bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Organic and Conventional Farming Systems with Different Tillage on Soil Properties and Enzymatic Activity
Authors: Kobierski Mirosław , Lemanowicz Joanna , Wojewódzki Piotr , Kondratowicz-Maciejewska Krystyna
Published: November 2020

The chemical properties and enzymatic activity of the surface soil horizon were compared between an organic farm (OF) (crop rotation with legume plants, fertilisation with manure) and a conventional farm (CF) (simplified crop rotation, mineral fertilisation, chemical crop protection products). In the years 2001-2017 on the OF (near the village of Juchowo, northern Poland), a reduced tillage system (ploughless) was used, while plough cultivation was used on a CF located in its immediate vicinity. The parameters used to assess the properties of soils were: particle size composition, pH, total organic carbon (TOC) and total nitrogen (TN), dissolved organic carbon (DOC) and dissolved organic nitrogen (DON). The activity of dehydrogenases (DEH), catalase (CAT), alkaline phosphatase (AlP) and acid phosphatase (AcP) and the content of easily extractable glomalin-related soil protein (EEGRSP) were also determined. Sixteen years of soil use in accordance with ecological principles significantly increased the average content of TOC, NT, DOC and DON. Soil samples rich in TOC and DOC showed significantly higher DEH and AcP activity, and EEGRSP content. Statistical analysis showed that the activity of DEH, AlP and CAT in the soil was significantly higher for the OF than for the conventional cultivation system. Limiting soil cultivation procedures on the OF improved the balance of soil organic matter (SOM) and pH value, and significantly increased the content of EEGRSP as compared to the cultivation system used on the CF.
Social Network Analysis of Agonistic Behaviour and Its Association with Economically Important Traits in Pigs
Authors: Agha Saif , Fàbrega Emma , Quintanilla Raquel , Sánchez Juan Pablo
Published: November 2020

Aggression behaviour has several negative consequences on the performance and welfare of pigs. Here, the Social Network Analysis (SNA) approach was employed to (1) identify individual traits that describe the role of each animal in the aggression; (2) investigate the association of these traits with performance and feeding behaviour traits. The study was conducted on 326 Duroc pigs reared in 29 pens. Several individual centrality traits were identified and used to calculate the Social Rank Index. The Dominant, Subordinate, and Isolated animals represented 21.1%, 57.5% and 21.4%, respectively. No significant correlations were observed between out-degree (number of initiated agonistic behaviours) and growth traits, indicating the similarity of growth patterns for dominant and non-dominant animals. Furthermore, out-degree was correlated positively with average daily occupation time (time at the feeder/day) and average daily feeding frequency (number of visits to the feeder/day) but negatively with average daily feeding rate (gr/min). This may indicate the ability of non-dominant pigs to modify their behaviour to obtain their requirements. The Hamming distances between networks showed that there is no common behaviour pattern between pens. In conclusion, SNA showed the potential for extracting behaviour traits that could be used to improve pig performance and welfare.
Effect of Heat Stress on Dairy Cow Performance and on Expression of Protein Metabolism Genes in Mammary Cells
Authors: Corazzin Mirco , Saccà Elena , Lippe Giovanna , Romanzin Alberto , Foletto Vinicius , Da Borso Francesco , Piasentier Edi
Published: November 2020

The aim of this study was to assess the effect of heat stress on dairy cow performance and on the expression of selected genes involved in milk protein metabolism. Eight Italian Holstein Friesian cows were kept under thermoneutral conditions (temperature–humidity index (THI) < 72, CON) for 8 days and under mild heat stress conditions (72 < THI < 78, HS) for an additional 8 days. The rectal temperature, feed intake, and milk yield were recorded during the last 3 days of the CON and HS periods. During the same time period, milk samples were collected to assess the composition and expression of selected genes involved in milk protein metabolism. Gene expression analyses were performed on somatic cells from milk, which are representative of mammary tissue. In terms of dairy cow performance, HS resulted in lower milk and protein yields and feed intake but higher rectal temperature than for CON (p < 0.05). Under HS, there were greater abundances of HSPA1A (p < 0.05) and BCL2 (p < 0.05), compared to CON, but similar levels of CSN2 (p > 0.05), CSN3 (p > 0.05), HSPA8 (p > 0.05), and STAT5B (p > 0.05) mRNA. Mild heat stress reduced the performance of dairy cows without affecting the expression of genes coding for caseins.
Enhancing CDC and ADCC of CD19 Antibodies by Combining Fc Protein-Engineering with Fc Glyco-Engineering
Authors: Roßkopf Sophia , Eichholz Klara Marie , Winterberg Dorothee , Diemer Katarina Julia , Lutz Sebastian , Münnich Ira Alexandra , Klausz Katja , Rösner Thies , Valerius Thomas , Schewe Denis Martin , Humpe Andreas , Gramatzki Martin , Peipp Matthias , Kellner Christian
Published: November 2020

Background: Native cluster of differentiation (CD) 19 targeting antibodies are poorly effective in triggering antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which are crucial effector functions of therapeutic antibodies in cancer immunotherapy. Both functions can be enhanced by engineering the antibody’s Fc region by altering the amino acid sequence (Fc protein-engineering) or the Fc-linked glycan (Fc glyco-engineering). We hypothesized that combining Fc glyco-engineering with Fc protein-engineering will rescue ADCC and CDC in CD19 antibodies. Results: Four versions of a CD19 antibody based on tafasitamab’s V-regions were generated: a native IgG1, an Fc protein-engineered version with amino acid exchanges S267E/H268F/S324T/G236A/I332E (EFTAE modification) to enhance CDC, and afucosylated, Fc glyco-engineered versions of both to promote ADCC. Irrespective of fucosylation, antibodies carrying the EFTAE modification had enhanced C1q binding and were superior in inducing CDC. In contrast, afucosylated versions exerted an enhanced affinity to Fcγ receptor IIIA and had increased ADCC activity. Of note, the double-engineered antibody harboring the EFTAE modification and lacking fucose triggered both CDC and ADCC more efficiently. Conclusions: Fc glyco-engineering and protein-engineering could be combined to enhance ADCC and CDC in CD19 antibodies and may allow the generation of antibodies with higher therapeutic efficacy by promoting two key functions simultaneously.
Fc-Engineering for Modulated Effector Functions—Improving Antibodies for Cancer Treatment
Authors: Liu Rena , Oldham Robert , Teal Emma , Beers Stephen , Cragg Mark
Published: November 2020

The majority of monoclonal antibody (mAb) therapeutics possess the ability to engage innate immune effectors through interactions mediated by their fragment crystallizable (Fc) domain. By delivering Fc-Fc gamma receptor (FcγR) and Fc-C1q interactions, mAb are able to link exquisite specificity to powerful cellular and complement-mediated effector functions. Fc interactions can also facilitate enhanced target clustering to evoke potent receptor signaling. These observations have driven decades-long research to delineate the properties within the Fc that elicit these various activities, identifying key amino acid residues and elucidating the important role of glycosylation. They have also fostered a growing interest in Fc-engineering whereby this knowledge is exploited to modulate Fc effector function to suit specific mechanisms of action and therapeutic purposes. In this review, we document the insight that has been generated through the study of the Fc domain; revealing the underpinning structure-function relationships and how the Fc has been engineered to produce an increasing number of antibodies that are appearing in the clinic with augmented abilities to treat cancer.
Impact of the COVID-19 Pandemic on Antimicrobial Consumption and Hospital-Acquired Candidemia and Multidrug-Resistant Bloodstream Infections
Authors: Guisado-Gil Ana , Infante-Domínguez Carmen , Peñalva Germán , Praena Julia , Roca Cristina , Navarro-Amuedo María , Aguilar-Guisado Manuela , Espinosa-Aguilera Nuria , Poyato-Borrego Manuel , Romero-Rodríguez Nieves , Aldabó Teresa , Salto-Alejandre Sonsoles , Ruiz-Pérez de Pipaón Maite , Lepe José , Martín-Gutiérrez Guillermo , Gil-Navarro María , Molina José , Pachón Jerónimo , Cisneros José ,   On behalf of the PRIOAM Team
Published: November 2020

During the COVID-19 pandemic, the implementation of antimicrobial stewardship strategies has been recommended. This study aimed to assess the impact of the COVID-19 pandemic in a tertiary care Spanish hospital with an active ongoing antimicrobial stewardship programme (ASP). For a 20-week period, we weekly assessed antimicrobial consumption, incidence density, and crude death rate per 1000 occupied bed days of candidemia and multidrug-resistant (MDR) bacterial bloodstream infections (BSI). We conducted a segmented regression analysis of time series. Antimicrobial consumption increased +3.5% per week (p = 0.016) for six weeks after the national lockdown, followed by a sustained weekly reduction of −6.4% (p = 0.001). The global trend for the whole period was stable. The frequency of empirical treatment of patients with COVID-19 was 33.7%. No change in the global trend of incidence of hospital-acquired candidemia and MDR bacterial BSI was observed (+0.5% weekly; p = 0.816), nor differences in 14 and 30-day crude death rates (p = 0.653 and p = 0.732, respectively). Our work provides quantitative data about the pandemic effect on antimicrobial consumption and clinical outcomes in a centre with an active ongoing institutional and education-based ASP. However, assessing the long-term impact of the COVID-19 pandemic on antimicrobial resistance is required.
Oxidative Stress and Preeclampsia-Associated Prothrombotic State
Authors: Han Cha , Huang Pengzhu , Lyu Meilu , Dong Jingfei
Published: November 2020

Preeclampsia (PE) is a common obstetric disease characterized by hypertension, proteinuria, and multi-system dysfunction. It endangers both maternal and fetal health. Although hemostasis is critical for preventing bleeding complications during pregnancy, delivery, and post-partum, PE patients often develop a severe prothrombotic state, potentially resulting in life-threatening thrombosis and thromboembolism. The cause of this thrombotic complication is multi-factorial, involving endothelial cells, platelets, adhesive ligands, coagulation, and fibrinolysis. Increasing evidence has shown that hemostatic cells and factors undergo oxidative modifications during the systemic inflammation found in PE patients. However, it is largely unknown how these oxidative modifications of hemostasis contribute to development of the PE-associated prothrombotic state. This knowledge gap has significantly hindered the development of predictive markers, preventive measures, and therapeutic agents to protect women during pregnancy. Here we summarize reports in the literature regarding the effects of oxidative stress and antioxidants on systemic hemostasis, with emphasis on the condition of PE.
The Antioxidant Role of One-Carbon Metabolism on Stroke
Authors: Burgess Kassidy , Bennett Calli , Mosnier Hannah , Kwatra Neha , Bethel Forrest , Jadavji Nafisa M.
Published: November 2020

One-carbon (1C) metabolism is a metabolic network that is centered on folate, a B vitamin; it integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics. This metabolic pathway also reduces levels of homocysteine, a non-protein amino acid. High levels of homocysteine are linked to increased risk of hypoxic events, such as stroke. Several preclinical studies have suggested that 1C metabolism can impact stroke outcome, but the clinical data are unclear. The objective of this paper was to review preclinical and clinical research to determine whether 1C metabolism has an antioxidant role on stroke. To accomplish the objective, we searched for publications using the following medical subject headings (MeSH) keywords: antioxidants, hypoxia, stroke, homocysteine, one-carbon metabolism, folate, methionine, and dietary supplementation of one-carbon metabolism. Both pre-clinical and clinical studies were retrieved and reviewed. Our review of the literature suggests that deficiencies in 1C play an important role in the onset and outcome of stroke. Dietary supplementation of 1C provides beneficial effects on stroke outcome. For stroke-affected patients or individuals at high risk for stroke, the data suggest that nutritional modifications in addition to other therapies could be incorporated into a treatment plan.
Sustainable Reduction of the Odor Impact of Painting Wooden Products for Interior Design
Authors: Amato Alessia , Bigi Gabriele Pietro , Baldini Cristina , Beolchini Francesca
Published: November 2020

The construction and building field represents a key sector for the recent Circular Economy Action Plan (March 2020). Therefore, the production of low impact materials represents an essential step towards the implementation of a sustainable market. In this regard, the present paper focused on the production of painting wooden products for interior design. These industrial processes include an essential phase consisting of the reduction of odor emissions, which produce negative impacts on the environment and a persistent annoyance for the population close to the facilities. The main cause of the odor emissions in wood painting manufacturing is the production of volatile organic compounds (VOCs). In this context, the present research aimed to develop an innovative process able to combine the use of lower impact paints with a more efficient UV system for the abatement of the emissions.
Preparation and Evaluation of Microcapsules Encapsulating Royal Jelly Sieve Residue: Flavor and Release Profile
Authors: He Rongjun , Ye Jiahao , Wang Lina , Sun Peilong
Published: November 2020

This study aimed to improve the flavor of royal jelly residue via microencapsulation technology using Arabic gum and gelatin as wall materials. This microencapsulation technology showed a good encapsulation yield of 85.71 ± 2.84% and encapsulation efficiency of 92.34 ± 3.17%. The intact structures of the microcapsules were observed using optical and scanning electron microscopes. The results of the simulated gastrointestinal digestion proved that the microcapsules were well-tolerated in the gastric environment (a release rate of 32.95 ± 2.34%). Both electronic nose and electronic tongue evaluations showed that microencapsulation improved the sensory index of the royal jelly sieve residue. After microencapsulation, the astringency, bitterness, and irritant odors of the royal jelly residue were reduced. Simultaneously, the release rate in the intestine was 98.77 ± 1.91%, which demonstrated that microencapsulation would not prevent the human body from absorbing the royal jelly. The results from this study are expected to facilitate the development of mild flavor products made from royal jelly.
Orchard Floor Management Affects Tree Functionality, Productivity and Water Consumption of a Late Ripening Peach Orchard under Semi-Arid Conditions
Authors: Losciale Pasquale , Gaeta Liliana , Manfrini Luigi , Tarricone Luigi , Campi Pasquale
Published: November 2020

Semi-arid conditions are favorable for the cultivation of late ripening peach cultivars; however, seasonal water scarcity and reduction in soil biological fertility, heightened by improper soil management, are jeopardizing this important sector. In the present two-year study, four soil managements were compared on a late ripening peach orchard: (i) completely tilled (control); (ii) mulched with reusable reflective plastic film; (iii) mulching with a Leguminosae cover-crop flattened after peach fruit set; (iv) completely tilled, supplying the water volumes of the plastic mulched treatment, supposed to be lower than the control. Comparison was performed for soil features, water use, tree functionality, fruit growth, fruit quality, yield and water productivity. Even receiving about 50% of the regular irrigation, reusable reflective mulching reduced water loss and soil carbon over mineralization, not affecting (sometimes increasing) net carbon assimilation, yield, and fruit size and increasing water productivity. The flattening technique should be refined in the last part of the season as in hot and dry areas with clay soils and low organic matter, soil cracking increased water evaporation predisposing the orchard at water stress. The development and implementation of appropriate soil management strategies could be pivotal for making peach production economically and environmentally sustainable.
State Machine Approach for Lane Changing Driving Behavior Recognition
Authors: David Ruth , Rothe Sandra , Söffker Dirk
Published: November 2020

Research in understanding human behavior is a growing field within the development of Advanced Driving Assistance Systems (ADASs). In this contribution, a state machine approach is proposed to develop a driving behavior recognition model. The state machine approach is a behavior model based on the current state and a given set of inputs. Transitions to different states occur or we remain in the same state producing outputs. The transition between states depends on a set of environmental and driving variables. Based on a heuristic understanding of driving situations modeled as states, as well as one of the related actions modeling the state, using an assumed relation between them as the state machine topology, in this paper, a crisp approach is applied to adapt the model to real behaviors. An important aspect of the contribution is to introduce a trainable state machine-based model to describe drivers’ lane changing behavior. Three driving maneuvers are defined as states. The training of the model is related to the definition/tuning of transition variables (and state definitions). Here, driving data are used as the input for training. The non-dominated sorting genetic algorithm II is used to generate the optimized transition threshold. Comparing the data of actual human driving behaviors collected using driving simulator experiments and the calculated driving behaviors, this approach is able to develop a personalized behavior recognition model. The newly established algorithm presents an easy to apply, reliable, and interpretable AI approach.
Detention in Juvenile Correctional Facilities Is Associated with Higher Platelet Monoamine Oxidase B Activity in Males
Authors: Podobnik Josip , Nikolac Perkovic Matea , Nedic Erjavec Gordana , Dodig Curkovic Katarina , Curkovic Mario , Kovac Vlatka , Svob Strac Dubravka , Cusek Melita , Bortolato Marco , Pivac Nela
Published: November 2020

Juvenile delinquency is related to several biological factors, yet very few vulnerability biomarkers have been identified. Previous data suggest that the enzyme monoamine oxidase B (MAO-B) influences several personality traits linked to the propensity to engage in delinquent behavior. Building on this evidence, we assessed whether conduct disorder (CD), juvenile delinquency adjudications, or detention in a correctional facility were associated with either platelet MAO-B activity or the MAOB rs1799836 polymorphism. The study enrolled 289 medication-free male youths, including 182 individuals detained in a correctional facility (with or without a diagnosis of CD). Of the remaining 107 participants, 26 subjects had a diagnosis of CD, and 81 were mentally healthy controls. Platelet MAO-B activity was determined by spectrophotofluorometry, while MAOB rs1799836 was genotyped using qPCR. Platelet MAO-B activity, corrected for age and smoking, was significantly higher in juvenile detainees (p < 0.001), irrespective of CD diagnosis. MAOB rs1799836 was not associated with platelet MAO-B activity or with detention in a correctional facility, CD diagnosis, or delinquent behavior. These data suggest that detention in a juvenile correctional facility increases platelet MAO-B activity in male adolescents. Future studies are needed to determine the mechanisms and functional significance of MAO-B peripheral elevation in juvenile male detainees.
Oxidative Stress and Mitochondrial Dysfunction in Human Diseases: Pathophysiology, Predictive Biomarkers, Therapeutic
Authors: Li Chia-Jung
Published: November 2020

Mitochondria are important sites for a variety of cellular processes, including amino acid and fatty acid metabolism, the citric acid cycle, nitrogen metabolism, and oxidative phosphorylation to produce ATP [...]
Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability
Authors: Sulkshane Prasad , Ram Jonathan , Glickman Michael H
Published: November 2020

Mitochondria are constantly subjected to stressful conditions due to their unique physiology and organization. The resulting damage leads to mitochondrial dysfunction, which underlies many pathophysiological conditions. Hence, constant surveillance is required to closely monitor mitochondrial health for sound maintenance of cellular metabolism and thus, for viability. In addition to internal mitochondrial chaperones and proteases, mitochondrial health is also governed by host cell protein quality control systems. The ubiquitin-proteasome system (UPS) and autophagy constitute the main pathways for removal of damaged or superfluous proteins in the cytosol, nucleus, and from certain organelles such as the Endoplasmic Reticulum (ER) and mitochondria. Although stress-induced ubiquitin-dependent degradation of mitochondrial outer membrane proteins has been widely studied, mechanisms of intramitochondrial protein ubiquitination has remained largely elusive due to the predominantly cytosolic nature of UPS components, separated from internal mitochondrial proteins by a double membrane. However, recent research has illuminated examples of intramitochondrial protein ubiquitination pathways and highlighted their importance under basal and stressful conditions. Owing to the dependence of mitochondria on the error-prone process of protein import from the cytosol, it is imperative that the cell eliminate any accumulated proteins in the event of mitochondrial protein import deficiency. Apparently, a significant portion of this activity involves ubiquitination in one way or another. In the present review article, following a brief introduction to mitochondrial protein quality control mechanisms, we discuss our recent understanding of intramitochondrial protein ubiquitination, its importance for basal function of mitochondria, metabolic implications, and possible therapeutic applications.
4-Benzyloxylonchocarpin and Muracatanes A-C from Ranunculus muricatus L. and Their Biological Effects
Authors: Hussain Hidayat , Ali Iftikhar , Wang Daijie , Mamadalieva Nilufar Z. , Hussain Wahid , Csuk René , Loesche Anne , Fischer Lucie , Staerk Dan , Anam Syariful , AlZain Mashail N. , Mushtaq Maria , Ul-Haq Zaheer , Ullah Riaz , Noman Omar M. , Abbas Ghulam , Green Ivan R.
Published: November 2020

Ranunculus muricatus L. is a spiny fruit buttercup that is used in various traditional medicinal systems. In the current investigation of R. muricatus, the new chalcone 4-benzyloxylonchocarpin (1), the new anthraquinone muracatanes A (2), the new-to-nature anthraquinone muracatanes B (3), and the new naphthalene analog muracatanes C (4) were isolated, in addition to the three previously reported compounds, 4-methoxylonchocarpin (5), β-sitosterol (6), and β-sitosterol β-D-glucopyranoside (7). Their structures were elucidated using 1D (1H and 13C) and 2D (COSY, HSQC, and HMBC) NMR spectroscopy and HR-ESI-MS. Chalcone 1 showed potent acetylcholinesterase inhibitory effects with Ki of 5.39 µM and Ki′ of 3.54 µM, but none of the isolated compounds showed inhibitory activity towards butyrylcholinesterase. Anthraquinone 3 illustrated α-glucosidase inhibitory effects with IC50-values of 164.46 ± 83.04 µM. Compound 5 displayed moderate cytotoxic activity towards ovarian carcinoma (A2780, IC50 = 25.4 µM), colorectal adenocarcinoma (HT29, IC50 = 20.2 µM), breast cancer (MCF7, IC50 = 23.7 µM), and thyroid carcinoma (SW1736, IC50 = 26.2 µM) while it was inactive towards pharynx carcinoma (FaDu: IC50 > 30 µM).
Trypanosoma cruzi Presenilin-Like Transmembrane Aspartyl Protease: Characterization and Cellular Localization
Authors: Lechuga Guilherme C. , Napoleão-Pêgo Paloma , Bottino Carolina C. G. , Pinho Rosa T. , Provance-Jr David W. , De-Simone Salvatore G.
Published: November 2020

The increasing detection of infections of Trypanosoma cruzi, the etiological agent of Chagas disease, in non-endemic regions beyond Latin America has risen to be a major public health issue. With an impact in the millions of people, current treatments rely on antiquated drugs that produce severe side effects and are considered nearly ineffective for the chronic phase. The minimal progress in the development of new drugs highlights the need for advances in basic research on crucial biochemical pathways in T. cruzi to identify new targets. Here, we report on the T. cruzi presenilin-like transmembrane aspartyl enzyme, a protease of the aspartic class in a unique phylogenetic subgroup with T. vivax separate from protozoans. Computational analyses suggest it contains nine transmembrane domains and an active site with the characteristic PALP motif of the A22 family. Multiple linear B-cell epitopes were identified by SPOT-synthesis analysis with Chagasic patient sera. Two were chosen to generate rabbit antisera, whose signal was primarily localized to the flagellar pocket, intracellular vesicles, and endoplasmic reticulum in parasites by whole-cell immunofluorescence. The results suggest that the parasitic presenilin-like enzyme could have a role in the secretory pathway and serve as a target for the generation of new therapeutics specific to the T. cruzi.
Optimising Window Design on Residential Building Facades by Considering Heat Transfer and Natural Lighting in Nontropical Regions of Australia
Authors: Chen Zixuan , Hammad Ahmed , Kamardeen Imriyas , Haddad Assed
Published: November 2020

Windows account for a significant proportion of the total energy lost in buildings. The interaction of window type, Window-to-Wall Ratio (WWR) scheduled and window placement height influence natural lighting and heat transfer through windows. This is a pressing issue for nontropical regions considering their high emissions and distinct climatic characteristics. A limitation exists in the adoption of common simulation-based optimisation approaches in the literature, which are hardly accessible to practitioners. This article develops a numerical-based window design optimisation model using a common Building Information Modelling (BIM) platform adopted throughout the industry, focusing on nontropical regions of Australia. Three objective functions are proposed; the first objective is to maximise the available daylight, and the other two emphasize undesirable heat transfer through windows in summer and winter. The developed model is tested on a case study located in Sydney, Australia, and a set of Pareto-optimum solutions is obtained. Through the use of the proposed model, energy savings of up to 8.57% are achieved.
Using Hepatocellular Carcinoma Tumor Burden Score to Stratify Prognosis after Liver Transplantation
Authors: Moris Dimitrios , Shaw Brian I. , McElroy Lisa , Barbas Andrew S.
Published: November 2020

Liver transplantation (LT) remains a mainstay of treatment for hepatocellular carcinoma (HCC). Tumor factors such as size and number of tumors define eligibility for LT using the Milan criteria. The tumor burden score (TBS) incorporates both tumor number and size into a single continuous variable and has been used to differentiate prognosis among patients undergoing resection for HCC. The objective of the present study was to evaluate the ability of the TBS to predict overall and recurrence-free survival in patients undergoing LT for HCC. The Scientific Registry of Transplant Recipients (SRTR) was used to analyze all liver transplants for HCC, with initial tumor size data from 2004 to 2018. There were 12,486 patients in the study period. In the unadjusted analyses, patients with a high TBS had worse overall (p < 0.0001) and recurrence-free (p < 0.0001) survival. In the adjusted analyses, a high TBS was associated with a greater hazard ratio (HR) of death (HR = 1.21; 95%CI, [1.13–1.30]; p < 0.001) and recurrence (HR = 1.49; 95%CI [1.3–1.7]; p < 0.001). When we superimposed the TBS on the Milan criteria, we saw that a higher TBS was associated with a higher hazard of recurrence at values that were either all within (HR = 1.20; 95%CI, [1.04–1.37]; p = 0.011) or variably within (HR = 1.53; 95%CI, [1.16–2.01]; p = 0.002) the Milan criteria. In conclusion, the TBS is a promising tool in predicting outcomes in patients with HCC after LT.
Tumor MHC Expression Guides First-Line Immunotherapy Selection in Melanoma
Authors: Shklovskaya Elena , Lee Jenny H , Lim Su Yin , Stewart Ashleigh , Pedersen Bernadette , Ferguson Peter , Saw Robyn PM , Thompson John F , Shivalingam Brindha , Carlino Matteo S , Scolyer Richard A , Menzies Alexander M , Long Georgina V , Kefford Richard F , Rizos Helen
Published: November 2020

Immunotherapy targeting T-cell inhibitory receptors, namely programmed cell death-1 (PD-1) and/or cytotoxic T-lymphocyte associated protein-4 (CTLA-4), leads to durable responses in a proportion of patients with advanced metastatic melanoma. Combination immunotherapy results in higher rates of response compared to anti-PD-1 monotherapy, at the expense of higher toxicity. Currently, there are no robust molecular biomarkers for the selection of first-line immunotherapy. We used flow cytometry to profile pretreatment tumor biopsies from 36 melanoma patients treated with anti-PD-1 or combination (anti-PD-1 plus anti-CTLA-4) immunotherapy. A novel quantitative score was developed to determine the tumor cell expression of antigen-presenting MHC class I (MHC-I) molecules, and to correlate expression data with treatment response. Melanoma MHC-I expression was intact in all tumors derived from patients who demonstrated durable response to anti-PD-1 monotherapy. In contrast, melanoma MHC-I expression was low in 67% of tumors derived from patients with durable response to combination immunotherapy. Compared to MHC-I high tumors, MHC-I low tumors displayed reduced T-cell infiltration and a myeloid cell-enriched microenvironment. Our data emphasize the importance of robust MHC-I expression for anti-PD-1 monotherapy response and provide a rationale for the selection of combination immunotherapy as the first-line treatment in MHC-I low melanoma.
IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype
Authors: Nakamura Mano , Souri Elmira Amiri , Osborn Gabriel , Laddach Roman , Chauhan Jitesh , Stavraka Chara , Lombardi Sara , Black Anna , Khiabany Atousa , Khair Duaa O. , Figini Mariangela , Winship Anna , Ghosh Sharmistha , Montes Ana , Spicer James F. , Bax Heather J. , Josephs Debra H. , Lacy Katie E. , Tsoka Sophia , Karagiannis Sophia N.
Published: November 2020

IgE contributes to host-protective functions in parasitic and bacterial infections, often by monocyte and macrophage recruitment. We previously reported that monocytes contribute to tumour antigen-specific IgE-mediated tumour growth restriction in rodent models. Here, we investigate the impact of IgE stimulation on monocyte response, cellular signalling, secretory and tumour killing functions. IgE cross-linking on human monocytes with polyclonal antibodies to mimic formation of immune complexes induced upregulation of co-stimulatory (CD40, CD80, CD86), and reduced expression of regulatory (CD163, CD206, MerTK) monocyte markers. Cross-linking and tumour antigen-specific IgE antibody-dependent cellular cytotoxicity (ADCC) of cancer cells by cancer patient-derived monocytes triggered release of pro-inflammatory mediators (TNFα, MCP-1, IL-10, CXCL-10, IL-1β, IL-6, IL-23). High intratumoural gene expression of these mediators was associated with favourable five-year overall survival in ovarian cancer. IgE cross-linking of trimeric FcεRI on monocytes stimulated the phosphorylation of intracellular protein kinases widely reported to be downstream of mast cell and basophil tetrameric FcεRI signalling. These included recently-identified FcεRI pathway kinases Fgr, STAT5, Yes and Lck, which we now associate with monocytes. Overall, anti-tumour IgE can potentiate pro-inflammatory signals, and prime tumour cell killing by human monocytes. These findings will inform the development of IgE monoclonal antibody therapies for cancer.
The Non-Coding Landscape of Cutaneous Malignant Melanoma: A Possible Route to Efficient Targeted Therapy
Authors: Lazăr Andreea D. , Dinescu Sorina , Costache Marieta
Published: November 2020

Considered to be highly lethal if not diagnosed in early stages, cutaneous malignant melanoma is among the most aggressive and treatment-resistant human cancers, and its incidence continues to rise, largely due to ultraviolet radiation exposure, which is the main carcinogenic factor. Over the years, researchers have started to unveil the molecular mechanisms by which malignant melanoma can be triggered and sustained, in order to establish specific, reliable biomarkers that could aid the prognosis and diagnosis of this fatal disease, and serve as targets for development of novel efficient therapies. The high mutational burden and heterogeneous nature of melanoma shifted the main focus from the genetic landscape to epigenetic and epitranscriptomic modifications, aiming at elucidating the role of non-coding RNA molecules in the fine tuning of melanoma progression. Here we review the contribution of microRNAs and lncRNAs to melanoma invasion, metastasis and acquired drug resistance, highlighting their potential for clinical applications as biomarkers and therapeutic targets.
Application of Supported TiO2 in Carbonated Binding Material and Its Photocatalytic Performance
Authors: Si Heyang , Fang Yongle , Yang Lu
Published: November 2020

Although photocatalytic concrete can significantly contribute to the degradation of air pollutants and improving the sustainability levels, the complexity of ordinary cement system often caused the uncertain performance of mixed photocatalysts, which limited the real application of photocatalysts. Since the rapid carbonization hardening and relatively simple composition, γ-C2S carbonated binding material has gained considerable attention for its application in construction material. In this work, quartz sand-supported TiO2-C2S(γ) composites (TQSC) were prepared by mixing photocatalytic quartz sand with γ-C2S and mounting in γ-C2S matrix surface methods. The TiO2-coated quartz sand (TQS) was characterized by X-ray diffraction (XRD), quantitative X-ray fluorescence (XRF) and scanning electron microscopy (SEM). The photocatalytic performance and durability (washing resistance) of TQSC were also investigated by the degradation ability of NOx and rhodamine B (RhB). The results show that a uniform TiO2 layer on quartz sand was prepared, and the photocatalytic De-NOx (degradation of NOx) performance increased with increasing the mounted amounts of TiO2/quartz sand in γ-C2S carbonated matrix surface, but would decrease the photocatalytic durability. After water-washing, the De-NOx efficiencies of TQSC specimens decreased quickly at the beginning, which were adhering to the mounted amounts of TiO2/quartz sand, but would become stable after water-washing for 3600 s for all samples. The relatively high De-NOx stability and good self-cleaning effect of the water-washed TQSC-60% specimen can be considered a promising photocatalytic product for real applications.
The Role of Brachypodium distachyon Wall-Associated Kinases (WAKs) in Cell Expansion and Stress Responses
Authors: Wu Xingwen , Bacic Antony , Johnson Kim L. , Humphries John
Published: November 2020

The plant cell wall plays a critical role in signaling responses to environmental and developmental cues, acting as both the sensing interface and regulator of plant cell integrity. Wall-associated kinases (WAKs) are plant receptor-like kinases located at the wall—plasma membrane—cytoplasmic interface and implicated in cell wall integrity sensing. WAKs in Arabidopsis thaliana have been shown to bind pectins in different forms under various conditions, such as oligogalacturonides (OG)s in stress response, and native pectin during cell expansion. The mechanism(s) WAKs use for sensing in grasses, which contain relatively low amounts of pectin, remains unclear. WAK genes from the model monocot plant, Brachypodium distachyon were identified. Expression profiling during early seedling development and in response to sodium salicylate and salt treatment was undertaken to identify WAKs involved in cell expansion and response to external stimuli. The BdWAK2 gene displayed increased expression during cell expansion and stress response, in addition to playing a potential role in the hypersensitive response. In vitro binding assays with various forms of commercial polysaccharides (pectins, xylans, and mixed-linkage glucans) and wall-extracted fractions (pectic/hemicellulosic/cellulosic) from both Arabidopsis and Brachypodium leaf tissues provided new insights into the binding properties of BdWAK2 and other candidate BdWAKs in grasses. The BdWAKs displayed a specificity for the acidic pectins with similar binding characteristics to the AtWAKs.
Zika Virus Induces Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL)-Mediated Apoptosis in Human Neural Progenitor Cells
Authors: Lee Jae Kyung , Kim Ji-Ae , Oh Soo-Jin , Lee Eun-Woo , Shin Ok Sarah
Published: November 2020

Zika virus (ZIKV) remains as a public health threat due to the congenital birth defects the virus causes following infection of pregnant women. Congenital microcephaly is among the neurodevelopmental disorders the virus can cause in newborns, and this defect has been associated with ZIKV-mediated cytopathic effects in human neural progenitor cells (hNPCs). In this study, we investigated the cellular changes that occur in hNPCs in response to ZIKV (African and Asian lineages)-induced cytopathic effects. Transmission electron microscopy showed the progress of cell death as well as the formation of numerous vacuoles in the cytoplasm of ZIKV-infected hNPCs. Infection with both African and Asian lineages of ZIKV induced apoptosis, as demonstrated by the increased activation of caspase 3/7, 8, and 9. Increased levels of proinflammatory cytokines and chemokines (IL-6, IL-8, IL-1β) were also detected in ZIKV-infected hNPCs, while z-VAD-fmk-induced inhibition of cell death suppressed ZIKV-mediated cytokine production in a dose-dependent manner. ZIKV-infected hNPCs also displayed significantly elevated gene expression levels of the pro-apoptotic Bcl2-mediated family, in particular, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Furthermore, TRAIL signaling led to augmented ZIKV-mediated cell death and the knockdown of TRAIL-mediated signaling adaptor, FADD, resulted in enhanced ZIKV replication. In conclusion, our findings provide cellular insights into the cytopathic effects induced by ZIKV infection of hNPCs.
Regulatory microRNAs in Brown, Brite and White Adipose Tissue
Authors: Gharanei Seley , Shabir Kiran , Brown James E. , Weickert Martin O. , Barber Thomas M. , Kyrou Ioannis , Randeva Harpal S.
Published: November 2020

MicroRNAs (miRNAs) constitute a class of short noncoding RNAs which regulate gene expression by targeting messenger RNA, inducing translational repression and messenger RNA degradation. This regulation of gene expression by miRNAs in adipose tissue (AT) can impact on the regulation of metabolism and energy homeostasis, particularly considering the different types of adipocytes which exist in mammals, i.e., white adipocytes (white AT; WAT), brown adipocytes (brown AT; BAT), and inducible brown adipocytes in WAT (beige or brite or brown-in-white adipocytes). Indeed, an increasing number of miRNAs has been identified to regulate key signaling pathways of adipogenesis in BAT, brite AT, and WAT by acting on transcription factors that promote or inhibit adipocyte differentiation. For example, MiR-328, MiR-378, MiR-30b/c, MiR-455, MiR-32, and MiR-193b-365 activate brown adipogenesis, whereas MiR-34a, MiR-133, MiR-155, and MiR-27b are brown adipogenesis inhibitors. Given that WAT mainly stores energy as lipids, whilst BAT mainly dissipates energy as heat, clarifying the effects of miRNAs in different types of AT has recently attracted significant research interest, aiming to also develop novel miRNA-based therapies against obesity, diabetes, and other obesity-related diseases. Therefore, this review presents an up-to-date comprehensive overview of the role of key regulatory miRNAs in BAT, brite AT, and WAT.
Clinical Actionability of the Genomic Landscape of Metastatic Castration Resistant Prostate Cancer
Authors: Devlies Wout , Eckstein Markus , Cimadamore Alessia , Devos Gaëtan , Moris Lisa , Van den Broeck Thomas , Montironi Rodolfo , Joniau Steven , Claessens Frank , Gevaert Thomas
Published: November 2020

The development of targeted therapies increases treatment options for metastatic castration resistant prostate cancer (mCRPC) patients. There is a need for strong predictive and prognostic signatures to guide physicians in treating mCRPC patients. In this review we unravel the possible actionability in the AR pathway, PI3K AKT signaling, and DNA repair pathways. Additionally, we make recommendations on biomarker trial design, and the clinical use of this new type of data.
The Endoplasmic Reticulum Stress/Unfolded Protein Response and Their Contributions to Parkinson’s Disease Physiopathology
Authors: Costa Cristine Alves da , Manaa Wejdane El , Duplan Eric , Checler Frédéric
Published: November 2020

Parkinson’s disease (PD) is a multifactorial age-related movement disorder in which defects of both mitochondria and the endoplasmic reticulum (ER) have been reported. The unfolded protein response (UPR) has emerged as a key cellular dysfunction associated with the etiology of the disease. The UPR involves a coordinated response initiated in the endoplasmic reticulum that grants the correct folding of proteins. This review gives insights on the ER and its functioning; the UPR signaling cascades; and the link between ER stress, UPR activation, and physiopathology of PD. Thus, post-mortem studies and data obtained by either in vitro and in vivo pharmacological approaches or by genetic modulation of PD causative genes are described. Further, we discuss the relevance and impact of the UPR to sporadic and genetic PD pathology.
Proteomic Insights into Senescence of Testicular Peritubular Cells from a Nonhuman Primate Model
Authors: Stöckl Jan B. , Schmid Nina , Flenkenthaler Florian , Drummer Charis , Behr Rüdiger , Mayerhofer Artur , Arnold Georg J. , Fröhlich Thomas
Published: November 2020

Age-related changes in the human testis may include morphological alterations, disturbed steroidogenesis, and impaired spermatogenesis. However, the specific impact of cell age remains poorly understood and difficult to assess. Testicular peritubular cells fulfill essential functions, including sperm transport, contributions to the spermatogonial stem cell niche, and paracrine interactions within the testis. To study their role in age-associated decline of testicular functions, we performed comprehensive proteome and secretome analyses of repeatedly passaged peritubular cells from Callithrix jacchus. This nonhuman primate model better reflects the human testicular biology than rodents and further gives access to young donors unavailable from humans. Among 5095 identified proteins, 583 were differentially abundant between samples with low and high passage numbers. The alterations indicate a reduced ability of senescent peritubular cells to contract and secrete proteins, as well as disturbances in nuclear factor (NF)-κB signaling and a reduced capacity to handle reactive oxygen species. Since this in vitro model may not exactly mirror all molecular aspects of in vivo aging, we investigated the proteomes and secretomes of testicular peritubular cells from young and old donors. Even though the age-related alterations at the protein level were less pronounced, we found evidence for impaired protein secretion, altered NF-κB signaling, and reduced contractility of these in vivo aged peritubular cells.
Spark Plasma Sintering of Ceramics: From Modeling to Practice
Authors: Stuer Michael , Bowen Paul , Zhao Zhe
Published: November 2020

Summarizing the work of nearly a decade of research on spark plasma sintering (SPS), a review is given on the specificities and key factors to be considered in SPS of ceramic materials, based on the authors’ own research. Alumina is used primarily as a model material throughout the review. Intrinsic inhomogeneities linked to SPS and operational parameters, which depend on the generation of atomistic scale defects, are discussed in detail to explain regularly observed inhomogeneities reported in literature. Adopting an engineering approach to overcome these inherent issues, a successful processing path is laid out towards the mastering of SPS in a wide range of research and industrial settings.
The Nutritional Profile of Food Advertising for School-Aged Children via Television: A Longitudinal Approach
Authors: Campos Daniel , Escudero-Marín Mireia , Snitman Camila M. , Torres-Espínola Francisco J. , Azaryah Hatim , Catena Andrés , Campoy Cristina
Published: November 2020

The prevalence of childhood obesity continues to increase. Screen time, one of the most documented reasons for the obesogenic environment, enhances childhood obesity, since advertisements for unhealthy food products are still broadcast on channels for children. This is presently one of the main challenges for the government in Spain, since the current laws and obligations are not updated. This study aims to analyze food advertising aimed at children on Spanish television in 2013 and 2018 on children’s and general channels to test the effect of laws and obligations over time. In total, we viewed 512 h of the most viewed channels, two children’s and two general channels, during the week and on weekends during specific periods of 2013 and 2018. Food advertising was categorized as core, non-core, and other food advertisement (CFA, NCFA, and OFA, respectively) according to the nutritional profile. A total of 2935 adverts were analyzed, 1263 in 2013 and 1672 in 2018. A higher proportion of NCFAs were broadcast on children’s channels than in prior years, rising from 52.2% to 69.8% (p < 0.001). Nowadays, the risk of watching NCFAs on children’s channels compared to general channels turns out to be higher (Odds ratio > 2.5; p < 0.001), due to exposure to adverts for high-sugar and high-fat foods such as cakes, muffins, cookies, and fried and frozen meals rich in fat. In conclusion, the trends of nutritional profiles in food advertising on television are worsening over time, since the prevalence of NCFAs was higher in 2018 than in 2013. Currently, CFAs are not mainly broadcast on children’s channels, confirming high-risk exposure to non-core food advertising by watching them. Thus, food advertising laws and obligations should be adapted to increase compliance.