bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating Public Participation, Transparency and Accountability Into Governance of Marketing Authorisation for Genome Editing Products
Authors: Nielsen Jane , Eckstein Lisa , Nicol Dianne , Stewart Cameron
Published: October 2021

Public participation, transparency and accountability are three of the pillars of good governance. These pillars become particularly important for innovative, personalised health technologies, because of the tendency of these technologies to raise distinct scientific, ethical, legal and social issues. Genome editing is perhaps the most personal of all innovative health technologies, involving precise modifications to an individual’s genome. This article focuses on the adequacy of current requirements for public participation, transparency and accountability in the governance of the market authorisation for genome edited products. Although clinical trials for genome edited products are only just underway, lessons can be drawn from the marketing approvals pathways for related gene therapy products. This article provides a broad overview of the regulatory pathways that have been adopted by the US Food and Drugs Administration, the European Medicines Authority, and the Australian Therapeutic Goods Administration for reviewing gene therapy products for marketing approval. This analysis focuses on the extent to which public participation processes and transparency and accountability of review pathways are incorporated into marketing approval policy and practice. Following this review, the article proposes the application of Sheila Jasanoff’s “technologies of humility” as a foundation for meaningfully incorporating these pillars of good governance into regulatory processes for the review of products of genome editing. We conclude by articulating clear mechanisms for operationalising technologies of humility in the context of public participation, transparency and accountability, providing a blueprint for future policy development.
Psychological Capital and Job Satisfaction Among Chinese Residents: A Moderated Mediation of Organizational Identification and Income Level
Authors: Zhang Fang , Liu Ying , Wei Tongqi
Published: October 2021

The present study examined the mediating effect of organizational identification on the relationship between psychological capital and job satisfaction, and whether the mediation was moderated by income level. A total of 310 Chinese residents were surveyed using the Psychological Capital Scale, Organizational Identification Scale, Job Satisfaction Scale, and a demographic questionnaire. The findings showed a significant positive correlation between psychological capital and job satisfaction of residents, and this relationship was partially mediated by organizational identification. Moreover, income level played a moderating role in the relationship between organizational identification and job satisfaction. For residents with more income, their organizational identification influenced their job satisfaction more strongly than those with less income. The current study contributes to a better understanding of the relationship between psychological capital and job satisfaction. Implications for resident management and policymaking are discussed.
Assessing the Nomological Network of the South African Personality Inventory With Psychological Traits
Authors: Hill Carin , Nel Jan Alewyn , de Beer Leon T. , Fetvadjiev Velichko H. , Stevens Lyle I , Bruwer Monique
Published: October 2021

The purpose of this study was to expand internal construct validity and equivalence research of the South African Personality Inventory (SAPI), as well as to investigate the nomological validity of the SAPI by examining its relationship with specific and relevant psychological outcomes. The internal and external validity of the SAPI was assessed within three separate samples (N= 936). Using the combined data from all three samples, Exploratory Structural Equation Modelling (ESEM) indicated that the six-factor SAPI model fit proved to be excellent. Measurement invariance analyses showed that the SAPI dimensions in the ESEM model were invariant across gender and race groups. Next, two separate studies explored the associations of the SAPI factors with relevant psychological outcomes. An ESEM-within-CFA (set ESEM) method was used to add the factors into a new input file to correlate them with variables that were not part of the initial ESEM model. Both models generated excellent fit. In Study 1, psychological well-being and cultural intelligence were correlated with the SAPI factors within a sample of students and working adults. All of the psychological well-being dimensions significantly correlated with the SAPI factors, while for cultural intelligence, the highest correlations were between Meta-cognition and Openness and Meta-cognition and Positive Social-Relational Disposition. In Study 2, work locus of control and trait anxiety was correlated with the SAPI factors within a sample of adults from the general South African workforce. Work Locus of Control correlated with most factors of the SAPI, but more prominently with Positive Social-Relational Disposition, while Neuroticism correlated strongly with trait anxiety. Finding an appropriate internal structure that measures personality without bias in a culturally diverse context is difficult. This study provided strong evidence that the SAPI meets the demanding requirements of personality measurement in this context and generated promising results to support the relevance of the SAPI factors.
Building Scientific Capability and Reducing Biological Threats: The Effect of Three Cooperative Bio-Research Programs in Kazakhstan
Authors: Yeh Kenneth B. , Tabynov Kairat , Parekh Falgunee K. , Maltseva Elina , Skiba Yuriy , Shapiyeva Zhanna , Sansyzbai Ablay , Frey Stefan , Essbauer Sandra , Hewson Roger , Richards Allen L. , Hay John
Published: October 2021

Cooperative research programs aimed at reducing biological threats have increased scientific capabilities and capacities in Kazakhstan. The German Federal Foreign Office's German Biosecurity Programme, the United Kingdom's International Biological Security Programme and the United States Defense Threat Reduction Agency's Biological Threat Reduction Program provide funding for partner countries, like Kazakhstan. The mutual goals of the programs are to reduce biological threats and enhance global health security. Our investigation examined these cooperative research programs, summarizing major impacts they have made, as well as common successes and challenges. By mapping various projects across the three programs, research networks are highlighted which demonstrate best communication practices to share results and reinforce conclusions. Our team performed a survey to collect results from Kazakhstani partner scientists on their experiences that help gain insights into enhancing day-to-day approaches to conducting cooperative scientific research. This analysis will serve as a basis for a capability maturity model as used in industry, and in addition builds synergy for future collaborations that will be essential for quality and sustainment.
The Millions of Microbial Reasons You Need to Brush Your Teeth
Authors: Gancz Abigail Shahar , Wright Sterling , Moore Nicole E. , Weyrich Laura S.
Published: October 2021

Millions of tiny critters called microorganisms live in your mouth. Each one is unique and has a specific job. For instance, some microorganisms help with digesting food and others protect you from dangerous infections. Some microorganisms come from your parents, some from the foods you eat, and some from not brushing your teeth. All these microorganisms need food. The good microorganisms that help your mouth stay healthy enjoy eating vegetables, fruits, and grains; the bad ones like sugar. When you eat too much sugar, the bad microorganisms can cause painful problems in your mouth. They may even cause you to lose your teeth or make your gums bleed. Fortunately, brushing your teeth helps remove these rogue bacteria. While we know some things about the microorganisms in the mouth, there is still much we do not know and are still working to discover.
Can Plants Be Engineers?
Authors: Conrad J. Louise
Published: October 2021

When we think of engineers, we think of making a machine, like a car. Are there engineers for ecosystems? When an organism can make big changes to its environment, we call it an ecosystem engineer. In aquatic ecosystems like the San Francisco Estuary, underwater plants can be important ecosystem engineers because they can change water flow and water clarity. In the Estuary, a plant called Brazilian waterweed, which was introduced by humans, is one of the most important ecosystem engineers. With its leaves and stems, this plant traps tiny particles floating in the water, making the water clearer. Clearer water has made it easier for more plants to grow and these changes helped some non-native fish species to increase in number, while some native species declined. Introduction of Brazilian waterweed has led to an entirely different ecosystem, which has also affected how people use and take care of the Estuary.
Ant Colony Optimization with Warm-Up
Authors: Neroni Mattia
Published: October 2021

The Ant Colony Optimization (ACO) is a probabilistic technique inspired by the behavior of ants for solving computational problems that may be reduced to finding the best path through a graph. Some species of ants deposit pheromone on the ground to mark some favorable paths that should be used by other members of the colony. Ant colony optimization implements a similar mechanism for solving optimization problems. In this paper a warm-up procedure for the ACO is proposed. During the warm-up, the pheromone matrix is initialized to provide an efficient new starting point for the algorithm, so that it can obtain the same (or better) results with fewer iterations. The warm-up is based exclusively on the graph, which, in most applications, is given and does not need to be recalculated every time before executing the algorithm. In this way, it can be made only once, and it speeds up the algorithm every time it is used from then on. The proposed solution is validated on a set of traveling salesman problem instances, and in the simulation of a real industrial application for the routing of pickers in a manual warehouse. During the validation, it is compared with other ACO adopting a pheromone initialization technique, and the results show that, in most cases, the adoption of the proposed warm-up allows the ACO to obtain the same or better results with fewer iterations.
A Review on the Modified Atmosphere Preservation of Fruits and Vegetables with Cutting-Edge Technologies
Authors: Fang Yujie , Wakisaka Minato
Published: October 2021

Respiration and microbial infection are important causes of postharvest spoilage of fruits and vegetables (F&V). Atmosphere storage technology can significantly reduce postharvest losses. This comprehensive review aims to cover recent progress in the application of atmosphere storage to F&V preservation, not only focusing on the effect of gas conditions but also evaluating combination applications involving newer preservation technologies, including ethylene scavengers, high-pressure and decompression technology, ozone, ultraviolet radiation, active packaging, high-voltage electrostatic field, plasma treatment, and pulse-controlled atmosphere. Appropriate choice of storage conditions optimal for each F&V is essential since the physiological properties and sensory qualities are affected by them. The combination of atmosphere storage with these emerging technologies could contribute to significant reductions in food loss during storage.
Pet Reptiles—Are We Meeting Their Needs?
Authors: Azevedo Alexandre , Guimarães Leonor , Ferraz Joel , Whiting Martin , Magalhães-Sant’Ana Manuel
Published: October 2021

The ability to meet the needs of each species in captivity is at the heart of the ethical debate on the acceptability of keeping reptiles and other animals as pets. Little is known about the ability of reptile owners to understand their pets’ behavior and to meet their welfare requirements. In this study, we surveyed pet reptile owners in Portugal (N = 220) to assess their behavioral knowledge and the provision of essential husbandry needs. Although two-thirds of respondents (68%) scored very good to excellent in terms of knowledge of their pet reptile’s behaviors, only 15% of respondents met four essential reptile husbandry needs (temperature, lighting, diet and refuge) and 43% met two or less. None of the respondents reported their reptile’s welfare as very poor, and only a single respondent reported it as poor. Logistic regression model showed that while snake owners had fourteen times higher odds of reporting adequate husbandry provision, lizard owners had the highest odds of reporting good or very good welfare despite providing less of their animals’ basic husbandry needs. These results suggest that many pet reptiles in Portugal live in, at best, ‘controlled deprivation’ and are at risk of suffering poor welfare throughout their captive lives. Moreover, behaviors indicative of poor welfare and captivity stress were considered ‘normal’ by up to one quarter of respondents. We suggest that the frequency of these behaviors in pet reptiles has led to their acceptance as normal, precluding the search for ways to prevent them. These results suggest that campaigns aimed at challenging the current norm for adequate reptile welfare are warranted.
Behaviour in Slower-Growing Broilers and Free-Range Access on Organic Farms in Sweden
Authors: Göransson Lina , Gunnarsson Stefan , Wallenbeck Anna , Yngvesson Jenny
Published: October 2021

Two slower-growing hybrids (Rowan Ranger and Hubbard) are currently reared in organic broiler production in Sweden, but knowledge of bird welfare on commercial farms is limited. This study examined chicken behaviour, including free-range use and features of this, in order to enhance knowledge, describe the current situation and identify practical solutions on Swedish organic broiler farms. Eight of 12 available farms were visited once each, when average flock age was 55 ± 6 days. Farmer interviews were followed by avoidance distance tests, group behavioural observations, and assessment of use of environmental enrichment and free-range by the chickens. On average, almost half of all birds observed indoors were in a sitting posture. However, even when approaching slaughter age, the chickens were agile enough to perch and used some of the variety of items provided for perching, but the quantity of environmental enrichment equipment appeared to be insufficient. Free-range areas generally lacked sufficient vegetation cover or artificial shelters, and chickens were predominantly observed ranging near the house. Further research should explore feasible ways for farmers to make key improvements to the indoor and outdoor environment, in order to improve broiler welfare.
Metabolic Flexibility in Canine Mammary Tumors: Implications of the Carnitine System
Authors: Cacciola Nunzio Antonio , Sgadari Mariafrancesca , Sepe Fabrizia , Petillo Orsolina , Margarucci Sabrina , Martano Manuela , Maiolino Paola , Restucci Brunella
Published: October 2021

Deregulation of fatty acid catabolism provides an alternative energy source to glycolysis for cancer cell survival and proliferation. The regulator enzymes of the carnitine system (CS), responsible for the transport of fatty acids across mitochondrial membranes for β-oxidation are deregulated in tumorigenesis. Recently, we found that Carnitine Palmitoyl Transferase 1 (CPT1), a crucial regulator of CS components, is expressed and dysregulated in canine mammary tumor (CMT) tissues and cells. In this study, we examined the protein expression of the three remaining enzymes of CS (Carnitine Acylcarnitine Translocase (CACT), Carnitine Palmitoyl Transferase 2 (CPT2), Carnitine O-acetyltransferase (CrAT), in canine mammary cells and tissues by Western blot and immunohistochemistry. Protein expression of the components of CS was found in normal mammary glands and a concomitant deregulation of expression in CMT tissues that inversely correlated with the degree of tumor differentiation. Moreover, the expression and a different deregulation of CS-related proteins was also observed in CF33, CMT-U27, CMT-U309, and P114 cell lines used as in vitro model. These results demonstrate for the first time the expression of CS components in CMT tissues and cancer cells; however, further studies are needed to elucidate their roles in dogs as well.
Diurnal Dynamics of the Umov Kinetic Energy Density Vector in the Atmospheric Boundary Layer from Minisodar Measurements
Authors: Potekaev Alexander , Krasnenko Nikolay , Shamanaeva Liudmila
Published: October 2021

The diurnal hourly dynamics of the kinetic energy flux density vector, called the Umov vector, and the mean and turbulent components of the kinetic energy are estimated from minisodar measurements of wind vector components and their variances in the lower 200 m layer of the atmosphere. During a 24 h period of continuous minisodar observations, it was established that the mean kinetic energy density dominated in the surface atmospheric layer at altitudes below ~50 m. At altitudes from 50 to 100 m, the relative contributions of the mean and turbulent wind kinetic energy densities depended on the time of the day and the sounding altitude. At altitudes below 100 m, the contribution of the turbulent kinetic energy component is small, and the ratio of the turbulent to mean wind kinetic energy components was in the range 0.01–10. At altitudes above 100 m, the turbulent kinetic energy density sharply increased, and the ratio reached its maximum equal to 100–1000 at altitudes of 150–200 m. A particular importance of the direction and magnitude of the wind effect, that is, of the direction and magnitude of the Umov vector at different altitudes was established. The diurnal behavior of the Umov vector depended both on the time of the day and the sounding altitude. Three layers were clearly distinguished: a near-surface layer at altitudes of 5–15 m, an intermediate layer at altitudes from 15 m to 150 m, and the layer of enhanced turbulence above. The feasibility is illustrated of detecting times and altitudes of maximal and minimal wing kinetic energy flux densities, that is, time periods and altitude ranges most and least favorable for flights of unmanned aerial vehicles. The proposed novel method of determining the spatiotemporal dynamics of the Umov vector from minisodar measurements can also be used to estimate the effect of wind on high-rise buildings and the energy potential of wind turbines.
Sulfur and Nitrogen Oxides in the Atmosphere of Lake Baikal: Sources, Automatic Monitoring, and Environmental Risks
Authors: Obolkin Vladimir , Molozhnikova Elena , Shikhovtsev Maxim , Netsvetaeva Olga , Khodzher Tamara
Published: October 2021

This paper analyzes the results of the automatic (in situ) recording of the regional transport of pollutants from the large regional coal-fired thermal power plants in the atmospheric boundary layer above the southern basin of Lake Baikal. Due to high stacks (about 200 m), emissions from large thermal power plants rise to the altitudes of several hundreds of meters and spread over long distances from their source by tens and hundreds of kilometers. The continuous automatic monitoring of the atmosphere in the southern basin of Lake Baikal on top of the coastal hill (200 m above the lake) revealed the transport of a large number of sulfur oxides and nitrogen oxides in the form of high-altitude plumes from thermal power plants of the large cities located 70 to 100 km to the northwest of the lake (Irkutsk and Angarsk). The consequence of such transport is the increased acidity of precipitation in the southern basin of Lake Baikal and the additional influx of biogenic nitrogen compounds to the lake ecosystem. The spatial scale and possible risks of such regional transport of air pollution for the lake ecosystem require further closer study.
Introduction to Neuromechanics, a New MDPI Open Access Section of Biomechanics
Authors: Hortobágyi Tibor
Published: October 2021

Welcome to Neuromechanics, a section of Biomechanics published by the Multidisciplinary Digital Publishing Institute, MDPI [...]
Genomic Characterization of Serotype III/ST-17 Group B Streptococcus Strains with Antimicrobial Resistance Using Whole Genome Sequencing
Authors: Hsu Jen-Fu , Tsai Ming-Horng , Lin Lee-Chung , Chu Shih-Ming , Lai Mei-Yin , Huang Hsuan-Rong , Chiang Ming-Chou , Yang Peng-Hong , Lu Jang-Jih
Published: October 2021

Background: Antibiotic-resistant type III/ST-17 Streptococcus agalactiae (group B Streptococcus, GBS) strain is predominant in neonatal invasive GBS diseases. We aimed to investigate the antibiotic resistance profiles and genetic characteristics of type III/ST-17 GBS strains. Methods: A total of 681 non-duplicate GBS isolates were typed (MLST, capsular types) and their antibiotic resistances were performed. Several molecular methods (WGS, PCR, sequencing and sequence analysis) were used to determine the genetic context of antibiotic resistant genes and pili genes. Results: The antibiotic resistant rates were significantly higher in type Ib (90.1%) and type III (71.1%) GBS isolates. WGS revealed that the loss of PI-1 genes and absence of ISSag5 was found in antibiotic-resistant III/ST-17 GBS isolates, which is replaced by a ~75-kb integrative and conjugative element, ICESag37, comprising multiple antibiotic resistance and virulence genes. Among 190 serotype III GBS isolates, the most common pilus island was PI-2b (58.4%) alone, which was found in 81.3% of the III/ST-17 GBS isolates. Loss of PI-1 and ISSag5 was significantly associated with antibiotic resistance (95.5% vs. 27.8%, p < 0.001). The presence of ICESag37 was found in 83.6% of all III/ST-17 GBS isolates and 99.1% (105/106) of the antibiotic-resistant III/ST-17 GBS isolates. Conclusions: Loss of PI-1 and ISSag5, which is replaced by ICESag37 carrying multiple antibiotic resistance genes, accounts for the high antibiotic resistance rate in III/ST-17 GBS isolates. The emerging clonal expansion of this hypervirulent strain with antibiotic resistance after acquisition of ICESag37 highlights the urgent need for continuous surveillance of GBS infections.
Water Thermodynamics and Its Effects on the Protein Stability and Activity
Authors: Mallamace Francesco , Mallamace Domenico , Chen Sow-Hsin , Lanzafame Paola , Papanikolaou Georgia
Published: October 2021

We discuss a phenomenon regarding water that was until recently a subject of scientific interest: i.e., the dynamical crossover, from the fragile to strong glass forming material, for both bulk and protein hydration water. Such crossover is characterized by a temperature TL in which significant dynamical changes like the decoupling (or the violation of the Stokes-Einstein relation) of homologous transport parameters, e.g., the density relaxation time τ and the viscosity η, occur in the system. On this respect we considered the dynamic properties of water-protein systems. More precisely, we focused our study on proteins and their hydration water, as far as bulk and confined water. In order to clarify the effects of the water dynamical crossover on the protein properties we considered and discussed in a comparative way previous and new experimental data, obtained from different techniques and molecular dynamic simulation (MD). We pointed out the reasons for different dynamical findings from the use of different experimental techniques.
Applicability of Atmospheric Pressure Plasma Jet (APPJ) Discharge for the Reduction in Graphene Oxide Films and Synthesis of Carbon Nanomaterials
Authors: Vinoth Kumar Sri Hari Bharath , Ibaceta-Jaña Josefa , Maticuic Natalia , Kowiorski Krystian , Zelt Matthias , Gernert Ulrich , Lipińska Ludwika , Szyszka Bernd , Schlatmann Rutger , Hartmann Uwe , Muydinov Ruslan
Published: October 2021

Atmospheric pressure plasma jets (APPJ) are widely used in industry for surface cleaning and chemical modification. In the recent past, they have gained more scientific attention especially in the processing of carbon nanomaterials. In this work, a novel power generation technique was applied to realize the stable discharge in N2 (10 vol.% H2) forming gas in ambient conditions. This APPJ was used to reduce solution-processed graphene oxide (GO) thin films and the result was compared with an established and optimized reduction process in a low–pressure capacitively coupled (CCP) radiofrequency (RF) hydrogen (H2) plasma. The reduced GO (rGO) films were investigated by Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). Effective deoxygenation of GO was observed after a quick 2 s treatment by AAPJ. Further deoxygenation at longer exposure times was found to proceed with the expense of GO–structure integrity. By adding acetylene gas into the same APPJ, carbon nanomaterials on various substrates were synthesized. The carbon materials were characterized by Raman spectroscopy, scanning electron microscopy (SEM), and energy-dispersive X-ray (EDX) analyses. Fullerene-like particles and graphitic carbon with short carbon nanotubes were detected on Si and Ag surfaces, respectively. We demonstrate that the APPJ tool has obvious potential for the versatile processing of carbon nanomaterials.
Long-Term Outcome and Comparison of Treatment Modalities of Temporal Bone Paragangliomas
Authors: Yildiz Erdem , Dahm Valerie , Gstoettner Wolfgang , Rössler Karl , Bauer Belinda , Wressnegger Alexander , Schwarz-Nemec Ursula , Gatterbauer Brigitte , Matula Christian , Arnoldner Christoph
Published: October 2021

Introduction: Temporal bone paragangliomas are rare tumors with high vascularization and usually benign entity. A variety of modalities, including gross total resection, subtotal resection, conventional or stereotactic radiotherapy including gamma-knife, embolization, and wait-and-scan strategy can be considered. The aim of this study was to compare long-term outcomes of different primary treatment modalities in temporal bone paragangliomas. Materials and Methods: Patients with temporal bone paragangliomas treated between 1976 and 2018 at a tertiary referral center were retrospectively analyzed in this study. Collected patient data of 42 years were analyzed and long-term results including interdisciplinary management were assessed. Patient outcomes were compared within the different therapy modalities according to tumor control rate and complications. Clinical characteristics, radiological imaging, tumor extent and location (according to Fisch classification), symptoms, and follow-up were evaluated and a descriptive analysis for each treatment modality was performed. Tumor recurrence or growth progression and respective cranial nerve function before and after therapy were described. Results: A total of 59 patients were treated with a single or combined treatment modality and clinical follow-up was 7 (13) years (median, interquartile range). Of the included patients 45 (76%) were female and 14 (24%) male (ratio 3:1) with a patient age range from 18 to 83 years. Total resection was performed on 31 patients, while 14 patients underwent subtotal resection. Eleven patients were treated with conventional primary radiotherapy or gamma-knife radiosurgery. Pulsatile tinnitus (n = 17, 29%) and hearing impairment (n = 16, 27%) were the most common symptoms in our patient group. Permanent lower cranial nerve deficits were observed only in patients with large tumors (Fisch C and D, n = 14, 24%). Among the 45 patients who were treated surgically, 88% of patients with Fisch A and B paragangliomas had no recurrent disease, while no tumor growth was perceived in 83% of patients with Fisch C and D paragangliomas. Conclusion: In conclusion, we propose surgery as a treatment option for patients with small tumors, due to a high control rate and less cranial nerve deficits compared to larger tumors. Although patients with Fisch C and D temporal bone paraganglioma can be treated surgically, only subtotal resections are possible in many cases. Additionally, frequent occurrence of cranial nerve deficits in those patients and tumor growth progression in long-term follow-up examinations make a combination of the therapy modalities or a primary radiotherapy more suitable in larger tumors.
The Prevalence of Pathogenic or Likely Pathogenic Germline Variants in a Nationwide Cohort of Young Colorectal Cancer Patients Using a Panel of 18 Genes Associated with Colorectal Cancer
Authors: Frostberg Erik , Petersen Annabeth Høgh , Bojesen Anders , Rahr Hans Bjarke , Lindebjerg Jan , Rønlund Karina
Published: October 2021

Introduction: The prevalence of pathogenic or likely pathogenic germline variants (PGV) in colorectal cancer (CRC) in young patients is seen in approximately one in five patients, with the majority of cases having gene variants associated with Lynch syndrome (LS). The primary aim was to describe the prevalence of 18 genes, all associated with hereditary polyposis and CRC, in a nationwide population of young CRC (yCRC) patients, and outline disease characteristics in patients with or without germline variants. Methods: We screened 98 patients aged 18–40 with CRC diagnosed in 2010–2013 for variants in MSH2, MSH6, MLH1, PMS2, EPCAM, APC, MUTYH, SMAD4, BMPR1A, STK11, PTEN, POLE, POLD1, NTHL1, AXIN2, MSH3, GREM1 and RNF43 using Next Generation Sequencing. Comparisons between patients’ characteristics in patients with PGV, and patients without germline variants (NPGV) were analyzed. Results: PGV were detected in twenty-four patients (24.5%), and twenty-one patients (21.1%) had variants in the mismatch repair (MMR) genes associated with LS. Variants in the APC and MUTYH genes were detected in 1% and 4%, respectively. Patients with NPGV had more advanced disease with adverse histopathological features. Conclusion: PGV was detected in one in four yCRC patients, and one in five yCRC patients had disease causing variants in the mismatch repair genes associated with LS.
Impact of Epithelial–Mesenchymal Transition on the Immune Landscape in Breast Cancer
Authors: Khadri Fatima-Zohra , Issac Marianne Samir Makboul , Gaboury Louis Arthur
Published: October 2021

The impact of epithelial–mesenchymal transition (EMT) signature on the immune infiltrate present in the breast cancer tumor microenvironment (TME) is still poorly understood. Since there is mounting interest in the use of immunotherapy for the treatment of subsets of breast cancer patients, it is of major importance to understand the fundamental tumor characteristics which dictate the inter-tumor heterogeneity in immune landscapes. We aimed to assess the impact of EMT-related markers on the nature and magnitude of the inflammatory infiltrate present in breast cancer TME and their association with the clinicopathological parameters. Tissue microarrays were constructed from 144 formalin-fixed paraffin-embedded invasive breast cancer tumor samples. The protein expression patterns of Snail, Twist, ZEB1, N-cadherin, Vimentin, GRHL2, E-cadherin, and EpCAM were examined by immunohistochemistry (IHC). The inflammatory infiltrate in the TME was assessed semi-quantitatively on hematoxylin and eosin (H&E)-stained whole sections and was characterized using IHC. The inflammatory infiltrate was more intense in poorly differentiated carcinomas and triple-negative carcinomas in which the expression of E-cadherin and GRHL2 was reduced, while EpCAM was overexpressed. Most EMT-related markers correlated with plasma cell infiltration of the TME. Taken together, our findings reveal that the EMT signature might impact the immune response in the TME.
MiRNA-424-5p Suppresses Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma and Attenuates Expression of O-GlcNAc-Transferase
Authors: Kalantzakos Thomas J. , Sullivan Travis B. , Gloria Thales , Canes David , Moinzadeh Alireza , Rieger-Christ Kimberly M.
Published: October 2021

MicroRNAs (miRNAs) are non-coding post-transcriptional regulators of gene expression that are dysregulated in clear cell renal cell carcinoma (ccRCC) and play an important role in tumor progression. Our prior work identified a subset of miRNAs in pT1 ccRCC tumors, including miR-424-5p, that are associated with an aggressive phenotype. We investigate the impact of this dysregulated miRNA and its protein target O-GlcNAc-transferase (OGT) to better understand the mechanisms behind aggressive stage I ccRCC. The ccRCC cell lines 786-O and Caki-1 were used to assess the impact of miR-424-5p and OGT. Cells were transfected with pre-miR-424-5p, a lentiviral anti-OGT shRNA, or were treated with the demethylating agent 5-Aza-2′-deoxycytidine. Cell proliferation was measured via MT cell viability assay. Cell migration and invasion were analyzed using Transwell assays. The expression of miR-424-5p was determined through qRT-PCR, while OGT protein expression was evaluated through Western blotting. The interaction between miR-424-5p and OGT was confirmed via luciferase reporter assay. The transfection of ccRCC cells with pre-miR-424-5p or anti-OGT shRNA significantly inhibited cell proliferation, migration, and OGT expression, while miR-424-5p also attenuated cell invasion. Addition of the demethylating agent significantly reduced cell proliferation, migration, invasion, and OGT expression, while significantly increasing the expression of miR-424-5p. Altogether, these findings suggest that epigenetic downregulation of miR-424-5p, which in turn augments OGT expression, contributes to the creation of aggressive forms of stage I ccRCC.
Safety and Efficacy Evaluation In Vivo of a Cationic Nucleolipid Nanosystem for the Nanodelivery of a Ruthenium(III) Complex with Superior Anticancer Bioactivity
Authors: Piccolo Marialuisa , Ferraro Maria Grazia , Raucci Federica , Riccardi Claudia , Saviano Anella , Russo Krauss Irene , Trifuoggi Marco , Caraglia Michele , Paduano Luigi , Montesarchio Daniela , Maione Francesco , Misso Gabriella , Santamaria Rita , Irace Carlo
Published: October 2021

Selectivity and efficacy towards target cancer cells, as well as biocompatibility, are current challenges of advanced chemotherapy powering the discovery of unconventional metal-based drugs and the search for novel therapeutic approaches. Among second-generation metal-based chemotherapeutics, ruthenium complexes have demonstrated promising anticancer activity coupled to minimal toxicity profiles and peculiar biochemical features. In this context, our research group has recently focused on a bioactive Ru(III) complex—named AziRu—incorporated into a suite of ad hoc designed nucleolipid nanosystems to ensure its chemical stability and delivery. Indeed, we proved that the structure and properties of decorated nucleolipids can have a major impact on the anticancer activity of the ruthenium core. Moving in this direction, here we describe a preclinical study performed by a mouse xenograft model of human breast cancer to establish safety and efficacy in vivo of a cationic Ru(III)-based nucleolipid formulation, named HoThyRu/DOTAP, endowed with superior antiproliferative activity. The results show a remarkable reduction in tumour with no evidence of animal suffering. Blood diagnostics, as well as biochemical analysis in both acute and chronic treated animal groups, demonstrate a good tolerability profile at the therapeutic regimen, with 100% of mice survival and no indication of toxicity. In addition, ruthenium plasma concentration analysis and tissue bioaccumulation were determined via appropriate sampling and ICP-MS analysis. Overall, this study supports both the efficacy of our Ru-containing nanosystem versus a human breast cancer model and its safety in vivo through well-tolerated animal biological responses, envisaging a possible forthcoming use in clinical trials.
On the Additional Information Provided by 3T-MRI ADC in Predicting Tumor Cellularity and Microscopic Behavior
Authors: Santucci Domiziana , Faiella Eliodoro , Calabrese Alessandro , Beomonte Zobel Bruno , Ascione Andrea , Cerbelli Bruna , Iannello Giulio , Soda Paolo , de Felice Carlo
Published: October 2021

Background: to evaluate whether Apparent Diffusion Coefficient (ADC) values of invasive breast cancer, provided by 3T Diffusion Weighted-Images (DWI), may represent a non-invasive predictor of pathophysiologic tumor aggressiveness. Methods: 100 Patients with histologically proven invasive breast cancers who underwent a 3T-MRI examination were included in the study. All MRI examinations included dynamic contrast-enhanced and DWI/ADC sequences. ADC value were calculated for each lesion. Tumor grade was determined according to the Nottingham Grading System, and immuno-histochemical analysis was performed to assess molecular receptors, cellularity rate, on both biopsy and surgical specimens, and proliferation rate (Ki-67 index). Spearman’s Rho test was used to correlate ADC values with histological (grading, Ki-67 index and cellularity) and MRI features. ADC values were compared among the different grading (G1, G2, G3), Ki-67 (<20% and >20%) and cellularity groups (<50%, 50–70% and >70%), using Mann–Whitney and Kruskal-Wallis tests. ROC curves were performed to demonstrate the accuracy of the ADC values in predicting the grading, Ki-67 index and cellularity groups. Results: ADC values correlated significantly with grading, ER receptor status, Ki-67 index and cellularity rates. ADC values were significantly higher for G1 compared with G2 and for G1 compared with G3 and for Ki-67 < 20% than Ki-67 > 20%. The Kruskal-Wallis test showed that ADC values were significantly different among the three grading groups, the three biopsy cellularity groups and the three surgical cellularity groups. The best ROC curves were obtained for the G3 group (AUC of 0.720), for G2 + G3 (AUC of 0.835), for Ki-67 > 20% (AUC of 0.679) and for surgical cellularity rate > 70% (AUC of 0.805). Conclusions: 3T-DWI ADC is a direct predictor of cellular aggressiveness and proliferation in invasive breast carcinoma, and can be used as a supporting non-invasive factor to characterize macroscopic lesion behavior especially before surgery.
SCFA Treatment Alleviates Pathological Signs of Migraine and Related Intestinal Alterations in a Mouse Model of NTG-Induced Migraine
Authors: Lanza Marika , Filippone Alessia , Ardizzone Alessio , Casili Giovanna , Paterniti Irene , Esposito Emanuela , Campolo Michela
Published: October 2021

Background: There is a growing realization that the gut–brain axis signaling is critical for maintaining the health and homeostasis of the Central Nervous System (CNS) and the intestinal environment. The role of Short-Chain Fatty Acids (SCFAs), such as Sodium Propionate (SP) and Sodium Butyrate (SB), has been reported to counteract inflammation activation in the central and Enteric Nervous System (ENS). Methods: In this study, we evaluated the role of the SCFAs in regulating the pathophysiology of migraine and correlated dysregulations in the gut environment in a mouse model of Nitroglycerine (NTG)-induced migraine. Results: We showed that, following behavioral tests evaluating pain and photophobia, the SP and SB treatments attenuated pain attacks provoked by NTG. Moreover, treatments with both SCFAs reduced histological damage in the trigeminal nerve nucleus and decreased the expression of proinflammatory mediators. Ileum evaluation following NTG injection reported that SCFA treatments importantly restored intestinal mucosa alterations, as well as the release of neurotransmitters in the ENS. Conclusions: Taken together, these results provide evidence that SCFAs exert powerful effects, preventing inflammation through the gut–brain axis, suggesting a new insight into the potential application of SCFAs as novel supportive therapies for migraine and correlated intestinal alterations.
Sperm Cyst “Looping”: A Developmental Novelty Enabling Extreme Male Ornament Evolution
Authors: Syed Zeeshan A. , Dallai Romano , Nasirzadeh Negar , Brill Julie A. , O’Grady Patrick M. , Cong Siyuan , Leef Ethan M. , Rice Sarah , Asif Amaar , Nguyen Stephanie , Hansen Matthew M. , Dorus Steve , Pitnick Scott
Published: October 2021

Postcopulatory sexual selection is credited as a principal force behind the rapid evolution of reproductive characters, often generating a pattern of correlated evolution between interacting, sex-specific traits. Because the female reproductive tract is the selective environment for sperm, one taxonomically widespread example of this pattern is the co-diversification of sperm length and female sperm-storage organ dimension. In Drosophila, having testes that are longer than the sperm they manufacture was believed to be a universal physiological constraint. Further, the energetic and time costs of developing long testes have been credited with underlying the steep evolutionary allometry of sperm length and constraining sperm length evolution in Drosophila. Here, we report on the discovery of a novel spermatogenic mechanism—sperm cyst looping—that enables males to produce relatively long sperm in short testis. This phenomenon (restricted to members of the saltans and willistoni species groups) begins early during spermatogenesis and is potentially attributable to heterochronic evolution, resulting in growth asynchrony between spermatid tails and the surrounding spermatid and somatic cyst cell membranes. By removing the allometric constraint on sperm length, this evolutionary innovation appears to have enabled males to evolve extremely long sperm for their body mass while evading delays in reproductive maturation time. On the other hand, sperm cyst looping was found to exact a cost by requiring greater total energetic investment in testes and a pronounced reduction in male lifespan. We speculate on the ecological selection pressures underlying the evolutionary origin and maintenance of this unique adaptation.
Functional Proteomic Profiling of Triple-Negative Breast Cancer
Authors: Gromova Irina , Espinoza Jaime A. , Grauslund Morten , Santoni-Rugiu Eric , Møller Talman Maj-Lis , van Oostrum Jan , Moreira José M. A.
Published: October 2021

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that comprises various disease entities, all of which share a set of common features: a lack of expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, respectively. Because of their receptor status, conventional chemotherapy remains the main therapeutic option for TNBC patients. We employed a reverse phase protein array approach (RPPA), complemented by immunohistochemistry, to quantitatively profile the activation state of 84 actionable key signaling intermediates and phosphoproteins in a set of 44 TNBC samples. We performed supervised and unsupervised approaches to proteomic data analysis to identify groups of samples sharing common characteristics that could be amenable to existing therapies. We found the heterogenous activation of multiple pathways, with PI3 K/AKT/mTOR signaling being the most common event. Some specific individualized therapeutic possibilities include the expression of oncogenic KIT in association with cytokeratin 15 and Erk1/2 positive tumors, both of which may have clinical value.
A Comprehensive Review of Graphene-Based Anode Materials for Lithium-ion Capacitors
Authors: Sui Dong , Si Linqi , Li Changle , Yang Yanliang , Zhang Yongsheng , Yan Weibo
Published: October 2021

Lithium-ion capacitors (LICs) are considered to be one of the most promising energy storage devices which have the potential of integrating high energy of lithium-ion batteries and high power and long cycling life of supercapacitors into one system. However, the current LICs could only provide high power density at the cost of low energy density due to the sluggish Li+ diffusion and/or low electrical conductivity of the anode materials. Moreover, the serious capacity and kinetics imbalances between anode and cathode result in not only inferior rate performance but also unsatisfactory cycling stability. Therefore, designing high-power and structure stable anode materials is of great significance for practical LICs. Under this circumstance, graphene-based materials have been intensively explored as anodes in LICs due to their unique structure and outstanding electrochemical properties and attractive achievements have been made. In this review, the recent progresses of graphene-based anode materials for LICs are systematically summarized. Their synthesis procedure, structure and electrochemical performance are discussed with a special focus on the role of graphene. Finally, the outlook and remaining challenges are presented with some constructive guidelines for future research.
Molecular Profiling of DNA Methylation and Alternative Splicing of Genes in Skeletal Muscle of Obese Rabbits
Authors: Li Yanhong , Wang Jie , Elzo Mauricio A. , Fan Huimei , Du Kun , Xia Siqi , Shao Jiahao , Lai Tianfu , Hu Shenqiang , Jia Xianbo , Lai Songjia
Published: October 2021

DNA methylation and the alternative splicing of precursor messenger RNAs (pre-mRNAs) are two important genetic modification mechanisms. However, both are currently uncharacterized in the muscle metabolism of rabbits. Thus, we constructed the Tianfu black rabbit obesity model (obese rabbits fed with a 10% high-fat diet and control rabbits from 35 days to 70 days) and collected the skeletal muscle samples from the two groups for Genome methylation sequencing and RNA sequencing. DNA methylation data showed that the promoter regions of 599 genes and gene body region of 2522 genes had significantly differential methylation rates between the two groups, of which 288 genes had differential methylation rates in promoter and gene body regions. Analysis of alternative splicing showed 555 genes involved in exon skipping (ES) patterns, and 15 genes existed in differential methylation regions. Network analysis showed that 20 hub genes were associated with ubiquitinated protein degradation, muscle development pathways, and skeletal muscle energy metabolism. Our findings suggest that the two types of genetic modification have potential regulatory effects on skeletal muscle development and provide a basis for further mechanistic studies in the rabbit.
Mechanical Properties of Hybrid Structures Incorporating Nano-Silica and Basalt Fiber Pellets
Authors: Bediwy Ahmed , El-Salakawy Ehab F.
Published: October 2021

Recently, developing a nonferrous reinforcement system (corrosion-free system) using durable and ductile cement-based materials that incorporate discrete fibers has been a promising option for exposed concrete structures in cold regions or marine environments. Therefore, in this study, properties of a novel type of cementitious composite comprising nano-silica and a high dosage of slag were investigated. The hybrid (layered) composites assessed in this study were composed of two layers of different types of cementitious composites. Normal concrete (NC) was used in the top layer combined with a layer of fiber-reinforced cementitious composite (FRCC) reinforced with either the recently developed basalt fiber (BF) pellets (basalt fiber strands encapsulated by a polymeric resin or steel fibers (SF)) that were used at different dosages. The post-cracking behavior in terms of residual strength, residual index, and toughness are presented and discussed. The analysis of results showed the effectiveness of the BF pellets in enhancing the post-cracking behavior of specimens, as they behaved comparably to counterpart specimens comprising SF, which makes them a good candidate for infrastructural applications including rehabilitation such as new bridge girders or overlays.