bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-causal Explanations in the Humanities: Some Examples
Authors: den Boef Roland , van Woudenberg René
Published: April 2023

The humanistic disciplines aim to offer explanations of a wide variety of phenomena. Philosophical theories of explanation have focused mostly on explanations in the natural sciences; a much discussed theory of explanation is the causal theory of explanation. Recently it has come to be recognized that the sciences sometimes offer respectable explanations that are non-causal. This paper broadens the discussion by discussing explanations that are offered in the fields of history, linguistics, literary theory, and archaeology that do not seem to fit the causal theory of explanation. We conducted an exploratory survey in acclaimed humanities textbooks to find explicitly so-called explanations and analyze their nature. The survey suggests that non-causal explanations are an integral part of the humanities and that they are of distinct kinds. This paper describes three kinds that are suggested by our survey: teleological, formal, and normative explanations. We suggest that such humanistic explanations strengthen the case for explanatory pluralism.
Potential effects of carbon monoxide donor and its nanoparticles on experimentally induced gastric ulcer in rats
Authors: Elsisi Alaa E. , Mekky Esraa F. , Abu-Risha Sally E.
Published: April 2023

The prevalence of gastric ulcers is increasing worldwide, especially those brought on by non-steroidal anti-inflammatory drugs (NSAIDS), so prevention is extremely crucial. The protective potential of carbon monoxide (CO) in several inflammatory disorders has been clarified. The goal of the current study was to investigate the gastroprotective effect of CO produced by its pharmacological donor (CORM2) and its nanoparticles (NPs) against indomethacin (INDO)-induced ulcers. Investigations on CORM2's dose-dependent effects were also conducted. For induction of gastric ulcer, 100 mg kg−1 of INDO was given orally. Before ulcer induction, CORM2 (5, 10, and 15 mg kg−1), CORM2 nanoparticles (5 mg kg−1), or ranitidine (30 mg kg−1) were given intraperitoneally for 7 days. Ulcer score, gastric acidity, gastric contents of malondialdehyde (MDA), nitric oxide (NO), heme oxygenase-1 (HO-1), and carboxyhemoglobin (COHb) blood content were estimated. Additionally, gene expression of nuclear factor erythroid 2-related factor 2 (NRF2) and immunohistochemical staining of cyclooxygenase-1 (COX-1) as well as cyclooxygenase-2 (COX-2) were analyzed. Results demonstrated a substantial dose-dependent decrease in ulcer score, pro-inflammatory indicators, and oxidative stress markers with CORM2 and its NPs. Furthermore, CORM2 and its NPs markedly increased NRF2, COX-1, and HO-1, but CORM2 NPs outperformed CORM2 in this regard. In conclusion, the CO released by CORM2 can protect against INDO-induced gastric ulcers dose dependently, and the highest used dose had no effect on COHb concentration.
Organizational transformation for greater sustainability impact: recent changes in a scientific research infrastructure in Europe
Authors: Holzer Jennifer M. , Orenstein Daniel E.
Published: April 2023

Context

Scholars across holistic, transdisciplinary, place-based fields of research, such as landscape ecology and social ecology, have increasingly called for an ‘all-hands-on-deck’ approach for transformations toward greater sustainability of social-ecological systems. This Perspective showcases organizational transformation toward sustainability in the context of a research network dedicated to place-based, social-ecological research in Europe.

Objectives

Using the European LTER research infrastructure (eLTER RI) as a case, we analyze recent organizational-level shifts motivated by desires to increase sustainability impact. These shifts include knowledge integration between the natural and social sciences, stakeholder engagement, and a reformulation of administrative guidelines and practices.

Methods

Following a program evaluation, new conversations led to new initiatives in the eLTER RI. As researchers who were involved in the program evaluation and the development of new initiatives, we rely on our professional experience and participant observation to provide insights about this process and its developments.

Results

Recommendations from a recent assessment that critiqued and provided recommendations for the research infrastructure have recently been implemented in the eLTER RI. eLTER has leveraged a unique and timely opportunity—formal recognition and project funding by the EU—to upscale and standardize its infrastructure by creating novel protocols and enacting steps towards implementation.

Conclusions

This Perspective demonstrates how eLTER’s research agenda and related protocols have evolved to better integrate multiple knowledge types, promote stakeholder integration into research, and foster greater equity and reflexivity in doing science, all of which are considered necessary to increase sustainability impact. We conclude by considering current and potential future challenges.
A tale of two interfaces: vitrivr at the lifelog search challenge
Authors: Heller Silvan , Spiess Florian , Schuldt Heiko
Published: April 2023

The past decades have seen an exponential growth in the amount of data which is produced by individuals. Smartphones which capture images, videos and sensor data have become commonplace, and wearables for fitness and health are growing in popularity. Lifelog retrieval systems aim to aid users in finding and exploring their personal history. We present two systems for lifelog retrieval: vitrivr and vitrivr-VR, which share a common retrieval model and backend for multi-modal multimedia retrieval. They differ in the user interface component, where vitrivr relies on a traditional desktop-based user interface and vitrivr-VR has a Virtual Reality user interface. Their effectiveness is evaluated at the Lifelog Search Challenge 2021, which offers an opportunity for interactive retrieval systems to compete with a focus on textual descriptions of past events. Our results show that the conventional user interface outperformed the VR user interface. However, the format of the evaluation campaign does not provide enough data for a thorough assessment and thus to make robust statements about the difference between the systems. Thus, we conclude by making suggestions for future interactive evaluation campaigns which would enable further insights.
Trends in Light and Temperature Sensitivity Recommendations among Licensed Biotechnology Drug Products
Authors: Kim Jennifer J. , Pritts Jordan D. , Ngo Mai , Estoll Corey R. , Rao V. Ashutosh
Published: April 2023

Purpose

Inherent structural and functional properties of biotechnology-derived therapeutic biologics make them susceptible to light- and temperature-induced degradation and consequently can influence their quality. Photosensitivity of therapeutic proteins continues to be examined, but the commonalities and trends of storage conditions and information about light and temperature sensitivity among currently licensed therapeutic proteins has not been previously surveyed.

Methods

Using a comprehensive and relational database approach, we conducted a scientific survey of all licensed biotechnology-derived drug products with the goal of providing evidence-based information about recommended storage conditions of formulations sorted by light- and temperature-related attributes as described for each product at licensure.

Results

We report the prevalence of indications for light and temperature sensitivity in formulations categorized by their presentation type, number of doses, container type, dosage form and active molecule type. We also report the storage temperature range across formulations and diluents for reconstitution and dilution. Formulations with excipients that potentially facilitate light-induced and thermal degradation were also noted.

Conclusions

The result of our analysis indicates that light and temperature sensitivity are prevalent across therapeutic protein formulations. However, when a formulation is reconstituted or diluted, both light and temperature sensitivity are less clear. In addition, light and temperature sensitivity are more well defined in liquid formulations than lyophilized powder formulations, and more well defined in products manufactured in autoinjectors, prefilled-syringes, and pens than products in vials. Overall, our report provides a data-driven summary of storage conditions among therapeutic protein formulations to support the development of future biologic drug products.
On k-regularity of sequences of valuations and last non-zero digits
Authors: Sobolewski Bartosz
Published: April 2023

Let$$b \ge 2$$b≥2be an integer base with prime factors$$p_1, \ldots , p_s$$p1,…,ps. In this paper we study sequences of “b-adic valuations” and last nonzero digits inb-adic expansions of the values$$f(n) = (f_1(n), \ldots , f_s(n))$$f(n)=(f1(n),…,fs(n)), where each$$f_i$$fiis a$$p_i$$pi-adic analytic function. We give a complete classification concerningk-regularity of these sequences, which generalizes a result obtained forbprime by Shu and Yao. As an application, we strengthen a theorem by Murru and Sanna onb-adic valuations of Lucas sequences of the first kind. Moreover, we derive a method to determine precisely which terms of these sequences can be represented as a sum of three squares.
Teachers' perception of aggressive student behavior through the lens of chronic worry and resignation, and its association with psychophysiological stress: An observational study
Authors: Wettstein Alexander , Jenni Gabriel , Schneider Sandra , Kühne Fabienne , grosse Holtforth Martin , La Marca Roberto
Published: April 2023

Aggressive student behavior is considered a leading risk factor for teacher stress. However, teachers' coping styles may affect how they perceive and respond to aggressive student behavior. This study tests whether teachers' perceptions of aggressive student behavior mainly mirror objectively observed aggression in presence of the teacher (as coded by external observers) or whether teachers' perception of aggressive student behavior primarily reflects teachers' avoidant coping styles, such as chronic worry and resignation. Finally, we examine whether observed and teacher-perceived aggression relates to increased vital exhaustion and psychophysiological stress among teachers (i.e., higher hair cortisol concentration). In an ambulatory assessment study, we administered self-reports to 42 Swiss teachers to assess perceived student aggression, chronic worry, resignation, and vital exhaustion. Additionally, four consecutive lessons per teacher were filmed, and aggressive student behavior in presence of the teacher was coded by four trained external observers. The concentration of cortisol was assessed in hair samples. Results showed that teacher-perceived and observed aggression were moderately associated. Observed aggression was related to teacher perceptions to a much lesser extent than teachers' avoidant coping styles, that is, chronic worry and resignation. While teacher-perceived student aggression was associated with teachers' self-reported vital exhaustion, we did not find any significant association with hair-cortisol concentration. Our findings suggest that teachers perceive student aggression through the lens of their coping styles. Teachers' dysfunctional coping styles are associated with an overestimation of student aggression. Teachers' overestimation of student aggression relates to higher levels of vital exhaustion. Therefore, it is crucial to identify and change teachers' dysfunctional coping styles to prevent a vicious cycle of dysfunctional teacher–student interactions.
The conjunctival fungal microflora of horses in a North Queensland tropical environment and their in vitro susceptibilities to antifungal agents
Authors: Mo Phu Mo , Picard Jacqueline , Gummow Bruce
Published: April 2023

Fungi are ubiquitous in the environment and part of the commensal microflora on the conjunctiva of equine eyes. North Queensland, being tropical, presents an ideal environment for fungi growth. When the cornea is injured, fungi can invade the corneal stroma, resulting in keratomycosis. The objectives of this study were to determine the fungal species specific to the eyes of horses in the Townsville region; to investigate the potential risk factors associated with the presence of fungi; and to test their susceptibility to antifungals to create an empirical guide for treatment. The eyes of forty ophthalmologically normal horses from James Cook University were sampled throughout the summer months of December 2017, January 2018, and January and February 2020. Cultured fungi were identified morphologically, and their identity confirmed by comparing partial 18sRNA DNA sequences with the NCBI nucleotide database. Minimum inhibitory concentration testing of common antifungal medications was performed. Sixty-one out of eighty conjunctival samples grew fungi, and 21 different fungi genera were isolated. The most common genera wereAspergillus(18%, 26/141),Curvularia(14%,20/141),Rhodotorula(12%,17/141) andPenicillium(12%,17/141). No significant association was found between age or environmental factors and fungal culture status. Most fungi were highly susceptible to voriconazole and ketoconazole but resistant to fluconazole and amphotericin B. This adds to the body of evidence on which species of fungi are present as normal ocular microflora of horses living in tropical regions of Australia, and an avenue for treating them.
In vivo Assessment of the Impact of Molecular Weight on Constructs of 68Ga-DOTA-Manocept in a Syngeneic Mouse Tumor Model
Authors: Bartels Jennifer L. , Fernandez Solana R. , Arnold Jeffrey S. , Parker Candace C. , Tekin Volkan , O’Malley Grace , Ralph David A. , Lapi Suzanne E.
Published: April 2023

Purpose

Manocept™ constructs are mannosylated amine dextrans (MADs) that bind with high affinity to the mannose receptor, CD206. Tumor-associated macrophages (TAMs) are the most numerous immune cells in the tumor microenvironment and a recognized target for tumor imaging and cancer immunotherapies. Most TAMs express CD206, suggesting utility of MADs to deliver imaging moieties or therapeutics to TAMs. The liver Kupffer cells also express CD206, making them an off-target localization site when targeting CD206 on TAMs. We evaluated TAM targeting strategies using two novel MADs differing in molecular weight in a syngeneic mouse tumor model to determine how varying MAD molecular weights would impact tumor localization. Increased mass dose of the non-labeled construct or a higher molecular weight (HMW) construct were also used to block liver localization and enhance tumor to liver ratios.

Procedures

Two MADs, 8.7 kDa and 22.6 kDa modified with DOTA chelators, were synthesized and radiolabeled with 68Ga. A HMW MAD (300 kDa) was also synthesized as a competitive blocking agent for Kupffer cell localization. Balb/c mice, with and without CT26 tumors, underwent dynamic PET imaging for 90 min followed by biodistribution analyses in selected tissues.

Results

The new constructs were readily synthesized and labeled with 68Ga with ≥ 95% radiochemical purity in 15 min at 65 °C. When injected at doses of 0.57 nmol, the 8.7 kDa MAD provided 7-fold higher 68Ga tumor uptake compared to the 22.6 kDa MAD (2.87 ± 0.73%ID/g vs. 0.41 ± 0.02%ID/g). Studies with increased mass of unlabeled competitors showed reduced liver localization of the [68Ga]MAD-8.7 to varying degrees without significant reductions in tumor localization, resulting in enhanced tumor to liver signal ratios.

Conclusion

Novel [68Ga]Manocept constructs were synthesized and studied in in vivo applications, showing that the smaller MAD localized to CT26 tumors more effectively than the larger MAD and that the unlabeled HMW construct could selectively block liver binding of [68Ga]MAD-8.7 without diminishing the localization to tumors. Promising results using the [68Ga]MAD-8.7 show a potential path to clinical applications.

Graphical Abstract
Effects of vegetation distribution along river transects on the morphology of a gravel bed braided river
Authors: Zhu Runye , Tsubaki Ryota , Toda Yuji
Published: April 2023

The interaction between vegetation, sediment, and water flow creates various fluvial landscapes. Hydrological conditions and flood disturbances, as well as the habitat preference of vegetation, regulate its spatial distribution. To describe the spatial distribution of vegetation cover, here, we focus on vegetation distributions along river transverse transects that define vertical and horizontal distances from water areas during low flow periods. As one of the most dynamic river types, braided rivers can be significantly influenced by vegetation encroachment. However, the effects of vegetation distributions along river transects on braided river morphology remain unknown. To study the potential influence of vegetation distribution along river transects, a depth-averaged, hydro-morphodynamic model was employed. Using the model, we investigated a medium-sized, braided river with a gravel bed affected by riparian vegetation. The following scenarios of vegetation transect distributions were examined: (1) vegetation established near or covering the low water channel, and (2) vegetation established on bar tops and kept at a distance from the low water channel. The model successfully reproduced a reduction in the braiding index for a vegetated braided river. Depending on the transect distribution scenarios employed, significantly different effects for river morphology were obtained. For example, compared to vegetation on bar tops, vegetation located near the low water channel played a more critical role for changing river morphology, redirecting water flow, and changing the statistical characteristics of the riverbed elevation distribution. Vegetation near the low water channel not only concentrated water flow to low water channels but also redirected flow to the high elevation area by reducing low water channel flow capacity. The revealed effects of the vegetation transect distribution on river morphology development helped to determine effective management protocols for reducing the negative impact of vegetation encroachment.
A Background of Bias: Subtle Changes in Lineup Backgrounds Increase the Own Race Bias
Authors: Havard Catriona , Breese Emily , Thirkettle Martin , Kask Kristjan , Leol Kris-Loreen , Mädamürk Kaja
Published: April 2023

In police photo lineups, there can sometimes be small variations in shades and hues of the background images due to the faces being filmed under different lighting and cameras. Own race bias refers to a situation where people are better at remembering the faces of those who are the same race as them and find it more difficult to recognise faces from a different race. In this paper, we investigated the influence of small colour variations in backgrounds for the recognition of Black and White faces. Across 3 experiments, we found when small changes were introduced into the backgrounds of the images this increased false identifications for previously unseen Black faces, but not White faces. This finding suggests that the police need to ensure that the backgrounds of the photo lineups they use are all uniform to reduce mistaken identifications of innocent suspects.
Selective Disruption of Perineuronal Nets in Mice Lacking Crtl1 is Sufficient to Make Fear Memories Susceptible to Erasure
Authors: Poli Andrea , Viglione Aurelia , Mazziotti Raffaele , Totaro Valentino , Morea Silvia , Melani Riccardo , Silingardi Davide , Putignano Elena , Berardi Nicoletta , Pizzorusso Tommaso
Published: April 2023

The ability to store, retrieve, and extinguish memories of adverse experiences is an essential skill for animals’ survival. The cellular and molecular factors that underlie such processes are only partially known. Using chondroitinase ABC treatment targeting chondroitin sulfate proteoglycans (CSPGs), previous studies showed that the maturation of the extracellular matrix makes fear memory resistant to deletion. Mice lacking the cartilage link protein Crtl1 (Crtl1-KO mice) display normal CSPG levels but impaired CSPG condensation in perineuronal nets (PNNs). Thus, we asked whether the presence of PNNs in the adult brain is responsible for the appearance of persistent fear memories by investigating fear extinction in Crtl1-KO mice. We found that mutant mice displayed fear memory erasure after an extinction protocol as revealed by analysis of freezing and pupil dynamics. Fear memory erasure did not depend on passive loss of retention; moreover, we demonstrated that, after extinction training, conditioned Crtl1-KO mice display no neural activation in the amygdala (Zif268 staining) in comparison to control animals. Taken together, our findings suggest that the aggregation of CSPGs into PNNs regulates the boundaries of the critical period for fear extinction.
Zugänge zu Ombudsstellen niedrigschwellig schaffen
Authors: Thomas Severine , Hagemeier Yannick , Rusack Tanja , Taphorn Mara
Published: April 2023

Die Praxis der Kinder- und Jugendhilfe zeigt, dass es bei der Leistungsbewilligung Konflikte zwischen den daran Beteiligten geben kann. Durch das Kinder- und Jugendstärkungsgesetz ist daher seit 2021 ist die Einrichtung ombudschaftlicher Beratungsstellen vorgeschrieben. Damit diese Beratungsstellen für Kinder, Jugendliche und ihre Eltern hilfreich sein können, sollte der Zugang zu ihnen möglichst niedrigschwellig sein. Der Beitrag erörtert, wie Niedrigschwelligkeit konkret aussehen muss, um ihrem Namen gerecht zu werden.
1H, 15N, 13C backbone and Cβ resonance assignments for UBQLN1 UBA and UBAA domains
Authors: Buel Gwen R. , Chen Xiang , Kayode Olumide , Cruz Anthony , Walters Kylie J.
Published: April 2023

UBQLN1 functions in autophagy and proteasome-mediated protein degradation. It contains an N-terminal ubiquitin-like domain (UBL), a C-terminal ubiquitin-associated domain (UBA), and a flexible central region which functions as a chaperone to prevent protein aggregation. Here, we report the 1H, 15N, and 13C resonance assignments for the backbone (NH, N, C’, Cα, and Hα) and sidechain Cβ atoms of the UBQLN1 UBA and an N-terminally adjacent segment called the UBA-adjacent domain (UBAA). We find a subset of the resonances corresponding to the UBAA to have concentration-dependent chemical shifts, likely due to self-association. We also find the backbone amide nitrogen of T572 to be shifted upfield relative to the average value for a threonine amide nitrogen, a phenomenon likely caused by T572 Hγ1 engagement in a hydrogen bond with adjacent backbone carbonyl atoms. The assignments described in this manuscript can be used to study the protein dynamics of the UBQLN1 UBA and UBAA as well as the interaction of these domains with other proteins.
How does the learning environment support vocational student learning of domain-general competencies?
Authors: Löfgren Sami , Ilomäki Liisa , Lipsanen Jari , Toom Auli
Published: April 2023

Studies and policy reports worldwide argue that a modern employee must possess domain-general competencies to become employed. However, competency studies within upper-secondary initial vocational education and training are scarce. Therefore, this study aimed to scrutinise this topic and examined how the experienced learning environment contributes to student learning of competencies. Study participants were students in automotive engineering, mechanical and metal engineering, electrical and automation engineering and building service technology. The data were collected with an online questionnaire and analysed statistically using structural equation modelling. The research findings indicate firstly that eight competency domains could be recognised: work organisation, cooperation ability, professional attitude, problem solving, willingness to learn, active listening, empathy and assertiveness. Secondly, students’ experienced learning environment was characterised by social support and recognition provided by educators, equal treatment between students and a positive climate for learning. Thirdly, the quality of the experienced learning environment contributed to learning of competencies. The research findings enhance the scientific and societal discussion about vocational graduate competencies and to what extent the experienced learning environment contributes to the learning of competencies.
Consensus for criteria of running a pediatric inflammatory bowel disease center using a modified Delphi approach
Authors: Luo You-You , Wu Kai-Chun , Gong Si-Tang , Huang Ying , Yang Hong , Tang Qing-Ya , Leung Ying-kit , Wu Jie , Geng Lan-Lan , Zhou Wei , Sun Mei , Wan Chao-Min , Li Zai-Ling , Fang Ying , Li Xiao-Qin , Li Mei , Wang Zhao-Xia , Xiao Yuan , Zhong Xue-Mei , Chen Xiao-Fei , Chen Jie
Published: April 2023

Background

Good quality of care for inflammatory bowel disease (IBD) depends on high-standard management and facility in the IBD center. Yet, there are no clear measures or criteria for evaluating pediatric IBD (PIBD) center in China. The aim of this study was to develop a comprehensive set of quality indicators (QIs) for evaluating PIBD center in China.

Methods

A modified Delphi consensus-based approach was used to identify a set of QIs of structure, process, and outcomes for defining the criteria. The process included an exhaustive search using complementary approaches to identify potential QIs, and two web-based voting rounds to select the QIs defining the criteria for PIBD center.

Results

A total of 101 QIs (35 structures, 48 processes and 18 outcomes) were included in this consensus. Structure QIs focused on the composition of multidisciplinary team, facilities and services that PIBD center should provide. Process QIs highlight core requirements in diagnosing, evaluating, treating PIBD, and disease follow-up. Outcome QIs mainly included criteria evaluating effectiveness of various interventions in PIBD centers.

Conclusion

The present Delphi consensus developed a set of main QIs that may be useful for managing a PIBD center.
Vertical segregation, innovation, and gender diversity in Spain’s industrial sector
Authors: Sánchez Rosario , Diaz Ángeles , Urbano Amparo
Published: April 2023

Innovation is a general measure of the success of a company and shows a positive relationship with several key factors such as collaboration with universities and technology centers or belonging to medium- and high-tech sectors. While many studies have found that gender diversity in company management teams has a positive influence on companies’ economic success, few have focused on the impact that the inclusion of women in the board of directors has on product, process, and organizational innovation. This paper builds on previous knowledge about the determinants of innovations and shows that greater gender management team diversity, compared to male-only teams, positively affects the achievement of said innovations. However, these results change when we incorporate the size of the companies as a moderating variable. In this case, we identify a turning point corresponding to firm size in the impact of gender diversity on product and process innovations, but not for innovations in organizational methods, where the impact is positive and significant for both SMEs and large enterprises. Collaboration with universities and technological centers is an important determinant of innovation for both SMEs and large enterprises.
Molecular dynamics simulation of pyruvate kinase to investigate improved thermostability of artificially selected strain in Enterococcus faecium
Authors: Li Vladimir , Lee Chul , Lee Youngho , Kim Heebal
Published: April 2023

Background

Enterococcus faecium (E. faecium) is a member of symbiotic lactic acid bacteria in gastrointestinal tract and it was successfully used to treat diarrhea cases in humans. For a lactobacteria to survive during the pasteurization process, resistance of proteins to denaturation at high temperatures is crucial. Pyruvate kinase (PYK) is one of the proteins possessing such property. It plays a major role during glycolysis by producing pyruvate and adenosine triphosphate (ATP).

Objective

To assess the acquired thermostability of PYK of ALE strain using in silico methods.

Methods

First, we predicted and assessed tertiary structures of our proteins using SWISS-MODEL homology modelling server. Second, we then applied molecular dynamics (MD) simulation to simulate and assess multiple properties of molecules. Therefore, we implemented comparative MD to evaluate thermostability of PYK of recently developed high temperature resistant strain of E. faecium using Adaptive Laboratory Evolution (ALE) method. After 20ns of simulation at different temperatures, we observed that ALE enhanced strain demonstrated slightly better stability at 300, 340 and 350 K compared to that of the wild type (WT) strain.

Results

We collected the results of MD simulation at four temperature points: 300, 340, 350 and 400 K. Our results showed that the protein demonstrated increased stability at 340 and 350 K.

Conclusion

Results of these study suggest that PYK of ALE enhanced strain of E. faecium demonstrates overall better stability at elevated temperatures compared to that of WT strain.
Tumour-derived extracellular vesicle based vaccines for melanoma treatment
Authors: Gonzalez-Melero Lorena , Hernandez Rosa Maria , Santos-Vizcaino Edorta , Igartua Manoli
Published: April 2023

The interest of extracellular vesicles (EVs) in cancer immunotherapy is increasing every day. EVs are lipid bilayer vesicles released by most cells, which contain the molecular signature of their parent cell. Melanoma-derived EVs present antigens specific to this aggressive type of cancer, but they also exert immunomodulatory and pro-metastatic activity. Until now, most reviews focus on the immunoevasive characteristics of tumour-derived EVs, but do not help to overcome the issues related to them. In this review, we describe isolation methods of EVs from melanoma patients and most interesting markers to oversee their effect if they are used as antigen carriers. We also discuss the methods developed so far to overcome the lack of immunogenicity of melanoma-derived EVs, which includes EV modification or adjuvant co-administration. In summary, we conclude that EVs can be an interesting antigen source for immunotherapy development once EV obtaining is optimised and the understanding of the mechanisms behind their multiple effects is further understood.

Graphical Abstract
Antimicrobial and anticancer activities of biosynthesized bimetallic silver-zinc oxide nanoparticles (Ag-ZnO NPs) using pomegranate peel extract
Authors: Hashem Amr H. , El-Sayyad Gharieb S.
Published: April 2023

In the last two decades, nanomaterials have received much attention for the treatment of multidrug-resistant microbes that threaten human health. In the current study, the novelty and scientific significance concentrated on the biogenic synthesis of bimetallic silver-zinc oxide nanoparticles (Ag-ZnO NPs) using pomegranate peel extract (PPE) for the first time. The new constructed bimetallic Ag-ZnO NPs possessed the synergistic activity at a low concentration to avoid toxicity and elevate the superior potential. UV-Vis. characterization illustrated that Ag-ZnO NPs were small in size (15.8 nm), which was observed at 395.0 nm. The SEM image of Ag-ZnO NPs, incorporated with PPE, exhibited uniform Ag-ZnO NP surfaces with a clear surface appearance. It can be detected that Ag-ZnO NPs were isolated typically as a rounded particle across the PPE, which showed as brilliant NPs combined and stabilized with the prepared PPE. Results also revealed that Ag-ZnO NPs exhibited potential antibacterial activity toward Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, and Enterococcus faecalis where minimum inhibitory concentrations (MICs) were 62.5, 125, 15.62, 62.5, and 250 µg/ml. Likewise, Ag-ZnO NPs appeared antifungal activity against Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, and Aspergillus brasiliensis, where MICs were 7.81, 31.25, 125, and 62.5 µg/ml, respectively. Moreover, Ag-ZnO NPs exhibited anticancer activities against MCF7 and Caco2, where IC50 was 104.9 and 52.4 µg/ml, respectively. Additionally, these concentrations are safe in use where results of cytotoxicity on Vero normal cell line confirmed that IC50 was 155.1 µg/ml. Overall, bimetallic Ag-ZnO NPs were for the first time, successfully biosynthesized using PPE; also, they had a promising antibacterial, antifungal, and anticancer activities.
Detection and explanation of anomalies in healthcare data
Authors: Samariya Durgesh , Ma Jiangang , Aryal Sunil , Zhao Xiaohui
Published: April 2023

The growth of databases in the healthcare domain opens multiple doors for machine learning and artificial intelligence technology. Many medical devices are available in the medical field; however, medical errors remain a severe challenge. Different algorithms are developed to identify and solve medical errors, such as detecting anomalous readings, anomalous health conditions of a patient, etc. However, they fail to answer why those entries are considered an anomaly. This research gap leads to an outlying aspect mining problem. The problem of outlying aspect mining aims to discover the set of features (a.k.a subspace) in which the given data point is dramatically different than others. In this paper, we present a framework that detects anomalies in healthcare data and then provides an explanation of anomalies. This paper aims to effectively and efficiently detect anomalies and explain why they are considered anomalies by detecting outlying aspects. First, we re-introduced four anomaly detection techniques and outlying aspect mining algorithms. Then, we evaluate the performance of anomaly detection techniques and choose the best anomaly detection algorithm. Later, we detect the top k anomaly as a query and detect their outlying aspect. Lastly, we evaluate their performance on 16 real-world healthcare datasets. The experimental results show that the latest isolation-based outlying aspect mining measure, SiNNE, has outstanding performance on this task and has promising results.
Microanalysis of TiN phases formed in inclusions of electrogas weld metal
Authors: Seo Kangmyung , Kang Yongjoon , Kim Hee Jin , Yoon Joong Geun
Published: April 2023

This study has been conducted to confirm the formation of TiN phase in the electrogas (EG) weld metal and, if it formed, to identify the nucleation potency of TiN for acicular ferrite. To facilitate this, a high-nitrogen EG weld meal deposited using a very high heat input was chosen. Inclusion analyses were mostly carried out in a scanning electron microscope (SEM) and analytical transmission electron microscope (TEM) equipped with energy dispersive analyzer (EDS) and electron energy loss spectroscopy (EELS). It was confirmed that the inclusions were nearly fully covered by TiO layer alloyed with a small amount of nitrogen, this TiO layer being partly coated with TiN phases having two different types of morphology: layer-type or patch-type. The layer-type was identified to be nearly pure TiN, being formed with a thickness of 10 nm on the outer surface of thick TiO layer. The patch-type appeared to be formed on the TiN/TiO layer and was characterized by its fine lamellar mixture of TiN and (Al,Mn)-oxide. As all these phases formed on the inclusion surface, they were suspected to influence the nucleation potency of inclusions but the relative potency of these phases to TiO layer was not clearly understood.
Modeling and simulation of biomass anaerobic digestion for high biogas yield and CO2 mineralization
Authors: Mokraoui Salim , Halilu Ahmed , Hashim Mohd Ali , Hadj-Kali Mohamed Kamel
Published: April 2023

Bioenergy is one of several renewable energy options derived from biomass that can help satisfy our energy needs.  Anaerobic digestion is a viable method for producing bioenergy in the form of biogas from biomass. The anaerobic digestion process is challenged with low biogas recovery, and low-quality effluent or CO2 emission, which contribute to environmental pollution and the carbon footprint in the atmosphere. Computational process modelling and simulation can provide realistic information for dealing with the technological challenges involved with anaerobic digestion. In this study, modeling and simulation of the simplified anaerobic digestion process were done using SuperPro Designer software fed with biomass feedstock containing carbohydrates, proteins, and fats, as well as yeast, at 37 °C mesophilic temperature. The anaerobic digestion process yielded 89.655% of CH4 and 10.345% of CO2 and confirmed that the carbohydrate feedstock produces more CH4 composition in the biogas. Mineralization of CO2 using MgO yielded 0.23% MgCO3, consuming > 99% of the CO2 produced during the anaerobic digestion process. Environmental impact assessment of the effluent discharge yielded 0.142 kg Slds/L volatile solid with 6.01% COD reduction per batch of the anaerobic digestion process in an anaerobic digester with 90% (1.925 kg/batch) feedstock dosage. The data indicate that single-batch effluent cannot be discharged into the environment, hence indicating the possible recycling for multiple anaerobic digestion processing. The results are a significant guide for the realistic scalable production of high-quality biogas for bioenergy application, CO2 mineralization, and environmental remediation.
Exclusion of older adults and immunocompromised individuals in influenza, pneumococcal and COVID-19 vaccine trials before and after the COVID-19 pandemic
Authors: Bukan Katrine , Pearce-Slade Toby , Eiberg Mads , Tinelli Marco , Yahav Dafna , Tuells Jose , Epaulard Olivier , Holler Jon G. , Roed Casper , Søborg Christian , Jensen Jens-Ulrik Stæhr , Harboe Zitta Barrella
Published: April 2023

Background

Older adults and immunocompromised individulas are often excluded from vaccine trials.

Aim

We hypothesised that during the coronavirus disease 2019 (COVID-19) pandemic, the proportion of trials excluding these patients decreased.

Methods

Using the US Food and Drug Administration and and European Medicines Agency search engines, we identified all vaccines approved against pneumococcal disease, influenza (quadrivalent vaccines), and COVID-19 from 2011 to 2021. Study protocols were screened for direct and indirect age exclusion criteria and exclusion of immunocompromised individuals. In addition, we reviewed the studies with no explicit exclusion criteria and investigated the actual inclusion of those individuals.

Results

We identified 2024 trial records; 1702 were excluded (e.g., use of other vaccine or risk group); and 322 studies were eligible for our review. Among the pneumococcal and influenza vaccine trials (n = 193), 81 (42%) had an explicit direct age exclusion, and 150 (78%) had an indirect age-related exclusion. In total, 163 trials (84%) trials were likely to exclude older adults. Among the COVID-19 vaccine trials (n = 129), 33 (26%) had direct age exclusion and 82 (64%) had indirect age exclusion; in total, 85 (66%) trials were likely to exclude older adults. Therefore was a 18% decrease in the proportion of trials with age-related exclusion between 2011 and 2021 (only influenza and pneumococcal vaccine trials) and 2020–2021 (only COVID-19 vaccine trials) (p = 0.014). In a sub-analysis assessing observational and randomised trials, the decrease was 25% and 9%, respectively. Immunocompromised individuals were included in 87 (45%) of the pneumococcal and influenza vaccine trials compared with 54 (42%) of the COVID-19 vaccine trials (p = 0.058).

Conclusions

During the COVID-19 pandemic, we found a decrease in the exclusion of older adults from vaccine trials but no significant change in the inclusion of immunocompromised individulas.
Iséki spaces of semirings
Authors: Goswami A.
Published: April 2023

The aim of this paper is to study Iséki spaces of distinguished classes of ideals of a semiring endowed with a topology. We show that every Iséki space is quasi-compact whenever the semiring is Noetherian. We characterize Iséki spaces for which every non-empty irreducible closed subset has a unique generic point. Furthermore, we provide a sufficient condition for the connectedness of Iséki spaces and show that the strongly connectedness of an Iséki space implies the existence of non-trivial idempotent elements of semirings.
Thyroid dysfunction during gestation and gestational diabetes mellitus: a complex relationship
Authors: Pinto S. , Croce L. , Carlier L. , Cosson E. , Rotondi M.
Published: April 2023

Purpose

Gestational diabetes mellitus (GDM) and thyroid dysfunction during gestation (GTD) are the two most prevalent endocrinopathies during pregnancy. The aim of the present review is to provide an overview of the peculiar aspects of GDM and GTD, to highlight the potential interactions and clinical consequences of these two frequent clinical conditions.

Methods

A literature review regarding GDM and GTD was carried out with particular interest on meta-analyses and human studies dealing with the (i) shared risk factors between GDM and GTD, (ii) the epidemiological link between GTD and GDM, (iii) physiopathologic link between GTD and GDM, (iv) clinical consequences of GDM and GTD, and (v) post-partum implications of GDM and GTD.

Results

The association between GDM and GTD is common and may be explained by the insulin-resistance state due to maternal GTD, to alterations in the placentation process or to the many shared risk factors. Discrepant results of epidemiologic studies can be explained, at least in part, by the changes in diagnostic criteria and screening strategies throughout the years for both conditions. GDM and GTD impact pregnancy outcome and have post-partum long-term consequences, but more studies are needed to prove an additional adverse effect.

Conclusions

Based on the epidemiological and physio-pathological link between GDM and GTD, it could be suggested that a diagnosis of GTD could lead to screen GDM and the other way round.
RetinaMOT: rethinking anchor-free YOLOv5 for online multiple object tracking
Authors: Cao Jie , Zhang Jianxun , Li Bowen , Gao Linfeng , Zhang Jie
Published: April 2023

In recent years, YOLOv5 networks have become a research focus in many fields because they are capable of outperforming state-of-the-art (SOTA) approaches in different computer vision tasks. Nevertheless, there is still room for improvement in YOLOv5 in terms of target tracking. We modified YOLOv5 according to the anchor-free paradigm to be on par with other state-of-the-art tracking paradigms and modified the network backbone to design an efficient module, thus proposing the RetinaYOLO detector, which, after combining state-of-the-art tracking algorithms, achieves state-of-the-art performance: we call it RetinaMOT. To the best of our knowledge, RetinaMOT is the first such approach. The anchor-free paradigm SOTA method for the YOLOv5 architecture and RetinaYOLO outperforms all lightweight YOLO architecture methods on the MS COCO dataset. In this paper, we show the details of the RetinaYOLO backbone, embedding Kalman filtering and the Hungarian algorithm into the network, with one framework used to accomplish two tasks. Our RetinaMOT shows that MOTA metrics reach 74.8, 74.1, and 66.8 on MOT Challenge MOT16, 17, and 20 test datasets, and our method is at the top of the list when compared with state-of-the-art methods.
Progressive multi-level distillation learning for pruning network
Authors: Wang Ruiqing , Wan Shengmin , Zhang Wu , Zhang Chenlu , Li Yu , Xu Shaoxiang , Zhang Lifu , Jin Xiu , Jiang Zhaohui , Rao Yuan
Published: April 2023

Although the classification method based on the deep neural network has achieved excellent results in classification tasks, it is difficult to apply to real-time scenarios because of high memory footprints and prohibitive inference times. Compared to unstructured pruning, structured pruning techniques can reduce the computation cost of the model runtime more effectively, but inevitably reduces the precision of the model. Traditional methods use fine tuning to restore model damage performance. However, there is still a large gap between the pruned model and the original one. In this paper, we use progressive multi-level distillation learning to compensate for the loss caused by pruning. Pre-pruning and post-pruning networks serve as the teacher and student networks. The proposed approach utilizes the complementary properties of structured pruning and knowledge distillation, which allows the pruned network to learn the intermediate and output representations of the teacher network, thus reducing the influence of the model subject to pruning. Experiments demonstrate that our approach performs better on CIFAR-10, CIFAR-100, and Tiny-ImageNet datasets with different pruning rates. For instance, GoogLeNet can achieve near lossless pruning on the CIFAR-10 dataset with 60% pruning. Moreover, this paper also proves that using the proposed distillation learning method during the pruning process achieves more significant performance gains than after completing the pruning.
Real-time permeability evolution of limestone under high temperature and triaxial stresses
Authors: Chen Zhengnan , Feng Zijun , Mi Chen , Zhang Chao
Published: April 2023

In deep underground geological disposal of nuclear waste, geothermal energy development, underground coal gasification, geothermal resources development and other underground high temperature projects, they are all closely related to the permeability and thermal expansion characteristics of rocks in high temperature high-pressure real-time state. In this experiment, the real-time evolution of permeability of limestone under high-temperature and triaxial stresses condition was studied using the HTHP rock mechanics triaxial test system and compared with the permeability of limestone after high temperature cooling treatment. The test results show that: the effect of temperature on limestone permeability facilitation under high temperature cooling condition is significant, and the permeability increases by 1–2 orders of magnitude relative to the initial permeability for every 100 °C increase in the preheat temperature after 300 °C. Under high-temperature and high-pressure in real time condition, the difference values of permeability at different temperature points relative to room temperature always do not more than one order of magnitude. During the heating process at 500 °C, the permeability curves of the triaxial pressures range from 15 to 35 MPa are very different. Under the pressure condition of 15 MPa, the permeability curve increases monotonically and rapidly with the increasing temperature; When the pressure reaches 25 MPa pressure, there is a peak value area in the permeability curve; the permeability decreases monotonically with temperature when the pressure up to 35 MPa. Compared with the only thermal effect, the thermal- mechanical coupling effect has a significant inhibitory effect on limestone permeability development, and the permeability disparity between the two types of heat treatment rocks become more and more significant with increasing temperature and hydrostatic pressure.