bluuebunny/crossref_metadata_2025 huggingface dataset:
The Behavioral and Mental Health Benefits of Speaking the Heritage Language within Immigrant Families: The Moderating Role of Family Relations
Authors: Kilpi-Jakonen Elina , Kwon Hye Won
Published: June 2023

Understanding the development of behavioral and mental health issues among adolescents, particularly those from immigrant families, is a key area of concern. Many prior studies have focused on the role of societal (country-of-destination) language skills, but we know less about the role played by the use of the heritage language in families. We examined this latter relationship with a focus on changes in heritage language use and internalizing and externalizing problems, and how family relations moderate this relationship. We used the first two waves (2010/2011 and 2011/2012) of the Children of Immigrants Longitudinal Survey in Four European Countries (CILS4EU) data collected from Germany (n = 1614; Mage = 14.8 years, 50% female), the Netherlands (n = 1203; Mage = 14.7 years, 54% female), Sweden (n = 1794; Mage = 14.2 years, 53% female), and England (n = 1359; Mage = 14.6 years, 50% female). Our results suggest that increased use of heritage language is associated with fewer externalizing problems only in families with greater family cohesion and parental warmth (in Germany and the U.K.) and with fewer internalizing problems only in families with higher parental monitoring (in the Netherlands and Sweden). Good family relations are thus an important precondition for increased heritage language use to lead to improved behavioral and mental health for children of immigrants.
VTnet+Handcrafted based approach for food cuisines classification
Authors: Nijhawan Rahul , Sinha Garima , Batra Ashita , Kumar Manoj , Sharma Himanshu
Published: June 2023

In this paper, we propose a novel hybrid transformer architecture for food cuisine detection and classification. The work carried out within this paper develops a combination of Vision Transformer ensemble architecture with hand-crafted features, thereby making a hybrid Vision Transformer food recognition system. Recently, Vision transformers have been introduced as an alternative means of classification to convolutional neural networks. It performs pattern detection and classification without convolutions and interprets an image as a sequence of patches. The combination of Vision Transformer and hand-crafted features like GIST, HoG (Histogram of Oriented Gradients), and LBP (Local Binary Pattern) were employed on the dataset. The dataset was specifically created (for this work) from the public logging system. It consisted of 13 food categories with 400 images of Indian food items like Ghevar, Idli, Dosa, and much more. It helped to capture a variety of images from every domain and culture. This work made use of the common and readily available food items, which can further be increased by adding on the specialties (dishes) from different regions. Various experiments were performed on CNN with various classifiers like Random forest, and SVM. Further, we compared our proposed approach with several ensembles of CNN architectures. The experiments proved that our proposed approach outperformed the state-of-the-art ensemble CNN architectures for detecting food cuisines. The proposed hybrid approach achieved an accuracy of 94.63%, sensitivity 84.42%, specificity 95.23%, and kappa coefficient 0.93, which was the best amongst all approaches.
Thermoresponsive Gel-loaded Oxcarbazepine Nanosystems for Nose- To-Brain Delivery: Enhanced Antiepileptic Activity in Rats
Authors: Abou-Taleb Basant A. , El-Ganainy Samar O.
Published: June 2023

Background

Oxcarbazepine (OXC) is a frequently prescribed antiepileptic drug for managing focal and generalized seizures. Its therapeutic benefits are limited by its dose-dependent side effects. Nose-to-brain delivery is a novel route for improving the efficacy of antiepileptics. Drug encapsulation in mucoadhesive nanoparticles offers even more advantages for the nasal route.

Objective

The study aimed to develop oxcarbazepine-loaded chitosan nanoparticles (OXC-NP) added to a mucoadhesive thermo-reversible gel for intranasal delivery and enhancement of antiepileptic activity.

Methods

The formulation was optimized based on entrapment efficiency, polydispersity index, particle size, zeta potential, and in vitro release analysis. The therapeutic efficacy of OXC-NP was assessed in an epileptic rat model and compared to intranasal OXC and oral OXC.

Results

The optimized OXC-NPs with chitosan exhibited particle size, zeta potential, and entrapment efficiency of 189 nm, + 31.4 mV ± 2.5 and 97.6% ± 0.14, respectively. The release of OXC was prolonged, reaching 47.1% after 6 h and 55% after 24 h. Enhanced antiepileptic activity of OXC-NP was manifested as decreased seizure score and prolonged survival. Halting of hippocampal TNF-α and IL-6 together with upregulated IL-10 could explain its anti-inflammatory mechanisms.

Conclusions

Intranasal OXC-NP-loaded in situ gel represents a promising formulation for enhanced antiepileptic potential achieved at low drug concentrations.
How Can We Measure Alcohol Outlet Density Around Schools? A Comparison Between Two Buffer-Based Methods
Authors: Martín-Turrero Irene , Sureda Xisca , Escobar Francisco , Bilal Usama , Berasaluce Maitane , Valiente Roberto
Published: June 2023

Measuring the density of alcohol outlets around schools is a critical step towards understanding the drivers of drinking among adolescents. Different methodologies have been used in the literature for this purpose, but the implications of using one methodology or another have not been clearly assessed. Our aim was to compare different methods to measure alcohol outlet density and highlight under which characteristics of the environment might be best using each approach. We used Geographic Information Systems to geolocate schools (n = 576) and alcohol outlets (n = 21,732) in Madrid. We defined the density of alcohol outlets as the number of establishments within an area of 400 m around schools measured using two buffering methods: crow flies’ and street network distances. We evaluated the agreement between both methods visually and through regression models, including street connectivity, population density, and density of recreational venues as predictors of disagreement. The density of alcohol outlets around schools was higher using crow flies’ distances compared to street network distances. The differences between methodologies were wider in areas of higher density of outlets, especially in the downtown areas, where there are higher population density and street connectivity. Our results suggest that the spatial characteristics and morphology of the study area (e.g., street connectivity and population density) should be considered when deciding the methodology to be used to measure alcohol outlet density. Future studies should explore the implications of different exposure measures in their association with drinking prevalence and consumption patterns among different geographical contexts.
Chest CT features of COVID-19 in vaccinated versus unvaccinated patients: use of CT severity score and outcome analysis
Authors: Masci Giorgio Maria , Izzo Antonella , Bonito Giacomo , Marchitelli Livia , Guiducci Elisa , Ciaglia Simone , Lucchese Sonia , Corso Laura , Valenti Alessandra , Malzone Lucia , Pasculli Patrizia , Ciardi Maria Rosa , La Torre Giuseppe , Galardo Gioacchino , Alessandri Francesco , Vullo Francesco , Manganaro Lucia , Iafrate Franco , Catalano Carlo , Ricci Paolo
Published: June 2023

Objectives

To evaluate the impact of vaccination on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moreover on coronavirus disease 2019 (COVID-19) pneumonia, by assessing the extent of lung disease using the CT severity score (CTSS).

Methods

Between September 2021 and February 2022, SARS-CoV-2 positive patients who underwent chest CT were retrospectively enrolled. Anamnestic and clinical data, including vaccination status, were obtained. All CT scans were evaluated by two readers using the CTSS, based on a 25-point scale. Univariate and multivariate logistic regression analyses were performed to evaluate the associations between CTSS and clinical or demographic variables. An outcome analysis was used to differentiate clinical outcome between vaccinated and unvaccinated patients.

Results

Of the 1040 patients (537 males, 503 females; median age 58 years), 678 (65.2%) were vaccinated and 362 (34.8%) unvaccinated. Vaccinated patients showed significantly lower CTSS compared to unvaccinated patients (p < 0.001), also when patients without lung involvement (CTSS = 0) were excluded (p < 0.001). Older age, male gender and lower number of doses administered were associated with higher CTSS, however, in the multivariate analysis, vaccination status resulted to be the variable with the strongest association with CTSS. Clinical outcomes were significantly worse in unvaccinated patients, including higher number of ICU admissions and higher mortality rates.

Conclusions

Lung involvement during COVID-19 was significantly less severe in vaccinated patients compared with unvaccinated patients, who also showed worse clinical outcomes. Vaccination status was the strongest variable associated to the severity of COVID-related, more than age, gender, and number of doses administered.
Reasonable Doubt, Robust Evidential Probability and the Unknown
Authors: Jellema Hylke
Published: June 2023

Most legal evidence scholars agree that proof of guilt beyond a reasonable doubt requires the belief that the defendant probably committed the alleged acts. However, they also agree that this is not a sufficient condition, as this belief may be unreasonable. I focus on two popular proposals for additional conditions: (i) that the degree of belief should be robust and (ii) that it should be reasonable given the available evidence (should be an evidential probability). Both criteria face difficulties regarding their meaning and utility. I propose an interpretation which overcomes these difficulties and which combines the two conditions into a single criterion on which both conditions are about the possibility of overlooked, exculpatory information. Proof of guilt beyond a reasonable doubt requires that we are sufficiently certain that we did not miss such information for the sake of achieving accurate beliefs and a just error distribution. How certain we can be that we did not miss anything relevant depends on our higher-order evidence. One important type of higher-order evidence is whether the hypotheses under consideration are sufficiently detailed. This point leads to a novel way of combining the Bayesian and explanation-based accounts of rational legal proof.
A new workflow of the on-line 1.5-T MR-guided adaptive radiation therapy
Authors: Uno Takashi , Tsuneda Masato , Abe Kota , Fujita Yukio , Harada Rintaro , Saito Makoto , Kanazawa Aki , Kodate Asuka , Abe Yukinao , Ikeda Yohei , Nemoto Miho Watanabe , Yokota Hajime
Published: June 2023

Purpose

The aim of this study was to develop a new workflow for 1.5-T magnetic resonance (MR)-guided on-line adaptive radiation therapy (MRgART) and assess its feasibility in achieving dose constraints.

Materials and methods

We retrospectively evaluated the clinical data of patients who underwent on-line adaptive radiation therapy using a 1.5-T MR linear accelerator (MR-Linac). The workflow in MRgART was established by reviewing the disease site, number of fractions, and re-planning procedures. Five cases of prostate cancer were selected to evaluate the feasibility of the new workflow with respect to achieving dose constraints.

Results

Between December 2021 and September 2022, 50 consecutive patients underwent MRgART using a 1.5-T MR-Linac. Of these, 20 had prostate cancer, 10 had hepatocellular carcinoma, 6 had pancreatic cancer, 5 had lymph node oligo-metastasis, 3 had renal cancer, 3 had bone metastasis, 2 had liver metastasis from colon cancer, and 1 had a mediastinal tumor. Among a total of 247 fractions, 235 (95%) were adapt-to-shape (ATS)-based re-planning. The median ATS re-planning time in all 50 cases was 17 min. In the feasibility study, all dose constraint sets were met in all 5 patients by ATS re-planning. Conversely, a total of 14 dose constraints in 5 patients could not be achieved by virtual plan without using adaptive re-planning. These dose constraints included the minimum dose received by the highest irradiated volume of 1 cc in the planning target volume and the maximum dose of the rectal/bladder wall.

Conclusion

A new workflow of 1.5-T MRgART was established and found to be feasible. Our evaluation of the dose constraint achievement demonstrated the effectiveness of the workflow.
Navigating ecological security research over the last 30 years: a scoping review
Authors: Zhu Benhui , Hashimoto Shizuka , Cushman Samuel A.
Published: June 2023

Intensification of human activities is pushing our use of ecosystems beyond thresholds of resiliency. Given the accelerating global crisis of ecological sustainability, there has been enormous growth in research related to ecological security. However, differences in opinions on ecological security have hindered understanding and effective applications of this concept. To understand the development of research on ecological security, we reviewed its achievements and limitations over the past 30 years from three dimensions: definition, evaluation method, and approach to identify measures to improve the ecological security level. We used the Web of Science search engine to retrieve peer-reviewed journal articles published from 1990 to 2021 containing the keywords “ecological security” or “ecological safety”. There are three main ethical perspectives among the definitions of ecological security: nature-centric, human-centric, and eclectic; the human-centric view, which focuses on human well-being, is predominant in the field. Most studies employed the following three evaluation methods: quantitative comparison, composite indicators, and spatial analysis. However, the results of ecological security analyses were difficult to compare. Three main approaches (causality, correlation, and landscape) were used to identify the drivers of ecological security and propose measures for ensuring or improving ecological security. Owing to the complexity and heterogeneity of ecosystems, universally effective measures to ensure ecological security rarely exist. For the definition and evaluation of ecological security, a broader, non-anthropocentric perspective that incorporates the intrinsic value of non-humans in the context of cost–benefit, security–efficiency evaluations is essential. When proposing evaluation methods, the comparability of evaluation results should be given priority. To improve ecological security level, identifying the key drivers and/or potential optimal patterns of ecological security may be a promising solution.
Making sense of (un)sustainable food: creation of sharable narratives in citizen-participating farming
Authors: Watabe Atsushi
Published: June 2023

There has been broad recognition that current food systems need to go through a process of transformation and transition. In the similar way that other areas have transitioned to be more sustainable, the transition process for food systems has some issues related to justice in terms of achieving more sustainable and inclusive food production, distribution and consumption. Acknowledging the importance of these issues, this article aims to understand how knowledge about desired changes is produced and shared among people engaged in activities to transform food production and consumption. To this end, it analyses the short narratives of urban citizens in Japan engaged in participatory farming, adopting the concepts focusing on the contrasts embedded in the short stories, learning from risk studies. The farmer, volunteer staff members and urban citizens collaborate to grow rice using traditional techniques. Their narratives reveal some contrasts in how they used to engage with food, farms and the local environment, and their engagement now. Furthermore, it was observed that these citizens reconfirm the importance of knowledge learned through actual work on the farm and the different roles played by the farmer, volunteers and local participants in creating and passing on knowledge. In such ways, people’s interaction leads to the creation of shared meanings of “appropriateness” in terms of existing and emerging food-related practices. This matter of meaning-making for “appropriateness” is often overlooked in the discussion of the justice in food systems’ transitions.
Prostitution und Kriminologie
Authors: Steffan Christian , Weinand Marisa , Brettel Hauke
Published: June 2023

Im Verhältnis von Kriminologie und Prostitution besteht schon mit Blick auf die Gefahr von Stigmatisierungen Klärungsbedarf. Zentrale Bedeutung hat dabei die Frage, ob das Anbieten oder die Inanspruchnahme von sexuellen Handlungen gegen Entgelt sowie damit im Zusammenhang stehende Verhaltensweisen als „Verbrechen“ anzusehen sind. Aber auch die aktuelle Handhabung der Prostitution durch die Rechtsordnung oder der Umgang mit Reformforderungen stehen mit Tatsachen im Zusammenhang, die an eine kriminologische Zuständigkeit denken lassen. Insbesondere widmet sich die Kriminologie – wie auch andere (forensische) Wissenschaften – der Faktenbasis einer Freiverantwortlichkeit, auf die es nicht zuletzt im Zusammenhang mit dem Anbieten von sexuellen Handlungen gegen Entgelt ankommt.
Implementing profession orientation as a design principle for overcoming Klein’s second discontinuity – preservice teacher’s perspectives on interface activities in the context of a geometry course
Authors: Hoffmann Max , Biehler Rolf
Published: June 2023

Intending to counteract Klein’s second discontinuity in teacher education, we explored and applied the innovation of “interface ePortfolio” in the context of a geometry course for preservice teachers (PSTs). The tool offers the possibility of implementing the design principle of profession orientation. In the article, we theoretically clarify what we understand by this principle and locate our innovative concept against this theoretical background. We empirically investigate the extent to which counteraction against the second discontinuity is successful by analyzing reflection texts created in the interface ePortfolio, focusing on PSTs’ perspectives. Our qualitative content analysis shows that most of them perceive the innovation as helpful in the intended sense and indicates that the course concept, in general, and the interface ePortfolio, in particular, have helped establish relevant links between the course content and their later work as teachers.
Modelling approaches to particle deposition and clearance in the human respiratory tract
Authors: Lazaridis Mihalis
Published: June 2023

Dosimetry models for the estimation of particle deposition in the human respiratory tract (RT) in conjunction with clearance transport models are vital components to relate human exposure with internal dose in a quantitative manner. The current work highlights knowledge and modelling approaches on particle deposition and translocation in the human body in an effort to determine health risks in respect to different particle physicochemical properties and human physiology parameters. These include breathing conditions, variability of the geometry of the RT, chemical composition and size of deposits. Different dosimetry modelling approaches have been studied including empirical formulations, one-dimensional flow modelling and computational fluid dynamic methods (CFD). The importance of a realistic modelling of hygroscopicity has been also investigated. A better understanding of the relationship between health effects and inhaled particle dose may be elaborated using dosimetry and clearance modelling tools. A future required approach is to combine dosimetry models with physiologically based pharmacokinetic models (PBPK) to simulate the transport and cumulative dose of particle-bound chemical species in different organs and tissues of the human body.
Pilot study in Hamburg on the prevalence of SARS-CoV-2 infections and pandemic survey in the German funeral industry
Authors: Schädler Julia , Lütgehetmann Marc , Schröder Ann Sophie , Edler Carolin , Püschel Klaus , Ondruschka Benjamin , Fitzek Antonia
Published: June 2023

Funeral home and crematorium workers are an important occupational group in the corona crisis. The occupational setting led to concerns about an increased risk of infection with SARS-CoV-2. The seroprevalence in this occupational group is unclear. A questionnaire-based retrospective survey of funeral home and crematorium staff was conducted in December 2020. A second survey of funeral and crematorium staff was conducted 6 months later, in June 2021, to determine changes in pandemic management. Seroprevalence or vaccination status for SARS-CoV-2 was determined at these two time points. In December 2020, a seroprevalence of 2.3% (n = 1/44) was detected in funeral home and crematorium workers. In June 2021, one additional participant tested positive for the SARS-CoV-2 nucleocapsid. Of the participants, 48.5% (n = 16) were vaccinated at this time. The risk of SARS-CoV-2 infection for funeral home and crematorium workers is more similar to that of the general population in Hamburg, Germany. We found no evidence of an increased risk of infection at these two time points in our cohort. Further education on communicable diseases or appropriate protective measures in this occupational group for other infectious diseases would be useful in the future.
Clathrin light chain A facilitates small extracellular vesicle uptake to promote hepatocellular carcinoma progression
Authors: Xu Yi , Yao Yue , Yu Liang , Fung Hiu Ling , Tang Alexander Hin Ning , Ng Irene Oi-Lin , Wong Melody Y. M. , Che Chi-Ming , Yun Jing Ping , Cui Yunfu , Yam Judy Wai Ping
Published: June 2023

Background

Endocytosis is a fundamental process for internalizing small extracellular vesicles (sEVs). The present study aimed to elucidate the role of clathrin light chain A (CLTA) in sEV uptake in hepatocellular carcinoma (HCC).

Materials and methods

CLTA expression was analyzed by bioinformatics, quantitative PCR and immunohistochemistry. The clinical relevance of CLTA was analyzed by Fisher’s exact test, Kaplan–Meier analysis, and multivariate cox regression model. The functions of CLTA in sEV uptake and cancerous properties were examined by PKH67-sEV uptake, MTT, colony formation, and transwell assays. Mass spectrometry was used to identify the downstream effectors of CLTA. CLTA inhibitor, Pitstop 2, was tested in a mouse model of patient-derived xenografts (PDXs).

Results

CLTA expression was higher in tumor tissues than in non-tumorous liver tissues and progressively increased from the early to late tumor stage. CLTA overexpression was associated with larger tumor size and poor prognosis in HCC. Cellular CLTA contributed to the sEV uptake, resulting in enhanced cancerous properties. Mechanistically, CLTA increases capping actin protein gelsolin-like (CAPG) expression to facilitate sEV uptake, thereby promoting the proliferation, motility, and invasiveness of HCC cells. What’s more, the CLTA inhibitor Pitstop 2 alone or in combination with sorafenib attenuated tumor growth in mice implanted with PDXs.

Conclusions

The study reveals the role of CLTA in sEV uptake to promote HCC progression. Inhibition of CLTA and its mediated pathway illuminate a new therapeutic strategy for HCC patients.
Empirical evidence of the parent company's influence on spin-off: from creation to performance
Authors: Oliveira Isabel , Figueiredo Jorge , Cardoso António , Cunha Maria Nascimento
Published: June 2023

Companies to adapt to today's society, characterized by continuous changes, adopt strategies to search for new opportunities, sometimes emerging business models, different from the parent company's business area. If they do not want to diversify their core business, they choose to create a new company that will be independent from the parent company, the spin-off. The aim of this study is to analyze and analyze the parent company's influence on spin-off performance, in terms of motivating factors for creation, transferred resources, relationship type and spin-off performance in the post-spin-off period. To achieve this objective, 31 surveys were analyzed, answered by workers who occupy management positions in spin-off companies in the USA and Canada. The statistical analysis of the data suggests that the concentration of the business area and the maximization of shareholder value are the main reasons for the creation of the spin-off. The most mentioned spin-off challenges are aggressive competition and efficient allocation of efficient resources. One of the characteristics of the spin-off is that it is an independent company, a fact that is not verified in the sample under analysis. However, the spin-off's performance does not change when it becomes independent.
MTHFR act as a potential cancer biomarker in immune checkpoints blockades, heterogeneity, tumor microenvironment and immune infiltration
Authors: Peng Jianheng , Wu Zhongjun
Published: June 2023

Purpose

To evaluate the role and landscape of 5-10-Methylenetetrahydrofolate reductase (MTHFR) to immune infiltration, tumor microenvironment, heterogeneity, immune checkpoints blockades, prognostic significance across cancer types.

Methods

Data sets of genomic, transcriptomic and clinic features of MTHFR across > 60,000 patients and up to 44 cancer types were comprehensively analyzed using R software.

Results

Expression of MTHFR gene is significantly lower in 17 tumors and correlated with overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI) in specific tumors. Gene alterations of MTHFR are observed significant differences across tumor types. Expression of MTHFR is negatively correlated with the stemness index (mDNAsi, mRNAsi, DMPsi, ENHsi, EREG-mDNAsi and EREG-mRNAsi) in the most cancers. MTHFR showed significantly correlated with 67 types of immune cell infiltration scores in 44 cancer types by XCELL algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis are conducted to show the core tumor mechanism and biological process. Correlations between MTHFR and biomarkers of heterogeneity (MSI, TMB, MATH, HRD, LOH, Neoantigen, ploidy and purity) are also significant in specific tumors. MTHFR is significantly positively correlated with biomarkers of immune related genes (CD19, CD274, CD80, CD86) and mismatched repair genes (MLH1, PMS2, MSH2, MSH6, EPCAM, MLH3, PMS1, EXO1) in most cancer types. Receiver Operating Characteristics (ROC) analyses show MTHFR could act as a potential biomarker in anti-PD-1 (nivolumab to melanoma) and anti-CTLA4 (ipilimumab to melanoma) group of ontreatment, in anti-PD-1 (pembrolizumab to melanoma) group of pretreatment. Two immunohistochemistry antibodies HPA076180 and HPA077255 are verified in 20 types of tumor and could be used to detect the expression of MTHFR efficiently in clinic.

Conclusions

MTHFR could predict the response of immune checkpoints blockades, heterogeneity, tumor microenvironment and immune infiltration.
LncRNA MIR4435-2HG drives cancer progression by modulating cell cycle regulators and mTOR signaling in stroma-enriched subtypes of urothelial carcinoma of the bladder
Authors: Pei Lu , Yan Dong , He Qingqing , Kong Jianqiu , Yang Meihua , Ruan Honglian , Lin Qiongqiong , Huang Lifang , Huang Jian , Lin Tianxin , Qin Haide
Published: June 2023

Background

The risk for recurrence and metastasis after treatment for urothelial carcinoma of the bladder (UCB) is high. Therefore, identifying efficient prognostic markers and novel therapeutic targets is urgently needed. Several long noncoding RNAs (lncRNAs) have been reported to be correlated with UCB progression. In this study, we found that the subtype-specific lncRNA MIR4435-2 host gene (MIR4435-2HG) plays a novel oncogenic role in UCB.

Methods

RNA-Seq data of TCGA/BLCA were analyzed. The expression of MIR4435-2HG was measured by qRT-PCR in 16 pairs of bladder cancer tissues and adjacent normal tissues. The clinical relecance of MIR4435-2HG was validated via in situ hybridization performed on an in-house cohort of 116 UCB patient samples. RNA pull-down followed by mass spectrometry was performed to identify MIR4435-2HG-binding proteins. To identify signaling pathways involved in MIR4435-2HG activity, comprehensive in vitro and in vivo studies and RNA-Seq assays were performed using UCB cells in which MIR4435-2HG expression was knocked down or exogenously overexpressed. In addition, we performed RNA immunoprecipitation and Western blot analyses to validate the identified MIR4435-2HG-binding proteins and to determine the molecular mechanisms by which MIR4435-2HG promotes UCB progression.

Results

We found that MIR4435-2HG was significantly upregulated in the stromal-enriched subtype of UCB. Increased MIR4435-2HG expression was positively correlated with a high histological grade, advanced T stages, larger tumors, lymph node metastasis and a poor prognosis. In vitro experiments revealed that MIR4435-2HG expression silencing suppressed cell proliferation and induced apoptosis. Inhibition of MIR4434-2HG delayed xenograft tumor growth, while MIR4435-2HG overexpression reversed the MIR4435-2HG silencing-induced inhibition of UCB tumor phenotype acquisition. Mechanistically, we found that MIR4435-2HG positively regulated the expression of a variety of cell cycle regulators, including BRCA2 and CCND1. Knocking down MIR4435-2HG increased the sensitivity of tumor cells to the VEGFR inhibitor cediranib. Furthermore, we found that MIR4435-2HG regulated mTOR signaling and epithelial-mesenchymal transition (EMT) signaling pathways by modulating the phosphorylation of mTOR, 70S6K and 4EBP1. Finally, we confirmed that MIR4435-2HG enhances tumor metastasis through regulation of the EMT pathway.

Conclusions

Our data indicate that upregulated MIR4435-2HG expression levels are significantly correlated with a poor prognosis of UCB patients. MIR4435-2HG promotes bladder cancer progression, mediates cell cycle (de)regulation and modulates mTOR signaling. MIR4435-2HG is an oncogenic lncRNA in UCB that may serve as a diagnostic and therapeutic target.
Ukraine–Russia Conflict and Stock Markets Reactions in Europe
Authors: Das Bijoy Chandra , Hasan Fakhrul , Sutradhar Soma Rani , Shafique Sujana
Published: June 2023

This paper analyses the impact of Ukraine–Russia conflict on stock markets in Europe. We consider the stock markets of nine EU countries and Russia. The analysis consists of day-firm which includes the time between 24 November 2021 and 23 May 2022. We consider ordinary least squared (OLS) and fixed effects as baseline models. Additionally, we consider the impact of this conflict on stock return for several months, the elasticity test, the instrumental variable—two-stage least squared (2SLS) approach for the robustness test and endogeneity concerns. We find evidence of the negative impact of the Ukraine–Russia conflict on stock return of that stock markets. In addition, our finding indicates that the impact of this war on the mining construction and manufacturing sectors is greater than on other sectors because Russia and Ukraine are the key suppliers or exporters of mining and manufacturing sector. Our finding also indicates that Ukraine–Russia conflict largely affects stock return of Russian stocks because Russia is directly involved in the conflict.
Chronic kidney disease, female infertility, and medically assisted reproduction: a best practice position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology
Authors: Attini Rossella , Cabiddu Gianfranca , Ciabatti Francesca , Montersino Benedetta , Carosso Andrea Roberto , Gernone Giuseppe , Gammaro Linda , Moroni Gabriella , Torreggiani Massimo , Masturzo Bianca , Santoro Domenico , Revelli Alberto , Piccoli Giorgina Barbara ,   On behalf of the Italian Society of Nephrology’s Project Group on Kidney and Pregnancy
Published: June 2023

Fertility is known to be impaired more frequently in patients with chronic kidney disease than in the general population. A significant proportion of chronic kidney disease patients may therefore need Medically Assisted Reproduction. The paucity of information about medically assisted reproduction for chronic kidney disease patients complicates counselling for both nephrologists and gynaecologists, specifically for patients with advanced chronic kidney disease and those on dialysis or with a transplanted kidney. It is in this context that the Project Group on Kidney and Pregnancy of the Italian Society of Nephrology has drawn up these best practice guidelines, merging a literature review, nephrology expertise and the experience of obstetricians and gynaecologists involved in medically assisted reproduction. Although all medically assisted reproduction techniques can be used for chronic kidney disease patients, caution is warranted. Inducing a twin pregnancy should be avoided; the risk of bleeding, thrombosis and infection should be considered, especially in some categories of patients. In most cases, controlled ovarian stimulation is needed to obtain an adequate number of oocytes for medically assisted reproduction. Women with chronic kidney disease are at high risk of kidney damage in case of severe ovarian hyperstimulation syndrome, and great caution should be exercised so that it is avoided. The higher risks associated with the hypertensive disorders of pregnancy, and the consequent risk of chronic kidney disease progression, should likewise be considered if egg donation is chosen. Oocyte cryopreservation should be considered for patients with autoimmune diseases who need cytotoxic treatment. In summary, medically assisted reproduction is an option for chronic kidney disease patients, but the study group strongly advises extensive personalised counselling with a multidisciplinary healthcare team and close monitoring during the chosen medically assisted reproduction procedure and throughout the subsequent pregnancy.

Graphical abstract
Real-time estimating method on rock strength via MWD of roofbolter and its application to in-situ grouting quality evaluation
Authors: Ma Bailong , Zhang Kai , Xiao Fangyuan , Yu Bosong , Xue Xinran , Jiang Tao , Zhang Houquan , Zhang Zhanrong
Published: June 2023

Grouting reinforcement is an effective method for controlling fractured rock in the deeply buried roadways of coal mines. However, quantitatively evaluating the strength of grouted rock masses remains a challenge. The design of grouting reinforcement is primarily based on empirical knowledge. Consequently, this study proposes a real-time in-situ method for evaluating grouting quality using measure while drilling (MWD) based on a roofbolter. Initially, we validated the method through a numerical study using the discrete element method. Several 3D rock samples with varying crack densities were established and drilled numerically, demonstrating that the strength of fractured rock masses can be better estimated using the rock drillability index rather than drilling specific energy. Therefore, a model, known as the Pd–Rc model, was established to estimate rock strength based on the rock drillability index. Subsequently, an in-situ validation was conducted using a self-developed MWD testing system to assess the grouting quality in fractured rock masses. The results show that the strength of the rock mass increases by 38%, 56.0%, and 49.7%, respectively, after grouting, as observed in three boreholes. This method allows for quantitative estimation of grouting quality.
Fit for solving the grand challenges? From organization design choices to ecosystem solutions
Authors: Ambos Tina C. , Tatarinov Katherine
Published: June 2023

This Point of View article discusses the implications of different organization designs for solving the Grand Challenges. In line with this Special Issue, we view “organization designs as problem-solving systems”. However, we are skeptical that contemporary organization designs indeed “foster collective action that is needed to solve these grand challenges”. We outline different organization design choices for solving the grand challenges and provide a categorization of how selected types of organizations are fit to respond to these based on organizational goals (social–profit), organizational scale (local–global), and organizational decision making (agile–bureaucratic). In conclusion, we offer ideas on how to harness complementarities in different organization designs to develop collaborative ecosystem solutions.
A Comparison of Football Fan Activism in Ukraine and Germany
Authors: Brandt Christian , Krugliak Maryna , Warnecke Robert
Published: June 2023

During the last decade, football fans in Germany and Ukraine have become increasingly active in the struggle for their interests. This article compares their respective activism based on reasons, tactics and spaces of activism over a span of eight years. The comparison shows that national politics are a dominant motive for Ukrainian fan activism, especially after the so-called Revolution of Dignity (Euromaidan) in 2014, including the Russian invasion. Politics is so important that activism is politically framed in this context even if non-political players like club management or the football association are addressed. In Germany, football’s governance is the major reason for fan activism, as fans strive to preserve or extend their influence on clubs’ and associations’ decisions. This difference emphasises the influence of national settings on fan activism. Concerning space and tactics, the samples show similarities, as in both countries ultras are the dominant type of fan group, an intersection of global ultra culture and activism tactics exists and activism mainly takes place in football stadiums. Therefore, fan activism can be understood as a globally connected movement that is nonetheless highly determined by the respective local context.
Reliability of the Non-linear Modeling in Predicting the Size Distribution of the Grinding Products Under Different Operating Conditions
Authors: Petrakis Evangelos , Varouchakis Emmanouil , Komnitsas Konstantinos
Published: June 2023

During the modeling of grinding systems, population balance modeling (PBM) which considers a constant breakage rate has been widely used over the past years. However, in some cases, PBM exhibited some limitations, and time-dependent approaches have been developed. Recently, a non-linear framework which considers the traditional linear theory of the PBM as a partial case was introduced, thus allowing the estimation of product particle size distribution in relation to grinding time or the specific energy input to the mill. In the proposed model the simplified form of the fundamental batch grinding equation was transformed into the well-known Rosin–Rammler (RR) distribution. Besides, the adaptability and reliability of the prediction model are among others dependent upon the operating conditions of the mill and the adjustment of the RR distribution to the experimental data. In this study, a series of grinding tests were performed using marble as test material, and the adaptability of the non-linear model was investigated using three loads of single size media, i.e., 40, 25.4, and 12.7 mm. The results indicate that the proposed model enables a more accurate analysis of grinding, compared to PBM, for different operating conditions.
A Comparison of Commercial Sentiment Analysis Services
Authors: Ermakova Tatiana , Fabian Benjamin , Golimblevskaia Elena , Henke Max
Published: June 2023

Empirical insights into promising commercial sentiment analysis solutions that go beyond the claims of their vendors are rare. Moreover, due to the constant evolution in the field, previous studies are far from reflecting the current situation. The goal of this article is to evaluate and compare current solutions using two experimental studies. In the first part of the study, based on tweets about airline service quality, we test the solutions of six vendors with different market power, such as Amazon, Google, IBM, Microsoft, Lexalytics, and MeaningCloud, and report their measures of accuracy, precision, recall, (macro)F1, time performance, and service level agreements (SLA). Furthermore, we compare two of the services in depth with multiple data sets and over time. The services tested here are Google Cloud Natural Language API and MeaningCloud Sentiment Analysis API. For evaluating the results over time, we use the same data set as in November 2020. In addition, further topic-specific and general Twitter data sets are used. The experiments show that the IBM Watson NLU and Google Cloud Natural Language API solutions may be preferred when negative text detection is the primary concern. When tested in July 2022, the Google Cloud Natural Language API was still the clear winner compared to the MeaningCloud Sentiment Analysis API, but only on the airline service quality data set; on the other data sets, both services provided specific benefits and drawbacks. Furthermore, we detected changes in the sentiment classification over time with both services. Our results motivate that an independent, critical, and longitudinal experimental analysis of sentiment analysis services can provide interesting insights into their overall reliability and particular classification accuracy beyond marketing claims to critically compare solutions based on real data and analyze potential weaknesses and margins of error before making an investment.
AB-Gen: Antibody Library Design with Generative Pre-Trained Transformer and Deep Reinforcement Learning
Authors: Xu Xiaopeng , Xu Tiantian , Zhou Juexiao , Liao Xingyu , Zhang Ruochi , Wang Yu , Zhang Lu , Gao Xin
Published: June 2023

Antibody leads must fulfill multiple desirable properties to be clinical candidates. Primarily due to the low throughput in the experimental procedure, the need for such multi-property optimization causes the bottleneck in preclinical antibody discovery and development, because addressing one issue usually causes another. We developed a reinforcement learning (RL) method, named AB-Gen, for antibody library design using a generative pre-trained transformer (GPT) as the policy network of the RL agent. We showed that this model can learn the antibody space of heavy chain complementarity determining region 3 (CDRH3) and generate sequences with similar property distributions. Besides, when using human epidermal growth factor receptor-2 (HER2) as the target, the agent model of AB-Gen was able to generate novel CDRH3 sequences that fulfill multi-property constraints. Totally, 509 generated sequences were able to pass all property filters, and three highly conserved residues were identified. The importance of these residues was further demonstrated by molecular dynamics simulations, consolidating that the agent model was capable of grasping important information in this complex optimization task. Overall, the AB-Gen method is able to design novel antibody sequences with an improved success rate than the traditional propose-then-filter approach. It has the potential to be used in practical antibody design, thus empowering the antibody discovery and development process. The source code of AB-Gen is freely available at Zenodo (https://doi.org/10.5281/zenodo.7657016) and BioCode (https://ngdc.cncb.ac.cn/biocode/tools/BT007341).
Regulating Antarctic Tourism: The Challenge of Consensus-Based Decision Making
Authors: Bastmeijer Kees , Shibata Akiho , Steinhage Imme , Ferrada Luis Valentin , Bloom Evan T.
Published: June 2023

In the 2022–2023 season, more than 104,000 tourists visited Antarctica. This represents an increase of more than 40 percent compared to the 2019–2020 pre-pandemic season. This Current Development discusses this trend and the limits of the Antarctic Treaty Consultative Parties, which govern on the basis of consensus, in responding with regulatory action. Options for strengthening regulation in this area are also considered.
Association between negative-pressure room utilization and hospital-acquired Aspergillus rates in patients with coronavirus disease 2019 (COVID-19) in two academic hospitals
Authors: Biebelberg Brett M. , Ye Shangyuan , Wang Rui , Klompas Michael , Rhee Chanu
Published: June 2023

Hospital-acquired Aspergillus rates among coronavirus disease 2019 (COVID-19) patients were initially higher at a hospital with high negative-pressure room utilization compared to a similar hospital with low utilization but with otherwise identical infection control policies. After the index hospital decreased negative-pressure utilization, hospital-acquired Aspergillus case rates at the 2 hospitals converged.
Healthcare providers consistently overestimate the diagnostic probability of ventilator-associated pneumonia
Authors: Soper Nathaniel S. , Albin Owen R.
Published: June 2023

Objective:

To assess the accuracy of provider estimates of ventilator-associated pneumonia (VAP) diagnostic probability in various clinical scenarios.

Design:

We conducted a clinical vignette-based survey of intensive care unit (ICU) physicians to evaluate provider estimates of VAP diagnostic probability before and after isolated cardinal VAP clinical changes and VAP diagnostic test results. Responses were used to calculate imputed diagnostic likelihood ratios (LRs), which were compared to evidence-based LRs.

Setting:

Michigan Medicine University Hospital, a tertiary-care center.

Participants:

This study included 133 ICU clinical faculty and house staff.

Results:

Provider estimates of VAP diagnostic probability were consistently higher than evidence-based diagnostic probabilities. Similarly, imputed LRs from provider-estimated diagnostic probabilities were consistently higher than evidence-based LRs. These differences were most notable for positive bronchoalveolar lavage culture (provider-estimated LR 5.7 vs evidence-based LR 1.4; P < .01), chest radiograph with air bronchogram (provider-estimated LR 6.0 vs evidence-based LR 3.6; P < .01), and isolated purulent endotracheal secretions (provider-estimated LR 1.6 vs evidence-based LR 0.8; P < .01). Attending physicians and infectious disease physicians were more accurate in their LR estimates than trainees (P = .04) and non-ID physicians (P = .03).

Conclusions:

Physicians routinely overestimated the diagnostic probability of VAP as well as the positive LRs of isolated cardinal VAP clinical changes and VAP diagnostic test results. Diagnostic stewardship initiatives, including educational outreach and clinical decision support systems, may be useful adjuncts in minimizing VAP overdiagnosis and ICU antibiotic overuse.
CONDITIONS FOR RECURRENCE AND TRANSIENCE FOR TIME-INHOMOGENEOUS BIRTH-AND-DEATH PROCESSES
Authors: ABRAMOV VYACHESLAV M.
Published: June 2023

We derive conditions for recurrence and transience for time-inhomogeneous birth-and-death processes considered as random walks with positively biased drifts. We establish a general result, from which the earlier known particular results by Menshikov and Volkov [‘Urn-related random walk with drift
$\rho x^\alpha /t^\beta $
’, Electron. J. Probab.13 (2008), 944–960] follow.