bluuebunny/crossref_metadata_2025 huggingface dataset:
Stabilization of Tuberculosis Reporter Enzyme Fluorescence (REFtb) Diagnostic Reagents for Use at the Point of Care
Authors: Lebedev Maxim , Benjamin Aaron B. , Koster Kent J. , Broyles Kathryn E. , Kumar Sathish , Jilka Joseph M. , Cirillo Jeffrey D.
Published: July 2022

Tuberculosis is one of the most frequent causes of death in humans worldwide. One of the primary reasons tuberculosis remains a public health threat is that diagnosis can take weeks to months, is often not very sensitive and cannot be accomplished in many remote environments. A rapid, sensitive and inexpensive point-of-care (POC) diagnostic would have a major impact on tuberculosis eradication efforts. The tuberculosis diagnostic system REFtb is based on specific detection of the constitutively expressed β-lactamase (BlaC) in Mycobacterium tuberculosis using a custom fluorogenic substrate designated as CDG-3. REFtb has potential as a diagnostic for tuberculosis that could be very inexpensive (<USD 2.00/test), used at the POC and could provide definitive diagnosis within 10 min. However, the reagents for REFtb are currently in liquid form, making them more susceptible to degradation and difficult to transport. We evaluated the improvement in the stability of REFtb reagents by lyophilization under a variety of conditions through their effects on the performance of REFtb. We found that lyophilization of REFtb components produces an easily reconstituted powder that displays similar performance to the liquid system and that lactose represents one of the most promising excipients for use in a final POC REFtb diagnostic system. These studies provide the foundation for the production of a stable POC REFtb system that could be easily distributed worldwide with minimal or no requirement for refrigeration.
Bioelectrical Impedance Analysis of Oral Cavity Mucosa in Patients with Lichen Planus and Healthy Controls
Authors: Bacci Christian , Cerrato Alessia , Frigo Anna Chiara , Cocco Matteo , Zanette Gastone
Published: July 2022

Objectives: Oral lichen planus (OLP) is an inflammatory disease. Bioelectrical impedance analysis (BIA) is a method for assessing tissue composition. Based on a combination of reactance and resistance data, a phase angle is calculated that may range from 90° to 0°, and that correlates with body cell mass. There is evidence to suggest that neoplastic tissue has a lower phase angle than normal tissue. The aim of the present experimental study was to establish whether OLP patients have a different tissue phase angle from healthy controls. Materials and Methods: Bioelectrical impedance measurements were obtained for the buccal mucosa, tongue, hard palate and upper anterior gums using an ad hoc device in a sample of 57 consecutive patients with OLP and 60 healthy controls, and their phase angles were calculated. Results: The mean resistance, reactance, and phase angle of the hard palate and gums were higher in the OLP group than in the controls, and the differences were statically significant. The resistance and reactance recorded for the adherent gingiva and hard palate were always higher in the OLP group (p = 0.044; p = 0.020; p = 0.054), and so was the phase angle for the adherent gingiva. No statistically significant differences emerged for the other areas of the oral cavity (p < 0.05). Conclusion: These findings confirm differences between the bioelectrical impedance of OLP lesions and that of healthy oral tissues. Clinical relevance: Bioelectrical impedance analysis could be useful in the diagnosis of OLP.
Exploring Regional Industrial Growth: Does Specialization Explain It?
Authors: Gamidullaeva Leyla , Korostyshevskaya Elena , Myamlin Alexey , Podkorytova Olga
Published: July 2022

Being a form of territorial division of labor, economic specialization should be considered as a strategic management priority, contributing to a competitive territorial production structure and, consequently, regional economic growth. The article is devoted, firstly, to the development of a method for assessing the level of territorial division of labor based on a new coefficient of regional economic specialization; and secondly, to the investigation of regional specialization effects on economic growth. The purpose of the to substantiate the influence of the territory specialization factor on industrial economic growth, along with other conventional factors of regional development, using econometric methods based on an extended exogenous growth model. Premised on the data from Russian manufacturing industries and using a new coefficient of regional specialization, the authors have developed and verified an original approach to substantiate the effectiveness of regional clustering for ensuring the growth of industrial output based on an extended exogenous growth model. Approbation of the proposed assessment method and verification of research hypothesis formulated by the authors have been carried out using regional statistical data of the Russian Federation for the period from 2005 to 2019. The empirical analysis results have contributed to a place-based theoretical approach, involving both the cluster concept and the concept of “smart specialization”. The practical significance of the research is to validate clustering feasibility as a form of territorial division of labor and provide a number of principles for the regional industrial policy based thereon to accelerate territorial economic growth.
Student Experiences and Changing Science Interest When Transitioning from K-12 to College
Authors: Reed David E. , Kaplita Emily C. , McKenzie David A. , Jones Rachel A.
Published: July 2022

Student attitude and involvement in the sciences may be positively or negatively influenced through both formal academic experiences and informal experiences outside the classroom. Researchers have reported that differences in science interest between genders begin early in a student’s career and that attitudes towards a particular field of science can be correlated to achievement in that field. In this study, we approach the question of how attitudes towards science have been shaped using college-age students. Survey data from students in similar academic positions were employed to control for differences in cultural and academic progress. Results from a self-reflection survey indicated that general personal interest in both science as a process and field-specific content increased from elementary school through high school until entering college. Differences arose between self-identified genders in student experiences with science, both while in groups and when on their own. Female students had higher rates of participation and enjoyment with science in groups, while male students more frequently enjoyed science alone. Students, regardless of gender, rarely had negative experiences with science outside of the classroom. However, male students’ interest in science surpassed female students’ during high school. Declining interests in quantitative aspects of science (mathematics and statistics) were more frequently reported by female students and non-STEM majors during and before their college experience. Connecting student attitudes regarding science to their pre-college experiences with science early in their college career may be important to understanding how to best engage all genders, as well as non-STEM majors, in their college science courses.
Batch-Wise Permutation Feature Importance Evaluation and Problem-Specific Bigraph for Learn-to-Branch
Authors: Niu Yajie , Peng Chen , Liao Bolin
Published: July 2022

The branch-and-bound algorithm for combinatorial optimization typically relies on a plethora of handcraft expert heuristics, and a research direction, so-called learn-to-branch, proposes to replace the expert heuristics in branch-and-bound with machine learning models. Current studies in this area typically use an imitation learning (IL) approach; however, in practice, IL often suffers from limited training samples. Thus, it has been emphasized that a small-dataset fast-training scheme for IL in learn-to-branch is worth studying, so that other methods, e.g., reinforcement learning, may be used for subsequent training. Thus, this paper focuses on the IL part of a mixed training approach, where a small-dataset fast-training scheme is considered. The contributions are as follows. First, to compute feature importance metrics so that the state-of-the-art bigraph representation can be effectively reduced for each problem type, a batch-wise permutation feature importance evaluation method is proposed, which permutes features within each batch in the forward pass. Second, based on the evaluated importance of the bigraph features, a reduced bigraph representation is proposed for each of the benchmark problems. The experimental results on four MILP benchmark problems show that our method improves branching accuracy by 8% and reduces solution time by 18% on average under the small-dataset fast-training scheme compared to the state-of-the-art bigraph-based learn-to-branch method. The source code is available online at GitHub.
Methane Hydrate Behavior for Water–Oil Systems Containing CTAB and Synperonic PE/F127 Surfactants
Authors: Pavón-García Antonio , Zúñiga-Moreno Abel , García-Morales Ricardo , Pérez-López Hugo I. , Elizalde-Solis Octavio
Published: July 2022

Methane hydrates were studied in systems containing aqueous dissolved surfactants in oil emulsions with a volume ratio of 40/60. Two commercial surfactants, named synperonic PE/F127 and cetyltrimethylammonium bromide, were evaluated at 0, 350, 700 and 1500 ppm. Experiments were made by applying the cooling–heating path in an isochoric high-pressure cell at different initial pressures of 5.5, 8.0, 10.0 and 12.0 MPa. The obtained parameters were induction time, temperature onset, pressure drop, and dissociation conditions. The results revealed that the dissociation curve for methane in water-in-oil emulsions was not modified by the surfactants. The crystallization (onset) temperature was higher using synperonic PE/F127 in comparison with zero composition, while the opposite occurred with cetyltrimethylammonium bromide. Both surfactants induced a delaying effect on the induction time and a lesser pressure drop.
Towards the Physiological Understanding of Yarrowia lipolytica Growth and Lipase Production Using Waste Cooking Oils
Authors: Colacicco Mattia , Ciliberti Cosetta , Agrimi Gennaro , Biundo Antonino , Pisano Isabella
Published: July 2022

The yeast Yarrowia lipolytica is an industrially relevant microorganism, which is able to convert low-value wastes into different high-value, bio-based products, such as enzymes, lipids, and other important metabolites. Waste cooking oil (WCO) represents one of the main streams generated in the food supply chain, especially from the domestic sector. The need to avoid its incorrect disposal makes this waste a resource for developing bioprocesses in the perspective of a circular bioeconomy. To this end, the strain Y. lipolytica W29 was used as a platform for the simultaneous production of intracellular lipids and extracellular lipases. Three different minimal media conditions with different pH controls were utilized in a small-scale (50 mL final volume) screening strategy, and the best condition was tested for an up-scaling procedure in higher volumes (800 mL) by selecting the best-performing possibility. The tested media were constituted by YNB media with high nitrogen restriction (1 g L−1 (NH4)2SO4) and different carbon sources (3% w v−1 glucose and 10% v v−1 WCO) with different levels of pH controls. Lipase production and SCO content were analyzed. A direct correlation was found between decreasing FFA availability in the media and increasing SCO levels and lipase activity. The simultaneous production of extracellular lipase (1.164 ± 0.025 U mL−1) and intracellular single-cell oil accumulation by Y. lipolytica W29 growing on WCO demonstrates the potential and the industrial relevance of this biorefinery model.
From Industry 4.0 towards Industry 5.0: A Review and Analysis of Paradigm Shift for the People, Organization and Technology
Authors: Zizic Marina Crnjac , Mladineo Marko , Gjeldum Nikola , Celent Luka
Published: July 2022

The industry is a key driver of economic development. However, changes caused by introduction of modern technologies, and increasing complexity of products and production, directly affect the industrial enterprises and workers. The critics of the Industry 4.0 paradigm emphasized its orientation to new technologies and digitalization in a technocratic way. Therefore, the new industrial paradigm Industry 5.0 appeared very soon and automatically triggered a debate about the role of, and reasons for applying, the new paradigm. Industry 5.0 is complementing the existing Industry 4.0 paradigm with the orientation to the worker who has an important role in the production process, and that role has been emphasized during the COVID-19 pandemic. In this research, there is a brief discussion on main drivers and enablers for introduction of these new paradigms, then a literature-based analysis is carried out to highlight the differences between two paradigms from three important aspects—people, organization, and technology. The conclusion emphasizes the main features and concerns regarding the movement towards Industry 5.0, and the general conclusion is that there is a significant change of the main research aims from sustainability towards human-centricity. At the end, the analysis of maturity models that evaluates enterprises’ readiness to introduce features of new paradigms is given as well.
Effects of Different Zn2+ Concentrations and High Hydrostatic Pressures (HHP) on Chlorophyll Stability
Authors: Hu Yuwei , Sun Hongnan , Mu Taihua
Published: July 2022

This study provides a new idea for improving chlorophyll stability and color quality of green leafy vegetables by Zn2+ synergistic HHP. Zn-chlorophyll was prepared with zinc acetate and chlorophyll under HHP treatment. The effects of different zinc acetate concentrations and pressures on chlorophyll color, antioxidant activity, Zn2+ replacement rate, structure, and thermal stability were analyzed. Results showed with increased zinc acetate concentration and pressure, −a* value, antioxidant activity, and Zn2+ replacement rate of samples gradually increased. However, FTIR indicated the structure did not change. HHP fluorescence online analysis showed fluorescence intensity of samples decreased with zinc acetate concentration and pressure increasing. With zinc acetate 10 mg/100 mL and HHP 500 MPa, the highest −a* value (5.19), antioxidant activity (ABTS, DPPH, and FRAP were 37.03 g ACE/100 g, 25.95 g ACE/100 g, 65.43 g TE/100 g DW, respectively), and Zn2+ replacement rate (42.34%) were obtained. Thermal stability of Zn-chlorophyll obtained by synergistic effect was improved significantly.
Chemical Authentication and Speciation of Salvia Botanicals: An Investigation Utilizing GC/Q-ToF and Chemometrics
Authors: Lee Joseph , Wang Mei , Zhao Jianping , Avula Bharathi , Chittiboyina Amar G. , Li Jing , Wu Charles , Khan Ikhlas A.
Published: July 2022

Members of the genus Salvia are used as culinary herbs and are prized for their purported medicinal attributes. Since physiological effects can vary widely between species of Salvia, it is of great importance to accurately identify botanical material to ensure safety for consumers. In the present study, an in-depth chemical investigation is performed utilizing GC/Q-ToF combined with chemometrics. Twenty-four authentic plant samples representing five commonly used Salvia species, viz. S. apiana, S. divinorum, S. mellifera, S. miltiorrhiza, and S. officinalis, are analyzed using a GC/Q-ToF technique. High-resolution spectral data are employed to construct a sample class prediction (SCP) model followed by principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA). This model demonstrates 100% accuracy for both prediction and recognition abilities. Additionally, the marker compounds present in each species are identified. Furthermore, to reduce the time required and increase the confidence level for compound identification and the classification of different Salvia species, a personal compound database and library (PCDL) containing marker and characteristic compounds is constructed. By combining GC/Q-ToF, chemometrics, and PCDL, the unambiguous identification of Salvia botanicals is achieved. This high-throughput method can be utilized for species specificity and to probe the overall quality of various Salvia-based products.
Whey Protein Hydrolysates Improved the Oxidative Stability and Water-Holding Capacity of Pork Patties by Reducing Protein Aggregation during Repeated Freeze–Thaw Cycles
Authors: Liu Chunyun , Kong Lingru , Yu Pengjuan , Wen Rongxin , Yu Xiaobo , Xu Xinglian , Peng Xinyan
Published: July 2022

The effects of whey protein hydrolysates (WPH) on myofibrillar protein (MP) oxidative stability and the aggregation behavior and the water-holding capacity of pork patties during freeze–thaw (F–T) cycles were investigated. During F–T cycles, the total sulfhydryl content and zeta potential of MP decreased, while peroxide value, surface hydrophobicity, particle size, pressure loss and transverse relaxation times increase. The oxidative stability and the water-holding capacity of pork patties were enhanced by the addition of WPH in a dose-dependent manner, whereas the MP aggregation decreased. The addition of 15% WPH had the most obvious effects on the pork patties, which was similar to that of the 0.02% BHA. After nine F–T cycles, the POV, surface hydrophobicity, particle size and pressure loss of the pork patties with 15% WPH were reduced by 17.20%, 30.56%, 34.67% and 13.96%, respectively, while total sulfhydryl content and absolute value of zeta potential increased by 69.62% and 146.14%, respectively. The results showed that adding 15% WPH to pork patties can be an effective method to inhibit lipid and protein oxidation, reducing protein aggregation and improving the water-holding capacity of pork patties during F–T cycles.
Oilseed Extracts from Local Markets as Promising Coagulant Agents for Milk from Various Mammalian Species
Authors: Liburdi Katia , Cucci Sofia , Esti Marco
Published: July 2022

The aim of this study was to identify novel milk coagulants to be used in cheesemaking. For this purpose, aqueous extracts from safflower (Carthamus tinctorius), sunflower (Helianthus annuus), flax (Linum usitatissimum) and sesame (Sesamum indicum) seeds were tested for their caseinolytic (CA) and milk coagulating properties (MCA) in skim milk at temperatures of 25, 37, 50, 65 and 80 °C. The seed oil samples with the highest temperature ranges in regard to coagulation efficiency were then tested in cow, buffalo, goat and sheep milks and the MCA and curd yield (CY) parameters were measured at different temperatures. Due to their high milk coagulation efficiency (CE) in all types of milk and at different temperatures, the sesame and sunflower seed extracts proved to be particularly interesting and their CY parameters were similar to those obtained with animal rennet. Moreover, our results confirm that oilseed coagulants are capable of coagulating milk and can also be considered as potential animal rennet substitutes. This study provides valuable insights into the development of potential vegetable coagulants that could be used for various production processes aimed at specific target consumers.
Effect of Osmotic Dehydration Pretreatment on the Drying Characteristics and Quality Properties of Semi-Dried (Intermediate) Kumquat (Citrus japonica) Slices by Vacuum Dryer
Authors: Özkan-Karabacak Azime , Özcan-Sinir Gülşah , Çopur Ali Eren , Bayizit Murat
Published: July 2022

The effect of osmotic dehydration (OD) pretreatments at different temperatures and immersion times on drying characteristics, total phenolic content (TPC), total antioxidant activity (TAA) (DPPH and CUPRAC methods), and color of kumquat slices dried under vacuum conditions (70 °C-100 mbar) was investigated. The OD pretreatment was performed in a sucrose solution (45 °Bx) at the temperatures of 40 and 50 °C and immersed at times of 30, 60, and 90 min. OD before vacuum drying decreased the total required drying time by up to 70 min compared to the control non-pretreated samples. Page, Modified Page, Henderson Pabis, and Two Terms Exponential models were found to satisfactorily describe the drying behavior of thin layer dried kumquat slices. The minimum and maximum values of effective moisture diffusivity (Deff) for semi-dried kumquat slices were 5.04 × 10−8 to 7.19 × 10−8, respectively. OD treatments induced a decline in TPC (5.30–33.92%) and TAA (23.63–59.34% and 4.17–31.67% for DPPH and CUPRAC assays, respectively) of kumquat slices. It was observed that OD pre-treatment can decrease the gross drying time, and make the color and sensorial attributes of dried kumquats better.
Modelling Financial Markets during Times of Extreme Volatility: Evidence from the GameStop Short Squeeze
Authors: Andreev Boris , Sermpinis Georgios , Stasinakis Charalampos
Published: July 2022

Ever since the start of the coronavirus pandemic, lockdowns to curb the spread of the virus have resulted in an increased interest of retail investors in the stock market, due to more free time, capital, and commission-free trading brokerages. This interest culminated in the January 2021 short squeeze wave, caused in no small part due to the coordinated trading moves of the r/WallStreetBets subreddit, which has rapidly grown in user base since the event. In this paper, we attempt to discover if coordinated trading by retail investors can make them a market moving force and attempt to identify proactive signals of such movements in the post activity of the forum, to be used as a part of a trading strategy. Data about the most mentioned stocks is collected, aggregated, combined with price data for the respective stock and analysed. Additionally, we utilise predictive modelling to be able to better classify trading signals. It is discovered that despite the considerable capital that retail investors can direct by coordinating their trading moves, additional factors, such as very high short interest, need to be present to achieve the volatility seen in the short squeeze wave. Furthermore, we find that autoregressive models are better suited to identifying signals correctly, with best results achieved by a Random Forest classifier. However, it became apparent that even the best performing model in our experimentation cannot make accurate predictions in extreme volatility, evidenced by the negative returns shown by conducted back-tests.
The Reception of Jane Austen in Early Modern China: A Canonical Perspective
Authors: Zhang Helong
Published: July 2022

In China, Jane Austen has undergone an amazing metamorphosis from an obscure foreign writer disregarded or disapproved of for a long period to a great novelist highly acclaimed and fully acknowledged. Only recent years have seen the publication of a few scholarly articles on the reception trajectories of Austen in the Chinese academic world. This article revisits the issue, particularly the reception of Austen in early modern China from a canonical perspective. During the first major wave of literary translation, Austen was absent in the translation projects of dominant male translators, especially in Lin Shu’s choice. It was not because of their gender discrimination as generally considered, but because of their lack of canon consciousness. The literary light of Austen, too bright and too sparkling to ignore, was finally shed upon the Chinese land, but her canonical place was not instantly recognized. The wartime translators’ efforts to render Pride and Prejudice into Chinese reflect the difficulty in the making of a canonical Austen under very different historical circumstances.
Minimal Residual Disease in Multiple Myeloma—Current Approaches and Future Clinical Implications
Authors: Akhlaghi Theresia , Firestone Ross , Hultcrantz Malin
Published: July 2022

The prognosis and clinical outcomes for patients with multiple myeloma have improved significantly over the past two decades. A substantial number of patients now achieve complete remission after induction therapy, and more sensitive methods are needed to assess response. Minimal or measurable residual disease (MRD) has been incorporated in many clinical trials as well as in clinical practice. The importance of MRD assessment and correlation between MRD negativity and prolonged progression-free and overall survival has been confirmed in numerous clinical trials and several meta-analyses. Recent studies have even suggested that MRD negativity can partly overcome the impact of the negative prognostic factors such as high-risk cytogenetics or adverse revised international scoring system (R-ISS) stage. MRD can be measured in the bone marrow via imaging and via emerging blood-based techniques. The most common methods are multicolor flow cytometry and next-generation sequencing of bone marrow samples. Using these methods in optimal settings, MRD negativity with a sensitivity level of 10−6 can be detected. In this review, we discuss the benefits and limitations of these techniques as well as the clinical implications.
Attachment Theory: A Barrier for Indigenous Children Involved with Child Protection
Authors: Choate Peter , Tortorelli Christina
Published: July 2022

Background: Attachment theory is an established theoretical understanding of the intimate relationships between parental figures and children. The theory frames the ways in which a child can be supported to develop within a secure base that prepares them for adulthood, including entering into and sustaining intimate relationships. The theory, built on the work of John Bowlby following World War II, has extensive literature supporting its application across multiple cultures and nations, although its roots are heavily tied to Eurocentric familial understandings. However, the theory has also been heavily criticized as not being appropriate for child intervention decision-making. Further, its application to Indigenous caregiving systems is also under question. Yet courts rely heavily on applying the theory to questions of sustaining Indigenous children in non-Indigenous care when return to biological parents is deemed impossible. Methods: This article draws upon the consistent arguments used in leading Canadian child welfare legal decisions and case examples to show how Attachment Theory is applied relative to Indigenous children and families. Results: Attachment Theory drawing upon Eurocentric framing, and as applied in Canadian child protection systems, as seen in precedent court decisions, is given priority over living in culture. This occurs even though the research reviewed has shown that the traditional dyadic version of the theory is not valid for Indigenous peoples. Conclusions: While all children will attach to a caregiver or caregiving system, such as kinship or community, leading legal decisions in Canada tend to rely on Eurocentric versions of the theory, which is contrary to the best interests of Indigenous children. Child protection needs to reconsider how attachment can be used from appropriate cultural lenses that involve the communal or extended caregiving systems common to many Canadian Indigenous communities. Child protection should also recognize that there is not a pan-Indigenous definition of attachment and child-rearing, so efforts to build working relationships with various Indigenous communities will be needed to accomplish culturally informed caregiving plans. In addition, continued advocacy in Canada is needed to have child protection decision-making conducted by the Indigenous communities, as opposed to Eurocentric provincial or territorial agencies.
Integration of Omics Approaches Enhances the Impact of Scientific Research in Environmental Applications
Authors: Gruszecka-Kosowska Agnieszka , Ampatzoglou Antonis , Aguilera Margarita
Published: July 2022

In the original article [...]
Incidence of Leader–Member Exchange Quality, Communication Satisfaction, and Employee Work Engagement on Self-Evaluated Work Performance
Authors: Santalla-Banderali Zuleima , Alvarado Jesús M.
Published: July 2022

Within the scope of the Theory of Demands and Labor Resources, the Healthy & Resilient Organizations (HERO) Model, and the Leader–Member Exchange (LMX) Theory, this research contrasts a mediation model in which evidence on the factors that affect work performance is integrated, thus establishing the direct and indirect relationships between LMX quality, communication satisfaction, employee work engagement, and self-rated work performance. A total of 488 workers participated in this research. Adequate goodness of fit was found in the model (χ2 = 3876.996, df = 3715, p = 0.031; χ2/df = 1.044; CFI = 0.999; TLI = 0.999; SRMR = 0.056; RMSEA = 0.010): the LMX–work performance relationship is mediated by communication satisfaction and work engagement, whereas the LMX–work engagement relationship is mediated by communication satisfaction. This has led to the conclusion that, as employees consider the relationship with their superiors to be of higher quality, the satisfaction they experience in terms of organizational communication increases, and as organizational communication satisfaction increases, the extent to which employees feel more vigorous, involved and concentrated, and absorbed by work also increases, which, in turn, leads them to perceive their work performance to be higher.
The Relationship between Late-Life Depression and Cognitive Function in Older Korean Adults: A Moderation Analysis of Physical Activity Combined with Lower-Body Muscle Strength
Authors: Kong Jiyoung , Kang Minjeong , Kang Hyunsik
Published: July 2022

Background: This study examined the relationship of physical activity (PA) combined with lower-body muscle strength to late-life depression and cognitive impairment in 10,097 participants (6062 females) ≥ 65 years of age. Methods: Exposures were PA, sit-to-stand test (STST), and depressive symptoms. Outcome was cognitive performance. Results: Depressed individuals had an increased risk of mild cognitive impairment (MCI; odds ratio (OR), adjusted OR = 1.845 and 95% confidence interval (CI) = 1.580–2.154, p < 0.001) compared with non-depressed individuals. Individuals who had insufficient PA and a poor STST and either insufficient PA or a poor STST had an increased risk of MCI (adjusted OR = 1.329 and 95% CI = 1.209–1.46, p < 0.001 and adjusted OR = 2.822 and 95% CI = 2.488–3.200, p < 0001, respectively) compared with individuals who had sufficient PA and a good STST. A significant moderation effect of PA combined with lower-body muscle strength on the relationship between depression and cognitive function was observed (β = −1.3923; 95% CI = −2.1505 to −0.6341, p < 0.003). Conclusions: The negative effect of late-life depression on cognitive function was incremental in the order of sufficient PA and a good STST, insufficient PA or a poor STST, and insufficient PA and a poor STST.
Stay Safe and Strong: Characteristics, Roles and Emotions of Student-Produced Comics Related to Cyberbullying
Authors: Mameli Consuelo , Menabò Laura , Brighi Antonella , Menin Damiano , Culbert Catherine , Hamilton Jayne , Scheithauer Herbert , Smith Peter K. , Völlink Trijntje , Willems Roy A. , Purdy Noel , Guarini Annalisa
Published: July 2022

The present study aimed at giving voice to students from disadvantaged socio-economic backgrounds using a co-participatory approach. Participants were 59 adolescents (52.5% males) aged between 14 and 16 from five European countries who created ten comics to illustrate cyberbullying for a broader audience of peers. We analyzed texts and images according to four primary themes: cyberbullying episodes (types, platforms, co-occurrence with bullying), coping strategies, characters (roles, gender, and group membership), and emotions. The content analysis showed that online denigration on social media platforms was widely represented and that cyberbullying co-existed with bullying. Social strategies were frequently combined with passive and confrontational coping, up to suicide. All roles (cyberbully, cybervictim, bystander, reinforcer, defender) were portrayed among the 154 characters identified, even if victims and defenders appeared in the vignettes more often. Males, females, peers, and adults were represented in all roles. Among the 87 emotions detected, sadness was the most frequently expressed, followed by joy, surprise, anger, and fear. Emotions, mainly represented by drawings or drawings with text, were most often represented in association with cybervictims. The results are discussed in terms of their methodological and practical implications, as they emphasize the importance of valorizing young peoples’ voices in research and interventions against cyberbullying.
Overnutrition, Nasopharyngeal Pathogenic Bacteria and Proinflammatory Cytokines in Infants with Viral Lower Respiratory Tract Infections
Authors: Arias-Bravo Guisselle , Valderrama Gustavo , Inostroza Jaime , Tapia Cecilia , Toro-Ascuy Daniela , Ramilo Octavio , Orellana Paz , Cifuentes-Muñoz Nicolás , Zorondo-Rodríguez Francisco , Mejias Asunción , Fuenzalida Loreto
Published: July 2022

Background: Little is known about the interaction between the nasopharyngeal bacterial profile and the nutritional status in children. In this study, our main goal was to evaluate the associations between overnutrition and the presence of four potentially pathogenic bacteria in the nasopharynx of infants with viral lower respiratory tract infections (LRTI). In addition, we determined whether changes in the nasopharyngeal bacterial profile were associated with mucosal and serum proinflammatory cytokines and with clinical disease severity. Methods: We enrolled 116 children less than 2 years old hospitalized for viral LRTI during two consecutive respiratory seasons (May 2016 to August 2017); their nutritional status was assessed, and nasopharyngeal and blood samples were obtained. S. aureus, S. pneumoniae, H. influenzae, M. catarrhalis, and respiratory viruses were identified in nasopharyngeal samples by qPCR. Cytokine concentrations were measured in nasopharyngeal and blood samples. Disease severity was assessed by the length of hospitalization and oxygen therapy. Results: Nasopharyngeal pathogenic bacteria were identified in 96.6% of the enrolled children, and 80% of them tested positive for two or more bacteria. The presence and loads of M. catarrhalis was higher (p = 0.001 and p = 0.022, respectively) in children with overnutrition (n = 47) compared with those with normal weights (n = 69). In addition, the detection of >2 bacteria was more frequent in children with overnutrition compared to those with normal weight (p = 0.02). Multivariate regression models showed that the presence and loads of S. pneumoniae and M. catarrhalis were associated with higher concentrations of IL-6 in plasma and TNF-α in mucosal samples in children with overnutrition. Conclusions: The nasopharyngeal profile of young children with overnutrition was characterized by an over representation of pathogenic bacteria and proinflammatory cytokines.
Structural Connectivity of Asia’s Protected Areas Network: Identifying the Potential of Transboundary Conservation and Cost-Effective Zones
Authors: Penagos Gaviria Melissa , Kaszta Żaneta , Farhadinia Mohammad S.
Published: July 2022

Human activities can degrade landscape connectivity and disrupt ecological flows, jeopardising the functional integrity of processes. This study presents a quantitative assessment of Asia’s protected areas’ (PAs) structural connectivity using landscape metrics, as well as analyses of the Cost-Effective Zones’ (CEZs). Using nine landscape metrics, we assessed connectivity at zonal (country borders and interior), national, regional, and geographical (islands and continent) levels. The results showed that the structural connectivity of Asia’s PAs network measured by a Connectance index was very low (0.08% without country borders and 9.06% for the average country analysis). In general, connectivity was higher within borders (0.36%) than within the countries (0.22%). Islands exhibited significantly higher Area-weighted mean patch area, Proximity index and Largest patch index, suggesting more integrity and connectiveness. When comparing Asian regions, Western Asia presented the lowest values for Percentage of landscape and Proximity index. We found that only 15% of the CEZs in Asia were under PAs designation, and more CEZs are located in the interior, but the majority with the highest priority was in the borders (9%). We advocate that expanding PAs coverage, specifically targeting areas that increase connectivity (e.g., through transboundary PAs), should be a priority to maintain their ecological function.
Delivery of mGluR5 siRNAs by Iron Oxide Nanocages by Alternating Magnetic Fields for Blocking Proliferation of Metastatic Osteosarcoma Cells
Authors: Kang Min A , Rao Pooja P. , Matsui Hiroshi , Mahajan Shahana S.
Published: July 2022

Although osteosarcoma is the most common primary malignant bone tumor, chemotherapeutic drugs and treatment have failed to increase the five-year survival rate over the last three decades. We previously demonstrated that type 5 metabotropic glutamate receptor, mGluR5, is required to proliferate metastatic osteosarcoma cells. In this work, we delivered mGluR5 siRNAs in vitro using superparamagnetic iron oxide nanocages (IO-nanocages) as delivery vehicles and applied alternating magnetic fields (AMFs) to improve mGluR5 siRNAs release. We observed functional outcomes when mGluR5 expression is silenced in human and mouse osteosarcoma cell lines. The results elucidated that the mGluR5 siRNAs were successfully delivered by IO-nanocages and their release was enhanced by AMFs, leading to mGluR5 silencing. Moreover, we observed that the proliferation of both human and mouse osteosarcoma cells decreased significantly when mGluR5 expression was silenced in the cells. This novel magnetic siRNA delivery methodology was capable of silencing mGluR5 expression significantly in osteosarcoma cell lines under the AMFs, and our data suggested that this method can be further used in future clinical applications in cancer therapy.
Molecular Characterization of a DNA Polymerase from Thermus thermophilus MAT72 Phage vB_Tt72: A Novel Type-A Family Enzyme with Strong Proofreading Activity
Authors: Dorawa Sebastian , Werbowy Olesia , Plotka Magdalena , Kaczorowska Anna-Karina , Makowska Joanna , Kozlowski Lukasz P. , Fridjonsson Olafur H. , Hreggvidsson Gudmundur O. , Aevarsson Arnthór , Kaczorowski Tadeusz
Published: July 2022

We present a structural and functional analysis of the DNA polymerase of thermophilic Thermus thermophilus MAT72 phage vB_Tt72. The enzyme shows low sequence identity (<30%) to the members of the type-A family of DNA polymerases, except for two yet uncharacterized DNA polymerases of T. thermophilus phages: φYS40 (91%) and φTMA (90%). The Tt72 polA gene does not complement the Escherichia colipolA− mutant in replicating polA-dependent plasmid replicons. It encodes a 703-aa protein with a predicted molecular weight of 80,490 and an isoelectric point of 5.49. The enzyme contains a nucleotidyltransferase domain and a 3′-5′ exonuclease domain that is engaged in proofreading. Recombinant enzyme with His-tag at the N-terminus was overproduced in E. coli, subsequently purified by immobilized metal affinity chromatography, and biochemically characterized. The enzyme exists in solution in monomeric form and shows optimum activity at pH 8.5, 25 mM KCl, and 0.5 mM Mg2+. Site-directed analysis proved that highly-conserved residues D15, E17, D78, D180, and D184 in 3′-5′ exonuclease and D384 and D615 in the nucleotidyltransferase domain are critical for the enzyme’s activity. Despite the source of origin, the Tt72 DNA polymerase has not proven to be highly thermoresistant, with a temperature optimum at 55 °C. Above 60 °C, the rapid loss of function follows with no activity > 75 °C. However, during heat treatment (10 min at 75 °C), trehalose, trimethylamine N-oxide, and betaine protected the enzyme against thermal inactivation. A midpoint of thermal denaturation at Tm = 74.6 °C (ΔHcal = 2.05 × 104 cal mol−1) and circular dichroism spectra > 60 °C indicate the enzyme’s moderate thermal stability.
A Comprehensive Evaluation of the Performance of Prediction Algorithms on Clinically Relevant Missense Variants
Authors: Qorri Erda , Takács Bertalan , Gráf Alexandra , Enyedi Márton Zsolt , Pintér Lajos , Kiss Ernő , Haracska Lajos
Published: July 2022

The rapid integration of genomic technologies in clinical diagnostics has resulted in the detection of a multitude of missense variants whose clinical significance is often unknown. As a result, a plethora of computational tools have been developed to facilitate variant interpretation. However, choosing an appropriate software from such a broad range of tools can be challenging; therefore, systematic benchmarking with high-quality, independent datasets is critical. Using three independent benchmarking datasets compiled from the ClinVar database, we evaluated the performance of ten widely used prediction algorithms with missense variants from 21 clinically relevant genes, including BRCA1 and BRCA2. A fourth dataset consisting of 1053 missense variants was also used to investigate the impact of type 1 circularity on their performance. The performance of the prediction algorithms varied widely across datasets. Based on Matthews Correlation Coefficient and Area Under the Curve, SNPs&GO and PMut consistently displayed an overall above-average performance across the datasets. Most of the tools demonstrated greater sensitivity and negative predictive values at the expense of lower specificity and positive predictive values. We also demonstrated that type 1 circularity significantly impacts the performance of these tools and, if not accounted for, may confound the selection of the best performing algorithms.
Unraveling the Influence of HHEX Risk Polymorphism rs7923837 on Multiple Sclerosis Pathogenesis
Authors: González-Jiménez Adela , López-Cotarelo Pilar , Agudo-Jiménez Teresa , Martínez-Ginés Marisa , García-Domínguez Jose Manuel , Urcelay Elena , Espino-Paisán Laura
Published: July 2022

One of the multiple sclerosis (MS) risk polymorphisms, rs7923837, maps near the HHEX (hematopoietically-expressed homeobox) gene. This variant has also been associated with type 2 diabetes susceptibility and with triglyceride levels, suggesting its metabolic involvement. HHEX plays a relevant role as a negative regulator of inflammatory genes in microglia. A reciprocal repression was reported between HHEX and BCL6, another putative risk factor in MS. The present study evidenced statistically significant lower HHEX mRNA levels in lymphocytes of MS patients compared to those of controls, showing a similar trend in MS patients to the already described eQTL effect in blood from healthy individuals. Even though no differences were found in protein expression according to HHEX genotypes, statistically significant divergent subcellular distributions of HHEX appeared in patients and controls. The epistatic interaction detected between BCL6 and HHEX MS-risk variants in healthy individuals was absent in patients, indicative of a perturbed reciprocal regulation in the latter. Lymphocytes from MS carriers of the homozygous mutant genotype exhibited a distinctive, more energetic profile, both in resting and activated conditions, and significantly increased glycolytic rates in resting conditions when compared to controls sharing the HHEX genotype. In contrast, significantly higher mitochondrial mass was evidenced in homozygous mutant controls.
Green Blends Based on Ionic Liquids with Improved Performance for Membrane Technology: Perspectives for Environmental Applications
Authors: Filimon Anca , Dobos Adina Maria , Dumbrava Oana , Doroftei Florica , Lupa Lavinia
Published: July 2022

Present research was directed towards the development of new high-performance and cost-effective polysulfone membranes (PSFQ) by introducing ionic liquids (ILs—Cyphos 101 IL and Aliquat 336) into their matrix. Variation of ILs was performed with the aim to find the one that brings new properties and improves the functionality and selectivity of PSFQ membranes in ultrafiltration processes. Based on the obtained results of the rheological study, we established the compatibility of compounds and optimal content of the used ILs, namely 3 wt% and 15 wt% Cyphos 101 IL and compositions varying between 3 and 15 wt % Aliquat 336. Results indicated that the ILs acted as plasticizers when they were added to the system, a helpful aspect in processing membranes used in water decontamination. The efficiency and performance of the membranes were evaluated by their use in the treatment of diclofenac (DCF)-containing waters. Membranes obtained from PSFQ/Aliquat 336 solution containing 15 wt% IL exhibited a 97% removal degree of DCF in the treatment process of 50 mL solution containing 3 mg/L DCF. The separation efficiency was kept constant for four filtration/cleaning cycles. The results indicated an improvement in membrane performance as the amount of IL in their structure increased, which confirms the potential for application in water treatment processes.
Investigating the Role of GABA in Neural Development and Disease Using Mice Lacking GAD67 or VGAT Genes
Authors: Bolneo Erika , Chau Pak Yan S. , Noakes Peter G. , Bellingham Mark C.
Published: July 2022

Normal development and function of the central nervous system involves a balance between excitatory and inhibitory neurotransmission. Activity of both excitatory and inhibitory neurons is modulated by inhibitory signalling of the GABAergic and glycinergic systems. Mechanisms that regulate formation, maturation, refinement, and maintenance of inhibitory synapses are established in early life. Deviations from ideal excitatory and inhibitory balance, such as down-regulated inhibition, are linked with many neurological diseases, including epilepsy, schizophrenia, anxiety, and autism spectrum disorders. In the mammalian forebrain, GABA is the primary inhibitory neurotransmitter, binding to GABA receptors, opening chloride channels and hyperpolarizing the cell. We review the involvement of down-regulated inhibitory signalling in neurological disorders, possible mechanisms for disease progression, and targets for therapeutic intervention. We conclude that transgenic models of disrupted inhibitory signalling—in GAD67+/− and VGAT−/− mice—are useful for investigating the effects of down-regulated inhibitory signalling in a range of neurological diseases.
Usability of NewSTEPs Data for Assessing the Characteristics of Infants with Newborn Screening Disorders
Authors: Omari Amel , Reeves Sarah L. , Prosser Lisa A. , Creary Melissa S. , Ahmad Ayesha , Chua Kao-Ping
Published: July 2022

Most state newborn screening programs in the U.S. currently contribute case data to the Newborn Screening Technical Assistance and Evaluation Program (NewSTEPs). To assess the usability of these data for research, we examined the completeness of key variables, particularly race and ethnicity. Data included 24,129 cases of 34 newborn screening disorders from 45 states available in NewSTEPs as of 31 August 2020. Birth years of cases ranged between 2006 and 2020. Rates of missing data for sex, gestational age, birth weight, and race/ethnicity were 3.8%, 31.7%, 7.0%, and 39.7%, respectively. After excluding 21 states for which ≥50% of cases had missing data on race and/or ethnicity, 16,010 cases from 24 states remained. The disorders with the highest proportions in which cases were recorded as Hispanic ethnicity/any race were methylmalonic acidemia (48.7%) and maple syrup urine disease (45.7%). Analyses indicated that sex and birth weight data in NewSTEPs are reasonably complete, but missing data are common for gestational age and race/ethnicity. Despite this, our analyses revealed several novel associations between race/ethnicity and newborn screening disorders, such as the high burden of maple syrup urine disease among Hispanic patients. This demonstrates the potential usefulness of NewSTEPs for research if investments in higher-quality data are made.