bluuebunny/crossref_metadata_2025 huggingface dataset:
Phytophagous Insects of Malus in Uzbekistan
Authors: Muminova R.
Published: June 2023

The paper presents descriptions of some of the most common apple pests. In Uzbekistan, the apple tree is one of the most important fruit trees. Damage to the apple tree must be controlled, and for this, all types of pests must be studied. Horticultural products from Uzbekistan are in demand on the world market. Currently, the export of food, fruit and vegetable products totaled about 5 billion dollars. Over the past three years, the volume of exported agricultural products has more than tripled. On fruit crops, one of the most dangerous pests are mites. Biological control measures on these crops have not yet been developed to the perfection as against pests belonging to the class of insects. There are studies where effects on the number of spider mites on an apple tree are noticed, where varieties with weak and medium pubescence are especially affected by the mite, and varieties with felt pubescence are slightly damaged.
Prince Vsevolod Karmazyn-Kakovsky scientist, teacher, artist
Authors:   Lviv National Academy of Arts, Stelmashchuk Halyna
Published: June 2023

The article is devoted to the creative work of the Ukrainian Diaspora scientist, teacher, historian of art, architect and graphic artist, Prince Vsevolod Karmazyn-Kakovsky (1898–1988), about whom there is very little information in Ukraine. The study emphasizes his Ukrainian roots. The publication is based on materials from the home archive of Ph.D., sculptor and artist Kristina Kishakevich-Kachaluba from Switzerland. Prince Vsevolod Karmazyn-Kakovsky studied and lived in Ukraine until 1944. In 1944 he left Ukraine for permanent residence in Romania. As a teacher he organized faculties of landscape architecture in universities in Ukraine (Odessa, Kharkiv) and Romania (Iasi). From 1978, professor lived and worked in Italy, then in France, Germany, lectured on the history of Ukrainian art, cooperated with Ukrainian research institutions in Western countries. As an artist he created and implemented the projects of health and recreational complexes on the Black Sea coast in Ukraine and Romania, which combined architecture with natural landscape, contributing to human health and longevity, and embodied the principles he established for enriching the expressiveness of landscapes. The Prince founded the Research Institute of Landscape Architecture (1921–1981), which worked in Ukraine, and then in Romania. This institution was focused on combining and harmonizing endogenous (internal) factors of human longevity with exogenous (external) factors — the synthesis of nature with art. The scientist argued that the tree crown shapes (triangular, ellipse-like, round) differently influence the mood and psychological state of a person, therefore, developed special health boxets in sanatorium complexes. This method of healing people, proposed by V. Karmazyn-Kakovsky in 1971–1981, was adopted in Czechoslovakia, Poland, France, Italy, Germany, and the United States of America. As a scientist he published more than 200 scientific works, including Monographs devoted to Ukrainian art, Lemkivska and Boykovska churches, art of Ukrainian houses, Ukrainian books. He designed his own works and covers for his books. He was skilled in the technique of pencil, sepia, watercolor, skillfully conveyed the space in the landscape, was perfect in the technique of pen and ink. The artist’s graphics is dominated by subjects closely related to his scientific works in the field of art history. Karmazyn-Kakovsky supplements almost all of his works with illustrations, headpieces, stylized folk motifs, architectural historical monuments of Romanian and Ukrainian cultures, valuable for the history of Ukrainian art, and landscape projects. V. Karmazyn-Kakovsky made more than 1200 drawings of wooden Ukrainian churches. He had personal exhibitions in Warsaw, Rome, Paris, Munich.
Setting the new European agenda for adult learning 2021-2030
Authors: Milana Marcella , Mikulec Borut
Published: June 2023

Following the COVID-19 pandemic, international organisations and governments have issued mitigation policies, and (re)oriented broader policy strategies to respond to new problematisations about the future. In this context, the education ministers of the European Union (EU) adopted a Council Resolution on a new European agenda for adult learning 2021-2030. Drawing on the Advocacy Coalition Framework (ACF), this paper examines the political mobilisation and agenda setting behind this Resolution through network ethnography and the analysis of belief systems. The findings point at an increased social dialogue, favoured by an ‘uncommon’ way – as by our informants – through which the Slovenian Ministry of Education pursued the agreed priority at EU level, while holding the rotating Presidency of the Council of the EU. While visibility of adult learning rose under COVID-19, advocacy coalitions formed at national (Slovenian) and European level facilitated stronger alignment in agenda setting among different actors towards a holistic approach that calls for inter-sectorial and multi-stakeholder collaboration.
Glutathione affinity chromatography for the scalable purification of an oncolytic virus immunotherapy from microcarrier cell culture
Authors: Swartz Andrew R. , Shieh Yvonne , Gulasarian Amanda , Curtis Erik , Hofmann Carl F. , Baker Jack B. , Templeton Neil , Olson Jessica W.
Published: June 2023

Therapeutic viral vectors are an emerging technology with several clinical applications in gene therapy, vaccines, and immunotherapy. Increased demand has required the redevelopment of conventional, low-throughput cell culture and purification manufacturing methods such as static cell stacks and ultracentrifugation. In this work, scalable methods were investigated for the manufacture of an oncolytic virus immunotherapy application consisting of a prototype strain of coxsackievirus A21 (CVA21) produced in adherent MRC-5 cells. Cell culture was established in stirred-tank microcarrier bioreactors, and an efficient affinity chromatography method was developed for the purification of harvested CVA21 through binding of the viral capsids to an immobilized glutathione (GSH) ligand. Bioreactor temperature during infection was investigated to maximize titer, and a decrease in temperature from 37°C to 34°C yielded a two–three-fold increase in infectivity. After purification of the 34°C harvests, the GSH affinity chromatography elution not only maintained a >two-fold increase in infectivity and viral genomes but also increased the proportion of empty capsids compared to 37°C harvests. Using material generated from both infection temperature setpoints, chromatographic parameters and mobile phase compositions were studied at the laboratory scale to maximize infectious particle yields and cell culture impurity clearance. Empty capsids that co-eluted with full capsids from 34°C infection temperature harvests were poorly resolved across the conditions tested, but subsequent polishing anion exchange and cation exchange chromatography steps were developed to clear residual empty capsids and other impurities. Oncolytic CVA21 production was scaled-up 75-fold from the laboratory scale and demonstrated across seven batches in 250 L single-use microcarrier bioreactors and purified with customized, prepacked, single-use 1.5 L GSH affinity chromatography columns. The large-scale bioreactors controlled at 34°C during infection maintained a three-fold increase in productivity in the GSH elution, and excellent clearance of host cell and media impurities was observed across all batches. This study presents a robust method for the manufacture of an oncolytic virus immunotherapy application that may be implemented for the scalable production of other viruses and viral vectors which interact with glutathione.
Computational methods applied to earthen historical structures
Authors: Jiménez Rios Alejandro , Ruiz-Capel Samuel , Plevris Vagelis , Nogal Maria
Published: June 2023

Earthen structures have an important representation among the UNESCO World Heritage List sites as well as among the built environment in general. Unfortunately, earthen heritage structures are also numerous within the UNESCO List of World Heritage in Danger whereas other existing common earthen structures are extremely vulnerable to seismic and climate change events. Within the field of heritage conservation, structural analysis contributes to the safety evaluation of the structure, the diagnosis of the causes of damage and decay, and to the validation of interventions. Thus, the need to develop effective and accurate computational methods suitable for the study of both monumental and vernacular earthen structures becomes evident. This paper compiles, summarizes, and highlights the latest developments and implementations of computational methods for the study of such structure typologies. The literature has been explored following the PRISMA-S checklist methodology and a narrative synthesis was used for the presentation of results. Finally, future trends, opportunities, and challenges are discussed.
Common and distinct functions of mouse Dot1l in the regulation of endothelial transcriptome
Authors: Yoo Hyunjin , La Hyeonwoo , Park Chanhyeok , Yoo Seonho , Lee Hyeonji , Song Hyuk , Do Jeong Tae , Choi Youngsok , Hong Kwonho
Published: June 2023

Epigenetic mechanisms are mandatory for endothelial called lymphangioblasts during cardiovascular development. Dot1l-mediated gene transcription in mice is essential for the development and function of lymphatic ECs (LECs). The role of Dot1l in the development and function of blood ECs blood endothelial cells is unclear. RNA-seq datasets from Dot1l-depleted or -overexpressing BECs and LECs were used to comprehensively analyze regulatory networks of gene transcription and pathways. Dot1l depletion in BECs changed the expression of genes involved in cell-to-cell adhesion and immunity-related biological processes. Dot1l overexpression modified the expression of genes involved in different types of cell-to-cell adhesion and angiogenesis-related biological processes. Genes involved in specific tissue development-related biological pathways were altered in Dot1l-depleted BECs and LECs. Dot1l overexpression altered ion transportation-related genes in BECs and immune response regulation-related genes in LECs. Importantly, Dot1l overexpression in BECs led to the expression of genes related to the angiogenesis and increased expression of MAPK signaling pathways related was found in both Dot1l-overexpressing BECs and LECs. Therefore, our integrated analyses of transcriptomics in Dot1l-depleted and Dot1l-overexpressed ECs demonstrate the unique transcriptomic program of ECs and the differential functions of Dot1l in the regulation of gene transcription in BECs and LECs.
Relative contributions of arterial stiffness to cardiovascular disease risk score in Chinese women in framingham and China-PAR model
Authors: Jin Lin , Chen Jianxiong , Wu Lingheng , Zhang Mengjiao , Sun Jiali , Shen Cuiqin , Du Lianfang , Wang Dingqian , Li Zhaojun
Published: June 2023

Background

Arterial stiffness played an important role in the development of cardiovascular disease (CVD) events. The aim of this study was to verify the relative importance of arterial stiffness for different CVD risk scores in a large sample of Chinese women.

Methods

We measured arterial velocity pulse index (AVI) and CVD risk scores in 2220 female participants (mean age 57 years). Framingham Risk Score (FRS), and the prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) were used to estimate CVD risk, respectively. The relationships between AVI and risk scores were investigated by linear regressions and restricted cubic spline (RCS) analysis. To determine the relative importance of AVI in predicting CVD risk scores, random forest analysis was used.

Results

There was a significant positive correlation between AVI and FRS, China-PAR in all subgroup groups stratified by age, blood pressure and BMI. AVI showed higher importance in predicting CVD risk scores in FRS model, compared with these traditional risk factors. In China-PAR model, although AVI was not as predictive as SBP, it had better predictive power than many known risk factors such as lipids. Furthermore, AVI had significant J-shaped associations both with FRS and China-PAR scores.

Conclusions

AVI was significantly associated with CVD risk score. In FRS and China-PAR model, AVI showed relatively high importance in predicting CVD risk scores. These findings may support the use of arterial stiffness measurements in CVD risk assessment.
Serum amyloid A and metabolic disease: evidence for a critical role in chronic inflammatory conditions
Authors: den Hartigh Laura J. , May Karolline S. , Zhang Xue-Song , Chait Alan , Blaser Martin J.
Published: June 2023

Serum amyloid A (SAA) subtypes 1–3 are well-described acute phase reactants that are elevated in acute inflammatory conditions such as infection, tissue injury, and trauma, while SAA4 is constitutively expressed. SAA subtypes also have been implicated as playing roles in chronic metabolic diseases including obesity, diabetes, and cardiovascular disease, and possibly in autoimmune diseases such as systemic lupus erythematosis, rheumatoid arthritis, and inflammatory bowel disease. Distinctions between the expression kinetics of SAA in acute inflammatory responses and chronic disease states suggest the potential for differentiating SAA functions. Although circulating SAA levels can rise up to 1,000-fold during an acute inflammatory event, elevations are more modest (∼5-fold) in chronic metabolic conditions. The majority of acute-phase SAA derives from the liver, while in chronic inflammatory conditions SAA also derives from adipose tissue, the intestine, and elsewhere. In this review, roles for SAA subtypes in chronic metabolic disease states are contrasted to current knowledge about acute phase SAA. Investigations show distinct differences between SAA expression and function in human and animal models of metabolic disease, as well as sexual dimorphism of SAA subtype responses.
MMV006087 is a potent Malaria Box compound against Plasmodium falciparum clinical parasites
Authors: Chirawurah Jersley D. , Adikah Bridget , Ansah Felix , Laryea-Akrong Elizabeth , Danwonno Harry , Morang’a Collins M. , Dosoo Daniel , Amenga-Etego Lucas , Awandare Gordon A. , Aniweh Yaw
Published: June 2023

The emergence of drug-resistant malaria parasites to artemisinin and its partner drugs highlights the need to increase the arsenal of new antimalarials with novel mechanisms of action. To help achieve this aim, this study tested the potency of three Malaria Box compounds (MMV006087, MMV085203, and MMV008956) against five laboratory strains and twenty clinical isolates of Plasmodium falciparum using optimized in vitro growth inhibitory assays. The results were compared to the response from four standard antimalarials-artesunate, chloroquine, mefloquine, and halofantrine. From the results, MMV006087 was the most potent compound with an average IC50 of 22.13 nM compared to MMV085203 (average IC50 of 137.90 nM) and MMV008956 (average IC50 of 262.30 nM). On average, the laboratory strains were also less susceptible to the three Malaria Box compounds (average IC50 of 162.30 nM) compared to the clinical isolates (average IC50 of 135.40 nM). Additionally, MMV006087 was less potent than artesunate but twice more efficacious than chloroquine against the laboratory strains and clinical isolates. The data from this study validate the potency of MMV006087 and MMV085203 as promising antimalarials worthy of further exploration. This study further substantiates the need to include clinical isolates in antimalarial compound screening activities.
Convection of snow: when and why does it happen?
Authors: Jafari Mahdi , Lehning Michael
Published: June 2023

Convection of water vapor in snowpacks is supposed to have a major impact on snow density and microstructure profiles with strong implications for the thermal regime and snow stability. However, the process has never been directly measured and only recently been simulated for idealized conditions. The analysis suggests that natural convection is not likely to happen in typical horizontally homogeneous polar or Alpine snow covers. This paper studies the potential impact of heterogeneity induced, e.g., by shrubs on convection of water vapor. We find that natural convection triggered by buoyancy occurs even with sub-critical Rayleigh number as low as 5 due to heterogeneity in snow density. This leads to complementing contributions of diffusive and convective flux divergence on snow density changes. The combined effect of diffusion and convection helps to generate the often-observed low density foot and high-density top of, e.g., Arctic snowpacks. The strongest effect of convection is not for very thin or thick snow covers but for snow covers with thickness in the order of 0.5 m. This scale facilitates the development of convection cells. Further work should address the additional effects of sub-snow lateral temperature variations and assess the effect of convective vapor fluxes on snow microstructure.
Between theory and practice: educators’ perceptions on assessment quality criteria and its impact on student learning
Authors: Schellekens Lonneke H. , Kremer Wim D. J. , Van der Schaaf Marieke F. , Van der Vleuten Cees P. M. , Bok Harold G. J.
Published: June 2023

Introduction

The shift toward an assessment for learning culture includes assessment quality criteria that emphasise the learning process, such as transparency and learning impact, in addition to the traditional validity and reliability criteria. In practice, the quality of the assessment depends on how the criteria are interpreted and applied. We explored how educators perceive and achieve assessment quality, as well as how they perceive assessment impact upon student learning.

Methods

We employed a qualitative research approach and conducted semi-structured interviews with 37 educators at one Dutch research university. The data were subsequently analysed using a template analysis.

Results

The findings indicate that educators predominantly perceive and achieve assessment quality through traditional criteria. The sampled curricular stakeholders largely perceived assessment quality at the course level, whilst few specified programme-level quality criteria. Furthermore, educators perceived the impact of assessment on student learning in two distinct ways: as a source of information to monitor and direct student learning, and as a tool to prompt student learning.

Discussion

The shift toward a culture of assessment for learning is not entirely reflected in educators’ current perceptions. The study’s findings set the stage for better assessment quality and alignment with an assessment for learning culture.
Association of physical activity and sitting with metabolic syndrome and hyperglycemic clamp parameters in adolescents – BRAMS pediatric study
Authors: Silva Talita Oliveira , Norde Marina Maintinguer , Vasques Ana Carolina , Zambom Mariana Porto , Antonio Maria Angela Reis de Góes Monteiro , Rodrigues Ana Maria De Bernardi ,   BRAMS group, Geloneze Bruno ,   Brazilian Metabolic Syndrome Study investigators
Published: June 2023

Introduction

Obesity and metabolic syndrome (MetS) have immediate and long-term consequences on adolescent health and well-being. Among the available treatments for MetS in adolescents, behavioral interventions such as increasing physical activity (PA) are preferred. This study aimed to investigate the association of PA and sitting time with MetS and a complete set of metabolic health parameters.

Methods

Data from the Pediatric Brazilian Metabolic Syndrome Study (BRAMS-P), a cross-sectional multicenter study conducted using a convenience sample of 448 Brazilian adolescents (10y–19y), were used. Sociodemographic and lifestyle information were collected using a standardized questionnaire. Daily PA and sitting time were estimated from the International PA Questionnaire. Anthropometric parameters, body composition, and blood pressure were measured by trained researchers. Blood lipids, uric acid, hepatic enzymes, creatinine, glycated hemoglobin, glucose, and insulin were measured in fasting blood samples, and the Homeostasis Model Assessment for Insulin Resistance was calculated. A subsample of 57 adolescents underwent the hyperglycemic clamp protocol.

Results

The odds for metabolic syndrome were higher among adolescents who spent >8h sitting (OR (95%CI)=2.11 (1.02 – 4.38)), but not in those classified as active (OR (95%CI)=0.98 (0.42 – 2.26)). Adolescents who spent more time sitting had higher BMI, waist circumference, sagittal abdominal diameter, neck circumference, percentage of body fat, and worse blood lipid profile. The insulin sensitivity index was moderately and positively correlated with moderate-to-high PA in minutes per day (rho=0.29; p=0.047).

Conclusion

Time spent sitting was associated with worse metabolic parameters and must be restricted in favor of adolescent health. Regular PA is associated with improved insulin sensitivity and may be encouraged not only in adolescents with obesity or metabolic disorders but also to prevent adverse metabolic outcomes in normal-weight adolescents.
Evidence for proton-pump inhibitor (PPI)-associated dysbiosis in metabolically unhealthy obesity
Authors: Burmeister Melissa A. , Smith Tara E. , Fincher Timothy K. , Weldon Abby J.
Published: June 2023

Obesity adversely impacts millions of American adults by predisposing them to significant health risks and further complications. Obesity is differentiated into two groups: metabolically healthy and metabolically unhealthy. In contrast to metabolically healthy counterparts, obese individuals who are metabolically unhealthy display hallmark symptoms of metabolic syndrome (e.g., hypertension, dyslipidemia, hyperglycemia, abdominal obesity). Gastroesophageal reflux disease (GERD) commonly occurs in all obese populations, as do poor dietary habits. Proton-pump inhibitors (PPIs), due to their wide availability, are most often used to treat GERD-related heartburn and other symptoms. Here, we review the evidence on how poor diet as well as short- and long-term use of PPIs adversely affect the gastrointestinal microbiota to cause dysbiosis. Key components of dysbiosis-induced metabolically unhealthy obesity (MUO) associated with PPI use include “leaky gut,” systemic low-grade inflammation, and reduced amounts of short-chain fatty acids (SCFAs) such as butyrate that promote metabolic health. The benefit of using probiotics to mitigate PPI-induced dysbiosis and MUO is also discussed.
Key policy interventions to limit infectious disease emergence and spread
Authors: Martinus Kirsten , Pauli Natasha , Kragt Marit
Published: June 2023

The COVID-19 pandemic provides a salient backdrop to consider what many experts across public health, conservation, and biology have long highlighted: that land use change, environmental degradation, habitat loss, and climate change contribute to outbreaks of emerging infectious diseases. Drawing on literature from across a range of disciplines, we present a conceptual model that shows how human-environment interactions and decisions by citizens, industry, and governments can drive disease emergence and spread. We suggest that local consumer and producer decisions at one location can have ramifications that extend around the world and lead to land use changes in other jurisdictions which could amplify or reduce the likelihood of novel disease outbreaks. Moving beyond the immediate health impacts and changes to healthcare systems, we propose that the long-term legacy of COVID-19 could be one that turns global society toward more socially, economically, and environmentally sustainable ways of production, consumption and landscape management through five “Key Policy Interventions.”
Sustainable assessment and carbon footprint analysis of polysaccharide biopolymer-amended soft soil as an alternate material to canal lining
Authors: Rasheed Romana Mariyam , Moghal Arif Ali Baig , Rambabu Sathyanarayanan , Almajed Abdullah
Published: June 2023

Kuttanad region in Kerala, India, is a place that predominantly consists of soft soil formations with low shear strength and low water resistance rendering them problematic for construction purposes. Pavements constructed on such soft deposits have been subjected to structural rutting and the high erodibility of the in-situ soil necessitates the need to use suitable ground improvement techniques. The present environmental scenario demands the implementation of sustainable techniques for ground rejuvenation and effective stabilizers for enhancing engineering properties. This study investigates the amelioration of Kuttanad soft soil using chitosan as a soil amendment to improve its durability and erodibility characteristics. The untreated and chitosan-treated samples were exposed to 5 h of wetting cycle followed by 43 h of drying cycles until their failure. The unconfined compressive strength (UCS) of samples prepared with different dosages (0.5, 2, 4%) and cured for 14, 28, 60, and 90 days was evaluated at the onset and after each drying cycle to measure their durability index. Kuttanad soil was amended with 2% and cured for 90 days withstood five cycles with a UCS of more than 1,000 kPa. The drip erosion tests were used to check the erodibility performance for the aforementioned different dosages and curing periods. The 2% and 4% chitosan amended samples resisted the entire test duration of 10 min indicating the highest water erosion resistance. The findings of the current study evaluated through durability and erosion tests reinforced the effectiveness of chitosan as an effective biopolymer for soft soils subjected to constant water attack and can be easily implemented in places with such vulnerability. A typical earthen canal lining amended with chitosan reduced the carbon emissions by 8.74 and 7.44 times compared to conventional amendments like lime and cement in Carbon Footprint Analysis.
Disentangling multiple relationships of species diversity, functional diversity, diatom community biomass and environmental variables in a mountainous watershed
Authors: Liu Chan , Sun Tingting , Wu Xuan , Tan Lu , Cai Qinghua , Tang Tao
Published: June 2023

Biodiversity and ecosystem functioning (BEF) relationships are important research issues in the context of biodiversity loss. However, most studies only explored BEF relationships using species richness as a proxy for biodiversity without considering the effects of species evenness and importance of functional diversity on ecosystem functioning. In the present study, we explored multiple relationships among in-stream environmental variables, species diversity (species richness and species evenness), functional diversity (functional richness, functional evenness and Rao’s quadratic entropy index) and biomass of benthic diatom communities from a Chinese mountainous river network. We tested two hypotheses: (1) species richness and evenness affect community biomass independently, and (2) species diversity directly affects community biomass and also indirectly affects community biomass by influencing functional diversity. We found that benthic diatom diversity and biomass were influenced by wetted width, conductivity, and pH. Species richness and evenness had positive and negative effects on community biomass, respectively; while, the effect of richness (with a pathway coefficient of 0.39) was stronger than that of evenness (−0.28). However, we have not found an interaction pathway between species richness and species evenness in structural equation models, indicating that the two effects on community biomass were independent of each other. Both functional richness and Rao’s quadratic entropy index had positive effects on community biomass, although effects of other variables blurred the relationship between functional richness and community biomass in structural equation modeling. Besides direct effects, species diversity also indirectly affected community biomass through influencing Rao’s quadratic entropy index, with direct effects (0.27) were more than twice stronger than indirect effects (0.12). Our findings imply that the selection effect played a dominant role in the relationship between diatom diversity and biomass, indicated by the negative species evenness and biomass relationship; meanwhile, the complementarity effect was also important. The inclusion of more diversity indices to explore the biodiversity-biomass relationship would help to provide a deeper and more comprehensive understanding of this relationship and its driving mechanisms. We suggest carrying out more studies on BEF relationships in streams and rivers to support protection practices for sustaining biodiversity and their ecosystem functions in natural lotic ecosystems.
Vascular and Non-HLA autoantibody profiles in hospitalized patients with COVID-19
Authors: Lichtenstein Brian , Zheng Ying , Gjertson David , Ferbas Kathie G. , Rimoin Anne W. , Yang Otto O. , Aldrovandi Grace M. , Schaenman Joanna M. , Reed Elaine F. , Fulcher Jennifer A.
Published: June 2023

Introduction

Severe COVID-19 illness is characterized by an overwhelming immune hyperactivation. Autoantibodies against vascular, tissue, and cytokine antigens have been detected across the spectrum of COVID-19. How these autoantibodies correlate with COVID-19 severity is not fully defined.

Methods

We performed an exploratory study to investigate the expression of vascular and non-HLA autoantibodies in 110 hospitalized patients with COVID-19 ranging from moderate to critically ill. Relationships between autoantibodies and COVID- 19 severity and clinical risk factors were examined using logistic regression analysis.

Results

There were no absolute differences in levels of expression of autoantibodies against angiotensin II receptor type 1 (AT1R) or endothelial cell proteins between COVID-19 severity groups. AT1R autoantibody expression also did not differ by age, sex, or diabetes status. Using a multiplex panel of 60 non- HLA autoantigens we did identify seven autoantibodies that differed by COVID-19 severity including myosin (myosin; p=0.02), SHC-transforming protein 3 (shc3; p=0.07), peroxisome proliferator-activated receptor gamma coactivator 1-beta (perc; p=0.05), glial-cell derived neurotrophic factor (gdnf; p=0.07), enolase 1 (eno1; p=0.08), latrophilin-1 (lphn1; p=0.08), and collagen VI (coll6; p=0.05) with greater breadth and higher expression levels seen in less severe COVID-19.

Discussion

Overall, we found that patients hospitalized with COVID-19 demonstrate evidence of auto-reactive antibodies targeting endothelial cells, angiotensin II receptors, and numerous structural proteins including collagens. Phenotypic severity did not correlate with specific autoantibodies. This exploratory study underscores the importance of better understanding of the role of autoimmunity in COVID-19 disease and sequelae.
Risk and Factors associated with disease manifestations in systemic lupus erythematosus – lupus nephritis (RIFLE-LN): a ten-year risk prediction strategy derived from a cohort of 1652 patients
Authors: Chan Shirley C. W. , Wang Yong-Fei , Yap Desmond Y. H. , Chan Tak Mao , Lau Yu Lung , Lee Pamela P. W. , Lai Wai Ming , Ying Shirley K. Y. , Tse Niko K. C. , Leung Alexander M. H. , Mok Chi Chiu , Lee Ka Lai , Li Teresa W. L. , Tsang Helen H. L. , Yeung Winnie W. Y. , Ho Carmen T. K. , Wong Raymond W. S. , Yang Wanling , Lau Chak Sing , Li Philip H.
Published: June 2023

Objectives

Lupus nephritis (LN) remains one of the most severe manifestations in patients with systemic lupus erythematosus (SLE). Onset and overall LN risk among SLE patients remains considerably difficult to predict. Utilizing a territory-wide longitudinal cohort of over 10 years serial follow-up data, we developed and validated a risk stratification strategy to predict LN risk among Chinese SLE patients – Risk and Factors associated with disease manifestations in systemic Lupus Erythematosus – Lupus Nephritis (RIFLE-LN).

Methods

Demographic and longitudinal data including autoantibody profiles, clinical manifestations, major organ involvement, LN biopsy results and outcomes were documented. Association analysis was performed to identify factors associated with LN. Regression modelling was used to develop a prediction model for 10-year risk of LN and thereafter validated.

Results

A total of 1652 patients were recruited: 1382 patients were assigned for training and validation of the RIFLE-LN model; while 270 were assigned for testing. The median follow-up duration was 21 years. In the training and validation cohort, 845 (61%) of SLE patients developed LN. Cox regression and log rank test showed significant positive association between male sex, age of SLE onset and anti-dsDNA positivity. These factors were thereafter used to develop RIFLE-LN. The algorithm was tested in 270 independent patients and showed good performance (AUC = 0·70).

Conclusion

By using male sex, anti-dsDNA positivity, age of SLE onset and SLE duration; RIFLE-LN can predict LN among Chinese SLE patients with good performance. We advocate its potential utility in guiding clinical management and disease monitoring. Further validation studies in independent cohorts are required.
Platelet formation and activation are influenced by neuronal guidance proteins
Authors: Tang Linyan , Liu Chao , Rosenberger Peter
Published: June 2023

Platelets are anucleate blood cells derived from megakaryocytes. They link the fundamental functions of hemostasis, inflammation and host defense. They undergo intracellular calcium flux, negatively charged phospholipid translocation, granule release and shape change to adhere to collagen, fibrin and each other, forming aggregates, which are key to several of their functions. In all these dynamic processes, the cytoskeleton plays a crucial role. Neuronal guidance proteins (NGPs) form attractive and repulsive signals to drive neuronal axon navigation and thus refine neuronal circuits. By binding to their target receptors, NGPs rearrange the cytoskeleton to mediate neuron motility. In recent decades, evidence has indicated that NGPs perform important immunomodulatory functions and influence platelet function. In this review, we highlight the roles of NGPs in platelet formation and activation.
Stable isotope ecology and interspecific dietary overlap among dolphins in the Northeast Atlantic
Authors: Plint Tessa , ten Doeschate Mariel T.I. , Brownlow Andrew C. , Davison Nicholas J. , Hantke Georg , Kitchener Andrew C. , Longstaffe Fred J. , McGill Rona A. R. , Simon-Nutbrown Cornelia , Magill Clayton R.
Published: June 2023

Dolphins are mobile apex marine predators. Over the past three decades, warm-water adapted dolphin species (short-beaked common and striped) have expanded their ranges northward and become increasingly abundant in British waters. Meanwhile, cold-water adapted dolphins (white-beaked and Atlantic white-sided) abundance trends are decreasing, with evidence of the distribution of white-beaked dolphins shifting from southern to northern British waters. These trends are particularly evident in Scottish waters and ocean warming may be a contributing factor. This mobility increases the likelihood of interspecific dietary overlap for prey among dolphin species previously separated by latitude and thermal gradients. Foraging success is critical to both individual animal health and overall population resilience. However, the degree of dietary overlap and plasticity among these species in the Northeast Atlantic is unknown. Here, we characterise recent (2015-2021) interspecific isotopic niche and niche overlap among six small and medium-sized delphinid species co-occurring in Scottish waters, using skin stable isotope composition (δ13C and δ15N), combined with stomach content records and prey δ13C and δ15N compiled from the literature. Cold-water adapted white-beaked dolphin have a smaller core isotopic niche and lower dietary plasticity than the generalist short-beaked common dolphin. Striped dolphin isotopic niche displayed no interspecific overlap, however short-beaked common dolphin isotopic niche overlapped with white-beaked dolphin by 30% and Atlantic white-sided dolphin by 7%. Increasing abundance of short-beaked common dolphin in British waters could create competition for cold-water adapted dolphin species as a significant portion of their diets comprise the same size Gadiformes and high energy density pelagic schooling fish. These priority prey species are also a valuable component of the local and global fishing industry. Competition for prey from both ecological and anthropogenic sources should be considered when assessing cumulative stressors acting on cold-water adapted dolphin populations with projected decline in available habitat as ocean temperatures continue to rise.
Electron beams near surfaces: the concept of partial intensities for surface analysis and perspective on the low energy regime
Authors: Werner Wolfgang S. M.
Published: June 2023

Electron beam techniques are indispensable tools for the analysis of surfaces in fundamental as well as applied fields of science and technology. Significant improvements have been made in the past decades in the quantitative understanding of electron spectra, particularly with respect to the near-surface transport of signal electrons. The concept of partial intensities is a simple approach providing physical insight into transport of electrons in solids, a numerically convenient means for spectrum modelling and an essential ingredient for spectrum interpretation. The energy-dissipation process of energetic electrons in solids is discussed from the perspective of the partial intensities, offering a unified model for any type of electron beam technique, be it in the quasi-elastic (QE) or the continuous slowing down (CSD) regime. Examples are given for modelling and analysis of electron spectra such as X-ray photoelectron spectra (XPS), Elastic peak electron spectra (EPES) and electron energy-loss spectra (EELS). The physical model as well as the quantities for electron beam interaction with solids are reviewed, and methods for spectrum modelling and analysis are presented. The examples considered demonstrate the high level of accuracy nowadays attainable for characterisation of surfaces and nanostructures employing techniques using medium energy electrons (>100 eV). This is in contrast to the low energy regime, where a number of problems prevent a similar level of understanding. The topic of low energy electrons (LEEs) is rapidly gaining importance since in this energy range the involved electrons not only act as signal carriers, but also actively participate in electrochemical processes of importance in fields ranging from nanotechnology to life sciences. Issues of future importance in the field of LEEs are discussed and recent developments such as the 2-dimensional electron cascade in the scanning field electron microscope are highlighted.
Apolipoprotein A1 is associated with osteocalcin and bone mineral density rather than high-density lipoprotein cholesterol in Chinese postmenopausal women with type 2 diabetes mellitus
Authors: Wang Wei , Chen Zhe Yuan , Lv Fen Yan , Tu Mei , Guo Xiu Li
Published: June 2023

Objective

Disturbances in high-density lipoprotein cholesterol (HDL-c) metabolic pathways can affect bone metabolism, which may rely on the particle function of apolipoprotein rather than HDL-c levels. This study aimed to evaluate the correlation of serum HDL-c and apolipoprotein A1 (APOA1) with bone metabolism in Chinese postmenopausal women with type 2 diabetes mellitus (T2DM).

Method

A total of 1,053 participants with complete data were enrolled and separated into three groups based on the HDL-c and APOA1 tertiles. The trained reviewer collected demographic and anthropometric information. Bone turnover markers (BTMs) were determined by standard methods. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry.

Results

Overall, the prevalence of osteoporosis was 29.7%. Groups with higher APOA1 have a remarkably more elevated level of osteocalcin (OC), L1-L4 BMD, and T-score across the APOA1 tertiles. APOA1 presented a positive correlation with OC (r = 0.194, p < 0.001), L1-L4 BMD (r = 0.165, p < 0.001), and T-score (r = 0.153, p < 0.001) rather than HDL-c. Meanwhile, APOA1 remained independently associated with OC (β = 0.126, p < 0.001), L1-L4 BMD (β = 0.181, p < 0.001), and T-score (β = 0.180, p < 0.001) after adjustment for confounding factors. APOA1 is also shown to be independently correlated with osteoporosis after adjustment for confounding factors, and the OR (95%CI) was 0.851 (0.784–0.924). In contrast, there was no significant association between HDL-c and osteoporosis. Furthermore, APOA1 seemed to have the largest areas under the curve (AUC) for osteoporosis. The AUC (95% CI) of APOA1 identifying osteoporosis was 0.615 (0.577–0.652). The optimal cut-off value of APOA1 was 0.89 g/L (sensitivity: 56.5%, specificity: 67.9%).

Conclusion

APOA1 is independently associated with OC, L1-L4 BMD, and osteoporosis rather than HDL-c in Chinese postmenopausal women with T2DM.
The influence of pterygium on corneal densitometry evaluated using the Oculus Pentacam system
Authors: Zhang Jing , Zhang Liyun , Hu Huiling , Sun Liangnan , He Wenling , Zhang Zhe , Wang Jiantao , Nie Danyao , Liu Xinhua
Published: June 2023

Purpose

To assess the effect of pterygium on corneal densitometry (CD) values.

Methods

One hundred and nine patients (155 eyes) with primary pterygium were divided into a severe pterygium group (79 eyes) and a mild-to-moderate pterygium group (76 eyes) according to pterygium severity. Among them, 63 patients had monocular pterygium; and 25 patients (38 eyes) underwent pterygium excision combined with conjunctival autograft follow-up. A Pentacam anterior segment analyzer was used to obtain the CD values and corneal morphological parameters, including central corneal thickness (CCT), flat-axis keratometry (K1), steep-axis keratometry (K2), corneal astigmatism, irregular astigmatism, and spherical aberration. CD was subdivided into four concentric radial regions based on corneal diameter and three layers according to depth.

Results

CD values at 0–12 mm of the anterior 120 μm layer, 0–10 mm of the center layer and full thickness, and 2–6 mm of the posterior 60 μm layer were significantly higher in eyes affected by pterygium than in the contralateral unaffected eyes (all P < 0.05). CD values were significantly higher in the severe pterygium group than in the mild to moderate pterygium group (all P < 0.05). Corneal astigmatism, irregular astigmatism, K1, K2, CCT, and spherical aberration correlated with CD values in eyes with pterygium (all P < 0.05). CD values at 6–10, 0–12 mm in the anterior 120 μm layer and full thickness, 10–12 and 0–12 mm in the center layer were significantly decreased 1 month after pterygium surgery compared with those before surgery (all P < 0.05).

Conclusion

Patients with pterygium had increased CD values, particularly in the anterior and central layers. CD values were correlated with pterygium severity grading and corneal parameters. Pterygium surgery partially reduced the CD values.
Patients' perspectives related to ethical issues and risks in precision medicine: a systematic review
Authors: Ahmed Lawko , Constantinidou Anastasia , Chatzittofis Andreas
Published: June 2023

Background

Precision medicine is growing due to technological advancements including next generation sequencing techniques and artificial intelligence. However, with the application of precision medicine many ethical and potential risks may emerge. Although, its benefits and potential harms are relevantly known to professional societies and practitioners, patients' attitudes toward these potential ethical risks are not well-known. The aim of this systematic review was to focus on patients' perspective on ethics and risks that may rise with the application of precision medicine.

Methods

A systematic search was conducted on 4/1/2023 in the database of PubMed, for the period 1/1/2012 to 4/1/2023 identifying 914 articles. After initial screening, only 50 articles were found to be relevant. From these 50 articles, 24 articles were included in this systematic review, 2 articles were excluded as not in English language, 1 was a review, and 23 articles did not include enough relevant qualitative data regarding our research question to be included. All full texts were evaluated following PRISMA guidelines for reporting systematic reviews following the Joanna Briggs Institute criteria.

Results

There were eight main themes emerging from the point of view of the patients regarding ethical concerns and risks of precision medicine: privacy and security of patient data, economic impact on the patients, possible harms of precision medicine including psychosocial harms, risk for discrimination of certain groups, risks in the process of acquiring informed consent, mistrust in the provider and in medical research, issues with the diagnostic accuracy of precision medicine and changes in the doctor-patient relationship.

Conclusion

Ethical issues and potential risks are important for patients in relation to the applications of precision medicine and need to be addressed with patient education, dedicated research and official policies. Further research is needed for validation of the results and awareness of these findings can guide clinicians to understand and address patients concerns in clinical praxis.
Co-administration of temozolomide (TMZ) and the experimental therapeutic targeting miR-10b, profoundly affects the tumorigenic phenotype of human glioblastoma cells
Authors: Chen Ming , Kim Bryan , Robertson Neil , Mondal Sujan Kumar , Medarova Zdravka , Moore Anna
Published: June 2023

Introduction: Recent studies have shown that miRNA-10b is highly expressed in high-grade glioblastoma multiforme (GBM), and its inhibition leads to deregulation of multiple pathways in tumorigenesis, resulting in repression of tumor growth and increased apoptosis. Thus, we hypothesized that suppressing miR-10b could enhance the cytotoxicity of conventional GBM chemotherapy with temozolomide (TMZ).

Methods: Inhibition of miR-10b in glioblastoma cells was achieved using an experimental therapeutic consisting of anti-miR10b antagomirs conjugated to iron oxide nanoparticles (termed MN-anti-miR10b). The nanoparticles serve as delivery vehicles for the antagomirs as well as imaging reporters guiding the delivery in future animal studies.

Results: Treatment of U251 and LN229 human glioblastoma cells with MN-anti-miR10b led to inhibition of miR-10b accompanied by repression of growth and increase in apoptosis. We next explored whether MN-anti-miR10b could enhance the cytotoxic effect of TMZ. During these studies, we unexpectedly found that TMZ monotherapy increased miR-10b expression and changed the expression of corresponding miR-10b targets. This discovery led to the design of a sequence-dependent combination treatment, in which miR-10b inhibition and induction of apoptosis by MN-anti-miR10b was followed by a sub-therapeutic dose of TMZ, which caused cell cycle arrest and ultimately cell death. This combination was highly successful in significant enhancement of apoptosis and decrease in cell migration and invasiveness.

Discussion: Considering the unexpected effects of TMZ on miR-10b expression and possible implications on its clinical application, we reasoned that comprehensive in vitro studies were warranted before embarking on studies in animals. These intriguing findings serve as a solid foundation for future in vivo studies and offer promise for the successful treatment of GBM.