bluuebunny/crossref_metadata_2025 huggingface dataset:
Scientific evidence of sodium-glucose cotransporter-2 inhibitors for heart failure with preserved ejection fraction: an umbrella review of systematic reviews and meta-analyses
Authors: Li Runmin , Dai Guohua , Guan Hui , Gao Wulin , Ren Lili , Wang Xingmeng , Qu Huiwen
Published: May 2023

Background

It remains controversial whether sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are effective in treating heart failure with preserved ejection fraction (HFpEF).

Purpose

The objective of this umbrella review is to provide a summary of the available evidence regarding the efficacy and safety of SGLT-2is for the treatment of HFpEF.

Methods

We extracted pertinent systematic reviews and meta-analyses (SRs/MAs) from PubMed, EMBASE, and the Cochrane Library that were published between the inception of the database and December 31, 2022. Two independent investigators assessed the methodological quality, risk of bias, report quality, and evidence quality of the included SRs/MAs in randomized controlled trials (RCTs). We further evaluated the overlap of the included RCTs by calculating the corrected covered area (CCA) and assessed the reliability of the effect size by performing excess significance tests. Additionally, the effect sizes of the outcomes were repooled to obtain objective and updated conclusions. Egger's test and sensitivity analysis were used to clarify the stability and reliability of the updated conclusion.

Results

This umbrella review included 15 SRs/MAs, and their methodological quality, risk of bias, report quality, and evidence quality were unsatisfactory. The total CCA for 15 SRs/MAs was 23.53%, indicating a very high level of overlap. The excess significance tests did not reveal any significant results. Our updated MA demonstrated that the incidence of the composite of hospitalization for heart failure (HHF) or cardiovascular death (CVD), first HHF, total HHF, and adverse events as well as the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) and 6 min-walk distance (6MWD) were all substantially improved in the SGLT-2i intervention group compared to the control group. However, there was limited evidence that SGLT-2is could improve CVD, all-cause death, plasma B-type natriuretic peptide (BNP) level, or plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level. Egger's test and sensitivity analysis proved that the conclusion was stable and reliable.

Conclusions

SGLT-2 is a potential treatment for HFpEF with favourable safety. Given the dubious methodological quality, reporting quality, evidence quality, and high risk of bias for certain included SRs/MAs, this conclusion must be drawn with caution.

Systematic Review Registration

https://inplasy.com/, doi: 10.37766/inplasy2022.12.0083, identifier INPLASY2022120083.
Assessing physical activity with the wearable cardioverter defibrillator in patients with newly diagnosed heart failure
Authors: Iliodromitis Konstantinos , Balogh Zsuzsanna , Triposkiadis Filippos , Deftereos Spyridon , Vrachatis Dimitrios , Bimpong-Buta Nana-Yaw , Schiedat Fabian , Bogossian Harilaos
Published: May 2023

Background

The wearable cardioverter defibrillator (WCD), (LifeVest, ZOLL, Pittsburgh, PA, USA) is a medical device designed for the temporary detection and treatment of malignant ventricular tachyarrhythmias. WCD telemonitoring features enable the evaluation of the physical activity (PhA) of the patients. We sought to assess with the WCD the PhA of patients with newly diagnosed heart failure.

Methods

We collected and analyzed the data of all patients treated with the WCD in our clinic. Patients with newly diagnosed ischemic, or non-ischemic cardiomyopathy and severely reduced ejection fraction, who were treated with the WCD for at least 28 consecutive days and had a compliance of at least 18 h the day were included.

Results

Seventy-seven patients were eligible for analysis. Thirty-seven patients suffered from ischemic and 40 from non-ischemic heart disease. The average days the WCD was carried was 77.3 ± 44.6 days and the mean wearing time was 22.8 ± 2.1 h. The patients showed significantly increased PhA measured by daily steps between the first two and the last two weeks (Mean steps in the first 2 weeks: 4,952.6 ± 3,052.7 vs. mean steps in the last 2 weeks: 6,119.6 ± 3,776.2, p-value:  < 0.001). In the end of the surveillance period an increase of the ejection fraction was observed (LVEF-before: 25.8 ± 6.6% vs. LVEF-after: 37.5 ± 10.6%, p < 0.001). Improvement of the EF did not correlate with the improvement of PhA.

Conclusion

The WCD provides useful information regarding patient PhA and may be additionally utilized for early heart failure treatment adjustment.
Just preparation for war and AI-enabled weapons
Authors: Regan Mitt , Davidovic Jovana
Published: May 2023

This paper maintains that the just war tradition provides a useful framework for analyzing ethical issues related to the development of weapons that incorporate artificial intelligence (AI), or “AI-enabled weapons.” While development of any weapon carries the risk of violations of jus ad bellum and jus in bello, AI-enabled weapons can pose distinctive risks of these violations. The article argues that developing AI-enabled weapons in accordance with jus ante bellum principles of just preparation for war can help minimize the risk of these violations. These principles impose two obligations. The first is that before deploying an AI-enabled weapon a state must rigorously test its safety and reliability, and conduct review of its ability to comply with international law. Second, a state must develop AI-enabled weapons in ways that minimize the likelihood that a security dilemma will arise, in which other states feel threatened by this development and hasten to deploy such weapons without sufficient testing and review. Ethical development of weapons that incorporate AI therefore requires that a state focus not only on its own activity, but on how that activity is perceived by other states.
Discoidin domain receptors; an ancient family of collagen receptors has major roles in bone development, regeneration and metabolism
Authors: Franceschi Renny T. , Hallett Shawn A. , Ge Chunxi
Published: May 2023

The extracellular matrix (ECM) niche plays a critical role in determining cellular behavior during bone development including the differentiation and lineage allocation of skeletal progenitor cells to chondrocytes, osteoblasts, or marrow adipocytes. As the major ECM component in mineralized tissues, collagen has instructive as well as structural roles during bone development and is required for bone cell differentiation. Cells sense their extracellular environment using specific cell surface receptors. For many years, specific β1 integrins were considered the main collagen receptors in bone, but, more recently, the important role of a second, more primordial collagen receptor family, the discoidin domain receptors, has become apparent. This review will specifically focus on the roles of discoidin domain receptors in mineralized tissue development as well as related functions in abnormal bone formation, regeneration and metabolism.
Papua New Guinea Moho inversion based on XGM 2019e gravity field model
Authors: Liu Yijun , Yang Guangliang , Zhang Jie , Zhao Bingjie
Published: May 2023

The construction of the high-resolution Moho depth model is significant for studying the characteristics of the complex tectonic movement (seafloor spreading, plate subduction phenomena) in Papua New Guinea. We calculate the region’s Moho relief and lithosphere thinning factor using the XGM 2019e gravity field model and nonlinear fast gravity inversion method under the GEMMA Moho depth model’s constraint considering the influence of lithosphere thermal gravity anomaly. The calculation result shows that the Moho depth is between 6—34 km, forming two large depressions in Woodlark Basin (WB) and Solomon Sea Plate (SSP) with deep scattered islands. In addition, the findings suggest that Significant differences exist in the shape and tectonic movement intensity of the North and South oceanic crust at the WB. Nevertheless, the lithosphere extends evenly in Manus Basin (MB). WB collided with the Solomon Islands at a higher angle than the SSP subducted under Bismarck Sea Plate (BSP); strong earthquakes may frequently occur on both sides and in deeper positions at West New Britain Trench in the future.
Tephra sedimentation and grainsize associated with pulsatory activity: the 2021 Tajogaite eruption of Cumbre Vieja (La Palma, Canary Islands, Spain)
Authors: Bonadonna Costanza , Pistolesi Marco , Dominguez Lucia , Freret-Lorgeril Valentin , Rossi Eduardo , Fries Allan , Biass Sebastien , Voloschina Marija , Lemus Jonathan , Romero Jorge E. , Zanon Vittorio , Pastore Camille , Reyes Hardy Maria-Paz , Di Maio Luigia Sara , Gabellini Pietro , Martin-Lorenzo Alba , Rodriguez Fatima , Perez Nemesio M.
Published: May 2023

Long-lasting eruptions are of complex characterization and are typically associated with challenging risk assessment and crisis management due to the usual occurrence of multiple interacting hazards evolving at different temporal and spatial scales (e.g., lava, tephra, and gas). The 2021 Tajogaite eruption of Cumbre Vieja (La Palma) demonstrated how even hybrid events that are mostly effusive can be associated with widespread and impacting tephra deposits as a result of a complex interplay among gas flux, conduit geometry, and magma feeding rate. In this novel study, direct observations, syn-eruptive and post-eruptive sampling, and statistical analysis of pulsatory activity have been combined to provide new insights into eruption dynamics. They show how rapid gas segregation and high magma ascent rate modulated the gas flux at multiple vents, resulting in short-time fluctuations among the different explosive styles (ash-poor gas puffing, Strombolian, violent Strombolian, and lava fountaining) and unsteady tephra ground accumulation. Various size-selective sedimentation processes were also observed, including particle aggregation and ash fingers, which have impacted the overall tephra dispersal. In fact, even though both local and total grainsize distributions of selected layers, units, and of the whole tephra blanket are unimodal with a low fine-ash content, grainsize analysis of 154 samples suggests no correlation of particles <63 μm with distance from vents. Our analyses demonstrate the need to include a detailed characterization of all products of hybrid eruptions for a comprehensive interpretation of eruptive dynamics and to use multiple classification strategies that can capture eruptive styles at different temporal scales.
Equity in learning paths and contrast to early school leaving: the complexity of the factors involved in the school experiences of foreign students
Authors: Bembich Caterina
Published: May 2023

The European guidelines and orientation in recent years have been focus on the promotion of equity in the learning paths and in the counteract early school leaving. Although many actions to reduce early school leaving have been implemented, today there remain many students who fail to achieve satisfactory school outcomes and who leave the school system early, especially among students with a migrant background. To understand the dynamics that can lead students in conditions of fragility toward negative educational paths, it is necessary to employ a complex and multidimensional analytical framework that considers the multiple variables involved. The ecological and cultural theoretical model of development highlights the complexity of the factors that can influence students’ learning trajectories, assuming a systemic and multifactorial interpretative approach. Starting from these premises, this study aims to explore the impact of individual and contextual factors in the learning pathways of foreign-born students, taking the students’ perspective. Two hundred and forty-four students attending the second level of secondary school answered to a survey, which explores their perception about: the meaning attributed to the school; the role of teachers and the family in supporting their learning path; their involvement in extra scholastic activities. The results highlight the inclusive role play by the school, which represent a place for integration into the community for foreign students; the central role of relationship with teachers and the emotional support received by the family, in counteracting early school living; the participation of students with a migratory background in their extra scholastic activities as element of protection. The results suggest that to respond to foreign students’ complex educational needs, school cannot act as an isolated entity, but rather should build networks that involve families and external contexts.
Text quality and changing perceptions of teacher feedback and affective-motivational variables: a study with secondary EFL students
Authors: Siekmann Lea , Parr Judy , Van Ophuysen Stefanie , Busse Vera
Published: May 2023

Introduction

Feedback can support students’ writing and has the potential to enhance writing motivation and reduce writing anxiety. However, for feedback to fulfill its potential, it has to be accepted by students and perceived as motivating.

Methods

In this study, we investigate changes in less proficient English as a foreign language (EFL) students’ (N = 53) writing motivation and affect, as well as their perceptions of teacher feedback and how these relate to students’ argumentative text quality. Measurements were taken before EFL teachers attended a professional learning intervention on feedback (T1) and 8 months later (T2).

Results

From T1 to T2, students felt that general feedback quality improved, their writing self-efficacy increased, and their writing anxiety decreased. However, no significant changes in text quality could be observed between T1 and T2, and students continued to struggle with creating structure and coherence in their texts. Regression analyses revealed that feedback perceptions and affective-motivational variables did not predict students’ text quality at T1. Yet at T2, students’ perception of general feedback quality and the effect of feedback on writing motivation were significant predictors of text quality; self-efficacy and writing anxiety were not.

Discussion

Our results suggest that more attention needs to be paid to feedback’s motivational impact, especially among less proficient EFL writers.
Ultrasonography-based radiomics and computer-aided diagnosis in thyroid nodule management: performance comparison and clinical strategy optimization
Authors: Xia Mengwen , Song Fulong , Zhao Yongfeng , Xie Yongzhi , Wen Yafei , Zhou Ping
Published: May 2023

Objectives

To compare ultrasonography (US) feature-based radiomics and computer-aided diagnosis (CAD) models for predicting malignancy in thyroid nodules, and to evaluate their utility for thyroid nodule management.

Methods

This prospective study included 262 thyroid nodules obtained between January 2022 and June 2022. All nodules previously underwent standardized US image acquisition, and the nature of the nodules was confirmed by the pathological results. The CAD model exploited two vertical US images of the thyroid nodule to differentiate the lesions. The least absolute shrinkage and operator algorithm (LASSO) was applied to choose radiomics features with excellent predictive properties for building a radiomics model. Ultimately, the area under the receiver operating characteristic curve (AUC) and calibration curves were assessed to compare diagnostic performance between the models. DeLong’s test was used to analyze the difference between groups. Both models were used to revise the American College of Radiology Thyroid Imaging Reporting and Data Systems (ACR TI-RADS) to provide biopsy recommendations, and their performance was compared with the original recommendations.

Results

Of the 262 thyroid nodules, 157 were malignant, and the remaining 105 were benign. The diagnostic performance of radiomics, CAD, and ACR TI-RADS models had an AUC of 0.915 (95% confidence interval (CI): 0.881–0.947), 0.814 (95% CI: 0.766–0.863), and 0.849 (95% CI: 0.804–0.894), respectively. DeLong’s test showed a statistically significant between the AUC values of models (p < 0.05). Calibration curves showed good agreement in each model. When both models were applied to revise the ACR TI-RADS, our recommendations significantly improved the performance. The revised recommendations based on radiomics and CAD showed an increased sensitivity, accuracy, positive predictive value, and negative predictive value, and decreased unnecessary fine-needle aspiration rates. Furthermore, the radiomics model’s improvement scale was more pronounced (33.3–16.7% vs. 33.3–9.7%).

Conclusion

The radiomics strategy and CAD system showed good diagnostic performance for discriminating thyroid nodules and could be used to optimize the ACR TI-RADS recommendation, which successfully reduces unnecessary biopsies, especially in the radiomics model.
Dermatologic manifestations of thyroid disease: a literature review
Authors: Cohen Benjamin , Cadesky Adam , Jaggi Shuchie
Published: May 2023

Introduction

Thyroid hormone is considered one of the key regulatory hormones for skin homeostasis. Multiple organs are affected by the release of peripheral thyroid hormones (T4 and T3) further regulating various functions at a cellular level. Specifically, skin is considered an important target organ in which the thyroid hormone has a significant impact. Multiple skin diseases are associated with thyroid hormone dysregulation. However, other striking dermatologic manifestations are seen in nails and hair as well. Hypothyroidism, hyperthyroidism, and thyroid cancer can have an array of cutaneous manifestations, and we present the recent updates in this field.

Methods

A PubMed search was performed for updates in any new skin disease findings and treatments between 2010 and 2022. Research published in the past decade and previously known foundational skin findings associated with thyroid disease were presented in this review.

Conclusion

Cutaneous manifestations of thyroid disease is one of the first notable signs of thyroid hormone dysregulation. This article reviews the recent updates on the thyroid and skin interplay, and it further discusses overt visible findings and various available treatment modalities.
Dose–response association of Chinese visceral adiposity index with comorbidity of hypertension and diabetes mellitus among elderly people
Authors: Ren Yongcheng , Cheng Lulu , Qie Ranran , Han Minghui , Kong Lingzhen , Yan Wei , Li Zheng , Li Yiduo , Lei Yicun
Published: May 2023

Background

Chinese visceral adiposity index (CVAI) is a reliable indicator of visceral obesity, but little is known about the association of CVAI with comorbidity of hypertension (HTN) and diabetes mellitus (DM). This study aimed to explore the associations of CVAI with HTN-DM comorbidity, HTN or DM, HTN, and DM in elderly people and evaluate the mediating role of insulin resistance in the associations.

Methods

A total of 3,316 Chinese participants aged ≥60 years were included in this cross-sectional study. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were applied to explore the dose–response associations. Mediation analyses were used to assess the mediating effect of triglyceride-glucose (TyG) index in the associations.

Results

The prevalence rate of HTN-DM comorbidity, HTN or DM, HTN, and DM was 13.78%, 72.26%, 67.16%, and 18.88%, respectively. Linear associations between CVAI and HTN-DM comorbidity, HTN or DM, HTN, and DM were found, and ORs (95%CIs) were 1.45 (1.30–1.61), 1.39 (1.28–1.52), 1.36 (1.25–1.48), and 1.28 (1.16–1.41) for per SD increase in CVAI. Compared with quartile 1 of CVAI, the risk of HTN-DM comorbidity, HTN or DM, HTN, and DM increased 190%, 125%, 112%, and 96% for quartile 4. In addition, we found TyG index playing a key role in the associations of CVAI with HTN-DM comorbidity, HTN or DM, and DM.

Conclusion

CVAI is linearly and positively correlated with HTN-DM comorbidity, HTN or DM, HTN, and DM. The potential mechanism is insulin resistance largely mediating the associations.
Competitiveness—the engine that boosts economic growth and revives the economy
Authors: Vîrjan D. , Manole A. M. , Stanef-Puică M. R. , Chenic A. S. , Papuc C. M. , Huru D. , Bănacu C. S.
Published: May 2023

Competitiveness is a concept that shows up in all aspects of human life, both at the micro level, in personal, social, and professional life, and at the macro level, linked to organizational and national competitiveness with long-term effects on global competitiveness. In this paper, we aim to address competitiveness in Romania in the current context, before and after the COVID-19 pandemic, highlighting its role in reviving the economy. While until the onset of the pandemic Romania’s competitiveness performance was growing, more recently, because of the global health crisis, it dropped a few places, according to the Global Competitiveness Index report. In order to have a clear picture of the degree of competitiveness in Romania, we have presented a series of statistical data for the most relevant macroeconomic indicators for our study for the 2017–2022 timeframe: the global competitiveness index, the minimum wage, labor productivity, the evolution of real labor productivity per employed person, the economic growth rate, the unemployment rate, the inflation rate, the European innovation index, gross domestic expenditure on research and development, export of goods and services as a share of GDP, etc. The methodology used involves the use of quantitative techniques, performing an econometric analysis, and correlating how the most important macroeconomic indicators can influence the degree of competitiveness at both the national and international level. For the post-pandemic timeframe, the analysis switches focus, just as the economic reality did, looking at energy costs and energy use as determinants of competitiveness. Since notions like circular economy and sustainable development correlate being energy-efficient with being competitive, however, at the same time, the high cost of investments necessary for individual businesses and countries to switch from polluting energies to clean energies impedes or at the very least heavily impacts their ability to compete with entities that don’t make that same switch, it becomes apparent that the energy market impacts competitiveness metrics. Competitiveness promotes valuable contributors and underpins performance at group and company level, and the effects from the micro level will propagate, with an emission effect, to the entire national economy with obvious implications at the international level, through real growth in macroeconomic indicators, increased labor productivity, increased economic performance (market share, export share, return on capital), raising living standards and economic and social wellbeing (life expectancy index, human development index, poverty rate), education (skills, knowledge, abilities, managerial and marketing skills, corporate culture), competitive potential (innovation, R&D, promotion), and in raising the Global Competitiveness Index by focusing on factors of production, efficiency, and innovation, etc.
Examining the role of digitalization and gig economy in achieving a low carbon society: an empirical study across nations
Authors: Liu Kai , Feng Zerong , Zhang Qihang
Published: May 2023

Introduction:This paper investigates the international relationship between digitalization, the gig economy, and low carbon development, providing valuable insights for governments and stakeholders seeking to advance sustainable development and a low-carbon society.

Methods:A large dataset comprising countries with varying degrees of digitalization and gig economy prevalence was analyzed to assess the impact of digitalization on the gig economy and its subsequent effects on greenhouse gas emissions.

Results:The study reveals that the impact of digitalization on the gig economy varies by income level, exhibiting a positive relationship in high-income countries and a negative relationship in low-income countries. Furthermore, the gig economy demonstrates a significant negative impact on greenhouse gas emissions, particularly CO2 emissions, indicating that its growth may support emissions reduction and facilitate the transition to a low-carbon society. The gig economy also mediates the connection between digitalization and low-carbon development.

Discussion:These findings carry substantial policy implications for governments and stakeholders working towards sustainable development and a low-carbon society. Moreover, the study highlights potential areas for future research, such as investigating the heterogeneous effects across income levels, exploring sectoral differences in the gig economy, and examining the dynamic nature of the gig economy and digitalization.
Reservoir ecological operation on sediment-laden river considering wetland protection
Authors: Yang Yichen , Liu Bojun
Published: May 2023

Reservoir ecological operation has become an important means of ecological protection and restoration. The operation of reservoirs on sediment-laden rivers with water supply, sediment transport, flood control, wetland protection, and power generation as the primary objectives is a challenge in water resources management. Currently, most studies on reservoir ecological operation models involve a single ecological objective, and the inadequacy of the corresponding ecological constraint conditions makes it difficult to optimize reservoir ecological operation. To address these challenges, this study considers comprehensive water shortage, ecological water shortage, effective sediment transport in the river, and reservoir power generation as objective functions to establish an ecological operation model of sediment-laden river reservoirs for wetland protection. In this model, the ecological flow at key sections and water quantity discharged into the ocean are added as the constraint conditions to generate optimal operation schemes that reflect ecological benefits. The case study of the Xiaolangdi Reservoir (XLDR) on the Yellow River, China shows that with this model, the multi-objective requirements of water supply, ecology, sediment transport, flood control, and power generation in the XLDR could be met synergistically by optimizing the average daily discharge of the reservoir. Although the generated ecological operation schemes consider the demand for wetland protection, the reservoir flood control, sediment transport and power generation were not affected, and the latter two even showed improvement. In addition, this model has stronger applicability for large reservoirs. In dry years, small and medium reservoirs require water transfer, water-saving, and other measures required to alleviate water shortage.
Measuring the coupling coordination of land use functions and influencing factors: a case study in Beijing
Authors: Wang Wenhui , Zhang Jian
Published: May 2023

Land use patterns significantly impact urban development by exerting production-living-ecological functions (PLEFs). Scientifically measuring the relationships among PLEFs is essential to support regional high-quality and sustainable development. However, the current identification methods of PLEFs are biased, and researches on the spatial distribution of coordination and conflict and their influencing factors in metropolitan are insufficient. This study proposed an improved PLEFs identification method to analyze the PLEFs in Beijing from 2000 to 2020 at a grid scale. Then, the coupling coordination degree (CCD) of PLEFS was estimated by employing spatiotemporal data and spatial statistical models. Finally, the impacts of the socioeconomic and natural factors on the CCD were quantified by the geographically weighted regression model (GWR). The results showed that from 2000 to 2020, (1) the areas with high CCD gathered in the plain areas with high PF and LF, and the low CCD areas clustered in the mountainous areas with low PF and LF; (2) the EF presented a closer positive relationship with CCD in the plain areas, while the positive impact of PF and LF on CCD was more substantial than EF in the mountainous areas; and (3) the population and GDP factors had high positive effects on CCD in the north and west mountain areas, and the altitude and slope factors negatively affected CCD in most areas of Beijing, except for a few areas in the southeast. Therefore, formulating a regional differentiation strategy to achieve the sustainable development of PLEFs in Beijing was crucial.
Increase in fine root biomass enhances root exudation by long-term soil warming in a temperate forest
Authors: Heinzle Jakob , Liu Xiaofei , Tian Ye , Kwatcho Kengdo Steve , Heinze Berthold , Nirschi Annika , Borken Werner , Inselsbacher Erich , Wanek Wolfgang , Schindlbacher Andreas
Published: May 2023

Trees can invest up to one-third of the carbon (C) fixed by photosynthesis into belowground allocation, including fine root exudation into the rhizosphere. It is still unclear how climate and soil warming affect tree root C exudation, in particular quantifying longer-term warming effects remains a challenge. In this study, using a C-free cuvette incubation method, in situ C exudation rates from tree fine roots of a mature spruce dominated temperate forest were measured in regular intervals during the 14th and 15th year of experimental soil warming (+ 4°C). In addition, a short-term temperature sensitivity experiment (up to + 10°C warming within 4 days) was conducted to determine the inherent temperature sensitivity of root exudation. Root exudation rates in the long-term warmed soil (17.9 μg C g–1 root biomass h–1) did not differ from those in untreated soil (16.2 μg C g–1 root biomass h–1). However, a clear increase (Q10 ∼5.0) during the short-term temperature sensitivity experiment suggested that fine root exudation can be affected by short-term changes in soil temperature. The absence of response in long-term warmed soils suggests a downregulation of C exudation from the individual fine roots in the warmed soils. The lack of any relationship between exudation rates and the seasonal temperature course, further suggests that plant phenology and plant C allocation dynamics have more influence on seasonal changes in fine root C exudation. Although exudation rates per g dry mass of fine roots were only marginally higher in the warmed soil, total fine root C exudation per m2 soil surface area increased by ∼30% from 0.33 to 0.43 Mg C ha–1 yr–1 because long-term soil warming has led to an increase in total fine root biomass. Mineralization of additional fine root exudates could have added to the sustained increase in soil CO2 efflux from the warmed forest soil at the experimental site.
Cell wall composition in Cryptococcus neoformans is media dependent and alters host response, inducing protective immunity
Authors: Upadhya Rajendra , Lam Woei C. , Hole Camaron R. , Vasselli Joseph G. , Lodge Jennifer K.
Published: May 2023

Introduction

Cryptococcus neoformans is a basidiomycete fungus that can cause meningoencephalitis, especially in immunocompromised patients. Cryptococcus grows in many different media, although little attention has been paid to the role of growth conditions on the cryptococcal cell wall or on virulence.

Objective

The purpose of this study was to determine how different media influenced the amount of chitin and chitosan in the cell wall, which in turn impacted the cell wall architecture and host response.

Methods

Yeast extract, peptone, and dextrose (YPD) and yeast nitrogen base (YNB) are two commonly used media for growing Cryptococcus before use in in vitro or in vivo experiments. As a result, C. neoformans was grown in either YPD or YNB, which were either left unbuffered or buffered to pH 7 with MOPS. These cells were then labeled with cell wall-specific fluorescent probes to determine the amounts of various cell wall components. In addition, these cells were employed in animal virulence studies using the murine inhalation model of infection.

Results

We observed that the growth of wild-type C. neoformans KN99 significantly changes the pH of unbuffered media during growth. It raises the pH to 8.0 when grown in unbuffered YPD but lowers the pH to 2.0 when grown in unbuffered YNB (YNB-U). Importantly, the composition of the cell wall was substantially impacted by growth in different media. Cells grown in YNB-U exhibited a 90% reduction in chitosan, the deacetylated form of chitin, compared with cells grown in YPD. The decrease in pH and chitosan in the YNB-U-grown cells was associated with a significant increase in some pathogen-associated molecular patterns on the surface of cells compared with cells grown in YPD or YNB, pH 7. This altered cell wall architecture resulted in a significant reduction in virulence when tested using a murine model of infection. Furthermore, when heat-killed cells were used as the inoculum, KN99 cells grown in YNB-U caused an aberrant hyper-inflammatory response in the lungs, resulting in rapid animal death. In contrast, heat-killed KN99 cells grown in YNB, pH 7, caused little to no inflammatory response in the host lung, but, when used as a vaccine, they conferred a robust protective response against a subsequent challenge infection with the virulent KN99 cells.

Conclusion

These findings emphasize the importance of culture media and pH during growth in shaping the content and organization of the C. neoformans cell wall, as well as their impact on fungal virulence and the host response.
Evaluation of low-density SNP panels and imputation for cost-effective genomic selection in four aquaculture species
Authors: Kriaridou Christina , Tsairidou Smaragda , Fraslin Clémence , Gorjanc Gregor , Looseley Mark E. , Johnston Ian A. , Houston Ross D. , Robledo Diego
Published: May 2023

Genomic selection can accelerate genetic progress in aquaculture breeding programmes, particularly for traits measured on siblings of selection candidates. However, it is not widely implemented in most aquaculture species, and remains expensive due to high genotyping costs. Genotype imputation is a promising strategy that can reduce genotyping costs and facilitate the broader uptake of genomic selection in aquaculture breeding programmes. Genotype imputation can predict ungenotyped SNPs in populations genotyped at a low-density (LD), using a reference population genotyped at a high-density (HD). In this study, we used datasets of four aquaculture species (Atlantic salmon, turbot, common carp and Pacific oyster), phenotyped for different traits, to investigate the efficacy of genotype imputation for cost-effective genomic selection. The four datasets had been genotyped at HD, and eight LD panels (300–6,000 SNPs) were generated in silico. SNPs were selected to be: i) evenly distributed according to physical position ii) selected to minimise the linkage disequilibrium between adjacent SNPs or iii) randomly selected. Imputation was performed with three different software packages (AlphaImpute2, FImpute v.3 and findhap v.4). The results revealed that FImpute v.3 was faster and achieved higher imputation accuracies. Imputation accuracy increased with increasing panel density for both SNP selection methods, reaching correlations greater than 0.95 in the three fish species and 0.80 in Pacific oyster. In terms of genomic prediction accuracy, the LD and the imputed panels performed similarly, reaching values very close to the HD panels, except in the pacific oyster dataset, where the LD panel performed better than the imputed panel. In the fish species, when LD panels were used for genomic prediction without imputation, selection of markers based on either physical or genetic distance (instead of randomly) resulted in a high prediction accuracy, whereas imputation achieved near maximal prediction accuracy independently of the LD panel, showing higher reliability. Our results suggests that, in fish species, well-selected LD panels may achieve near maximal genomic selection prediction accuracy, and that the addition of imputation will result in maximal accuracy independently of the LD panel. These strategies represent effective and affordable methods to incorporate genomic selection into most aquaculture settings.
An estrogen response-related signature predicts response to immunotherapy in melanoma
Authors: Lin Min , Du Tian , Tang Xiaofeng , Liao Ying , Cao Lan , Zhang Yafang , Zheng Wei , Zhou Jianhua
Published: May 2023

Background

Estrogen/estrogen receptor signaling influences the tumor microenvironment and affects the efficacy of immunotherapy in some tumors, including melanoma. This study aimed to construct an estrogen response-related gene signature for predicting response to immunotherapy in melanoma.

Methods

RNA sequencing data of 4 immunotherapy-treated melanoma datasets and TCGA melanoma was obtained from open access repository. Differential expression analysis and pathway analysis were performed between immunotherapy responders and non-responders. Using dataset GSE91061 as the training group, a multivariate logistic regression model was built from estrogen response-related differential expression genes to predict the response to immunotherapy. The other 3 datasets of immunotherapy-treated melanoma were used as the validation group. The correlation was also examined between the prediction score from the model and immune cell infiltration estimated by xCell in the immunotherapy-treated and TCGA melanoma cases.

Results

“Hallmark Estrogen Response Late” was significantly downregulated in immunotherapy responders. 11 estrogen response-related genes were significantly differentially expressed between immunotherapy responders and non-responders, and were included in the multivariate logistic regression model. The AUC was 0.888 in the training group and 0.654–0.720 in the validation group. A higher 11-gene signature score was significantly correlated to increased infiltration of CD8+ T cells (rho=0.32, p=0.02). TCGA melanoma with a high signature score showed a significantly higher proportion of immune-enriched/fibrotic and immune-enriched/non-fibrotic microenvironment subtypes (p<0.001)–subtypes with better response to immunotherapy–and significantly better progression-free interval (p=0.021).

Conclusion

In this study, we identified and verified an 11-gene signature that could predict response to immunotherapy in melanoma and was correlated with tumor-infiltrating lymphocytes. Our study suggests targeting estrogen-related pathways may serve as a combination strategy for immunotherapy in melanoma.
Human papillomavirus vaccination in low- and middle-income countries: progression, barriers, and future prospective
Authors: Ebrahimi Narges , Yousefi Zahra , Khosravi Gholamreza , Malayeri Fatemeh Eskandari , Golabi Marjan , Askarzadeh Monireh , Shams Mohammad Hossein , Ghezelbash Behrooz , Eskandari Nahid
Published: May 2023

Human papillomavirus (HPV) is a viral infection that, if does not go away, can cause health problems like genital warts and cancer. The national immunization schedules for individuals before sexual debut, significantly decreased HPV-associated mortality and it will be affordable. However, immunization programs remain vulnerable to macroeconomic factors such as inflation, fiscal policy, employment levels, and national income. This review aims to investigate the association between national income in lower-middle-income countries to explore recent advances and potential issues, as well as how to deal with challenges.
Serum albumin binding knob domains engineered within a VH framework III bispecific antibody format and as chimeric peptides
Authors: Adams Ralph , Joyce Callum , Kuravskiy Mikhail , Harrison Katriona , Ahdash Zainab , Balmforth Matthew , Chia Kelda , Marceddu Cinzia , Coates Matthew , Snowden James , Goursaud Emmanuel , Ménochet Karelle , Elsen Jean van den , Payne Richard J. , Lawson Alastair D. G. , Scott-Tucker Anthony , Macpherson Alex
Published: May 2023

Background

Serum albumin binding is an established mechanism to extend the serum half-life of antibody fragments and peptides. The cysteine rich knob domains, isolated from bovine antibody ultralong CDRH3, are the smallest single chain antibody fragments described to date and versatile tools for protein engineering.

Methods

Here, we used phage display of bovine immune material to derive knob domains against human and rodent serum albumins. These were used to engineer bispecific Fab fragments, by using the framework III loop as a site for knob domain insertion.

Results

By this route, neutralisation of the canonical antigen (TNFα) was retained but extended pharmacokinetics in-vivo were achieved through albumin binding. Structural characterisation revealed correct folding of the knob domain and identified broadly common but non-cross-reactive epitopes. Additionally, we show that these albumin binding knob domains can be chemically synthesised to achieve dual IL-17A neutralisation and albumin binding in a single chemical entity.

Conclusions

This study enables antibody and chemical engineering from bovine immune material, via an accessible discovery platform.
Update on transfusion-related acute lung injury: an overview of its pathogenesis and management
Authors: Yu Yunhong , Lian Zhengqiu
Published: May 2023

Transfusion-related acute lung injury (TRALI) is a severe adverse event and a leading cause of transfusion-associated death. Its poor associated prognosis is due, in large part, to the current dearth of effective therapeutic strategies. Hence, an urgent need exists for effective management strategies for the prevention and treatment of associated lung edema. Recently, various preclinical and clinical studies have advanced the current knowledge regarding TRALI pathogenesis. In fact, the application of this knowledge to patient management has successfully decreased TRALI-associated morbidity. This article reviews the most relevant data and recent progress related to TRALI pathogenesis. Based on the existing two-hit theory, a novel three-step pathogenesis model composed of a priming step, pulmonary reaction, and effector phase is postulated to explain the process of TRALI. TRALI pathogenesis stage-specific management strategies based on clinical studies and preclinical models are summarized with an explication of their models of prevention and experimental drugs. The primary aim of this review is to provide useful insights regarding the underlying pathogenesis of TRALI to inform the development of preventive or therapeutic alternatives.
Increase in gut permeability and oxidized ldl is associated with post-acute sequelae of SARS-CoV-2
Authors: Mouchati Christian , Durieux Jared C. , Zisis Sokratis N. , Labbato Danielle , Rodgers Michael A. , Ailstock Kate , Reinert Brian L. , Funderburg Nicholas T. , McComsey Grace A.
Published: May 2023

Background

Post-acute sequelae of SARS-CoV-2 (PASC) is marked by persistent or newly developing symptoms beyond 4 weeks of infection. Investigating gut integrity, oxidized lipids and inflammatory markers is important for understanding PASC pathogenesis.

Methods

A cross-sectional study including COVID+ with PASC, COVID+ without PASC, and COVID-negative (COVID-) participants. We measured plasma markers by enzyme-linked immunosorbent assay to assess intestinal permeability (ZONULIN), microbial translocation (lipopolysaccharide-binding protein or LBP), systemic inflammation (high-sensitivity C-reactive protein or hs-CRP), and oxidized low-density lipoprotein (Ox-LDL).

Results

415 participants were enrolled in this study; 37.83% (n=157) had prior COVID diagnosis and among COVID+, 54% (n=85) had PASC. The median zonulin among COVID- was 3.37 (IQR: 2.13, 4.91) mg/mL, 3.43 (IQR: 1.65, 5.25) mg/mL among COVID+ no PASC, and highest [4.76 (IQR: 3.2, 7.35) mg/mL] among COVID+ PASC+ (p<.0001). The median ox-LDL among COVID- was 47.02 (IQR: 35.52, 62.77) U/L, 57.24 (IQR: 40.7, 75.37) U/L among COVID+ No PASC, and the highest [76.75 (IQR: 59.95, 103.28) U/L] among COVID+ PASC+ (p<.0001). COVID+ PASC+ was positively associated with zonulin (p=0.0002) and ox-LDL (p<.0001), and COVID- was negatively associated with ox-LDL (p=0.01), compared to COVID+ No PASC. Every unit increase in zonulin was associated with 44% higher predicted odds of having PASC [aOR: 1.44 (95%CI: 1.1, 1.9)] and every one-unit increase in ox-LDL was associated with more than four-fold increased odds of having PASC [aOR: 2.44 (95%CI: 1.67, 3.55)].

Conclusions

PASC is associated with increased gut permeability and oxidized lipids. Further studies are needed to clarify whether these relationships are causal which could lead to targeted therapeutics.
Interferon regulatory factor 7 in inflammation, cancer and infection
Authors: Qing Furong , Liu Zhiping
Published: May 2023

Interferon regulatory factor 7 (IRF7), a member of the interferon regulatory factors (IRFs) family, is located downstream of the pattern recognition receptors (PRRs)-mediated signaling pathway and is essential for the production of type I interferon (IFN-I). Activation of IRF7 inhibits various viral and bacterial infections and suppresses the growth and metastasis of some cancers, but it may also affect the tumor microenvironment and promote the development of other cancers. Here, we summarize recent advances in the role of IRF7 as a multifunctional transcription factor in inflammation, cancer and infection by regulating IFN-I production or IFN-I-independent signaling pathways.
Gene silencing in adult Popillia japonica through feeding of double‐stranded RNA (dsRNA) complexed with branched amphiphilic peptide capsules (BAPCs)
Authors: Carroll Elijah , Kunte Nitish , McGraw Erin , Gautam Sujan , Range Ryan , Noveron-Nunez Jose A. , Held David W. , Avila L. Adriana
Published: May 2023

Gene silencing by feeding double-stranded (dsRNA) holds promise as a novel pest management strategy. Nonetheless, degradation of dsRNA in the environment and within the insect gut, as well as inefficient systemic delivery are major limitations to applying this strategy. Branched amphiphilic peptide capsules (BAPCs) complexed with dsRNA have been used to successfully target genes outside and inside the gut epithelium upon ingestion. This suggests that BAPCs can protect dsRNA from degradation in the gut environment and successfully shuttle it across gut epithelium. In this study, our objectives were to 1) Determine whether feeding on BAPC-dsRNA complexes targeting a putative peritrophin gene of P. japonica would result in the suppression of gut peritrophin synthesis, and 2) gain insight into the cellular uptake mechanisms and transport of BAPC-dsRNA complexes across the larval midgut of P. japonica. Our results suggest that BAPC-dsRNA complexes are readily taken up by the midgut epithelium, and treatment of the tissue with endocytosis inhibitors effectively suppresses intracellular transport. Further, assessment of gene expression in BAPC- peritrophin dsRNA fed beetles demonstrated significant downregulation in mRNA levels relative to control and/or dsRNA alone. Our results demonstrated that BAPCs increase the efficacy of gene knockdown relative to dsRNA alone in P. japonica adults. To our knowledge, this is the first report on nanoparticle-mediated dsRNA delivery through feeding in P. japonica.