bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the CMIP6 Anthropogenic Aerosol Radiative Effects with the Advantage of Prescribed Aerosol Forcing
Authors: Shi Xiangjun , Li Chunhan , Li Lijuan , Zhang Wentao , Liu Jiaojiao
Published: March 2021

The prescribed anthropogenic aerosol forcing recommended by Coupled Model Intercomparison Project Phase 6 (CMIP6) was implemented in an atmospheric model. With the reduced complexity of anthropogenic aerosol forcing, each component of anthropogenic aerosol effective radiative forcing (ERF) can be estimated by one or more calculation methods, especially for instantaneous radiative forcing (RF) from aerosol–radiation interactions (RFari) and aerosol–cloud interactions (RFaci). Simulation results show that the choice of calculation method might impact the magnitude and reliability of RFari. The RFaci—calculated by double radiation calls—is the definition-based Twomey effect, which previously was impossible to diagnose using the default model with physically based aerosol–cloud interactions. The RFari and RFaci determined from present-day simulations are very robust and can be used as offline simulation results. The robust RFari, RFaci, and corresponding radiative forcing efficiencies (i.e., the impact of environmental properties) are very useful for analyzing anthropogenic aerosol radiative effects. For instance, from 1975 to 2000, both RFari and RFaci showed a clear response to the spatial change of anthropogenic aerosol. The global average RF (RFari + RFaci) has enhanced (more negative) by ~6%, even with a slight decrease in the global average anthropogenic aerosol, and this can be explained by the spatial pattern of radiative forcing efficiency.
Impact on Ultrafine Particles Concentration and Turbulent Fluxes of SARS-CoV-2 Lockdown in a Suburban Area in Italy
Authors: Donateo Antonio , Dinoi Adelaide , Pappaccogli Gianluca
Published: March 2021

In order to slow the spread of SARS-CoV-2, governments have implemented several restrictive measures (lockdown, stay-in-place, and quarantine policies). These provisions have drastically changed the routines of residents, altering environmental conditions in the affected areas. In this context, our work analyzes the effects of the reduced emissions during the COVID-19 period on the ultrafine particles number concentration and their turbulent fluxes in a suburban area. COVID-19 restrictions did not significantly reduce anthropogenic related PM10 and PM2.5 levels, with an equal decrement of about 14%. The ultrafine particle number concentration during the lockdown period decreased by 64% in our measurement area, essentially due to the lower traffic activity. The effect of the restriction measures and the reduction of vehicles traffic was predominant in reducing concentration rather than meteorological forcing. During the lockdown in 2020, a decrease of 61% in ultrafine particle positive fluxes can be observed. At the same time, negative fluxes decreased by 59% and our observation site behaved, essentially, as a sink of ultrafine particles. Due to this behavior, we can conclude that the principal particle sources during the lockdown were far away from the measurement site.
P3CMQA: Single-Model Quality Assessment Using 3DCNN with Profile-Based Features
Authors: Takei Yuma , Ishida Takashi
Published: March 2021

Model quality assessment (MQA), which selects near-native structures from structure models, is an important process in protein tertiary structure prediction. The three-dimensional convolution neural network (3DCNN) was applied to the task, but the performance was comparable to existing methods because it used only atom-type features as the input. Thus, we added sequence profile-based features, which are also used in other methods, to improve the performance. We developed a single-model MQA method for protein structures based on 3DCNN using sequence profile-based features, namely, P3CMQA. Performance evaluation using a CASP13 dataset showed that profile-based features improved the assessment performance, and the proposed method was better than currently available single-model MQA methods, including the previous 3DCNN-based method. We also implemented a web-interface of the method to make it more user-friendly.
Meningioma: A Review of Epidemiology, Pathology, Diagnosis, Treatment, and Future Directions
Authors: Ogasawara Christian , Philbrick Brandon D. , Adamson D. Cory
Published: March 2021

Meningiomas are the most common intracranial tumor, making up more than a third of all primary central nervous system (CNS) tumors. They are mostly benign tumors that can be observed or preferentially treated with gross total resection that provides good outcomes. Meningiomas with complicated histology or in compromising locations has proved to be a challenge in treating and predicting prognostic outcomes. Advances in genomics and molecular characteristics of meningiomas have uncovered potential use for more accurate grading and prediction of prognosis and recurrence. With the study and detection of genomic aberrancies, specific biologic targets are now being trialed for possible management of meningiomas that are not responsive to standard surgery and radiotherapy treatment. This review summarizes current epidemiology, etiology, molecular characteristics, diagnosis, treatments, and current treatment trials.
Brown Spiders’ Phospholipases-D with Potential Therapeutic Applications: Functional Assessment of Mutant Isoforms
Authors: da Silva Thaís Pereira , de Castro Fernando Jacomini , Vuitika Larissa , Polli Nayanne Louise Costacurta , Antunes Bruno César , Bóia-Ferreira Marianna , Minozzo João Carlos , Mariutti Ricardo Barros , Matsubara Fernando Hitomi , Arni Raghuvir Krishnaswamy , Wille Ana Carolina Martins , Senff-Ribeiro Andrea , Gremski Luiza Helena , Veiga Silvio Sanches
Published: March 2021

Phospholipases-D (PLDs) found in Loxosceles spiders’ venoms are responsible for the dermonecrosis triggered by envenomation. PLDs can also induce other local and systemic effects, such as massive inflammatory response, edema, and hemolysis. Recombinant PLDs reproduce all of the deleterious effects induced by Loxosceles whole venoms. Herein, wild type and mutant PLDs of two species involved in accidents—L. gaucho and L. laeta—were recombinantly expressed and characterized. The mutations are related to amino acid residues relevant for catalysis (H12-H47), magnesium ion coordination (E32-D34) and binding to phospholipid substrates (Y228 and Y228-Y229-W230). Circular dichroism and structural data demonstrated that the mutant isoforms did not undergo significant structural changes. Immunoassays showed that mutant PLDs exhibit conserved epitopes and kept their antigenic properties despite the mutations. Both in vitro (sphingomyelinase activity and hemolysis) and in vivo (capillary permeability, dermonecrotic activity, and histopathological analysis) assays showed that the PLDs with mutations H12-H47, E32-D34, and Y228-Y229-W230 displayed only residual activities. Results indicate that these mutant toxins are suitable for use as antigens to obtain neutralizing antisera with enhanced properties since they will be based on the most deleterious toxins in the venom and without causing severe harmful effects to the animals in which these sera are produced.
Oxygen-Carrying Polymer Nanoconstructs for Radiodynamic Therapy of Deep Hypoxic Malignant Tumors
Authors: Clement Sandhya , Guller Anna , Mahbub Saabah B. , Goldys Ewa M.
Published: March 2021

Radiodynamic therapy (RDT) is an emerging non-invasive anti-cancer treatment based on the generation of the reactive oxygen species (ROS) at the lesion site following the interaction between X-rays and a photosensitizer drug (PS). The broader application of RDT is impeded by the tumor-associated hypoxia that results in low availability of oxygen for the generation of sufficient amounts of ROS. Herein, a novel nanoparticle drug formulation for RDT, which addresses the problem of low oxygen availability, is reported. It consists of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-loaded with a PS drug verteporfin (VP), and the clinically approved oxygen-carrying molecule, perfluorooctylbromide (PFOB). When triggered by X-rays (4 Gy), under both normoxic and hypoxic conditions, PLGA–VP–PFOB nanoconstructs (NCs) induced a significant increase of the ROS production compared with matching PLGA–VP nanoparticles. The RDT with NCs effectively killed ~60% of human pancreatic cancer cells in monolayer cultures, and almost completely suppressed the outgrowth of tumor cells in 2-weeks clonogenic assay. In a 3D engineered model of pancreatic cancer metastasis to the liver, RDT with NCs destroyed ~35% of tumor cells, demonstrating an exceptional efficiency at a tissue level. These results show that PLGA–VP–PFOB is a promising agent for RDT of deep-seated hypoxic tumors.
Distinctive Frontal and Occipitotemporal Surface Features in Neglectful Parenting
Authors: León Inmaculada , Rodrigo María José , Quiñones Ileana , Hernández-Cabrera Juan Andrés , García-Pentón Lorna
Published: March 2021

Although the brain signatures of adaptive human parenting are well documented, the cortical features associated with maladaptive caregiving are underexplored. We investigated whether cortical thickness and surface area vary in a small group of mothers who had neglected their children (24 in the neglect group, NG) compared to a control group of mothers with non-neglectful caregiving (21 in the control group, CG). We also tested whether the cortical differences were related to dyadic mother-child emotional availability (EA) in a play task with their children and whether alexithymia involving low emotional awareness that characterizes the NG could play a role in the cortical-EA associations. Whole-brain analysis of the cortical mantle identified reduced cortical thickness in the right rostral middle frontal gyrus and an increased surface area in the right lingual and lateral occipital cortices for the NG with respect to the CG. Follow-up path analysis showed direct effects of the right rostral middle frontal gyrus (RMFG) on the emotional availability (EA) and on the difficulty to identify feelings (alexithymia factor), with a marginal indirect RMFG-EA effect through this factor. These preliminary findings extend existing work by implicating differences in cortical features associated with neglectful parenting and relevant to mother-child interactive bonding.
Cortical Plasticity and Interneuron Recruitment in Adolescents Born to Women with Gestational Diabetes Mellitus
Authors: Van Dam Jago M. , Goldsworthy Mitchell R. , Hague William M. , Coat Suzette , Pitcher Julia B.
Published: March 2021

Exposure to gestational diabetes mellitus (GDM) in utero is associated with a range of adverse cognitive and neurological outcomes. Previously, we reported altered neuroplastic responses to continuous theta burst stimulation (cTBS) in GDM-exposed adolescents. Recent research suggests that the relative excitability of complex oligosynaptic circuits (late I-wave circuits) can predict these responses. We aimed to determine if altered I-wave recruitment was associated with neuroplastic responses in adolescents born to women with GDM. A total of 20 GDM-exposed adolescents and 10 controls (aged 13.1 ± 1.0 years) participated. cTBS was used to induce neuroplasticity. I-wave recruitment was assessed by comparing motor-evoked potential latencies using different TMS coil directions. Recruitment of late I-waves was associated with stronger LTD-like neuroplastic responses to cTBS (p = < 0.001, R2 = 0.36). There were no differences between groups in mean neuroplasticity (p = 0.37), I-wave recruitment (p = 0.87), or the association between these variables (p = 0.41). The relationship between I-wave recruitment and the response to cTBS previously observed in adults is also present in adolescents and does not appear to be altered significantly by in utero GDM exposure. Exposure to GDM does not appear to significantly impair LTD-like synaptic plasticity or interneuron recruitment.
A Scientometric Approach to Review the Role of the Medial Preoptic Area (MPOA) in Parental Behavior
Authors: Carollo Alessandro , Balagtas Jan Paolo Macapinlac , Neoh Michelle Jin-Yee , Esposito Gianluca
Published: March 2021

Research investigating the neural substrates underpinning parental behaviour has recently gained momentum. Particularly, the hypothalamic medial preoptic area (MPOA) has been identified as a crucial region for parenting. The current study conducted a scientometric analysis of publications from 1 January 1972 to 19 January 2021 using CiteSpace software to determine trends in the scientific literature exploring the relationship between MPOA and parental behaviour. In total, 677 scientific papers were analysed, producing a network of 1509 nodes and 5498 links. Four major clusters were identified: “C-Fos Expression”, “Lactating Rat”, “Medial Preoptic Area Interaction” and “Parental Behavior”. Their content suggests an initial trend in which the properties of the MPOA in response to parental behavior were studied, followed by a growing attention towards the presence of a brain network, including the reward circuits, regulating such behavior. Furthermore, while attention was initially directed uniquely to maternal behavior, it has recently been extended to the understanding of paternal behaviors as well. Finally, although the majority of the studies were conducted on rodents, recent publications broaden the implications of previous documents to human parental behavior, giving insight into the mechanisms underlying postpartum depression. Potential directions in future works were also discussed.
Effects of Dizocilpine, Midazolam and Their Co-Application on the Trimethyltin (TMT)-Induced Rat Model of Cognitive Deficit
Authors: Chvojkova Marketa , Kubova Hana , Vales Karel
Published: March 2021

Research of treatment options addressing the cognitive deficit associated with neurodegenerative disorders is of particular importance. Application of trimethyltin (TMT) to rats represents a promising model replicating multiple relevant features of such disorders. N-methyl-D-aspartate (NMDA) receptor antagonists and gamma-aminobutyric acid type A (GABAA) receptor potentiators have been reported to alleviate the TMT-induced cognitive deficit. These compounds may provide synergistic interactions in other models. The aim of this study was to investigate, whether co-application of NMDA receptor antagonist dizocilpine (MK-801) and GABAA receptor potentiator midazolam would be associated with an improved effect on the TMT-induced model of cognitive deficit. Wistar rats injected with TMT were repeatedly (12 days) treated with MK-801, midazolam, or both. Subsequently, cognitive performance was assessed. Finally, after a 17-day drug-free period, hippocampal neurodegeneration (neuronal density in CA2/3 subfield in the dorsal hippocampus, dentate gyrus morphometry) were analyzed. All three protective treatments induced similar degree of therapeutic effect in Morris water maze. The results of histological analyses were suggestive of minor protective effect of the combined treatment (MK-801 and midazolam), while these compounds alone were largely ineffective at this time point. Therefore, in terms of mitigation of cognitive deficit, the combined treatment was not associated with improved effect.
Hereditary Spastic Paraplegia: From Genes, Cells and Networks to Novel Pathways for Drug Discovery
Authors: Mackay-Sim Alan
Published: March 2021

Hereditary spastic paraplegia (HSP) is a diverse group of Mendelian genetic disorders affecting the upper motor neurons, specifically degeneration of their distal axons in the corticospinal tract. Currently, there are 80 genes or genomic loci (genomic regions for which the causative gene has not been identified) associated with HSP diagnosis. HSP is therefore genetically very heterogeneous. Finding treatments for the HSPs is a daunting task: a rare disease made rarer by so many causative genes and many potential mutations in those genes in individual patients. Personalized medicine through genetic correction may be possible, but impractical as a generalized treatment strategy. The ideal treatments would be small molecules that are effective for people with different causative mutations. This requires identification of disease-associated cell dysfunctions shared across genotypes despite the large number of HSP genes that suggest a wide diversity of molecular and cellular mechanisms. This review highlights the shared dysfunctional phenotypes in patient-derived cells from patients with different causative mutations and uses bioinformatic analyses of the HSP genes to identify novel cell functions as potential targets for future drug treatments for multiple genotypes.
Integration of BIM and Immersive Technologies for AEC: A Scientometric-SWOT Analysis and Critical Content Review
Authors: Khan Ayaz , Sepasgozar Samad , Liu Tingting , Yu Rongrong
Published: March 2021

With the outset of Industrial Revolution 4.0 (IR 4.0), every sector is escalating to get enrichment out of it, whether they are research- or industry-oriented. The Architecture Engineering and Construction (AEC) industry lags a bit in adopting it because of its multi-faceted dependencies and unique nature of work. Despite this, a trend has been seen recently to hone the IR 4.0 multitudes in the AEC industry. The upsurge has been seen in the usage of Immersive Technologies (ImTs) as one of the disruptive techniques. This paper studies the literature based on ImTs, which are Virtual Reality (VR), Augmented Reality (AR), and Mixed Reality (MR) integrating with Building Information Modelling (BIM) in the AEC sector. A total number of 444 articles were selected from Scopus following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) protocol of reviewing the literature. Among the selected database, 64 papers are identified as the result of following the protocol, and the articles are divided into eight domains relevant to the AEC industry, namely client/stakeholder, design exploration, design analysis, construction planning, construction monitoring, construction health/safety, facility/management, and education/training. This study adopts both a scientometric analysis for bibliometrics visualization and a critical review using Strength Weakness Opportunity Threat (SWOT) analysis for finding gaps and state of play. The novelty of this paper lies in the analysis techniques used in the literature to provide an insight into the literature, and it provides directions for the future with an emphasis on developing sustainable development goals (SDGs). In addition, research directions for the future growth on the adoption of ImTs are identified and presented based on categorization in immersive devices, graphical/non-graphical data and, responsive/integrative processes. In addition, five subcategories for each direction are listed, citing the limitations and future/needs. This study presents the roadmap for the successful adoption of ImTs for industry practitioners and stakeholders in the AEC industry for various domains. The paper shows that there are studies on ImTs with or without BIM; however, future studies should focus on the usage of ImTs in various sectors such as modular integrated construction (MiC) or emerging needs such as SDGs.
Training Simulators for Gastrointestinal Endoscopy: Current and Future Perspectives
Authors: Finocchiaro Martina , Cortegoso Valdivia Pablo , Hernansanz Albert , Marino Nicola , Amram Denise , Casals Alicia , Menciassi Arianna , Marlicz Wojciech , Ciuti Gastone , Koulaouzidis Anastasios
Published: March 2021

Gastrointestinal (GI) endoscopy is the gold standard in the detection and treatment of early and advanced GI cancers. However, conventional endoscopic techniques are technically demanding and require visual-spatial skills and significant hands-on experience. GI endoscopy simulators represent a valid solution to allow doctors to practice in a pre-clinical scenario. From the first endoscopy mannequin, developed in 1969, several simulation platforms have been developed, ranging from purely mechanical systems to more complex mechatronic devices and animal-based models. Considering the recent advancement of technologies (e.g., artificial intelligence, augmented reality, robotics), simulation platforms can now reach high levels of realism, representing a valid and smart alternative to standard trainee/mentor learning programs. This is particularly true nowadays, when the current demographic trend and the most recent pandemic demand, more than ever, the ability to cope with many patients. This review offers a broad view of the technology available for GI endoscopy training, including platforms currently in the market and the relevant advancements in this research and application field. Additionally, new training needs and new emerging technologies are discussed to understand where medical education is heading.
The Debatable Benefit of Gross-Total Resection of Brain Metastases in a Comprehensive Treatment Setting
Authors: Jünger Stephanie T. , Pennig Lenhard , Schödel Petra , Goldbrunner Roland , Friker Lea , Kocher Martin , Proescholdt Martin , Grau Stefan
Published: March 2021

Background and Purpose: The value of gross-total surgical resection remains debatable in patients with brain metastases (BMs) as most patients succumb to systemic disease progression. In this study, we evaluated the impact of the extent of resection of singular/solitary BM on in-brain recurrence (iBR), focusing on local recurrence (LR) and overall survival (OS) in an interdisciplinary adjuvant treatment setting. Patients and Methods: In this monocentric retrospective analysis, we included patients receiving surgery of one BM and subsequent adjuvant treatment. A radiologist and a neurosurgeon determined in consensus the extent of resection based on magnetic resonance imaging. The OS was calculated using Kaplan–Meier estimates; prognostic factors for LR and OS were analysed by Log rank test and Cox proportional hazards. Results: We analyzed 197 patients. Gross-total resection was achieved in 123 (62.4%) patients. All patients were treated with adjuvant radiotherapy, and 130 (66.0%) received systemic treatment. Ninety-six (48.7%) patients showed iBR with an LR rate of 23.4%. LR was not significantly influenced by the extent of resection (p = 0.139) or any other parameter. The median OS after surgery was 18 (95%CI 12.5–23.5) months. In univariate analysis, the extent of resection did not influence OS (p = 0.6759), as opposed to adjuvant systemic treatment (p < 0.0001) and controlled systemic disease (p = 0.039). Systemic treatment and controlled disease status remained independent factors for OS (p < 0.0001 and p = 0.009, respectively). Conclusions: In this study, the extent of resection of BMs neither influenced the LR nor the OS of patients receiving interdisciplinary adjuvant treatment.
CTLA-4 in Regulatory T Cells for Cancer Immunotherapy
Authors: Sobhani Navid , Tardiel-Cyril Dana Rae , Davtyan Aram , Generali Daniele , Roudi Raheleh , Li Yong
Published: March 2021

Immune checkpoint inhibitors (ICIs) have obtained durable responses in many cancers, making it possible to foresee their potential in improving the health of cancer patients. However, immunotherapies are currently limited to a minority of patients and there is a need to develop a better understanding of the basic molecular mechanisms and functions of pivotal immune regulatory molecules. Immune checkpoint cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and regulatory T (Treg) cells play pivotal roles in hindering the anticancer immunity. Treg cells suppress antigen-presenting cells (APCs) by depleting immune stimulating cytokines, producing immunosuppressive cytokines and constitutively expressing CTLA-4. CTLA-4 molecules bind to CD80 and CD86 with a higher affinity than CD28 and act as competitive inhibitors of CD28 in APCs. The purpose of this review is to summarize state-of-the-art understanding of the molecular mechanisms underlining CTLA-4 immune regulation and the correlation of the ICI response with CTLA-4 expression in Treg cells from preclinical and clinical studies for possibly improving CTLA-4-based immunotherapies, while highlighting the knowledge gap.
Retargeting of NK-92 Cells against High-Risk Rhabdomyosarcomas by Means of an ERBB2 (HER2/Neu)-Specific Chimeric Antigen Receptor
Authors: Gossel Leonie D. H. , Heim Catrin , Pfeffermann Lisa-Marie , Moser Laura M. , Bönig Halvard B. , Klingebiel Thomas E. , Bader Peter , Wels Winfried S. , Merker Michael , Rettinger Eva
Published: March 2021

The dismal prognosis of pediatric and young adult patients with high-risk rhabdomyosarcoma (RMS) underscores the need for novel treatment options for this patient group. In previous studies, the tumor-associated surface antigen ERBB2 (HER2/neu) was identified as targetable in high-risk RMS. As a proof of concept, in this study, a novel treatment approach against RMS tumors using a genetically modified natural killer (NK)-92 cell line (NK-92/5.28.z) as an off-the-shelf ERBB2-chimeric antigen receptor (CAR)-engineered cell product was preclinically explored. In cytotoxicity assays, NK-92/5.28.z cells specifically recognized and efficiently eliminated RMS cell suspensions, tumor cell monolayers, and 3D tumor spheroids via the ERBB2-CAR even at effector-to-target ratios as low as 1:1. In contrast to unmodified parental NK-92 cells, which failed to lyse RMS cells, NK-92/5.28.z cells proliferated and became further activated through contact with ERBB2-positive tumor cells. Furthermore, high amounts of effector molecules, such as proinflammatory and antitumoral cytokines, were found in cocultures of NK-92/5.28.z cells with tumor cells. Taken together, our data suggest the enormous potential of this approach for improving the immunotherapy of treatment-resistant tumors, revealing the dual role of NK-92/5.28.z cells as CAR-targeted killers and modulators of endogenous adaptive immunity even in the inhibitory tumor microenvironment of high-risk RMS.
Immunonutrition Changes Inflammatory Response in Colorectal Cancer: Results from a Pilot Randomized Clinical Trial
Authors: Wierdak Mateusz , Surmiak Marcin , Milian-Ciesielska Katarzyna , Rubinkiewicz Mateusz , Rzepa Anna , Wysocki Michał , Major Piotr , Kłęk Stanisław , Pędziwiatr Michał
Published: March 2021

Introduction: Surgery is the first choice of treatment for colorectal cancer. Nutritional support in the form of oral nutritional supplements (ONSs) in the preoperative period is widely accepted for reducing the incidence of perioperative complications, and immunonutrition is generally recommended. However, there is little clinical data regarding the impact of such treatment on tumor biology. Material and Methods: In this study, tumor tissue and blood samples were collected from 26 patients during preoperative colonoscopy at the time of clinical diagnosis (sample A). Group 1 received standard ONSs (3× Nutricia Nutridrink Protein per day) for 2 weeks before surgery. In group 2, immune ONSs (2× Nestle Impact Oral) were administered for the same duration. Tumor tissue (sample B) was then retrieved from the tumor after resection. Changes in the expression levels of inflammatory cytokines (TNF-α, interleukin 8 or chemokine (C-X-C motif) ligand (CXCL8), stromal cell-derived factor 1 (SDF1a), chemokine (C-X-C motif) ligand 6 (CXCL6), chemokine (C-X-C motif) ligand (CXCL2), myeloperoxidase (MPO), and CXCL1) were assessed during the perioperative course. Results: TNF-α expression differed after intervention between the two groups (immune group 31.63 ± 13.28; control group 21.54 ± 6.84; p = 0.049) and prior to and after intervention in the control group (prior to intervention 35.68 ± 24.41; after intervention 21.54 ± 6.84; p = 0.038). Changes in CXCL8 expression in the control group occurred prior to and after intervention (prior to intervention 2975.93 ± 1484.04; after intervention 1584.85 ± 1659.84; p = 0.041). CXCL1 expression was increased in the immune group and decreased in the control group (immune group 2698.27 (1538.14–5124.70); control group 953.75 (457.85–1534.60); p = 0.032). In both groups, a decrease in superficial neutrophil infiltration was observed, but this was only statistically significant in the immune group. There was no impact of the observed differences between the two groups on surgical outcomes (morbidity, length of stay, readmissions). Conclusions: Immunonutrition in the preoperative period compared with standard nutritional support may influence inflammatory cytokine expression and leukocyte infiltration in patients with colorectal cancer.
Specific Patterns of Blood ILCs in Metastatic Melanoma Patients and Their Modulations in Response to Immunotherapy
Authors: Rethacker Louise , Roelens Marie , Bejar Claudia , Maubec Eve , Moins-Teisserenc Hélène , Caignard Anne
Published: March 2021

Immunotherapy targeting immune checkpoint receptors brought a breakthrough in the treatment of metastatic melanoma patients. However, a number of patients still resist these immunotherapies. Present on CD8+T cells, immune checkpoint receptors are expressed by innate lymphoid cells (ILCs), which may contribute to the clinical response. ILCs are composed of natural killer (NK) cells, which are cytotoxic effectors involved in tumor immunosurveillance. NK cell activation is regulated by a balance between activating receptors that detect stress molecules on tumor cells and HLA-I-specific inhibitory receptors. Helper ILCs (h-ILCs) are newly characterized ILCs that secrete cytokines and regulate the immune homeostasis of tissue. We investigated the modulation of blood ILCs in melanoma patients treated with ipilimumab. Circulating ILCs from metastatic stage IV melanoma patients and healthy donors were studied for their complete phenotypic status. Patients were studied before and at 3, 6, and 12 weeks of ipilimumab treatment. A comparison of blood ILC populations from donors and melanoma patients before treatment showed changes in proportions of ILC subsets, and a significant inverse correlation of CD56dim NK cells and h-ILC subsets was identified in patients. During treatment with ipilimumab, percentages of all ILC subsets were reduced. Ipilimumab also impacted the expression of the CD96/TIGIT/DNAM-1 pathway in all ILCs and increased CD161 and CTLA-4 expression by h-ILCs. When considering the response to the treatment, patients without disease control were characterized by higher percentages of CD56bright NK cells and ILC1. Patients with disease control displayed larger populations of activated CD56dimCD16+ DNAM-1+ NK cells, while anergic CD56dimCD16−DNAM-1− NK cells were prominent in patients without disease control. These results provide original findings on the distribution of ILC subsets in advanced melanoma patients and their modulation through immunotherapy. The effects of ipilimumab on these ILC subsets may critically influence therapeutic outcomes. These data indicate the importance of considering these innate cell subsets in immunotherapeutic strategies for melanoma patients.
One-Year Morbidity Following Videoscopic Inguinal Lymphadenectomy for Stage III Melanoma
Authors: Jansen Marnix R. , Vrielink Otis M. , Faut Marloes , Deckers Eric A. , Been Lukas B. , van Leeuwen Barbara L.
Published: March 2021

Purpose: We aimed to elucidate morbidity following videoscopic inguinal lymphadenectomy for stage III melanoma. Methods: Melanoma patients who underwent a videoscopic inguinal lymphadenectomy between November 2015 and May 2019 were included. The measured outcomes were lymphedema and quality of life. Patients were reviewed one day prior to surgery and postoperatively every 3 months for one year. Results: A total number of 34 patients were included for participation; 19 (55.9%) patients underwent a concomitant iliac lymphadenectomy. Lymphedema incidence was 40% at 3 months and 50% at 12 months after surgery. Mean interlimb volume difference increased steadily from 1.8% at baseline to 6.9% at 12 months (p = 0.041). Median Lymph-ICF-LL total score increased from 0.0 at baseline to 12.0 at 3 months, and declined to 8.5 at 12 months (p = 0.007). Twelve months after surgery, Lymph-ICF-LL scores were higher for females (p = 0.021) and patients that received adjuvant radiotherapy (p = 0.013). The Median Distress Thermometer and EORTC QLQ-C30 summary score recovered to baseline at 12 months postoperatively (p = 0.747 and p = 0.203, respectively). Conclusions: The onset of lymphedema is rapid and continues to increase up to one year after videoscopic inguinal lymphadenectomy. Quality of life recovers to the baseline value.
Impact of Pathological Stratification on the Clinical Outcomes of Advanced Well-Differentiated/Dedifferentiated Liposarcoma Treated with Trabectedin
Authors: Fabbroni Chiara , Fucà Giovanni , Ligorio Francesca , Fumagalli Elena , Barisella Marta , Collini Paola , Morosi Carlo , Gronchi Alessandro , Dei Tos Angelo Paolo , Casali Paolo Giovanni , Sanfilippo Roberta
Published: March 2021

Background. We previously showed that grading can prognosticate the outcome of retroperitoneal liposarcoma (LPS). In the present study, we aimed to explore the impact of pathological stratification using grading on the clinical outcomes of patients with advanced well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) treated with trabectedin. Patients: We included patients with advanced WDLPS and DDLPS treated with trabectedin at the Fondazione IRCCS Istituto Nazionale dei Tumori between April 2003 and November 2019. Tumors were categorized in WDLPS, low-grade DDLPS, and high-grade DDLPS according to the 2020 WHO classification. Patients were divided in two cohorts: Low-grade (WDLPS/low-grade DDLPS) and high-grade (high-grade DDLPS). Results: A total of 49 patients were included: 17 (35%) in the low-grade cohort and 32 (65%) in the high-grade cohort. Response rate was 47% in the low-grade cohort versus 9.4% in the high-grade cohort (logistic regression p = 0.006). Median progression-free survival (PFS) was 13.7 months in the low-grade cohort and 3.2 months in the high-grade cohort. Grading was confirmed as an independent predictor of PFS in the Cox proportional-hazards regression multivariable model (adjusted hazard ratio low-grade vs. high-grade: 0.45, 95% confidence interval: 0.22–0.94; adjusted p = 0.035). Conclusions: In this retrospective case series, sensitivity to trabectedin was higher in WDLPS/low-grade DDLPS than in high-grade DDLPS. If confirmed in larger series, grading could represent an effective tool to personalize the treatment with trabectedin in patients with advanced LPS.
Nonthermal Plasma Induced Fabrication of Solid Acid Catalysts for Glycerol Dehydration to Acrolein
Authors: Liu Lu , Ye Xiaofei Philip
Published: March 2021

The feasibility of fabricating better solid acid catalysts using nonthermal plasma (NTP) technology for biobased acrolein production is demonstrated. NTP discharge exposure was integrated in catalyst fabrication in air or argon atmosphere. The fabricated catalysts were characterized by Brunauer–Emmett–Teller surface area analysis, temperature-programmed desorption of ammonia, X-ray powder diffraction and Fourier-transform infrared spectroscopy of pyridine adsorption, in comparison to regularly prepared catalysts as a control. Further, kinetic results collected via glycerol dehydration experiments were compared, and improvement in acrolein selectivity was displayed when the catalyst was fabricated in the argon NTP, but not in the air NTP. Possible mechanisms for the improvement were also discussed.
A Review of Hydrogen Purification Technologies for Fuel Cell Vehicles
Authors: Du Zhemin , Liu Congmin , Zhai Junxiang , Guo Xiuying , Xiong Yalin , Su Wei , He Guangli
Published: March 2021

Nowadays, we face a series of global challenges, including the growing depletion of fossil energy, environmental pollution, and global warming. The replacement of coal, petroleum, and natural gas by secondary energy resources is vital for sustainable development. Hydrogen (H2) energy is considered the ultimate energy in the 21st century because of its diverse sources, cleanliness, low carbon emission, flexibility, and high efficiency. H2 fuel cell vehicles are commonly the end-point application of H2 energy. Owing to their zero carbon emission, they are gradually replacing traditional vehicles powered by fossil fuel. As the H2 fuel cell vehicle industry rapidly develops, H2 fuel supply, especially H2 quality, attracts increasing attention. Compared with H2 for industrial use, the H2 purity requirements for fuel cells are not high. Still, the impurity content is strictly controlled since even a low amount of some impurities may irreversibly damage fuel cells’ performance and running life. This paper reviews different versions of current standards concerning H2 for fuel cell vehicles in China and abroad. Furthermore, we analyze the causes and developing trends for the changes in these standards in detail. On the other hand, according to characteristics of H2 for fuel cell vehicles, standard H2 purification technologies, such as pressure swing adsorption (PSA), membrane separation and metal hydride separation, were analyzed, and the latest research progress was reviewed.
Hypoxia-Driven Effects in Cancer: Characterization, Mechanisms, and Therapeutic Implications
Authors: Shi Rachel , Liao Chengheng , Zhang Qing
Published: March 2021

Hypoxia, a common feature of solid tumors, greatly hinders the efficacy of conventional cancer treatments such as chemo-, radio-, and immunotherapy. The depletion of oxygen in proliferating and advanced tumors causes an array of genetic, transcriptional, and metabolic adaptations that promote survival, metastasis, and a clinically malignant phenotype. At the nexus of these interconnected pathways are hypoxia-inducible factors (HIFs) which orchestrate transcriptional responses under hypoxia. The following review summarizes current literature regarding effects of hypoxia on DNA repair, metastasis, epithelial-to-mesenchymal transition, the cancer stem cell phenotype, and therapy resistance. We also discuss mechanisms and pathways, such as HIF signaling, mitochondrial dynamics, exosomes, and the unfolded protein response, that contribute to hypoxia-induced phenotypic changes. Finally, novel therapeutics that target the hypoxic tumor microenvironment or interfere with hypoxia-induced pathways are reviewed.
SRSF9 Regulates Cassette Exon Splicing of Caspase-2 by Interacting with Its Downstream Exon
Authors: Ha Jiyeon , Jang Hana , Choi Namjeong , Oh Jagyeong , Min Chanhyuk , Pradella Davide , Jung Da-Woon , Williams Darren R. , Park Daeho , Ghigna Claudia , Zheng Xuexiu , Shen Haihong
Published: March 2021

Alternative splicing (AS) is an important posttranscriptional regulatory process. Damaged or unnecessary cells need to be removed though apoptosis to maintain physiological processes. Caspase-2 pre-mRNA produces pro-apoptotic long mRNA and anti-apoptotic short mRNA isoforms through AS. How AS of Caspase-2 is regulated remains unclear. In the present study, we identified a novel regulatory protein SRSF9 for AS of Caspase-2 cassette exon 9. Knock-down (KD) of SRSF9 increased inclusion of cassette exon and on the other hand, overexpression of SRSF9 decreased inclusion of this exon. Deletion mutagenesis demonstrated that exon 9, parts of intron 9, exon 8 and exon 10 were not required for the role of SRSF9 in Caspase-2 AS. However, deletion and substitution mutation analysis revealed that AGGAG sequence located at exon 10 provided functional target for SRSF9. In addition, RNA-pulldown mediated immunoblotting analysis showed that SRSF9 interacted with this sequence. Gene ontology analysis of RNA-seq from SRSF9 KD cells demonstrates that SRSF9 could regulate AS of a subset of apoptosis related genes. Collectively, our results reveal a basis for regulation of Caspase-2 AS.
Defects in Cell Wall Differentiation of the Arabidopsis Mutant rol1-2 Is Dependent on Cyclin-Dependent Kinase CDK8
Authors: Schumacher Isabel , Ndinyanka Fabrice Tohnyui , Abdou Marie-Therese , Kuhn Benjamin M. , Voxeur Aline , Herger Aline , Roffler Stefan , Bigler Laurent , Wicker Thomas , Ringli Christoph
Published: March 2021

Plant cells are encapsulated by cell walls whose properties largely determine cell growth. We have previously identified the rol1-2 mutant, which shows defects in seedling root and shoot development. rol1-2 is affected in the Rhamnose synthase 1 (RHM1) and shows alterations in the structures of Rhamnogalacturonan I (RG I) and RG II, two rhamnose-containing pectins. The data presented here shows that root tissue of the rol1-2 mutant fails to properly differentiate the cell wall in cell corners and accumulates excessive amounts of callose, both of which likely alter the physical properties of cells. A surr (suppressor of the rol1-2 root developmental defect) mutant was identified that alleviates the cell growth defects in rol1-2. The cell wall differentiation defect is re-established in the rol1-2 surr mutant and callose accumulation is reduced compared to rol1-2. The surr mutation is an allele of the cyclin-dependent kinase 8 (CDK8), which encodes a component of the mediator complex that influences processes central to plant growth and development. Together, the identification of the surr mutant suggests that changes in cell wall composition and turnover in the rol1-2 mutant have a significant impact on cell growth and reveals a function of CDK8 in cell wall architecture and composition.
Biochar from Spent Malt Rootlets and Its Application to an Energy Conversion and Storage Device
Authors: Vakros John , Manariotis Ioannis D. , Dracopoulos Vassilios , Mantzavinos Dionissios , Lianos Panagiotis
Published: March 2021

Activated carbon obtained from biomass wastes was presently studied in order to evaluate its applicability in an energy storage device. Biochar was obtained by the carbonization of spent malt rootlets and was further processed by mild treatment in NaOH. The final product had a specific surface of 362 m2 g−1 and carried Na, P and a few mineral sites. This material was first characterized by several techniques. Then it was used to make a supercapacitor electrode, which reached a specific capacitance of 156 F g−1. The supercapacitor electrode was combined with a photocatalytic fuel cell, making a simple three-electrode device functioning with a single alkaline electrolyte. This device allows solar energy conversion and storage at the same time, promoting the use of biomass wastes for energy applications.
Establishment of a Pediatric Surgical Unit at a University Hospital in Eastern Africa
Authors: Hubertus Jochen , Abera Gersam , Haileamlak Abraham , Siebeck Matthias , von Schweinitz Dietrich , Wagner Ferdinand , Eckle Rosa , Wessel Lucas , Ritz Laura , Ardelean Mircia Aurel , Becker Kristina , Seifu Alemu
Published: March 2021

Introduction: Ethiopia is a rapidly developing country in Eastern Africa. In total, 43.2% of the population are younger than 15. In contrast, until a few years ago, pediatric surgery was only available in Addis Ababa. Now, Ethiopia is making great efforts to improve the care of children who require surgery. JimmaChild was established to set up a pediatric surgery in Jimma. Material and methods: JimmaChild developed from a scientific collaboration between Jimma University (JU) and Ludwig-Maximilians-University. The project was developed and realized by Ethiopian and German colleagues. A curriculum was written for this purpose. The pediatric surgical training of the fellows was carried out on-site by German pediatric surgeons. Results: A new pediatric surgery was established at JU with its own operating room, ward, and staff. After two and a half years, two fellows completed their final examinations as pediatric surgeons. Among others, 850 elective surgeries were performed, 82% assisted by the German colleagues. The German colleagues rated the preparation for the trip, the on-site support, and the professional progress of the fellows mostly as good to very good. Reported problems in the program flow were also recognized and solved in part. Conclusions: The best possible integration of the project into existing structures was achieved by close cooperation of Ethiopian and German colleagues during the project development. Problems were identified and addressed early on by external monitoring. As the project responsibility was mainly with the Ethiopian colleagues, a department was created that now exists independently of external funding and trains its own fellows.
Characteristics and Crystal Structure of Calcareous Deposit Films Formed by Electrodeposition Process in Artificial and Natural Seawater
Authors: Park Jun-Mu , Lee Myeong-Hoon , Lee Seung-Hyo
Published: March 2021

In this study, we tried to form the calcareous deposit films by the electrodeposition process. The uniform and compact calcareous deposit films were formed by electrodeposition process and their crystal structure and characteristics were analyzed and evaluated using various surface analytical techniques. The mechanism of formation for the calcareous deposit films could be confirmed and the role of magnesium was verified by experiments in artificial and natural seawater solutions. The highest amount of the calcareous deposit film was obtained at 5 A/m2 while current densities between 1–3 A/m2 facilitated the formation of the most uniform and dense layers. In addition, the adhesion characteristics were found to be the best at 3 A/m2. The excellent characteristics of the calcareous deposit films were obtained when the dense film of brucite-Mg(OH)2 and metastable aragonite-CaCO3 was formed in the appropriate ratio.
Recent Advances in Nanomaterials for Dermal and Transdermal Applications
Authors: Zoabi Amani , Touitou Elka , Margulis Katherine
Published: March 2021

The stratum corneum, the most superficial layer of the skin, protects the body against environmental hazards and presents a highly selective barrier for the passage of drugs and cosmetic products deeper into the skin and across the skin. Nanomaterials can effectively increase the permeation of active molecules across the stratum corneum and enable their penetration into deeper skin layers, often by interacting with the skin and creating the distinct sites with elevated local concentration, acting as reservoirs. The flux of the molecules from these reservoirs can be either limited to the underlying skin layers (for topical drug and cosmeceutical delivery) or extended across all the sublayers of the epidermis to the blood vessels of the dermis (for transdermal delivery). The type of the nanocarrier and the physicochemical nature of the active substance are among the factors that determine the final skin permeation pattern and the stability of the penetrant in the cutaneous environment. The most widely employed types of nanomaterials for dermal and transdermal applications include solid lipid nanoparticles, nanovesicular carriers, microemulsions, nanoemulsions, and polymeric nanoparticles. The recent advances in the area of nanomaterial-assisted dermal and transdermal delivery are highlighted in this review.
Concepts of Nucleation in Polymer Crystallization
Authors: Xu Jun , Reiter Günter , Alamo Rufina
Published: March 2021

Nucleation plays a vital role in polymer crystallization, in which chain connectivity and thus the multiple length and time scales make crystal nucleation of polymer chains an interesting but complex subject. Though the topic has been intensively studied in the past decades, there are still many open questions to answer. The final properties of semicrystalline polymer materials are affected by all of the following: the starting melt, paths of nucleation, organization of lamellar crystals and evolution of the final crystalline structures. In this viewpoint, we attempt to discuss some of the remaining open questions and corresponding concepts: non-equilibrated polymers, self-induced nucleation, microscopic kinetics of different processes, metastability of polymer lamellar crystals, hierarchical order and cooperativity involved in nucleation, etc. Addressing these open questions through a combination of novel concepts, new theories and advanced approaches provides a deeper understanding of the multifaceted process of crystal nucleation of polymers.