bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Early Mobilization on Recovery after Major Head and Neck Surgery with Free Flap Reconstruction
Authors: Twomey Rosie , Matthews T. Wayne , Nakoneshny Steven , Schrag Christiaan , Chandarana Shamir P. , Matthews Jennifer , McKenzie David , Hart Robert D. , Li Na , Sauro Khara M. , Dort Joseph C.
Published: June 2021

Surgery with free flap reconstruction is a standard treatment for head and neck cancer (HNC). Because of the complexity of HNC surgery, recovery can be challenging, and complications are common. One of the foundations of enhanced recovery after surgery (ERAS) is early postoperative mobilization. The ERAS guidelines for HNC surgery with free flap reconstruction recommend mobilization within 24 h. This is based mainly on evidence from other surgical disciplines, and the extent to which mobilization within 24 h improves recovery after HNC surgery has not been explored. This retrospective analysis included 445 patients from the Calgary Head and Neck Enhanced Recovery Program. Mobilization after 24 h was associated with more complications of any type (OR = 1.73, 95% CI [confidence interval] = 1.16–2.57) and more major complications (OR = 1.76; 95% CI = 1.00–3.16). When accounting for patient and clinical factors, mobilization after 48 h was a significant predictor of major complications (OR = 2.61; 95% CI = 1.10–6.21) and prolonged length of stay (>10 days; OR = 2.85, 95% CI = 1.41–5.76). This comprehensive analysis of the impact of early mobilization on postoperative complications and length of stay in a large HNC cohort provides novel evidence supporting adherence to the ERAS early mobilization recommendations. Early mobilization should be a priority for patients undergoing HNC surgery with free flap reconstruction.
In-Vivo LC-OCT Evaluation of the Downward Proliferation Pattern of Keratinocytes in Actinic Keratosis in Comparison with Histology: First Impressions from a Pilot Study
Authors: Ruini Cristel , Schuh Sandra , Gust Charlotte , Hartmann Daniela , French Lars Einar , Sattler Elke Christina , Welzel Julia
Published: June 2021

It is known that actinic keratoses (AKs) can progress to invasive squamous cell carcinoma (SCC). The histological PRO grading of AKs is based on the growth pattern of basal keratinocytes and relates to their progression risk. AKs can be non-invasively characterized by line-field confocal optical coherence tomography (LC-OCT). The aim of the study was to define criteria for an LC-OCT grading of AKs based on the PRO classification and to correlate it with its histological counterpart. To evaluate the interobserver agreement for the LC-OCT PRO classification, fifty AKs were imaged by LC-OCT and biopsied for histopathology. PRO histological grading was assessed by an expert consensus, while two evaluator groups separately performed LC-OCT grading on vertical sections. The agreement between LC-OCT and histological PRO grading was 75% for all lesions (weighted kappa 0.66, 95% CI 0.48–0.83, p ≤ 0.001) and 85.4% when comparing the subgroups PRO I vs. PRO II/III (weighted kappa 0.64, 95% CI 0.40–0.88, p ≤ 0.001). The interobserver agreement for LC-OCT was 90% (Cohen’s kappa 0.84, 95% CI 0.71–0.91, p ≤ 0.001). In this pilot study, we demonstrated that LC-OCT is potentially able to classify AKs based on the basal growth pattern of keratinocytes, in-vivo reproducing the PRO classification, with strong interobserver agreement and a good correlation with histopathology.
Palliative Care Service Utilization and Advance Care Planning for Adult Glioblastoma Patients: A Systematic Review
Authors: Wu Adela , Ruiz Colón Gabriela , Aslakson Rebecca , Pollom Erqi , Patel Chirag B.
Published: June 2021

Glioblastoma (GBM) has a median overall survival of 16–21 months. As patients with GBM suffer concurrently from terminal cancer and a disease with progressive neurocognitive decline, advance care planning (ACP) and palliative care (PC) are critical. We conducted a systematic review exploring published literature on the prevalence of ACP, end-of-life (EOL) services utilization (including PC services), and experiences among adults with GBM. We searched from database inception until 20 December 2020. Preferred reporting items for systematic reviews guidelines were followed. Included studies were assessed for quality using the Newcastle-Ottawa Scale. The 16 articles were all nonrandomized studies conducted in six countries with all but two published in 2014 or later. ACP documentation varied from 4–55%, PC referral was pursued in 39–40% of cases, and hospice referrals were made for 66–76% of patients. Hospitalizations frequently occurred at the EOL with 20–56% of patients spending over 25% of their overall survival time hospitalized. Many GBM patients do not pursue ACP or have access to PC. There is a dearth of focused and high-quality studies on ACP, PC, and hospice use among adults with GBM. Prospective studies that address these and additional aspects related to EOL care, such as healthcare costs and inpatient supportive care needs, are needed.
ctDNA to Guide Adjuvant Therapy in Localized Colorectal Cancer (CRC)
Authors: Masfarré Laura , Vidal Joana , Fernández-Rodríguez Concepción , Montagut Clara
Published: June 2021

Currently, the standard treatment for patients with localized colorectal cancer (CRC) includes surgical resection followed by adjuvant chemotherapy based on clinicopathological features. Recurrence risk stratification in those patients is of utmost importance to guide clinicians to avoid both under- and overtreatment. Recently, the concept of minimal residual disease (MRD) has emerged as the detection of circulating tumor DNA (ctDNA) carrying tumor-specific genomic or epigenomic alterations in the bloodstream of patients after surgery. Emerging studies described how the detection of MRD is a powerful prognostic biomarker to identify patients at higher risk of recurrence and who will potentially benefit the most from a systemic adjuvant treatment. Based on that unprecedented finding, several clinical trials involving stage II and III CRC patients are ongoing evaluating the impact of ctDNA guided treatment by escalating or deescalating adjuvant chemotherapy based on ctDNA MRD detection. This review provides a critical overview of current perspectives of liquid biopsy in early-stage CRC including technical, biological, and clinical key points, as well as ongoing ctDNA-based clinical trials that ultimately aim to improve clinical outcomes of patients with CRC.
Dynamic Physiological Culture of Ex Vivo Human Tissue: A Systematic Review
Authors: Hughes Daniel Ll , Hughes Aron , Soonawalla Zahir , Mukherjee Somnath , O’Neill Eric
Published: June 2021

Conventional static culture fails to replicate the physiological conditions that exist in vivo. Recent advances in biomedical engineering have resulted in the creation of novel dynamic culturing systems that permit the recapitulation of normal physiological processes ex vivo. Whilst the physiological benefit for its use in the culture of two-dimensional cellular monolayer has been validated, its role in the context of primary human tissue culture has yet to be determined. This systematic review identified 22 articles that combined dynamic physiological culture techniques with primary human tissue culture. The most frequent method described (55%) utilised dynamic perfusion culture. A diverse range of primary human tissue was successfully cultured. The median duration of successful ex vivo culture of primary human tissue for all articles was eight days; however, a wide range was noted (5 h–60 days). Six articles (27%) reported successful culture of primary human tissue for greater than 20 days. This review illustrates the physiological benefit of combining dynamic culture with primary human tissue culture in both long-term culture success rates and preservation of native functionality of the tissue ex vivo. Further research efforts should focus on developing precise biochemical sensors that would allow for real-time monitoring and automated self-regulation of the culture system in order to maintain homeostasis. Combining these techniques allows the creation of an accurate system that can be used to gain a greater understanding of human physiology.
Histological Heterogeneity of Primary Liver Cancers: Clinical Relevance, Diagnostic Pitfalls and the Pathologist’s Role
Authors: Komuta Mina
Published: June 2021

Primary liver cancers (PLCs) mainly comprise hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and cHCC-CCA. Combined HCC-CCA and small duct type iCCA show similar clinical presentations, and their histological features are more complex than seen in HCC. Therefore, while their treatment strategy differs, it is difficult to properly diagnose these tumors. Currently, HCC is the only tumor that can be treated by liver transplantation. In addition, small duct type iCCA harbors IDH1/2 mutations and FGFR2 fusions, which can be used for targeted therapy. Thus, improving diagnostic accuracy is crucial. A further point to note is that PLCs often present as multiple liver tumors, and they can be a combination of different types of PLCs or HCCs. In the case of HCCs, two different scenarios are possible, namely intrahepatic metastasis, or multicentric occurrence. Therefore, it is essential to characterize the type of multiple liver tumors. This review aims to clarify the pathological features of HCC, iCCA and cHCC-CCA, including their diagnostic pitfalls and clinical relevance. It is designed to be of use to clinicians who are dealing with PLCs, to provide a better understanding of the pathology of these tumors, and to enable a more accurate diagnosis and optimal treatment choice.
CBP/p300: Critical Co-Activators for Nuclear Steroid Hormone Receptors and Emerging Therapeutic Targets in Prostate and Breast Cancers
Authors: Waddell Aaron R. , Huang Haojie , Liao Daiqing
Published: June 2021

The CREB-binding protein (CBP) and p300 are two paralogous lysine acetyltransferases (KATs) that were discovered in the 1980s–1990s. Since their discovery, CBP/p300 have emerged as important regulatory proteins due to their ability to acetylate histone and non-histone proteins to modulate transcription. Work in the last 20 years has firmly established CBP/p300 as critical regulators for nuclear hormone signaling pathways, which drive tumor growth in several cancer types. Indeed, CBP/p300 are critical co-activators for the androgen receptor (AR) and estrogen receptor (ER) signaling in prostate and breast cancer, respectively. The AR and ER are stimulated by sex hormones and function as transcription factors to regulate genes involved in cell cycle progression, metabolism, and other cellular functions that contribute to oncogenesis. Recent structural studies of the AR/p300 and ER/p300 complexes have provided critical insights into the mechanism by which p300 interacts with and activates AR- and ER-mediated transcription. Breast and prostate cancer rank the first and forth respectively in cancer diagnoses worldwide and effective treatments are urgently needed. Recent efforts have identified specific and potent CBP/p300 inhibitors that target the acetyltransferase activity and the acetytllysine-binding bromodomain (BD) of CBP/p300. These compounds inhibit AR signaling and tumor growth in prostate cancer. CBP/p300 inhibitors may also be applicable for treating breast and other hormone-dependent cancers. Here we provide an in-depth account of the critical roles of CBP/p300 in regulating the AR and ER signaling pathways and discuss the potential of CBP/p300 inhibitors for treating prostate and breast cancer.
Chemotherapy Shifts the Balance in Favor of CD8+ TNFR2+ TILs in Triple-Negative Breast Tumors
Authors: Baram Tamir , Erlichman Nofar , Dadiani Maya , Balint-Lahat Nora , Pavlovski Anya , Meshel Tsipi , Morzaev-Sulzbach Dana , Gal-Yam Einav Nili , Barshack Iris , Ben-Baruch Adit
Published: June 2021

Triple-negative breast cancer (TNBC) is primarily treated via chemotherapy; in parallel, efforts are made to introduce immunotherapies into TNBC treatment. CD4+ TNFR2+ lymphocytes were reported as Tregs that contribute to tumor progression. However, our published study indicated that TNFR2+ tumor-infiltrating lymphocytes (TNFR2+ TILs) were associated with improved survival in TNBC patient tumors. Based on our analyses of the contents of CD4+ and CD8+ TILs in TNBC patient tumors, in the current study, we determined the impact of chemotherapy on CD4+ and CD8+ TIL subsets in TNBC mouse tumors. We found that chemotherapy led to (1) a reduction in CD4+ TNFR2+ FOXP3+ TILs, indicating that chemotherapy decreased the content of CD4+ TNFR2+ Tregs, and (2) an elevation in CD8+ TNFR2+ and CD8+ TNFR2+ PD-1+ TILs; high levels of these two subsets were significantly associated with reduced tumor growth. In spleens of tumor-bearing mice, chemotherapy down-regulated CD4+ TNFR2+ FOXP3+ cells but the subset of CD8+ TNFR2+ PD-1+ was not present prior to chemotherapy and was not increased by the treatment. Thus, our data suggest that chemotherapy promotes the proportion of protective CD8+ TNFR2+ TILs and that, unlike other cancer types, therapeutic strategies directed against TNFR2 may be detrimental in TNBC.
Influence of Boronizing on Steel Performance under Erosion-Abrasion-Corrosion Conditions Simulating Downhole Oil Production
Authors: Medvedovski Eugene , Leal Mendoza Gerardo , Vargas Giovanny
Published: June 2021

Downhole heavy oil production and oil sand processing are associated with severe damage and failures of production equipment components, e.g., production tubing and pumping systems, due to erosion-corrosion resulting in processing losses, production downtime, high maintenance and replacement cost. Protective coatings (layers) on the production components mostly fabricated from low-alloy steels can be applied to minimize these problems. In the present work, the performance of hard boronized coating on carbon steel obtained through the thermal diffusion process and consisted of two iron boride layers (FeB and Fe2B) was studied in synergistic erosion-abrasion-corrosion conditions simulating oil production environment in comparison with bare steel. Special wear testing equipment was designed and fabricated. In this testing, the inner surface of tubular sections was subjected to high velocity erosive flows of water-oil slurries containing silica sand and salts combined with rotating and oscillating motions of steel pony rods. Structural examination of the studied materials’ surfaces and their profilometry after wear testing were conducted. The iron boride coating demonstrated significantly higher performance in abrasion and erosion-abrasion-corrosion conditions compared to bare carbon steel due to its high hardness, high chemical inertness, dual-layer architecture and diffusion-induced bonding with the substrate. The boronized steel tubing and casing with inner surface protection can be effectively employed in the most critical operation conditions.
A New Strong Form Technique for Thermo-Electro-Mechanical Behaviors of Piezoelectric Solids
Authors: Lv Jun , Shao Minjie , Xue Yuting , Gao Xiaowei , Xie Zhaoqian
Published: June 2021

Piezoelectric materials are widely fabricated and investigated for potential applications in microelectromechanical systems as direct converters between mechanical and electrical signals, where some show pyroelectric features involving thermo-electro-mechanical interactions. This study aimed to introduce a novel numerical technique to predict the thermo-electro-mechanical behaviors of piezoelectric structures, based on a strong-form numerical framework called the element differential method. In this method, the shape functions of the isoparametric element and their first two derivatives were derived analytically by interpolating the temperature, displacement, and electric potentials. Then, a point collocation method based on node positions in the elements was proposed to generate the final system of equations without any domain integrations. Thus, the coupled behaviors of thermal piezoelectric structures, including the pyroelectric features, can be simulated by the strong-form formulation of the governing equations. Several numerical examples, including the piezoelectric composites structures, are presented, and the coupled thermo-electro-mechanical responses have been analyzed to validate the proposed method.
A Participatory Agrobiodiversity Conservation Approach in the Oases: Community Actions for the Promotion of Sustainable Development in Fragile Areas
Authors: Peano Cristiana , Caron Stefania , Mahfoudhi Mohamed , Zammel Khouloud , Zaidi Houda , Sottile Francesco
Published: June 2021

Rural development policies today include significant directions towards ecological transition and sustainability. Biodiversity plays a fundamental role, especially in fragile environments. The North African oases, for example, are socio-ecological structures with delicate balances in terms of natural resources, where the activation of participatory conservation approaches appears today to be very useful, aiming at long-lasting results. This type of approach was applied in the oasis of El Hamma, in Tunisia. The socio-ecological analysis was carried out through semi-structured interviews with different stakeholders of the oasis. The results were used to activate focus groups and to identify, in a participatory way, a conservation strategy for the species and the varieties at risk of erosion or disappearing. From this research, a wide spread of non-traditional date palm and vegetables emerged in a very diverse social context. These products were recognized as highly significant in terms of traditional knowledge by all stakeholders. Therefore, a Maison des semences and a public conservation center for perennial species were created, representing the first step of a participatory conservation model. Seeds of 11 traditional annual species, 10 date palm varieties and, in perspective, many other fruit species and vegetable varieties have been introduced into conservation.
Experimental Investigation of Wave Attenuation Using a Hybrid of Polymer-Made Artificial Xbloc Wall and Mangrove Root Models
Authors: Sabari Adam Ado , Oates Ashley Richard , Akib Shatirah
Published: June 2021

Rising sea levels, strong wave currents and destructive human activities put coastal areas at risk of erosion and potential flooding. Several countermeasures have been introduced—both artificial and natural—to tackle the issue. This study investigated the effectiveness of the use of hybrid polymer-made artificial Xbloc walls and mangrove root models for protection against water waves. One Xbloc wall was made up of three Xbloc units stacked on top of each other and joined together using water-resistant tape. The artificial models were designed using SolidWorks and AutoCAD software, 3D printed, laser cut and then superglued. The experiment was conducted at Nottingham Trent University Laboratory with a varying combination of single/multiple Xbloc walls and mangrove root models. The change in the wavelength, height, celerity and period was observed for six different model arrangements. The results revealed a successful decrease in the celerity, height and wavelength, as well as the elongation of the wave period (one cycle time). The hybrid arrangement of one Xbloc wall and two mangrove roots provided the best protection, reducing the wavelength, celerity and height by 5.50%, 26.46% and 58.97%, respectively, and also delaying the wave period by 28.34%. The lowest attenuation in the entire wave parameters stated was observed for the arrangement containing only one set of mangrove roots model. Therefore, the wave attenuation using the combined action of 3D printed polymer-made Xbloc walls and mangrove roots was better, because it facilitated the dissipation of wave energy to a greater degree compared to the use of only Xbloc walls or mangrove roots separately.
Confinement Situation of the Spanish Population during the Health Crisis of COVID-19: Resilience Mediation Process in the Relationship of Dispositional Optimism and Psychological Well-Being
Authors: Zayas Antonio , Merchán-Clavellino Ana , López-Sánchez José Antonio , Guil Rocío
Published: June 2021

The pandemic generated by COVID-19 is one of the most complex challenges humanity has faced in recent years. This study aims to explore the levels of dispositional optimism, resilience and psychological well-being in the sociodemographic and economic situation produced during the state of alarm and to investigate the resilience mediation between optimism and psychological well-being. The sample included 566 volunteers from Spain (73.5% women; M = 40.2 years, SD = 12.8). An ad hoc questionnaire was applied to request socioeconomic data and dispositional optimism (LOT-R). Resilience and psychological well-being were, respectively, evaluated by the Ryff scale and the Wagnild and Young scale. The results show that older and people with higher educational levels are more optimistic and have better psychological well-being. Well-being is also greater in married, divorced and widowed people and in those who have lived in outdoor spaces. However, those with spaced housing were more optimistic. Finally, it was found that the most optimistic people have better psychological well-being and that this is increased by the mediation process exercised by the ability to overcome adversity, provided age and educational level are controlled. It can be concluded that the design of preventive programs focused on improving strengths, positive emotions and skills in the population would be convenient to protect mental health.
Emotional Creativity in Art Education: An Exploratory Analysis and Research Trends
Authors: González-Zamar Mariana-Daniela , Abad-Segura Emilio
Published: June 2021

The emotions that human beings experience have a key role in the environments in which they operate. In art education, creative processes are influenced by the emotions and experiences lived by the individual, enabling a more emotional and creative design to make life more pleasant. The aim was to examine the research during the period 1917–2020 on the development of emotional creativity in art education. Mathematical and statistical techniques were applied to 984 articles carried from Elsevier’s Scopus database. The findings yielded data on the scientific productivity of the journal, authors, research institutions, and countries/territories that promoted this field. The data showed an exponential trend, mostly in the last decade. Five lines of research stand out: emotion, higher education, education, art, and leadership. Moreover, five future research directions related to visual art education, affective paradigm, metacompetency, expressive arts therapy group, and cognitive empathy were detected. This study establishes the link between psychology, neuroscience, and artistic education to constitute the decision-making of the promoters of this topic of research. The analysis of international research allowed us to focus the future publications of academics and researchers, in addition to guaranteeing an adequate approach to the objectives of the institutions and funding centers.
Analysis and Validation of Cross-Modal Generative Adversarial Network for Sensory Substitution
Authors: Kim Mooseop , Park YunKyung , Moon KyeongDeok , Jeong Chi Yoon
Published: June 2021

Visual-auditory sensory substitution has demonstrated great potential to help visually impaired and blind groups to recognize objects and to perform basic navigational tasks. However, the high latency between visual information acquisition and auditory transduction may contribute to the lack of the successful adoption of such aid technologies in the blind community; thus far, substitution methods have remained only laboratory-scale research or pilot demonstrations. This high latency for data conversion leads to challenges in perceiving fast-moving objects or rapid environmental changes. To reduce this latency, prior analysis of auditory sensitivity is necessary. However, existing auditory sensitivity analyses are subjective because they were conducted using human behavioral analysis. Therefore, in this study, we propose a cross-modal generative adversarial network-based evaluation method to find an optimal auditory sensitivity to reduce transmission latency in visual-auditory sensory substitution, which is related to the perception of visual information. We further conducted a human-based assessment to evaluate the effectiveness of the proposed model-based analysis in human behavioral experiments. We conducted experiments with three participant groups, including sighted users (SU), congenitally blind (CB) and late-blind (LB) individuals. Experimental results from the proposed model showed that the temporal length of the auditory signal for sensory substitution could be reduced by 50%. This result indicates the possibility of improving the performance of the conventional vOICe method by up to two times. We confirmed that our experimental results are consistent with human assessment through behavioral experiments. Analyzing auditory sensitivity with deep learning models has the potential to improve the efficiency of sensory substitution.
The Effects of Work Characteristics Related to Work–Life Imbalance on Presenteeism among Female Workers in the Health and Social Work Sectors: Mediation Analysis of Psychological and Physical Health Problems
Authors: Hwang Jee-Hyun , Jung Hye-Sun
Published: June 2021

This study is a multigroup path analysis aiming to create a theoretical model of presenteeism among female workers in the health and social work sectors, assess the mediating effects of mental health problems (sleeping trouble and psychological wellbeing), and physical health problems (fatigue and muscle aches) on the relationship between work characteristics (demands at work and social community at work) and presenteeism, and identify the differences between the effects of variables on those who reported low work–life imbalance and high work–life imbalance. Raw data from the fifth Korean Working Conditions Survey (KWCS) were analyzed. From the total sample of 50,205 people, 2209 women in health and social work were included in the study sample. The results were as follows: the demands at work had a significant and positive indirect effect on presenteeism (B = 0.0023, p < 0.001), mediated by trouble sleeping, fatigue, and muscle aches, in that order. Demands at work were also found to have a significant and negative indirect effect on presenteeism (B = −0.0017, p < 0.001), mediated by psychological wellbeing, fatigue, and muscle aches, in descending order. Social community at work had a significant and negative indirect effect on presenteeism (B = −0.0022, p < 0.001), mediated by trouble sleeping, fatigue, and muscle aches, in that order. Social community at work also had a significant and negative effect on presenteeism, mediated by psychological wellbeing, fatigue, and muscle aches, in descending order (B = −0.0097, p < 0.001). Demands at work did not have a significant effect on psychological wellbeing in the low work–life imbalance group, whereas its effect was significant and positive (β = 0.198, p < 0.001) in the high work–life imbalance group. In conclusion, in the path model of the low work–life imbalance group, demands at work did not influence psychological wellbeing. Therefore, strategies to ameliorate work–life imbalance may be helpful components of interventions to reduce presenteeism.
Strong Precipitation and Human Activity Spur Rapid Nitrate Deposition in Estuarine Delta: Multi-Isotope and Auxiliary Data Evidence
Authors: Xie Hanyou , Huang Chong , Li Jing , Zhang Yitao , Xu Xiangbo , Liu Deyao , Ouyang Zhu
Published: June 2021

The intensive development of the Yellow River Delta has caused huge transportation of non-point pollutants into the Bohai Sea through source river estuaries and thus poses a considerable threat to eco-environmental security in the region. Long-term irrigation in the Yellow River basin, with occasional heavy rainfall and the related effects of ensuring hydrological processes and human activities in terms of nitrate N transport via surface water systems, is unclear. Using stable isotope (δ2H-H2O and δ18O-H2O, δ15N-NO3− and δ18O-NO3−) and auxiliary geographic data, the ISO source model was run to quantitatively analyze the supply relationship of river systems and the rapid change in the spatial pattern of nitrate N due to heavy rainfall in the estuarine delta. This analysis made clear the dominant contribution of agricultural activities and urbanization to NO3−-N emission, on which basis refined management measures were proposed to deal with NO3− in surface water from the “source-process”. The results of the study show that: (1) The relationship of surface water replenishment in the Yellow River Delta was affected not only by rainfall, irrigation, and other water conservancy measures but also the proportion of water from Yellow River flow declined from the source to estuary; (2) To a certain extent, rainfall diluted the concentration of nitrate N in the river and increased instantaneous flux of nitrate N into the sea, where nitrate N flux continuously increased from upstream to downstream; (3) The rapid deposition of nitrate in the estuary delta was driven by heavy rainfall and human activities such as excessive use of nitrogen fertilizers, rapid urbanization, and livestock waste discharge, and; (4) Scientific measures were needed to realize the interactive effect of the output of non-point source pollutants and the carrying and absorption capacity of coastal fragile ecosystems of the exogenous inputs.
Modulation of PARP-1 Activity in a Broad Time Window Attenuates Memorizing Fear
Authors: Elharrar Einat , Dikshtein Yahav , Meninger-Mordechay Sapir , Lichtenstein Yehuda , Yadid Gal
Published: June 2021

The amygdala plays a critical role in the acquisition and consolidation of fear-related memories. Recent studies have demonstrated that ADP-ribosylation of histones, accelerated by PARPs, affects the chromatin structure and the binding of chromatin remodeling complexes with transcription factors. Inhibition of PARP-1 activity during the labile phase of re-consolidation may erase memory. Accordingly, we investigated the possibility of interfering with fear conditioning by PARP-1 inhibition. Herein, we demonstrate that injection of PARP-1 inhibitors, specifically into the CeA or i.p., in different time windows post-retrieval, attenuates freezing behavior. Moreover, the association of memory with pharmacokinetic timing of PARP inhibitor arrival to the brain enabled/achieved attenuation of a specific cue-associated memory of fear but did not hinder other memories (even traumatic events) associated with other cues. Our results suggest using PARP-1 inhibitors as a new avenue for future treatment of PTSD by disrupting specific traumatic memories in a broad time window, even long after the traumatic event. The safety of using these PARP inhibitors, that is, not interfering with other natural memories, is an added value.
T-Type Ca2+ Enhancer SAK3 Activates CaMKII and Proteasome Activities in Lewy Body Dementia Mice Model
Authors: Xu Jing , Kawahata Ichiro , Izumi Hisanao , Fukunaga Kohji
Published: June 2021

Lewy bodies are pathological characteristics of Lewy body dementia (LBD) and are composed of α-synuclein (α-Syn), which is mostly degraded via the ubiquitin–proteasome system. More importantly, 26S proteasomal activity decreases in the brain of LBD patients. We recently introduced a T-type calcium channel enhancer SAK3 (ethyl-8-methyl-2,4-dioxo-2-(piperidin-1-yl)- 2H-spiro[cyclopentane-1,3-imidazo [1,2-a]pyridin]-2-ene-3-carboxylate) for Alzheimer’s disease therapeutics. SAK3 enhanced the proteasome activity via CaMKII activation in amyloid precursor protein knock-in mice, promoting the degradation of amyloid-β plaques to improve cognition. At this point, we addressed whether SAK3 promotes the degradation of misfolded α-Syn and the aggregates in α-Syn preformed fibril (PFF)-injected mice. The mice were injected with α-Syn PFF in the dorsal striatum, and SAK3 (0.5 or 1.0 mg/kg) was administered orally for three months, either immediately or during the last month after injection. SAK3 significantly inhibited the accumulation of fibrilized phosphorylated-α-Syn in the substantia nigra. Accordingly, SAK3 significantly recovered mesencephalic dopamine neurons from cell death. Decreased α-Syn accumulation was closely associated with increased proteasome activity. Elevated CaMKII/Rpt-6 signaling possibly mediates the enhanced proteasome activity after SAK3 administration in the cortex and hippocampus. CaMKII/Rpt-6 activation also accounted for improved memory and cognition in α-Syn PFF-injected mice. These findings indicate that CaMKII/Rpt-6-dependent proteasomal activation by SAK3 recovers from α-Syn pathology in LBD.
Secure Remote Storage of Logs with Search Capabilities
Authors: Araújo Rui , Pinto António
Published: June 2021

Along with the use of cloud-based services, infrastructure, and storage, the use of application logs in business critical applications is a standard practice. Application logs must be stored in an accessible manner in order to be used whenever needed. The debugging of these applications is a common situation where such access is required. Frequently, part of the information contained in logs records is sensitive. In this paper, we evaluate the possibility of storing critical logs in a remote storage while maintaining its confidentiality and server-side search capabilities. To the best of our knowledge, the designed search algorithm is the first to support full Boolean searches combined with field searching and nested queries. We demonstrate its feasibility and timely operation with a prototype implementation that never requires access, by the storage provider, to plain text information. Our solution was able to perform search and decryption operations at a rate of, approximately, 0.05 ms per line. A comparison with the related work allows us to demonstrate its feasibility and conclude that our solution is also the fastest one in indexing operations, the most frequent operations performed.
1-Methyl-8-phenyl-1,3-diazaspiro[4.5]decane-2,4-dione
Authors: Pardali Vasiliki , Katsamakas Sotirios , Giannakopoulou Erofili , Zoidis Grigoris
Published: June 2021

A simple, fast and cost-effective three-step synthesis of 1-methyl-8-phenyl-1,3-diazaspiro[4.5]decane-2,4-dione has been developed. The reactions described herein proceed readily, with high yields and no further purification. Therefore, the proposed method, with an overall yield of 60%, offers a facile pathway to the synthesis of N-1 monosubstituted spiro carbocyclic imidazolidine-2,4-diones (hydantoins), which constitute a privileged class of heterocyclic scaffolds with pharmacological interest.
Plant Proteins and Exercise: What Role Can Plant Proteins Have in Promoting Adaptations to Exercise?
Authors: Kerksick Chad M. , Jagim Andrew , Hagele Anthony , Jäger Ralf
Published: June 2021

Adequate dietary protein is important for many aspects of health with current evidence suggesting that exercising individuals need greater amounts of protein. When assessing protein quality, animal sources of protein routinely rank amongst the highest in quality, largely due to the higher levels of essential amino acids they possess in addition to exhibiting more favorable levels of digestibility and absorption patterns of the amino acids. In recent years, the inclusion of plant protein sources in the diet has grown and evidence continues to accumulate on the comparison of various plant protein sources and animal protein sources in their ability to stimulate muscle protein synthesis (MPS), heighten exercise training adaptations, and facilitate recovery from exercise. Without question, the most robust changes in MPS come from efficacious doses of a whey protein isolate, but several studies have highlighted the successful ability of different plant sources to significantly elevate resting rates of MPS. In terms of facilitating prolonged adaptations to exercise training, multiple studies have indicated that a dose of plant protein that offers enough essential amino acids, especially leucine, consumed over 8–12 weeks can stimulate similar adaptations as seen with animal protein sources. More research is needed to see if longer supplementation periods maintain equivalence between the protein sources. Several practices exist whereby the anabolic potential of a plant protein source can be improved and generally, more research is needed to best understand which practice (if any) offers notable advantages. In conclusion, as one considers the favorable health implications of increasing plant intake as well as environmental sustainability, the interest in consuming more plant proteins will continue to be present. The evidence base for plant proteins in exercising individuals has seen impressive growth with many of these findings now indicating that consumption of a plant protein source in an efficacious dose (typically larger than an animal protein) can instigate similar and favorable changes in amino acid update, MPS rates, and exercise training adaptations such as strength and body composition as well as recovery.
Comparative Preclinical Evaluation of HER2-Targeting ABD-Fused Affibody® Molecules 177Lu-ABY-271 and 177Lu-ABY-027: Impact of DOTA Position on ABD Domain
Authors: Liu Yongsheng , Vorobyeva Anzhelika , Xu Tianqi , Orlova Anna , Loftenius Annika , Bengtsson Theresa , Jonasson Per , Tolmachev Vladimir , Frejd Fredrik Y.
Published: June 2021

Radiolabeled Affibody-based targeting agent 177Lu-ABY-027, a fusion of an anti-HER2 Affibody molecule with albumin binding domain (ABD) site-specifically labeled at the C-terminus, has demonstrated a promising biodistribution profile in mice; binding of the construct to albumin prevents glomerular filtration and significantly reduces renal uptake. In this study, we tested the hypothesis that site-specific positioning of the chelator at helix 1 of ABD, at a maximum distance from the albumin binding site, would further increase the strength of binding to albumin and decrease the renal uptake. The new construct, ABY-271 with DOTA conjugated at the back of ABD, has been labelled with 177Lu. Targeting properties of 177Lu-ABY-271 and 177Lu-ABY-027 were compared directly. 177Lu-ABY-271 specifically accumulated in SKOV-3 xenografts in mice. The tumor uptake of 177Lu-ABY-271 exceeded uptake in any other organ 24 h and later after injection. However, the renal uptake of 177Lu-ABY-271 was two-fold higher than the uptake of 177Lu-ABY-027. Thus, the placement of chelator on helix 1 of ABD does not provide desirable reduction of renal uptake. To conclude, minimal modification of the design of Affibody molecules has a strong effect on biodistribution, which cannot be predicted a priori. This necessitates extensive structure-properties relationship studies to find an optimal design of Affibody-based targeting agents for therapy.
Mesenchymal Stem Cells as a Gene Delivery Tool: Promise, Problems, and Prospects
Authors: Attia Noha , Mashal Mohamed , Puras Gustavo , Pedraz Jose Luis
Published: June 2021

The cell-based approach in gene therapy arises as a promising strategy to provide safe, targeted, and efficient gene delivery. Owing to their unique features, as homing and tumor-tropism, mesenchymal stem cells (MSCs) have recently been introduced as an encouraging vehicle in gene therapy. Nevertheless, non-viral transfer of nucleic acids into MSCs remains limited due to various factors related to the main stakeholders of the process (e.g., nucleic acids, carriers, or cells). In this review, we have summarized the main types of nucleic acids used to transfect MSCs, the pros and cons, and applications of each. Then, we have emphasized on the most efficient lipid-based carriers for nucleic acids to MSCs, their main features, and some of their applications. While a myriad of studies have demonstrated the therapeutic potential for engineered MSCs therapy in various illnesses, optimization for clinical use is an ongoing challenge. On the way of improvement, genetically modified MSCs have been combined with various novel techniques and tools (e.g., exosomes, spheroids, 3D-Bioprinting, etc.,) aiming for more efficient and safe applications in biomedicine.
Cylindrical Microparticles Composed of Mesoporous Silica Nanoparticles for the Targeted Delivery of a Small Molecule and a Macromolecular Drug to the Lungs: Exemplified with Curcumin and siRNA
Authors: Fischer Thorben , Winter Inga , Drumm Robert , Schneider Marc
Published: June 2021

The transport of macromolecular drugs such as oligonucleotides into the lungs has become increasingly relevant in recent years due to their high potency. However, the chemical structure of this group of drugs poses a hurdle to their delivery, caused by the negative charge, membrane impermeability and instability. For example, siRNA to reduce tumour necrosis factor alpha (TNF-α) secretion to reduce inflammatory signals has been successfully delivered by inhalation. In order to increase the effect of the treatment, a co-transport of another anti-inflammatory ingredient was applied. Combining curcumin-loaded mesoporous silica nanoparticles in nanostructured cylindrical microparticles stabilized by the layer-by-layer technique using polyanionic siRNA against TNF-α was used for demonstration. This system showed aerodynamic properties suited for lung deposition (mass median aerodynamic diameter of 2.85 ± 0.44 µm). Furthermore, these inhalable carriers showed no acute in vitro toxicity tested in both alveolar epithelial cells and macrophages up to 48 h incubation. Ultimately, TNF-α release was significantly reduced by the particles, showing an improved activity co-delivering both drugs using such a drug-delivery system for specific inhibition of TNF-α in the lungs.
Making Use of 3D Models for Plant Physiognomic Analysis: A Review
Authors: Paturkar Abhipray , Sen Gupta Gourab , Bailey Donald
Published: June 2021

Use of 3D sensors in plant phenotyping has increased in the last few years. Various image acquisition, 3D representations, 3D model processing and analysis techniques exist to help the researchers. However, a review of approaches, algorithms, and techniques used for 3D plant physiognomic analysis is lacking. In this paper, we investigate the techniques and algorithms used at various stages of processing and analysing 3D models of plants, and identify their current limiting factors. This review will serve potential users as well as new researchers in this field. The focus is on exploring studies monitoring the plant growth of single plants or small scale canopies as opposed to large scale monitoring in the field.
A Novel Query Strategy-Based Rank Batch-Mode Active Learning Method for High-Resolution Remote Sensing Image Classification
Authors: Luo Xin , Du Huaqiang , Zhou Guomo , Li Xuejian , Mao Fangjie , Zhu Di’en , Xu Yanxin , Zhang Meng , He Shaobai , Huang Zihao
Published: June 2021

An informative training set is necessary for ensuring the robust performance of the classification of very-high-resolution remote sensing (VHRRS) images, but labeling work is often difficult, expensive, and time-consuming. This makes active learning (AL) an important part of an image analysis framework. AL aims to efficiently build a representative and efficient library of training samples that are most informative for the underlying classification task, thereby minimizing the cost of obtaining labeled data. Based on ranked batch-mode active learning (RBMAL), this paper proposes a novel combined query strategy of spectral information divergence lowest confidence uncertainty sampling (SIDLC), called RBSIDLC. The base classifier of random forest (RF) is initialized by using a small initial training set, and each unlabeled sample is analyzed to obtain the classification uncertainty score. A spectral information divergence (SID) function is then used to calculate the similarity score, and according to the final score, the unlabeled samples are ranked in descending lists. The most “valuable” samples are selected according to ranked lists and then labeled by the analyst/expert (also called the oracle). Finally, these samples are added to the training set, and the RF is retrained for the next iteration. The whole procedure is iteratively implemented until a stopping criterion is met. The results indicate that RBSIDLC achieves high-precision extraction of urban land use information based on VHRRS; the accuracy of extraction for each land-use type is greater than 90%, and the overall accuracy (OA) is greater than 96%. After the SID replaces the Euclidean distance in the RBMAL algorithm, the RBSIDLC method greatly reduces the misclassification rate among different land types. Therefore, the similarity function based on SID performs better than that based on the Euclidean distance. In addition, the OA of RF classification is greater than 90%, suggesting that it is feasible to use RF to estimate the uncertainty score. Compared with the three single query strategies of other AL methods, sample labeling with the SIDLC combined query strategy yields a lower cost and higher quality, thus effectively reducing the misclassification rate of different land use types. For example, compared with the Batch_Based_Entropy (BBE) algorithm, RBSIDLC improves the precision of barren land extraction by 37% and that of vegetation by 14%. The 25 characteristics of different land use types screened by RF cross-validation (RFCV) combined with the permutation method exhibit an excellent separation degree, and the results provide the basis for VHRRS information extraction in urban land use settings based on RBSIDLC.
How Will the Cost Change after Transformation in Public Nature-Based Attractions? A Framework and Case Study
Authors: Liu Jun-Ya , Li Qun-Ji , Sigley Gary , Quan Hua
Published: June 2021

Financial viability is crucial for public nature-based attractions, especially in the context where many are seeking to transform their business model and goals in order to survive because of the heavy hit by COVID-19 and pressure from Chinese central government policies to lower entrance fees in state-owned attractions. However, there is little literature relating to the relationship between finance and transformation. To fill the gap, the framework “resource–function–transformation–cost” was proposed to explain the relationship between transformation and cost structure change by combining resource-based theory and function analysis. A case study of Shanghai Sheshan National Forest Park (SNFP) tested the framework and further revealed that (a) transformation happened because of the recombination of resources, followed by the change of functions, leading to capital expenditure being more prominent during the early stages and management costs more so in the latter stage. Further, we conclude that the elasticity of the cost structure is low; (b) the structure of functions tended to be stable over the years; and (c) the cost structure of the management, production and business, and tourism and leisure functions did not change much, while that of ecological protection functions changed significantly from capital expenditure to management costs.
Postgraduate Competence and Academic Research Performance: The Mediating Role of Psychological Capital
Authors: Guo Jinyuan , Chen Zhixia , Zheng Binyao
Published: June 2021

In this study, we developed and validated an instrument for measuring postgraduate competence and examined the relationships between postgraduate competence and academic research performance, along with the mediating role of psychological capital. Based on two independent samples, the results provided robust evidence of postgraduate competence composed of six dimensions. Adopting a two-wave survey at two different time periods, we conducted a questionnaire survey on 364 postgraduates from three top universities in China by random sampling. The results indicated that postgraduate competence was positively associated with academic research performance. Among the competences composed of six dimensions, research ability was the most predictive dimension of academic research performance. Additionally, psychological capital partially mediated the relationship between postgraduate competence and academic research performance. These findings contributed to the ongoing discussion about improving postgraduates’ academic research performance under the circumstance of competence-based education.