bluuebunny/crossref_metadata_2025 huggingface dataset:
El reto de la aplicación de la terapia con linfocitos T modificados por ingeniería genética al tratamiento de tumores de órgano sólido
Authors: Solana López Irene
Published: April 2023

La terapia con linfocitos T modificados por ingeniería genética se fundamenta en la inducción de la expresión en la membrana de linfocitos T extraídos del propio paciente de receptores quiméricos CAR o TCR. Estos receptores se diseñan para el reconocimiento específico de antígenos tumorales. Mientras que en el campo de la hematología la FDA aprobó en el 2017 la primera terapia con linfocitos T-CAR, en el caso de los tumores de órgano sólido numerosos fármacos han sido testados en ensayos clínicos, sin resultados concluyentes hasta la fecha. Por ello, hemos realizado una revisión del panorama de ensayos clínicos con T-CAR/T-TCR para el tratamiento de tumores de órgano sólido con el objetivo de analizar en qué punto de desarrollo se encuentra actualmente esta terapia, cuáles son sus límites y sus retos y si existen fundamentos teóricos o preclínicos destinados a superarlos. Encontramos 297 ensayos publicados desde el 2003 en NIH’s ClinicalTrials.gov, desarrollados en 15 países, mayoritariamente China (51,9%) y EEUU (39,4%).  El 84,8% emplearon el receptor CAR y el 15,2% TCR. Únicamente el 2,7% se encontraban en fase 2 o fase 2/3, sólo el 14,5% figuraban como completados o terminados y exclusivamente el 3,4% disponían de resultados publicados. Estos datos sustentan la conclusión de que probablemente sea necesario el fortalecimiento de la fase preclínica antes de lograr una aproximación exitosa mediante la terapia con T-CAR/T-TCR para el tratamiento de tumores de órgano sólido.
The application of additive manufacturing technology in pelvic surgery: A bibliometrics analysis
Authors: Li Jian , Wang Jiani , Lv Jia , Bai Junjun , Meng Shichao , Li Jinxuan , Wu Hua
Published: April 2023

With the development of material science, additive manufacturing technology has been employed for pelvic surgery, addressing the challenges, such as the complex structure of the pelvis, difficulty in exposing the operative area, and poor visibility, of the traditional pelvic surgery. However, only limited studies have been done to review the research hotspots and trends of the additive manufacturing technology applied for pelvic surgery. In this study, we comprehensively analyzed the literatures related to additive manufacturing technology in pelvic surgery by a bibliometrics analysis and found that additive manufacturing technology is widely used in several aspects of preoperative diagnosis, preoperative planning, intraoperative navigation, and personalized implants for pelvic surgery. Firstly, we searched and screened 856 publications from the Web of Science Core Collection (WoSCC) with TS = (3D printing OR 3D printed OR three-dimensional printing OR additive manufacturing OR rapid prototyping) AND TS = (pelvis OR sacrum OR ilium OR pubis OR ischium OR ischia OR acetabulum OR hip) as the search strategy. Then, 565 of these were eliminated by evaluating the titles and abstracts, leaving 291 pieces of research literature whose relevant information was visually displayed using VOSviewer. Furthermore, 10 publications with high citations were selected by reading all publications extensively for carefully evaluating their Titles, Purposes, Results, Limitations, Journal of affiliation, and Citations. Our results of bibliometric analysis demonstrated that additive manufacturing technology is increasingly applied in pelvic surgery, providing readers with a valuable reference for fully comprehending the research hotspots and trends in the application of additive manufacturing technology in pelvic surgery.
Morphology engineering for novel antibiotics: Effect of glass microparticles and soy lecithin on rebeccamycin production and cellular morphology of filamentous actinomycete Lentzea aerocolonigenes
Authors: Dinius Anna , Schrinner Kathrin , Schrader Marcel , Kozanecka Zuzanna Justyna , Brauns Henry , Klose Leon , Weiß Hannah , Kwade Arno , Krull Rainer
Published: April 2023

Lentzeaaerocolonigenes, as an actinomycete, is a natural producer of the antibiotic and antitumoral drug rebeccamycin. Due to the filamentous cellular morphology handling in cultivations is challenging; therefore, morphology engineering techniques are mandatory to enhance productivity. One promising approach described in the literature is the addition of mineral particles in the micrometer range to precisely adjust cellular morphology and the corresponding product synthesis (microparticle-enhanced cultivation, MPEC). Glass microparticles are introduced in this study as a novel supplementation type for bioprocess intensification in filamentous organisms. Several investigations were conducted to screen for an optimal particle setup, including particle size and concentration regarding their impact and effects on enhanced productivity, microparticle incorporation behavior into the biopellets, the viability of pellets, and morphological changes. Glass microparticles (10 g·L−1) with a median diameter of 7.9 µm, for instance, induced an up to fourfold increase in product synthesis accompanied by overall enhanced viability of biomass. Furthermore, structural elucidations showed that biopellets isolated from MPEC tend to have lower hyphal density than unsupplemented control pellets. In this context, oxygen microprofiling was conducted to better understand how internal structural changes interwind with oxygen supply into the pellets. Here, the resulting oxygen profiles are of a contradictive trend of steeper oxygen consumption with increasing glass microparticle supplementation. Eventually, MPEC was combined with another promising cultivation strategy, the supplementation of soy lecithin (7.5 g·L−1), to further increase the cultivation performance. A combination of both techniques in an optimized setup resulted in a rebeccamycin concentration of 213 mg·L−1 after 10 days of cultivation, the highest value published so far for microparticle-supplemented shake flask cultivations of L. aerocolonigenes.
Suspended sediment transport in Rio Colorado agricultural basin, Argentina
Authors: Cancio Nicolas C. O. , Pierini Jorge O.
Published: April 2023

The nutrient input from inland water discharges is vital for the development of marine aquatic fauna, being significantly sensitive to changes in water quality (WQ). The assessment of the contribution and distribution of some water quality parameters (e.g., nutrients, metals and inland organic compounds) is of vital importance, especially in irrigation basins. The study area is the Bonaerense Valley of the Colorado River (BVCR) and Mar Argentino, near the mouth of the Colorado River (Buenos Aires, Argentina). The study of water quality parameters is performed in an indirect way, by studying the spatiotemporal dynamics of cohesive sediment (CS), this is possible because the CS has a fundamental role in the transport of substances by adsorption/desorption interactions. We used numerical models (MOHID Land and MOHID Water) in a coupled way, evaluating the complex dynamics involved. The evaluated parameters (flow, velocity, cohesive sediment, salinity and temperature) were calibrated and subsequently validated with data from 7 monitoring stations, located along the Colorado River and adjacent water collectors. Calibration and validation values are within an acceptable range for the purposes, with mean values of 0.8 for NSE (Nash-Sutcliffe model efficiency coefficient), 0.9 (Pearson correlation) for calibration and 0.6 (NSE), 0.9 (Pearson) for validation. The irrigation zone (through the collectors) shows a significative contribution of cohesive sediment, on the order of 300 ppm. The river presents approximately 100 ppm and generates a plume along the coast to the northwest.
The bisphenol S contamination level observed in human follicular fluid affects the development of porcine oocytes
Authors: Žalmanová Tereza , Hošková Kristýna , Prokešová Šárka , Nevoral Jan , Ješeta Michal , Benc Michal , Yi Young-Joo , Moravec Jiří , Močáryová Beáta , Martínková Stanislava , Fontana Josef , Elkalaf Moustafa , Trnka Jan , Žáková Jana , Petr Jaroslav
Published: April 2023

Bisphenol S (BPS), the main replacement for bisphenol A (BPA), is thought to be toxic, but limited information is available on the effects of Bisphenol S on ovarian follicles. In our study, we demonstrated the presence of Bisphenol S in the follicular fluid of women at a concentration of 22.4 nM. The effect of such concentrations of Bisphenol S on oocyte maturation and subsequent embryo development is still unknown. Therefore, we focused on the effect of Bisphenol S on in vitro oocyte maturation, fertilization, and embryo development. As a model, we used porcine oocytes, which show many physiological similarities to human oocytes. Oocytes were exposed to Bisphenol S concentrations similar to those detected in female patients in the ART clinic. We found a decreased ability of oocytes to successfully complete meiotic maturation. Mature oocytes showed an increased frequency of meiotic spindle abnormalities and chromosome misalignment. Alarming associations of oocyte Bisphenol S exposure with the occurrence of aneuploidy and changes in the distribution of mitochondria and mitochondrial proteins were demonstrated for the first time. However, the number and quality of blastocysts derived from oocytes that successfully completed meiotic maturation under the influence of Bisphenol S was not affected.
Kefir peptides attenuate atherosclerotic vascular calcification and osteoporosis in atherogenic diet-fed ApoE−/− knockout mice
Authors: Chang Gary Ro-Lin , Cheng Wei-Yuan , Fan Hueng-Chuen , Chen Hsiao-Ling , Lan Ying-Wei , Chen Ming-Shan , Yen Chih-Ching , Chen Chuan-Mu
Published: April 2023

Aims: Vascular calcification (VC) and osteoporosis were previously considered two distinct diseases. However, current understanding indicates that they share common pathogenetic mechanisms. The available medicines for treating VC and osteoporosis are limited. We previously demonstrated that kefir peptides (KPs) alleviated atherosclerosis in high-fat diet (HFD)-induced apolipoprotein E knockout (ApoE−/−) mice. The present study further addressed the preventive effects of KPs on VC and osteoporosis in ApoE−/− mice fed a high-cholesterol atherogenic diet (AD).

Main methods: Seven-week-old ApoE−/− and wild-type C57BL/6 mice were randomly divided into five groups (n = 6). The development of VC and osteoporosis was evaluated after AD feeding for 13 weeks in KP-treated ApoE−/− mice and compared to C57BL/6 and ApoE−/− mice fed a standard chow diet (CD).

Key findings: The results indicated that KP-treated ApoE−/− mice exhibited lower serum total cholesterol, oxidized low-density lipoprotein (ox-LDL), malondialdehyde (MDA) levels, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatine kinase (CK) activities, which suggested that KPs prevented hyperlipidemia and possible damages to the liver and muscle in ApoE−/− mice. KPs reduced serum tumor necrosis factor-α (TNF-α) and the local expression of TNF-α, IL-1β, and macrophage-specific CD68 markers in aortic tissues, which suggested that KPs inhibited inflammatory responses in AD-fed ApoE−/− mice. KPs reduced the deposition of lipid, collagen, and calcium minerals in the aortic roots of AD-fed ApoE−/− mice, which suggested that KPs inhibited the calcific progression of atherosclerotic plaques. KPs exerted osteoprotective effects in AD-fed ApoE−/− mice, which was evidenced by lower levels of the bone resorption marker CTX-1 and higher levels of the bone formation marker P1NP. KPs improved cortical bone mineral density and bone volume and reduced trabecular bone loss in femurs.

Significance: The present data suggested that KPs attenuated VC and osteoporosis by reducing oxidative stress and inflammatory responses in AD-fed ApoE−/− mice. Our findings contribute to the application of KPs as preventive medicines for the treatment of hyperlipidemia-induced vascular and bone degeneration.
Manufacturing flow batteries using advanced 3D printing technology—A review
Authors: Wu Ji , Xu Shaowen
Published: April 2023

In the past decade, electrochemical energy storage systems such as rechargeable batteries have been explored as potential candidates for the large-scale storage of intermittent power sources. Among these, redox flow batteries stand out due to their low fabrication costs, high scalability, and long cycle life. Several redox flow battery pilot plants with MWh capacity have been constructed worldwide, although their commercial profitability is currently under investigation. 3D printing as a burgeoning technology offers unlimited opportunities in the process of optimizing the design, performance, and fabrication cost of redox flow batteries as compared to traditional top-down manufacturing techniques. This review discusses the principles of various redox flow batteries and 3D printing techniques, followed by explaining the advantages, disadvantages, and major factors to consider when using 3D printing in the construction of efficient redox flow batteries. The practical applications of 3D printing for redox flow batteries with different redox chemistries in the past decade are critically summarized, including classical all-vanadium, Zn/Br, and novel competitors. Lastly, a summary is provided along with outlooks that may provide valuable guidance for scientists interested in this research frontier.
Ruthenium nanoclusters modified by zinc species towards enhanced electrochemical hydrogen evolution reaction
Authors: Zhang Hefeng , Qi Shengliang , Zhu Kaixin , Zong Xu
Published: April 2023

Ruthenium (Ru) has been considered a promising electrocatalyst for electrochemical hydrogen evolution reaction (HER) while its performance is limited due to the problems of particle aggregation and competitive adsorption of the reaction intermediates. Herein, we reported the synthesis of a zinc (Zn) modified Ru nanocluster electrocatalyst anchored on multiwalled carbon nanotubes (Ru-Zn/MWCNTs). The Ru-Zn catalysts were found to be highly dispersed on the MWCNTs substrate. Moreover, the Ru-Zn/MWCNTs exhibited low overpotentials of 26 and 119 mV for achieving current intensities of 10 and 100 mA cm−2 under alkaline conditions, respectively, surpassing Ru/MWCNTs with the same Ru loading and the commercial 5 wt% Pt/C (47 and 270 mV). Moreover, the Ru-Zn/MWCNTs showed greatly enhanced stability compared to Ru/MWCNTs with no significant decay after 10,000 cycles of CV sweeps and long-term operation for 90 h. The incorporation of Zn species was found to modify the electronic structure of the Ru active species and thus modulate the adsorption energy of the Had and OHad intermediates, which could be the main reason for the enhanced HER performance. This study provides a strategy to develop efficient and stable electrocatalysts towards the clean energy conversion field.
Transcriptomic analysis of the adaptation to prolonged starvation of the insect-dwelling Trypanosoma cruzi epimastigotes
Authors: Smircich Pablo , Pérez-Díaz Leticia , Hernández Fabricio , Duhagon María Ana , Garat Beatriz
Published: April 2023

Trypanosoma cruzi is a digenetic unicellular parasite that alternates between a blood-sucking insect and a mammalian, host causing Chagas disease or American trypanosomiasis. In the insect gut, the parasite differentiates from the non-replicative trypomastigote forms that arrive upon blood ingestion to the non-infective replicative epimastigote forms. Epimastigotes develop into infective non-replicative metacyclic trypomastigotes in the rectum and are delivered via the feces. In addition to these parasite stages, transitional forms have been reported. The insect-feeding behavior, characterized by few meals of large blood amounts followed by long periods of starvation, impacts the parasite population density and differentiation, increasing the transitional forms while diminishing both epimastigotes and metacyclic trypomastigotes. To understand the molecular changes caused by nutritional restrictions in the insect host, mid-exponentially growing axenic epimastigotes were cultured for more than 30 days without nutrient supplementation (prolonged starvation). We found that the parasite population in the stationary phase maintains a long period characterized by a total RNA content three times smaller than that of exponentially growing epimastigotes and a distinctive transcriptomic profile. Among the transcriptomic changes induced by nutrient restriction, we found differentially expressed genes related to managing protein quality or content, the reported switch from glucose to amino acid consumption, redox challenge, and surface proteins. The contractile vacuole and reservosomes appeared as cellular components enriched when ontology term overrepresentation analysis was carried out, highlighting the roles of these organelles in starving conditions possibly related to their functions in regulating cell volume and osmoregulation as well as metabolic homeostasis. Consistent with the quiescent status derived from nutrient restriction, genes related to DNA metabolism are regulated during the stationary phase. In addition, we observed differentially expressed genes related to the unique parasite mitochondria. Finally, our study identifies gene expression changes that characterize transitional parasite forms enriched by nutrient restriction. The analysis of the here-disclosed regulated genes and metabolic pathways aims to contribute to the understanding of the molecular changes that this unicellular parasite undergoes in the insect vector.
Addressing uncertainty in the safety assurance of machine-learning
Authors: Burton Simon , Herd Benjamin
Published: April 2023

There is increasing interest in the application of machine learning (ML) technologies to safety-critical cyber-physical systems, with the promise of increased levels of autonomy due to their potential for solving complex perception and planning tasks. However, demonstrating the safety of ML is seen as one of the most challenging hurdles to their widespread deployment for such applications. In this paper we explore the factors which make the safety assurance of ML such a challenging task. In particular we address the impact of uncertainty on the confidence in ML safety assurance arguments. We show how this uncertainty is related to complexity in the ML models as well as the inherent complexity of the tasks that they are designed to implement. Based on definitions of uncertainty as well as an exemplary assurance argument structure, we examine typical weaknesses in the argument and how these can be addressed. The analysis combines an understanding of causes of insufficiencies in ML models with a systematic analysis of the types of asserted context, asserted evidence and asserted inference within the assurance argument. This leads to a systematic identification of requirements on the assurance argument structure as well as supporting evidence. We conclude that a combination of qualitative arguments combined with quantitative evidence are required to build a robust argument for safety-related properties of ML functions that is continuously refined to reduce residual and emerging uncertainties in the arguments after the function has been deployed into the target environment.
AI-based radiodiagnosis using chest X-rays: A review
Authors: Akhter Yasmeena , Singh Richa , Vatsa Mayank
Published: April 2023

Chest Radiograph or Chest X-ray (CXR) is a common, fast, non-invasive, relatively cheap radiological examination method in medical sciences. CXRs can aid in diagnosing many lung ailments such as Pneumonia, Tuberculosis, Pneumoconiosis, COVID-19, and lung cancer. Apart from other radiological examinations, every year, 2 billion CXRs are performed worldwide. However, the availability of the workforce to handle this amount of workload in hospitals is cumbersome, particularly in developing and low-income nations. Recent advances in AI, particularly in computer vision, have drawn attention to solving challenging medical image analysis problems. Healthcare is one of the areas where AI/ML-based assistive screening/diagnostic aid can play a crucial part in social welfare. However, it faces multiple challenges, such as small sample space, data privacy, poor quality samples, adversarial attacks and most importantly, the model interpretability for reliability on machine intelligence. This paper provides a structured review of the CXR-based analysis for different tasks, lung diseases and, in particular, the challenges faced by AI/ML-based systems for diagnosis. Further, we provide an overview of existing datasets, evaluation metrics for different[][15mm][0mm]Q5 tasks and patents issued. We also present key challenges and open problems in this research domain.
Combined direct-sun ultraviolet and infrared spectroscopies at Popocatépetl volcano (Mexico)
Authors: Taquet N. , Rivera Cárdenas C. , Stremme W. , Boulesteix T. , Bezanilla A. , Grutter M. , García O. , Hase F. , Blumenstock T.
Published: April 2023

Volcanic plume composition is strongly influenced by both changes in magmatic systems and plume-atmosphere interactions. Understanding the degassing mechanisms controlling the type of volcanic activity implies deciphering the contributions of magmatic gases reaching the surface and their posterior chemical transformations in contact with the atmosphere. Remote sensing techniques based on direct solar absorption spectroscopy provide valuable information about most of the emitted magmatic gases but also on gas species formed and converted within the plumes. In this study, we explore the procedures, performances and benefits of combining two direct solar absorption techniques, high resolution Fourier Transform Infrared Spectroscopy (FTIR) and Ultraviolet Differential Optical Absorption Spectroscopy (UV-DOAS), to observe the composition changes in the Popocatépetl’s plume with high temporal resolution. The SO2 vertical columns obtained from three instruments (DOAS, high resolution FTIR and Pandora) were found similar (median difference <12%) after their intercalibration. We combined them to determine with high temporal resolution the different hydrogen halide and halogen species to sulfur ratios (HF/SO2, BrO/SO2, HCl/SO2, SiF4/SO2, detection limit of HBr/SO2) and HCl/BrO in the Popocatépetl’s plume over a 2.5-years period (2017 to mid-2019). BrO/SO2, BrO/HCl, and HCl/SO2 ratios were found in the range of (0.63 ± 0.06 to 1.14 ± 0.20) × 10−4, (2.6 ± 0.5 to 6.9 ± 2.6) × 10−4, and 0.08 ± 0.01 to 0.21 ± 0.01 respectively, while the SiF4/SO2 and HF/SO2 ratios were found fairly constant at (1.56 ± 0.25) × 10−3 and 0.049 ± 0.001. We especially focused on the full growth/destruction cycle of the most voluminous lava dome of the period that took place between February and April 2019. A decrease of the HCl/SO2 ratio was observed with the decrease of the extrusive activity. Furthermore, the short-term variability of BrO/SO2 is measured for the first time at Popocatépetl volcano together with HCl/SO2, revealing different behaviors with respect to the volcanic activity. More generally, providing such temporally resolved and near-real-time time series of both primary and secondary volcanic gaseous species is critical for the management of volcanic emergencies, as well as for the understanding of the volcanic degassing processes and their impact on the atmospheric chemistry.
Mantle structure beneath the Macaronesian volcanic islands (Cape Verde, Canaries, Madeira and Azores): A review and future directions
Authors: Civiero Chiara , Carvalho Joana , Silveira Graça
Published: April 2023

Ocean island volcanism provides a unique window into the nature of mantle composition, dynamics and evolution. The four Macaronesian archipelagos–Cape Verde, the Canaries, Madeira and the Azores–are the main magmatic systems of the Central-East Atlantic Ocean with volcanic activity that in some islands poses significant risk for the population. The recent development of regional seismic networks in these settings has provided an important step forward in mapping the underlying mantle. However, difficulties in resolving the small-scale structure with geophysical techniques persist leading to discrepancies in the interpretation of the mechanisms responsible for volcanism. Here we review results from a number of studies on the seismic mantle structure beneath the Macaronesian archipelagos including seismic tomography, receiver functions, precursors and shear-wave splitting. Several regional models show low-velocity features in the asthenosphere below the islands, a relatively thinned transition zone and complex anisotropic patterns and attribute the volcanism to mantle plumes. This inference is supported by whole-mantle tomography models, which find broad low-velocity anomalies in the lower mantle below the Central-East Atlantic. Other models call for alternative mechanisms associated with shallower mantle upwellings and purely plate tectonism. Thus, there is still no generally accepted mechanism that explains volcanism in the Macaronesia region. Future research requires improvements in the resolving power of seismic techniques to better illuminate the velocity structure at a much higher resolution than the currently achieved and ultimately define the mechanisms controlling the ocean island volcanism.
Towards fine-grained object-level damage assessment during disasters
Authors: Sadiq Rizwan , Akhtar Zainab , Peterson Steve , Keegan Katelyn , El-Sakka Aya , Imran Muhammad , Ofli Ferda
Published: April 2023

Social media can play an important role in current-day disaster management. Images shared from the disaster areas may include objects relevant to operations. If these objects are identified correctly, they can offer a preliminary damage assessment report and situational awareness for response and recovery. This research is carried out in collaboration with a Community Emergency Response Team (CERT) to understand the state-of-the-art object detection model’s capability to detect objects in multi-hazard disaster scenes posted on social media. Specifically, 946 images were collected from social media during major earthquake and hurricane disasters. All the images were inspected by trained volunteers from CERT and, 4,843 objects were analyzed for applicability to specific functions in disaster operations. The feedback provided by the volunteers helped determine the existing model’s key strengths and weaknesses and led to the development of a disaster object taxonomy relevant to specific disaster support functions. Lastly, using a subset of classes from the taxonomy, an instance segmentation dataset is developed to fine-tune state-of-the-art models for damage object detection. Empirical analysis demonstrates promising applications of transfer learning for disaster object detection.
Hate speech in adolescents: A binational study on prevalence and demographic differences
Authors: Castellanos Melisa , Wettstein Alexander , Wachs Sebastian , Kansok-Dusche Julia , Ballaschk Cindy , Krause Norman , Bilz Ludwig
Published: April 2023

Hate speech, or intentional derogatory expressions about people based on assigned group characteristics, has been studied primarily in online contexts. Less is known about the occurrence of this phenomenon in schools. As it has negative consequences for victims, perpetrators, and those who witness it, it is crucial to characterize the occurrence of offline (i.e., in the school) and online hate speech to describe similarities and differences between these two socialization contexts. The present study aimed to investigate the prevalence of hate speech witnessing, victimization, and perpetration, in a sample of 3,620 7–9th graders (51% self-identified as female) from 42 schools in Germany and Switzerland. We found that 67% of the students witnessed hate speech in their school, and 65% witnessed online hate speech at least once in the past 12 months. Approximately 21% of the students self-identified as offline perpetrators and 33% as offline victims, whereas these percentages were lower for online hate speech (13 and 20%, respectively). In both settings, skin color and origin were the most common group references for hate speech (50% offline and 63% online). Offline hate speech mainly came from classmates (88%), unknown sources (e.g., graffiti; 19%), or teachers (12%), whereas online hate speech mostly came from unknown persons (77%). The most frequent forms of offline hate speech were offensive jokes (94%) and the spread of lies and rumors about the members of a specific social group (84%). Significant differences by country, gender, and migration background were observed. Girls reported more offline victimization experiences, less perpetration, and a greater frequency of witnessing hate speech. This difference was larger in magnitude in the online setting. Students in Switzerland reported being exposed to hate speech more often than students in Germany. Students with a migration background reported higher hate speech victimization based on skin color and origin than students without a migration background. The high prevalence of hate speech highlights the need for school-based prevention programs. Our findings are discussed in terms of the practical implications.
Social–emotional skills of teachers: Mapping the content space and defining taxonomy requirements
Authors: Scheirlinckx Joyce , Van Raemdonck Lisa , Abrahams Loes , Teixeira Karen Cristine , Alves Gisele , Primi Ricardo , John Oliver P. , De Fruyt Filip
Published: April 2023

Many studies acknowledge the importance of social–emotional skills1 (SEMS) to function in contemporary society. Understanding these skills and how these develop presents several conceptual and methodological challenges, with emerging consensus on what kind of skills should be fostered in education. Less work, however, has considered SEMS specifically for teachers, despite the fact that they are presumed to be the primary agents to affect SEMS of students. The current article examines different conceptualizations of teacher SEMS and provides a first attempt at defining and structuring this broad conceptual space. We further propose a conceptual teacher SEMS framework that may serve as a basis of an empirical one to guide future educational research and policy-making.
Influence of maternal socioeconomic deprivation and living environment on newborn bloodspot 25-hydroxyvitamin D levels
Authors: Högler Wolfgang , Tischlinger Katharina , Fraser William D. , Tang Jonathan C. Y. , Uday Suma
Published: April 2023

Objectives

Vitamin D deficiency in neonates can have life-threatening consequences, hence the knowledge of risk factors is essential. This study aimed to explore the effect of maternal socioeconomic status (SES) on newborn 25-hydroxyvitamin D (25OHD) concentrations.

Design

Over two 1-week periods (winter and summer of 2019), 3000 newborn heel prick dried blood spots (DBS) and additional data of newborns, from a regional newborn screening laboratory (52° N) in the West Midlands, UK, were gathered. Post code was replaced with lower layer super output area (LSOA). Index of Multiple Deprivation (IMD) quintiles for the corresponding LSOA was used to assess SES [quintile one (Q1): most deprived 20%, quintile five (Q5): least deprived 20%]. Each of the seven domains of deprivation were examined (income, employment, education, health, barriers to housing and services, crime and living environment). 25OHD was measured on 6mm sub-punch from DBS using quantitative liquid chromatography tandem mass spectrometry and equivalent plasma values were derived.

Results

In total 2999 (1500 summer-born, 1499 winter-born) newborn DBS (1580 males) were analysed. Summer-born newborns had significantly higher 25OHD (IQR) concentrations [49.2 (34.3; 64.8) nmol/l] than winter-born newborns [29.1 (19.8; 40.6) nmol/l, p<0.001].25OHD levels varied significantly between the different IMD quintiles in the whole (p<0.001) and summer-born cohort (p<0.001), but not in the winter-born cohort (p=0.26), whereby Q1 had the lowest 25OHD concentrations. Among the domains of deprivation, living environment had a significant influence on 25OHD levels (β=0.07, p=0.002). In this subdomain, 25OHD levels varied significantly between quintiles in the whole (p<0.001) and summer-born cohort (mean 25OHD Q1 46.45 nmol/l, Q5 54.54 nmol/l; p<0.001) but not in the winter-born cohort (mean 25OHD Q1 31.57 nmol/l, Q5 31.72 nmol/l; p=0.16). In a regression model, living environment was still significant (p=0.018), albeit less than season of birth and ethnicity.

Conclusion

Among the seven domains of deprivation, maternal living environment had the greatest effect on newborn 25OHD levels. Whilst improved living environment positively influenced vitamin D status in the summer-born babies, winter-born had low 25OHD levels irrespective of the environment. Strategies such as enhanced supplementation and food fortification with vitamin D should be considered to overcome the non-modifiable main risk factors for vitamin D deficiency.
Carbon resilience calibration as a carbon management technology
Authors: Talebian Seyedeh Hosna , Jahanbakhsh Amir , Maroto-Valer M. Mercedes
Published: April 2023

In the path to a net-zero carbon and energy transition from fossil fuel, the world is facing a dilemma of growing global energy demand and required actions on climate-related risks. While over 80% of the current global energy needs are supplied by fossil fuels, the number of carbon capture, utilization and storage (CCUS) projects is limited in this sector. There is a huge gap between the scale and distribution of ongoing CCUS projects and the carbon intensity (CI) of energy-intensive industries. Furthermore, the climate impact of growing reliance on unconventional resources (Tar sands and shales) as well as the depletion of conventional resources poses challenges to the oil and gas sector to meet energy demand, while limiting their greenhouse gas (GHG) emissions. On the other hand, the economic viability of CCUS projects is highly sensitive to carbon credits policies, which are not yet fully integrated in a way to fill the current gap in the number, scale and distribution of these projects. Moreover, there is limited consistency between the allocated decarbonization funds and the anticipated economic growth of fossil fuel economies to promote wide-scale global resilience to carbon exposure. Therefore, it is essential to take climate-related risks, including socioeconomic impacts, into consideration for the decision-making process of companies and governments to embrace low-carbon energy. The focus of this article is on carbon resilience calibration and emissions scenario analysis in investment decisions to realize decarbonization goals through balancing short-term actions with long-term energy transition plans. The challenges and prospects of the application of CCUS technologies as an industrial decarbonization approach are discussed. Carbon footprint (CFP) observing, factoring and reporting workflows for correlating carbon exposure and resilience as part of climate assessment are introduced. Moreover, the main elements of carbon resilience scenarios are analyzed to fill the gap between the current industrial activities and decarbonization plans and to avoid making decisions solely based on economic aspects. Finally, we propose a workflow for carbon resilience calibration and a cash flow model for a sample CCUS project in the upstream oil and gas industry.
Evaluation and optimization of a novel cascade refrigeration system driven by waste heat
Authors: Zheng Weibo , Zhou Hongbin , Xiao Zhiyong , Sun Dong , Song Changshan , Zhang Xiaohan , Li Jianbo
Published: April 2023

Direct discharge of waste heat from internal combustion engines (ICEs) is unfavorable for the efficient and clean fuel utilization. Here, a novel combined absorption-compression cascade refrigeration cycle is proposed to efficiently capture low-grade waste heat and supply cooling capacity for food freezing in vessels or refrigerated trucks. The intention of this work lies in: i) Comprehensively evaluating the performances of the proposed system; ii) Gaining the optimal operating conditions of the system. Aimed that, analysis models of energy, exergy, economy, and environment are set up to evaluate the sweeping performances. Further, multi-objective optimization is introduced to obtain the optimal operating parameters including evaporation and condensation temperature of the low-temperature stage, generation temperature and condensation temperature of the high-temperature stage, and cascade temperature differences. By applying multi-objective optimization, the coefficient of performance and exergy efficiency of the system are elevated from 1.283 to 1.547, and 0.222 to 0.246, respectively, the discharge amount of carbon dioxide are reduced from 71.40 to 59.57 tons year−1, and annual total cost are decreased from 16,028 to 15,055 $ year−1 compared to initial operating conditions.
Employing the agricultural classification and estimation service (ACES) for mapping smallholder rice farms in Bhutan
Authors: Mayer Timothy , Bhandari Biplov , Martínez Filoteo Gómez , Walker Kaitlin , Jiménez Stephanie A. , Kruskopf Meryl , Maganini Micky , Phalke Aparna , Wangchen Tshering , Phuntsho Loday , Dorji Nidup , Tshering Changa , Dorji Wangdrak
Published: April 2023

Creating annual crop type maps for enabling improved food security decision making has remained a challenge in Bhutan. This is in part due to the level of effort required for data collection, technical model development, and reliability of an on-the-ground application. Through focusing on advancing Science, Technology, Engineering, and Mathematics (STEM) in Bhutan, an effort to co-develop a geospatial application known as the Agricultural Classification and Estimation Service (ACES) was created. This paper focuses on the co-development of an Earth observation informed climate smart crop type framework which incorporates both modeling and training sample collection. The ACES web application and subsequent ACES modeling software package enables stakeholders to more readily use Earth observation into their decision making process. Additionally, this paper offers a transparent and replicable approach for addressing and combating remote sensing limitations due to topography and cloud cover, a common problem in Bhutan. Lastly, this approach resulted in a Random Forest “LTE 555” model, from a set of 3,600 possible models, with an overall test Accuracy of 85% and F-1 Score of .88 for 2020. The model was independently validated resulting in an independent accuracy of 83% and F-1 Score of .45 for 2020. The insight into the model perturbation via hyperparameter tuning and input features is key for future practitioners.
Novel hypoxia-related gene signature for predicting prognoses that correlate with the tumor immune microenvironment in NSCLC
Authors: Li Zhaojin , Cui Yu , Zhang Shupeng , Xu Jie , Shao Jianping , Chen Hekai , Chen Jingzhao , Wang Shun , Zeng Meizhai , Zhang Hao , Lu Siqian , Qian Zhi Rong , Xing Guoqiang
Published: April 2023

Background: Intratumoral hypoxia is widely associated with the development of malignancy, treatment resistance, and worse prognoses. The global influence of hypoxia-related genes (HRGs) on prognostic significance, tumor microenvironment characteristics, and therapeutic response is unclear in patients with non-small cell lung cancer (NSCLC).

Method: RNA-seq and clinical data for NSCLC patients were derived from The Cancer Genome Atlas (TCGA) database, and a group of HRGs was obtained from the MSigDB. The differentially expressed HRGs were determined using the limma package; prognostic HRGs were identified via univariate Cox regression. Using the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression, an optimized prognostic model consisting of nine HRGs was constructed. The prognostic model’s capacity was evaluated by Kaplan‒Meier survival curve analysis and receiver operating characteristic (ROC) curve analysis in the TCGA (training set) and GEO (validation set) cohorts. Moreover, a potential biological pathway and immune infiltration differences were explained.

Results: A prognostic model containing nine HRGs (STC2, ALDOA, MIF, LDHA, EXT1, PGM2, ENO3, INHA, and RORA) was developed. NSCLC patients were separated into two risk categories according to the risk score generated by the hypoxia model. The model-based risk score had better predictive power than the clinicopathological method. Patients in the high-risk category had poor recurrence-free survival in the TCGA (HR: 1.426; 95% CI: 0.997–2.042; p = 0.046) and GEO (HR: 2.4; 95% CI: 1.7–3.2; p < 0.0001) cohorts. The overall survival of the high-risk category was also inferior to that of the low-risk category in the TCGA (HR: 1.8; 95% CI: 1.5–2.2; p < 0.0001) and GEO (HR: 1.8; 95% CI: 1.4–2.3; p < 0.0001) cohorts. Additionally, we discovered a notable distinction in the enrichment of immune-related pathways, immune cell abundance, and immune checkpoint gene expression between the two subcategories.

Conclusion: The proposed 9-HRG signature is a promising indicator for predicting NSCLC patient prognosis and may be potentially applicable in checkpoint therapy efficiency prediction.
Integrated analysis of circulating cell free nucleic acids for cancer genotyping and immune phenotyping of tumor microenvironment
Authors: Chaddha Muskan , Rai Hemlata , Gupta Ritu , Thakral Deepshi
Published: April 2023

The circulating cell-free nucleic acids (ccfNAs) consist of a heterogenous cocktail of both single (ssNA) and double-stranded (dsNA) nucleic acids. These ccfNAs are secreted into the blood circulation by both healthy and malignant cells via various mechanisms including apoptosis, necrosis, and active secretion. The major source of ccfNAs are the cells of hematopoietic system under healthy conditions. These ccfNAs include fragmented circulating cell free DNA (ccfDNA), coding or messenger RNA (mRNA), long non-coding RNA (lncRNA), microRNA (miRNA), and mitochondrial DNA/RNA (mtDNA and mtRNA), that serve as prospective biomarkers in assessment of various clinical conditions. For, e.g., free fetal DNA and RNA migrate into the maternal plasma, whereas circulating tumor DNA (ctDNA) has clinical relevance in diagnostic, prognostic, therapeutic targeting, and disease progression monitoring to improve precision medicine in cancer. The epigenetic modifications of ccfDNA as well as circulating cell-free RNA (ccfRNA) such as miRNA and lncRNA show disease-related variations and hold potential as epigenetic biomarkers. The messenger RNA present in the circulation or the circulating cell free mRNA (ccf-mRNA) and long non-coding RNA (ccf-lncRNA) have gradually become substantial in liquid biopsy by acting as effective biomarkers to assess various aspects of disease diagnosis and prognosis. Conversely, the simultaneous characterization of coding and non-coding RNAs in human biofluids still poses a significant hurdle. Moreover, a comprehensive assessment of ccfRNA that may reflect the tumor microenvironment is being explored. In this review, we focus on the novel approaches for exploring ccfDNA and ccfRNAs, specifically ccf-mRNA as biomarkers in clinical diagnosis and prognosis of cancer. Integrating the detection of circulating tumor DNA (ctDNA) for cancer genotyping in conjunction with ccfRNA both quantitatively and qualitatively, may potentially hold immense promise towards precision medicine. The current challenges and future directions in deciphering the complexity of cancer networks based on the dynamic state of ccfNAs will be discussed.
OncoRTT: Predicting novel oncology-related therapeutic targets using BERT embeddings and omics features
Authors: Thafar Maha A. , Albaradei Somayah , Uludag Mahmut , Alshahrani Mona , Gojobori Takashi , Essack Magbubah , Gao Xin
Published: April 2023

Late-stage drug development failures are usually a consequence of ineffective targets. Thus, proper target identification is needed, which may be possible using computational approaches. The reason being, effective targets have disease-relevant biological functions, and omics data unveil the proteins involved in these functions. Also, properties that favor the existence of binding between drug and target are deducible from the protein’s amino acid sequence. In this work, we developed OncoRTT, a deep learning (DL)-based method for predicting novel therapeutic targets. OncoRTT is designed to reduce suboptimal target selection by identifying novel targets based on features of known effective targets using DL approaches. First, we created the “OncologyTT” datasets, which include genes/proteins associated with ten prevalent cancer types. Then, we generated three sets of features for all genes: omics features, the proteins’ amino-acid sequence BERT embeddings, and the integrated features to train and test the DL classifiers separately. The models achieved high prediction performances in terms of area under the curve (AUC), i.e., AUC greater than 0.88 for all cancer types, with a maximum of 0.95 for leukemia. Also, OncoRTT outperformed the state-of-the-art method using their data in five out of seven cancer types commonly assessed by both methods. Furthermore, OncoRTT predicts novel therapeutic targets using new test data related to the seven cancer types. We further corroborated these results with other validation evidence using the Open Targets Platform and a case study focused on the top-10 predicted therapeutic targets for lung cancer.
RETRACTED: Bioinformatics analysis based on crucial genes of endothelial cells in rheumatoid
Authors: Zhou Xing , Wu Lidong
Published: April 2023

Objectives: Synovial neovascularization is an early and remarkable event that promotes the development of rheumatoid arthritis (RA) synovial hyperplasia. This study aimed to find potential diagnostic markers and molecular therapeutic targets for RA at the mRNA molecular level.

Method: We download the expression profile dataset GSE46687 from the gene expression ontology (GEO) microarray, and used R software to screen out the differentially expressed genes between the normal group and the disease group. Then we performed functional enrichment analysis, used the STRING database to construct a protein-protein interaction (PPI) network, and identify candidate crucial genes, infiltration of the immune cells and targeted molecular drug.

Results: Rheumatoid arthritis datasets included 113 differentially expressed genes (DEGs) including 104 upregulated and 9 downregulated DEGs. The enrichment analysis of genes shows that the differential genes are mainly enriched in condensed chromosomes, ribosomal subunits, and oxidative phosphorylation. Through PPI network analysis, seven crucial genes were identified: RPS13, RPL34, RPS29, RPL35, SEC61G, RPL39L, and RPL37A. Finally, we find the potential compound drug for RA.

Conclusion: Through this method, the pathogenesis of RA endothelial cells was further explained. It provided new therapeutic targets, but the relationship between these genes and RA needs further research to be validated in the future.