authors: Debone Daniela , Martins Tiago Dias , Miraglia Simone Georges El Khouri
Published: January 2022

Despite the concern about climate change and the associated negative impacts, fossil fuels continue to prevail in the global energy consumption. This paper aimed to propose the first model that relates CO2 emissions of Sao Paulo, the main urban center emitter in Brazil, with gross national product and energy consumption. Thus, we investigated the accuracy of three different methods: multivariate linear regression, elastic-net regression, and multilayer perceptron artificial neural networks. Comparing the results, we clearly demonstrated the superiority of artificial neural networks when compared with the other models. They presented better results of mean absolute percentage error (MAPE = 0.76%) and the highest possible coefficient of determination (R2 = 1.00). This investigation provides an innovative integrated climate-economic approach for the accurate prediction of carbon emissions. Therefore, it can be considered as a potential valuable decision-support tool for policymakers to design and implement effective environmental policies.
Microstructure and Mechanical Properties of TiC/TiB Composite Ceramic Coatings In-Situ Synthesized by Ultrasonic Vibration-Assisted Laser Cladding
Authors: Mi Hangbiao , Chen Tao , Deng Zixin , Li Shengchen , Liu Jian , Liu Defu
Published: January 2022

Laser cladding coating has many advantages in surface modification, such as a small heat-affected zone, and good metallurgical bonding. However, some serious problems such as pores, and poor forming quality still exist in the coating. To suppress these problems, a novel process of ultrasonic vibration-assisted laser cladding process was adopted to in-situ synthesize TiC/TiB composite ceramic coating on the surface of titanium alloy. Results showed that the introduction of ultrasonic vibration effectively improved the surface topography of the coating, reduced the number of pores in the coating, refined the crystal grains of the coating, decreased the residual tensile stress in the coating, and increased the micro-hardness of the coating. The tribological properties of the coating were significantly improved by the ultrasonic vibration, the wear resistance of the coating fabricated with ultrasonic vibration at power of 400 W increased about 1.2 times compared with the coating fabricated without ultrasonic vibration, and the friction coefficient decreased by 50%.