bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of SARS-CoV-2 infection by diet-modulated gut microbiota
Authors: Tieu Vivian , Tibi Sedra , Ling Jun
Published: June 2023

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has claimed millions of lives since late 2019, yet there are still many unexplored areas in its pathogenesis and clinical outcomes. COVID-19 is a disease that can affects multiple systems, some of which are overlapped with those modulated by gut microbiota, especially the immune system, thus leading to our concentration on analyzing the roles of microbiota in COVID-19 pathogenesis through the gut-lung axis. Dysbiosis of the commensal intestinal microbes and their metabolites (e.g., SCFAs) as well as the expression and activity of ACE2 in the gut could influence the host’s immune system in COVID-19 patients. Moreover, it has been known that the elderly and individuals diagnosed with comorbidities (e.g., hypertension, type 2 diabetes mellitus, cardiovascular disease, etc.) are more susceptible to gut flora alterations, SARS-CoV-2 infection, and death. Thus, in this review we will focus on analyzing how the gut microbiota regulates the immune system that leads to different responses to SARS-CoV-2 infection. Since diet is a major factor to modulate the status of gut microbiota, dietary influence on COVID-19 pathogenesis will be also discussed, aiming to shed light on how diet-modulated gut microbiota regulates the susceptibility, severity, and treatment of SARS-CoV-2 infection.
Changing patterns of infectious diseases in children during the COVID-19 pandemic
Authors: Yang Ming-Chun , Su Yu-Tsun , Chen Ping-Hong , Tsai Ching-Chung , Lin Ting-I , Wu Jiunn-Ren
Published: June 2023

Each infectious disease has had its own epidemic pattern and seasonality for decades. However, public health mitigation measures during the coronavirus disease 2019 (COVID-19) pandemic have resulted in changing epidemic patterns of infectious diseases. Stringent measures resulted in low incidences of various infectious diseases during the outbreak of COVID-19, including influenza, respiratory syncytial virus, pneumococcus, enterovirus, and parainfluenza. Owing to the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and subsequent immunity development, decreasing virulence of SARS-CoV-2, and worldwide immunization against SARS-CoV-2 in children beyond 6 months of age, mitigation measures are lifted country by country. Consequently, the immunity debt to infectious respiratory viruses other than SARS-CoV-2 contributed to the “off-season,” “see-saw,” and “upsurge” patterns of various infectious diseases in children. Moreover, apart from the persistence of SARS-CoV-2, the coexistence of other circulating viruses or bacterial outbreaks may lead to twindemics or tripledemics during the following years. Therefore, it is necessary to maintain hand hygiene and immunization policies against various pathogens to alleviate the ongoing impact of infectious diseases on children.
Humoral immune responses to inactivated COVID-19 vaccine up to 1 year in children with chronic hepatitis B infection
Authors: Zhou Yingzhi , Chen Zhiwei , He Yi , Peng Xiaorong , Chang Yunan , Tan Aoxue , Li Hu , Cai Dachuan , Hu Peng , Chen Min , Peng Mingli , Xu Hongmei , Ren Hong
Published: June 2023

Background

Inactivated SARS-CoV-2 vaccination has recently been approved for children aged 3-17 years in China. However, data on long-term humoral responses to inactivated vaccines in children with chronic hepatitis B (CHB) are still limited.

Methods

In this prospective observational study, CHB children after primary inactivated SARS-CoV-2 vaccines were recruited consecutively and followed up for 1 year. CHB adults from another cohort study (NCT05007665) were used as a control. The receptor-binding domain IgG antibody (anti-RBD-IgG), neutralizing antibody (NAb), neutralization against Omicron (BA2.12.1, BA.4 and BA.5), and memory B -cell (MBC) responses were evaluated.

Results

Overall, 115 CHB children and 351 CHB adults were included in this analysis. The antibody titers decreased over the first ~180 days and then plateaued up to 1 year in CHB children. However, lower and faster declines in antibody responses were observed in CHB adults. Interestingly, the seroprevalence of antibodies was still high after over 8 months in CHB children (anti-RBD-IgG [90%] and NAbs [83%]). However, neutralization against Omicron subvariants was significantly reduced in CHB children (-3.68-fold to -8.60-fold). Notably, neutralization against the BA.5 subvariant was obviously diminished in CHB children compared with adults. Moreover, CHB children had similar RBD-specific MBCs but higher RBD-specific atypical MBCs compared with adults.

Conclusion

Inactivated vaccination could elicit more robust and durable antibody responses to the wild-type SARS-CoV-2 strain in CHB children than in CHB adults but showed inferior responses to Omicron subvariants (especially to the BA.5 strain). Hence, new Omicron-related or all-in-one vaccines are needed immediately for CHB children.
The delayed bloodstream clearance of Plasmodium falciparum parasites after M5717 treatment is attributable to the inability to modify their red blood cell hosts
Authors: Parkyn Schneider Molly , Looker Oliver , Rebelo Maria , Khoury David S. , Dixon Matthew W. A. , Oeuvray Claude , Crabb Brendan S. , McCarthy James , Gilson Paul R.
Published: June 2023

M5717 is a promising antimalarial drug under development that acts against multiple stages of the life cycle of Plasmodium parasites by inhibiting the translation elongation factor 2 (PfeEF2), thereby preventing protein synthesis. The parasite clearance profile after drug treatment in preclinical studies in mice, and clinical trials in humans showed a notable delayed clearance phenotype whereby parasite infected red blood cells (iRBCs) persisted in the bloodstream for a significant period before eventual clearance. In a normal P. falciparum infection iRBCs sequester in the deep circulation by cytoadherence, allowing them to avoid surveillance and clearance in the spleen. We found that M5717 blocks parasite modification of their host red blood cells (RBCs) by preventing synthesis of new exported proteins, rather than by directly blocking the export of these proteins into the RBC compartment. Using in vitro models, we demonstrated that M5717 treated ring/trophozoite stage iRBCs became less rigid, and cytoadhered less well compared to untreated iRBCs. This indicates that in vivo persistence of M5717 treated iRBCs in the bloodstream is likely due to reduced cytoadherence and splenic clearance.
What makes people adapt together? An empirically grounded conceptual model on the enablers and barriers of collective climate change adaptation
Authors: Wannewitz Mia , Petzold Jan , Garschagen Matthias
Published: June 2023

Coping with and adapting to climate change impacts are collective action problems that require broad joint efforts to reduce current and future risks. This is most obvious for highly vulnerable and exposed individuals, whose capacities to adapt to recurrent environmental threats are mostly bound in their ability to work together – not only in the immediate disaster situation but also in the long-term to secure their livelihoods. While there are explanatory models for collective action in the context of climate change, there is still a need to validate them further for vulnerable residents in high-risk contexts that prioritize cultural values of collective self-understanding, mutual support, and reciprocity. Additionally, the identified factors that facilitate collective climate action are currently quite abstract and may not be very useful for practical application and policy development. Addressing these gaps, we build on existing collective action models and a qualitative analysis of empirical data from kampung cooperatives in Jakarta to develop a conceptual framework explaining what triggers individuals to start acting collectively and which factors motivate them to keep being engaged in long-term collective adaptation action. It highlights the need to differentiate between what we will call initial triggers and long-term motivators to better understand and advance collective adaptation efforts in high-risk contexts. This novel differentiation of motivation factors enhances our conceptual understanding of collective adaptation. Furthermore, the findings may inform practice and policy-making toward enhancing and maintaining collective adaptation initiatives.
Compensatory effects of individual differences, language proficiency, and reading behavior: an eye-tracking study of second language reading assessment
Authors: Tywoniw Rurik
Published: June 2023

Reading in a second language (L2) is a complex process that incorporates linguistic knowledge and literacy abilities, as well as strategic competence to approach different types of reading tasks depending on reading goals. However, much of the previous research was limited to correlational studies and focused on the relative contribution of broad categories of L2 proficiency and first-language (L1) literacy to L2 reading comprehension. However, investigations into L2 reading performance can benefit from advances in real-time, concurrent data collection methodologies such as eye-tracking. This study utilized eye-tracking methods to examined L2 reading comprehension of 102 readers across three different reading tasks [Cloze reading, Multiple-choice (MC) quiz, and reading-to-summarize], comparing the comprehension scores to L2 proficiency, individual differences (reasoning, working memory, motivation) and reading behavior (eye-tracking metrics related to attention to reading texts and tasks, length of fixations). Results indicate that the score on each task could be modeled each using a different mix of predictors, with the cloze task being most strongly predicted and the MC task being least predicted. The Summary task was in-between, but with a highly interpretable model. Interactions between fixation duration and cognitive abilities were found, showing how efficient fixation is generally important for comprehension, but the impact can be compensated for with motivation and reasoning ability.
Self-attention in vision transformers performs perceptual grouping, not attention
Authors: Mehrani Paria , Tsotsos John K.
Published: June 2023

Recently, a considerable number of studies in computer vision involve deep neural architectures called vision transformers. Visual processing in these models incorporates computational models that are claimed to implement attention mechanisms. Despite an increasing body of work that attempts to understand the role of attention mechanisms in vision transformers, their effect is largely unknown. Here, we asked if the attention mechanisms in vision transformers exhibit similar effects as those known in human visual attention. To answer this question, we revisited the attention formulation in these models and found that despite the name, computationally, these models perform a special class of relaxation labeling with similarity grouping effects. Additionally, whereas modern experimental findings reveal that human visual attention involves both feed-forward and feedback mechanisms, the purely feed-forward architecture of vision transformers suggests that attention in these models cannot have the same effects as those known in humans. To quantify these observations, we evaluated grouping performance in a family of vision transformers. Our results suggest that self-attention modules group figures in the stimuli based on similarity of visual features such as color. Also, in a singleton detection experiment as an instance of salient object detection, we studied if these models exhibit similar effects as those of feed-forward visual salience mechanisms thought to be utilized in human visual attention. We found that generally, the transformer-based attention modules assign more salience either to distractors or the ground, the opposite of both human and computational salience. Together, our study suggests that the mechanisms in vision transformers perform perceptual organization based on feature similarity and not attention.
Inflammation as a therapeutic target in heart failure with preserved ejection fraction
Authors: Peh Zhen Hui , Dihoum Adel , Hutton Dana , Arthur J. Simon C. , Rena Graham , Khan Faisel , Lang Chim C. , Mordi Ify R.
Published: June 2023

Heart failure with preserved ejection fraction (HFpEF) accounts for around half of all cases of heart failure and may become the dominant type of heart failure in the near future. Unlike HF with reduced ejection fraction there are few evidence-based treatment strategies available. There is a significant unmet need for new strategies to improve clinical outcomes in HFpEF patients. Inflammation is widely thought to play a key role in HFpEF pathophysiology and may represent a viable treatment target. In this review focusing predominantly on clinical studies, we will summarise the role of inflammation in HFpEF and discuss potential therapeutic strategies targeting inflammation.
Personalized remotely guided preventive exercise therapy for a healthy heart (PRIORITY): protocol for an assessor-blinded, multicenter randomized controlled trial
Authors: De Wilde Camille , Bekhuis Youri , Kuznetsova Tatiana , Claes Jomme , Claessen Guido , Coninx Karin , Decorte Elise , De Smedt Delphine , Hansen Dominique , Lannoo Matthias , Van Craenenbroeck Emeline M. , Verhaeghe Nick , Cornelissen Véronique A.
Published: June 2023

Aims

A key treatment for patients with varying stages of heart failure with preserved ejection fraction (HFpEF) is exercise. Yet, despite a Class 1A recommendation, only one-third of patients exercise sufficiently. A huge treatment gap exists between guidelines and clinical practice. PRIORITY aims to establish the feasibility, clinical effectiveness and cost-effectiveness of a hybrid centre and home-based personalized exercise and physical activity intervention for patients along the HFpEF continuum.

Methods

An assessor-blinded, multicenter randomized controlled trial will be conducted among 312 patients along the HFpEF continuum. Participants will be randomized (1:1) to the PRIORITY intervention or a comparator group receiving only a written exercise prescription. Participants in the PRIORITY group will receive 18 supervised centre-based exercise sessions during one year, supplemented with a remotely guided home-based physical activity program. Outcomes will be assessed at baseline, 4 months, one and two years. The primary outcome is the peak oxygen uptake (pVO2) at 1-year. Secondary outcomes include physical activity, other physical fitness parameters, cardiovascular health, echocardiographic parameters, health-related quality of life and costs at 1-year FU. Machine learning algorithms will analyse big data on physical activity collected during the 1-year intervention to develop models that can predict physical activity uptake and adherence as well as changes in fitness and health. A cost-utility analysis will be performed to evaluate the cost-effectiveness of the PRIORITY intervention compared to the control condition.

Discussion

We anticipate that participants in the supervised home-based exercise intervention group will have a greater increase in pVO2 compared to those receiving a written exercise prescription.

Trial registration number

This trial is registered at ClinicalTrials.gov (NCT04745013) and is currently in the recruitment stage.
Seasonal variations of nitrous oxide in a populous urban estuary and its adjacent sea
Authors: Tseng Hsiao-Chun , Yuh Han Yokie Tai , Lin Chia-Chia , Gong Gwo-Ching
Published: June 2023

The first investigations of seasonal N2O variations and water-to-air fluxes in the Tamsui River estuary and its adjacent sea were carried out in this study. In the Tamsui River estuary, the concentration of N2O decreased with increasing salinity. The seasonal variations of N2O concentrations in the estuary were 46.8–148.5 nM in autumn, 15.9–82.5 nM in spring, 11.0–42.0 nM in summer and 13.1–120.6 nM in winter. When salinity regressed to zero, N2O concentration was highest in autumn, followed by winter, spring, and summer, which might be influenced by the DO and NO3− concentrations as well as temperature. Because of mountains occlusion, the seasonal variations in wind speed were not large in the Tamsui River estuary. Seasonal variations of N2O fluxes in the estuary were 10.9–35.6 μmol m−2 d−1 in autumn, 2.8–15.1 μmol m−2 d−1 in spring, 2.4–9.5 μmol m−2 d−1 in summer and 2.7–26.8 μmol m−2 d−1 in winter. In the adjacent sea of Tamsui River estuary, seasonal average N2O concentrations in the surface seawater were 10.3 ± 0.2 nM in autumn, 11.6 ± 1.2 nM in spring, 11.4 ± 0.7 nM in summer and 13.8 ± 0.9 nM in winter, with no significantly seasonal changes while wind speed varied greatly seasonally. Seasonal variations of average N2O fluxes in Tamsui River estuary’s adjacent sea were 40.3 ± 0.7 μmol m−2 d−1 in autumn, 19.7 ± 2.1 μmol m−2 d−1 in spring, 20.9 ± 1.3 μmol m−2 d−1 in summer and 49.0 ± 3.3 μmol m−2 d−1 in winter. As a result, seasonal variations in N2O fluxes in the estuary were dominated by N2O concentrations in the water, whereas in the sea, it was dominated by wind speed. Overall, the Tamsui River estuary and its adjacent sea were net sources of atmospheric N2O with annual average fluxes 10.6 ± 6.7 and 32.5 ± 14.5 μmol m−2 d−1, respectively.
Unraveling the roles of endoplasmic reticulum-associated degradation in metabolic disorders
Authors: Luo Hui , Jiao Qibin , Shen Chuanbin , Shao Chenyi , Xie Jinyan , Chen Yue , Feng Xinglin , Zhang Xingwei
Published: June 2023

Misfolded proteins retained in the endoplasmic reticulum cause many human diseases. ER-associated degradation (ERAD) is one of the protein quality and quantity control system located at ER, which is responsible for translocating the misfolded proteins or properly folded but excess proteins out of the ER for proteasomal degradation. Recent studies have revealed that mice with ERAD deficiency in specific cell types exhibit impaired metabolism homeostasis and metabolic diseases. Here, we highlight the ERAD physiological functions in metabolic disorders in a substrate-dependent and cell type-specific manner.
Cysteine residues in signal transduction and its relevance in pancreatic beta cells
Authors: Holendova Blanka , Plecita-Hlavata Lydie
Published: June 2023

Cysteine is one of the least abundant but most conserved amino acid residues in proteins, playing a role in their structure, metal binding, catalysis, and redox chemistry. Thiols present in cysteines can be modified by post-translational modifications like sulfenylation, acylation, or glutathionylation, regulating protein activity and function and serving as signals. Their modification depends on their position in the structure, surrounding amino acids, solvent accessibility, pH, etc. The most studied modifications are the redox modifications by reactive oxygen, nitrogen, and sulfur species, leading to reversible changes that serve as cell signals or irreversible changes indicating oxidative stress and cell damage. Selected antioxidants undergoing reversible oxidative modifications like peroxiredoxin-thioredoxin system are involved in a redox-relay signaling that can propagate to target proteins. Cysteine thiols can also be modified by acyl moieties’ addition (derived from lipid metabolism), resulting in protein functional modification or changes in protein anchoring in the membrane. In this review, we update the current knowledge on cysteine modifications and their consequences in pancreatic β-cells. Because β-cells exhibit well-balanced redox homeostasis, the redox modifications of cysteines here serve primarily for signaling purposes. Similarly, lipid metabolism provides regulatory intermediates that have been shown to be necessary in addition to redox modifications for proper β-cell function and, in particular, for efficient insulin secretion. On the contrary, the excess of reactive oxygen, nitrogen, and sulfur species and the imbalance of lipids under pathological conditions cause irreversible changes and contribute to oxidative stress leading to cell failure and the development of type 2 diabetes.
Regional assessment of trash in Southern California coastal watersheds, United States
Authors: McLaughlin Karen , Mazor Raphael , Sutula Martha , Schiff Kenneth
Published: June 2023

Trash impairment of watersheds has been recognized as a worldwide environmental problem. Trash monitoring in streams and rivers is necessary to enhance our understanding of its effects on freshwater habitats and the role of streams as a conduit for transport to marine environments. Southern California, with a population of over 22 million, is home to nearly 7,400 km of wadeable streams in watersheds spanning a variety of land uses, making it an ideal region to study the extent and magnitude of trash and trash types (plastic, metal, glass, etc.) and identify relationships between land use and the amount of trash. These data can be used to develop mitigation strategies and evaluate management successes. We found that 77% of Southern California’s coastal stream kilometers contained trash, with an estimated stock of 7 million pieces of trash. Of the types enumerated, plastic trash was the most ubiquitous, present in 69% of stream kilometers, and the most abundant, with an estimated stock of over 4.3 million pieces of plastic. The most common items were single-use plastic containers, wrappers, and plastic bags. Urban land use was associated with the greatest extent and magnitude of trash, with levels nearly double those found in open land uses. Trash was strongly associated with indicators of human activity and development in watersheds. Road density and proximity to roads and parking lots were strongly associated with increased trash in watersheds. This survey also suggested that management actions had a positive effect on trash count. After the previous trash survey in Southern California streams in 2011–2013, a statewide ban on plastic bags was implemented in 2016. We found a significant decrease in the number of plastic bags within streams in the present survey compared to the previous survey.
Complex drivers of primary production along an anthropised estuary (Seine estuary—France)
Authors: Serre-Fredj Léon , Chasselin Léo , Jolly Orianne , Claquin Pascal
Published: June 2023

The Seine estuary is a typical model of a system in which phosphorus (P) inputs have been considerably reduced to reduce past eutrophication, with a parallel decrease in phytoplankton biomass. However, reducing P alone while concentrations of nitrate (N) remains high led to a dystrophic nutrient balance in the estuary (high N/P and N/Si). To identify the drivers of primary production and phytoplankton communities in the highly anthropised Seine estuary, sampling was performed along a 110-km stretch over a period of 3 years. Photosynthetic parameters were measured with a single turnover active fluorimeter and the phytoplankton community was assessed using a fluoroprobe and flow cytometry. The results revealed an annual primary production of 33 g C.m−2.y−1 which was largely controlled by light availability (turbidity) but also by nutrients in late spring and summer period. Massive blooms, not seen since 2002, were observed in a specific area of the estuary. None of the nutrients measured explained the particular location of the blooms but phytoplankton production and productivity indicators were higher in this specific zone excluding a biomass accumulation phenomenon. The local effect of tide slowdown increasing water residence time in this exact part of the estuary could explain the bloom area. The question thus arises: does phosphate play a role as a limiting nutrient? The diatom bloom led to total depletion of Si, but no clear limitation of P was observed. Nevertheless, the decrease in Si appears to have played a key role by triggering a succession from diatoms (microphytoplankton) to chlorophytes (nanophytoplankton) and hence affecting phytoplankton composition. The N/P balance appeared to be more important than the absolute concentration of P to explain the phytoplankton dynamics and the biomass decrease observed the last decades.
Toward a forest transition across the Brazilian Atlantic Forest biome
Authors: Bicudo da Silva Ramon Felipe , Moran Emilio , Viña Andrés , Millington James D. A. , Dou Yue , Vieira Simone A. , Lopez Maria Claudia , Liu Jianguo
Published: June 2023

The world has entered the United Nations Decade on Ecosystem Restoration (2021–2030), yet many regions of the world still face environmental degradation. In this context a question arises: under what conditions may a given region shift from a trajectory of environmental degradation to environmental recovery? Answering this question constitutes an important endeavor for the scientific community, policymakers, and organizations leading the planning and implementation of restoration projects. This study examines some of the human-environment conditions underpinning the net gains in natural forest cover in a region that has experienced environmental degradation: the Atlantic Forest biome, Brazil. Using land-use/cover (LULC) data, we assessed the loss and successive gain in forest cover during the 1987–2001 and 2001–2015 periods. Municipality-level statistics on agriculture and economy, together with LULC and biophysical data, were used to develop models for assessing forest cover trajectories. Of the 1,972 municipalities experiencing net forest loss during the 1987–2001 period, 59% shifted their trajectory to a net gain during the 2001–2015 period. This shift, known as forest transition, followed a complex socio-economic pathway characterized by (i) the stagnation of traditional agricultural activities favoring the replacement of pasturelands by mechanized agriculture, and (ii) the emergence of non-agricultural rural activities together with multifunctional landscapes. Furthermore, a trend of decrease in precipitation seems to be associated with land abandonment, thus, favoring the return of natural vegetation. Our findings suggest that forest transition at the biome level is possible if environmental and land regulations take advantage of specific context-dependent situations that foster net forest gains.
COVID-19 severity: does the genetic landscape of rare variants matter?
Authors: Khadzhieva Maryam B. , Gracheva Alesya S. , Belopolskaya Olesya B. , Kolobkov Dmitry S. , Kashatnikova Darya A. , Redkin Ivan V. , Kuzovlev Artem N. , Grechko Andrey V. , Salnikova Lyubov E.
Published: June 2023

Rare variants affecting host defense against pathogens may be involved in COVID-19 severity, but most rare variants are not expected to have a major impact on the course of COVID-19. We hypothesized that the accumulation of weak effects of many rare functional variants throughout the exome may contribute to the overall risk in patients with severe disease. This assumption is consistent with the omnigenic model of the relationship between genetic and phenotypic variation in complex traits, according to which association signals tend to spread across most of the genome through gene regulatory networks from genes outside the major pathways to disease-related genes. We performed whole-exome sequencing and compared the burden of rare variants in 57 patients with severe and 29 patients with mild/moderate COVID-19. At the whole-exome level, we observed an excess of rare, predominantly high-impact (HI) variants in the group with severe COVID-19. Restriction to genes intolerant to HI or damaging missense variants increased enrichment for these classes of variants. Among various sets of genes, an increased signal of rare HI variants was demonstrated predominantly for primary immunodeficiency genes and the entire set of genes associated with immune diseases, as well as for genes associated with respiratory diseases. We advocate taking the ideas of the omnigenic model into account in COVID-19 studies.
A chromosomal microarray analysis-based laboratory algorithm for the detection of genetic etiology of early pregnancy loss
Authors: Liao Na , Zhang Zhu , Liu Xijing , Wang Jiamin , Hu Rui , Xiao Like , Yang Yunyuan , Lai Yi , Zhu Hongmei , Li Lingping , Liu Shanling , Wang He , Hu Ting
Published: June 2023

Background: Chromosomal abnormalities are a major cause of early pregnancy loss. However, models synthesizing existing genetic technologies to improve pregnancy outcomes are lacking. We aim to provide an integrated laboratory algorithm for the genetic etiology of couples who experienced pregnancy loss.

Methods: Over a 6-year period, 3,634 products of conception (POCs) following early pregnancy loss were collected. The clinical outcomes from a laboratory algorithm based on single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and parental chromosomal karyotyping assays were comprehensively evaluated.

Results: In total, 3,445 of 3,634 (94.8%) POCs had no maternal-cell contamination. Of those POCs, the detection rate of abnormal results was 65.2% (2,247/3,445), of which 91.2% (2,050/2,247) had numerical chromosomal abnormalities, 2.7% (60/2,247) had copy-number variations (CNVs) ≥10 Mb, 2.7% (61/2,247) had CNVs of terminal deletion and duplication, 2.8% (62/2,247) had CNVs <10 Mb, and 0.6% (14/2,247) had uniparental disomy. Furthermore, FISH confirmed 7 of the 60 POCs with mosaic aneuploids below 30% based on the SNP array results as tetraploid. Of the 52 POCs with CNVs of terminal deletion and duplication, 29 couples had balanced rearrangements based on chromosomal karyotyping.

Conclusion: The integrated SNP array-based algorithm combined with optional FISH and parental chromosomal karyotyping is an effective laboratory testing strategy, providing a comprehensive and reliable genetic investigation for the etiology of miscarriage, regardless of the number of miscarriages and the method of conception.
Role of salivary miRNAs in the diagnosis of gastrointestinal disorders: a mini-review of available evidence
Authors: Săsăran Maria Oana , Bănescu Claudia
Published: June 2023

MiRNAs are short, non-coding RNA molecules, which are involved in the regulation of gene expression and which play an important role in various biological processes, including inflammation and cell cycle regulation. The possibility of detecting their extracellular expression, within body fluids, represented the main background for their potential use as non-invasive biomarkers of various diseases. Salivary miRNAs particularly gained interest recently due to the facile collection of stimulated/unstimulated saliva and their stability among healthy subjects. Furthermore, miRNAs seem to represent biomarker candidates of gastrointestinal disorders, with miRNA-based therapeutics showing great potential in those conditions. This review aimed to highlight available evidence on the role of salivary miRNAs in different gastrointestinal conditions. Most salivary-based miRNA studies available in the literature that focused on pathologies of the gastrointestinal tract have so far been conducted on pancreatic cancer patients and delivered reliable results. A few studies also showed the diagnostic utility of salivary miRNAs in conditions such as esophagitis, esophageal cancer, colorectal cancer, or inflammatory bowel disease. Moreover, several authors showed that salivary miRNAs may confidently be used as biomarkers of gastric cancer, but the use of salivary miRNA candidates in gastric inflammation and pre-malignant lesions, essential stages of Correa’s cascade, is still put into question. On the other hand, besides miRNAs, other salivary omics have shown biomarker potential in gastro-intestinal conditions. The limited available data suggest that salivary miRNAs may represent reliable biomarker candidates for gastrointestinal conditions. However, their diagnostic potential requires validation through future research, performed on larger cohorts.
Pan-cancer analysis shows that IBSP is a potential prognostic and immunotherapeutic biomarker for multiple cancer types including osteosarcoma
Authors: Pan Boyu , Cheng Xiaoyun , Tan Wei , Liu Renfeng , Wu Xin , He Jinpeng , Fan Qizhi , Zhang Yan , Cheng Jun , Deng Youwen
Published: June 2023

Background

IBSP is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family that plays a vital role in bone formation, renewal and repair. Emerging evidence revealed that IBSP participated in the tumorigenesis and progression in some cancers. However, its significance in tumour prognosis and immunotherapy is still unknown.

Methods

In the current study, we studied the role of IBSP in tumorigenesis, tumor diagnosis, genomic heterogeneity, methylation modifications, immune infiltration, and therapy response in pan-cancer. In addition, we constructed a risk score model to assessed the prognostic classification efficiency of IBSP using the co-expression genes of IBSP in osteosarcoma (OS), and analyzed the expression and role of IBSP in OS through a series of assays in vitro.

Results

IBSP was upregulated in various cancers compared to the paired normal tissues, and it was strongly correlated with the prognosis, pathological stage, diagnostic accuracy, genomic heterogeneity, methylation modification, immune infiltration, immune and checkpoint. Moreover, the predictive model we established in combination with the clinical characteristics of OS patients showed high survival predictive power in these individuals. The assays in vitro showed that IBSP promoted the proliferation, migration and invasion of OS cells, which further confirmed IBSP’s role in cancers.

Conclusions

Our research revealed the multifunctionality of IBSP in the tumorigenesis, progression and therapy in various cancers, which demonstrated that IBSP may serve as a potential prognostic biomarker and a novel immunotherapy target in pan-cancer.
Targeted delivery of oral vaccine antigens to aminopeptidase N protects pigs against pathogenic E. coli challenge infection
Authors: Van der Weken Hans , Jahantigh Hamid Reza , Cox Eric , Devriendt Bert
Published: June 2023

Oral subunit vaccines are an interesting alternative strategy to traditional live-attenuated or inactivated vaccines for conferring protection against gut pathogens. Despite being safer and more cost-effective, the development of oral subunit vaccines remains challenging due to barriers imposed by the gastrointestinal tract, such as digestive enzymes, a tolerogenic immune environment and the inability of larger proteins to cross the epithelial barrier. Recent advances have focused on overcoming these barriers by using potent mucosal adjuvants or pH-responsive delivery vehicles to protect antigens from degradation and promote their release in the intestinal lumen. A promising approach to allow vaccine antigens to pass the epithelial barrier is by their targeting towards aminopeptidase N (APN; CD13), an abundant membrane protein present on small intestinal enterocytes. APN is a peptidase involved in digestion, but also a receptor for several enteric pathogens. In addition, upon antibody-mediated crosslinking, APN facilitated the transport of antibody-antigen fusion constructs across the gut epithelium. This epithelial transport resulted in antigen-specific immune responses. Here, we present evidence that oral administration of APN-specific antibody-antigen fusion constructs comprising the porcine IgA Fc-domain and the FedF tipadhesin of F18-fimbriated E. coli elicited both mucosal and systemic immune responses and provided at least partial protection to piglets against a subsequent challenge infection with an F18-fimbriated STEC strain. Altogether, these findings will contribute to the further development of new oral subunit vaccines and provide a first proof-of-concept for the protective efficacy of APN-targeted vaccine antigens.
Targeting transcription factors for therapeutic benefit in rheumatoid arthritis
Authors: Balendran Thivya , Lim Keith , Hamilton John A. , Achuthan Adrian A.
Published: June 2023

Rheumatoid arthritis (RA) is a destructive inflammatory autoimmune disease that causes pain and disability. Many of the currently available drugs for treating RA patients are aimed at halting the progression of the disease and alleviating inflammation. Further, some of these treatment options have drawbacks, including disease recurrence and adverse effects due to long-term use. These inefficiencies have created a need for a different approach to treating RA. Recently, the focus has shifted to direct targeting of transcription factors (TFs), as they play a vital role in the pathogenesis of RA, activating key cytokines, chemokines, adhesion molecules, and enzymes. In light of this, synthetic drugs and natural compounds are being explored to target key TFs or their signaling pathways in RA. This review discusses the role of four key TFs in inflammation, namely NF-κB, STATs, AP-1 and IRFs, and their potential for being targeted to treat RA.
Recent advances and future perspectives of CAR-T cell therapy in head and neck cancer
Authors: Hu Chunmei , Liu Min , Li Yutao , Zhao Yi , Sharma Amit , Liu Haotian , Schmidt-Wolf Ingo G. H.
Published: June 2023

Head and neck cancer (HNC) ranks as the sixth most prevalent type of cancer globally and accounts for about 4% of all types of cancer. Among all HNC, most are head and neck squamous cell carcinoma (HNSCC) with clinical therapies that include surgery, radiation therapy, chemotherapy, immunotherapy, targeted therapy, and multimodal treatments. In recent years, chimeric antigen receptor (CAR)-T cell immunotherapy has significantly transformed the therapeutic approaches for leukemia and lymphoma and has garnered increased attention as a potential treatment for a wide range of cancers. However, CAR-T immunotherapy in solid tumors, especially HNSCCs, lags significantly behind due to the paucity of tumor-specific antigens, high levels of tumor heterogeneity, immunosuppressive tumor microenvironment, the risk of treatment-related toxicities and off-target adverse events in HNSCCs. The objective of this review is to explore the advancement of CAR-T cell therapy in the treatment of HNSCCs. We aim to outline the targeted antigens in HNSCCs, highlight the challenges and potential solutions, and discuss the relevant combination therapies. Our review presents a comprehensive overview of the recent developments in CAR-T cell therapy for HNSCCs, and provides valuable insights into future research avenues.
Immunogenicity and protective efficacy of an RSV G S177Q central conserved domain nanoparticle vaccine
Authors: Bergeron Harrison C. , Murray Jackelyn , Juarez Maria G. , Nangle Samuel J. , DuBois Rebecca M. , Tripp Ralph A.
Published: June 2023

Introduction

Respiratory syncytial virus (RSV) can cause lower respiratory tract disease in infants and elderly populations. Despite decades of research, there remains no safe and approved RSV vaccine. Previously, we showed that an RSV G glycoprotein subunit vaccine candidate with a single point mutation within the central conserved domain (CCD), i.e. S177Q, considerably improved immunogenicity.

Methods

Here, we examine the development of nanoparticle (NP) vaccines having either an RSV G protein CCD with wild-type sequence (NPWT) or an S177Q mutation (NP-S177Q). The NP vaccine immunogens were adjuvanted with monophosphoryl lipid A (MPLA), a TLR4 agonist to improve Th1- type responses. BALB/c mice were primed with 10 μg of NP-WT vaccine, NPS177Q, or vehicle, rested, and then boosted with a high (25 μg) or low (10 μg) dose of the NP-WT or NP-S177Q homologous candidate and subsequently challenged with RSV A2.

Results

The results showed that mice boosted with NP-S177Q developed superior immunogenicity and neutralizing antibodies compared to NP-WT boosting. IgG from either NP-S177Q or NP-WT vaccinated mice did not interfere with fractalkine (CX3CL1) binding to CX3CR1 and effectively blocked G protein CX3C-CX3CR1 binding. Both NP-WT and NP-S177Q vaccination induced similar neutralizing antibodies to RSV in challenged mice compared to vehicle control. NP-S177Q boosting improved correlates of protection including reduced BAL cell infiltration following RSV challenge. However, the NP vaccine platform will require improvement due to the poor solubility and the unexpectedly weaker Th1-type IgG2a response.

Discussion

The results from this study support further NP-S177Q vaccine candidate development.
Deep learning system for distinguishing optic neuritis from non-arteritic anterior ischemic optic neuropathy at acute phase based on fundus photographs
Authors: Liu Kaiqun , Liu Shaopeng , Tan Xiao , Li Wangting , Wang Ling , Li Xinnan , Xu Xiaoyu , Fu Yue , Liu Xiaoning , Hong Jiaming , Lin Haotian , Yang Hui
Published: June 2023

Purpose

To develop a deep learning system to differentiate demyelinating optic neuritis (ON) and non-arteritic anterior ischemic optic neuropathy (NAION) with overlapping clinical profiles at the acute phase.

Methods

We developed a deep learning system (ONION) to distinguish ON from NAION at the acute phase. Color fundus photographs (CFPs) from 871 eyes of 547 patients were included, including 396 ON from 232 patients and 475 NAION from 315 patients. Efficientnet-B0 was used to train the model, and the performance was measured by calculating the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Also, Cohen’s kappa coefficients were obtained to compare the system’s performance to that of different ophthalmologists.

Results

In the validation data set, the ONION system distinguished between acute ON and NAION achieved the following mean performance: time-consuming (23 s), AUC 0.903 (95% CI 0.827–0.947), sensitivity 0.796 (95% CI 0.704–0.864), and specificity 0.865 (95% CI 0.783–0.920). Testing data set: time-consuming (17 s), AUC 0.902 (95% CI 0.832–0.944), sensitivity 0.814 (95% CI 0.732–0.875), and specificity 0.841 (95% CI 0.762–0.897). The performance (κ = 0.805) was comparable to that of a retinal expert (κ = 0.749) and was better than the other four ophthalmologists (κ = 0.309–0.609).

Conclusion

The ONION system performed satisfactorily distinguishing ON from NAION at the acute phase. It might greatly benefit the challenging differentiation between ON and NAION.
Cholesterol 25-hydroxylase suppresses avian reovirus replication by its enzymatic product 25-hydroxycholesterol
Authors: Wang Yuyang , Zuo Wei , Zhang Yangyang , Bo Zongyi , Zhang Chengcheng , Zhang Xiaorong , Wu Yantao
Published: June 2023

Avian reovirus (ARV) causing viral arthritis/tenosynovitis and viral enteritis in domestic fowl has significantly threatened on the poultry industry worldwide. ARV is a non-enveloped fusogenic virus that belongs to the Reoviridae family. Previous research revealed that cellular cholesterol in lipid rafts is essential for ARV replication. It has been reported that cholesterol 25-hydroxylase (CH25H) and its product 25-hydroxycholesterol (25HC) have antiviral activities against enveloped viruses. However, few studies characterized the association of non-enveloped viruses with CH25H and the role of CH25H in the regulation of ARV replication. In this study, the expression of chicken CH25H (chCH25H) was found to be upregulated in ARV-infected cells at the early stage of infection. The results of overexpression and knockdown assays revealed that chCH25H has a significant antiviral effect against ARV infection. Furthermore, a 25HC treatment significantly inhibited ARV replication in a dose-dependent manner at both the entry and post-entry stages, and a chCH25H mutant lacking hydroxylase activity failed to inhibit ARV infection. These results indicate that CH25H, depending on its enzyme activity, exerts the antiviral effect against ARV via the synthesis of 25HC. In addition, we revealed that 25HC produced by CH25H inhibits viral entry by delaying the kinetics of ARV uncoating, and CH25H blocks cell–cell membrane fusion induced by the p10 protein of ARV. Altogether, our findings showed that CH25H, as a natural host restriction factor, possessed antiviral activity against ARV targeting viral entry and syncytium formation, through an enzyme activity-dependent way. This study may provide new insights into the development of broad-spectrum antiviral therapies.
Effect of biochar and bioorganic fertilizer on the microbial diversity in the rhizosphere soil of Sesbania cannabina in saline-alkaline soil
Authors: Gu Yin-yu , Liang Xiao-yan , Zhang Hai-yang , Fu Rao , Li Meng , Chen Chuan-jie
Published: June 2023

Introduction

Biochar and bioorganic fertilizer (BOF) application in agriculture has garnered increasing interest recently. However, the effects of biochar and BOF on rhizosphere soil microecology, especially in a region with saline-alkaline soil, remain largely unexplored.

Methods

In this study, we performed Illumina-based 16S rRNA sequencing to investigate the effects of biochar with or without BOF addition, as well as at different addition rates and particles sizes, on the microecology of saline-alkaline rhizosphere soil.

Results

In the field experiment, biochar and BOF application altered the rhizosphere soil microecology. Actinobacteriota, Proteobacteria, and Chloroflexi accounted for >60% of the total bacterial population in each treatment. In the different treatments, Actinobacteria and Alphaproteobacteria were the predominant classes; Micromonosporales and Vicinamibacterales were the dominant orders; norank_f__Geminicoccaceae and Micromonosporaceae were the most abundant families; and Micromonospora and norank_f_Geminicoccaceae were the predominant genera. Application of biochar with or without BOF decreased soil electrical conductivity (EC) by 7% -11.58% only at the depth of 10 cm below the surface, again, soil EC can be significantly reduced by an average of 4% at 10 cm depth soil after planting Sesbania cannabina. Soil organic carbon, organic matter, available potassium, and available phosphorus contents had significant effects on the soil bacterial community structure.

Conclusion

Co-application of biochar and BOF resulted in the greatest improvement of rhizosphere soil microecology, either by promoting plant growth or improving the nutrition and physicochemical properties of soil, followed by BOF alone and biochar alone. Additionally, higher application rate of biochar was better than lower application rate, and fine biochar had a stronger effect than coarse biochar. These results provide guidance for the development of new saline-alkaline soil remediation strategies.