bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential breeding targets in wheat influence non-target traits related to grain quality, but not crop nitrogen requirement
Authors: Guardia-Velarde Lorena , Liu Hui , Cope Jonathan E. , Westerbergh Anna , Weih Martin
Published: April 2023

Wheat is considered an established crop with a long breeding history. Its varieties are being developed with differential breeding targets, e.g. high grain yield or high grain protein content. The different breeding targets strongly influence performance in the targeted traits, but may also influence non-target traits related to grain quality, biofortification potential, and nutrient accumulation. This influence of non-targeted traits may, in turn, affect the environmental performance and ecological sustainability of the crop. The aim of this study was to evaluate the relationships between breeding target traits such as grain yield and grain quality, and non-target traits for three groups of spring wheat varieties differing in breeding targets, i.e. high yield (I), organic high protein (II), and intermediate (III) wheat types. Data from a field trial with nine spring wheat varieties grown under two soil compaction treatments over two years with contrasting weather were used. We found that wheat type affected most target and non-target traits with partly large effect sizes (0.874≤ηp  2≤0.173), but not nitrogen (N) uptake efficiency ( ηp  2=0.006), which reflects the potential N resource requirement of the crop. Associations shown between target and non-target traits will be advantageous for wheat breeding programs. Wheat type and environment had similarly sized effects on grain yield and quality traits. Grain concentrations of various macro- and micro-nutrients were frequently, but not always, correlated, indicating that the biofortification potential varied between wheat types and was affected by environmental conditions. The grain and starch yields per accumulated plant N were higher in the wheat varieties bred for high grain yields than those bred for high grain protein content; whilst the protein yield per accumulated whole-plant N was similar across all wheat types despite much higher grain N concentrations in the high-protein varieties. Additionally, most of the evaluated traits tended to preserve their static stability across environments. The results link grain yield and grain quality traits to crop nutrient accumulation aspects relevant for the environmental performance and ecological sustainability of the crop. Future breeding strategies should consider the non-target effects in traits that influence the environmental performance of the crop.
Characterization of muscle recruitment during gait of bilateral transfemoral and through-knee persons with limb loss
Authors: Benton Alice M. , Amiri Pouya , Henson David P. , Sivapuratharasu Biranavan , Mcgregor Alison H. , Bull Anthony M. J.
Published: April 2023

Introduction: Due to loss in musculoskeletal capacity, there is an increased burden on the residual limbs of bilateral transfemoral and through-knee persons with limb loss. This reduced capacity is associated with an increased cost of walking that is detrimental to functionality. Compensatory gait strategies are adopted by this population. However, how these strategies relate to specific muscle recruitment is not known. The primary aim of this study is to characterize muscle recruitment during gait of this population. The secondary aim is to assess whether the measured kinematics can be actuated when the endurance of specific muscles is reduced and if this is the case, which alternative muscles facilitate this.

Methods: 3D gait data and high-resolution magnetic resonance images were acquired from six bilateral transfemoral and through-knee persons with limb loss. Subject-specific anatomical muscle models were developed for each participant, and a validated musculoskeletal model was used to quantify muscle forces in two conditions: during normal gait (baseline) and when muscles, which were identified as functioning above a “healthy” level at baseline, have a reduced magnitude of maximum force capacity (reduced endurance simulation). To test the hypothesis that there are differences in muscle forces between the baseline trials and the simulations with reduced muscular endurance, a Bonferroni corrected two-way ANOVA with repeated measures was completed between the two states.

Results: The baseline analysis showed that the hip flexors experience relatively high muscle activations during gait. The reduced endurance simulation found two scenarios. First, for 5 out of the 12 simulations, the baseline kinematics could not be reproduced with the reduced muscular capacity. Second, for 7 out of 12 cases where the baseline kinematics were achieved, this was possible with compensatory increased activation of some muscles with similar functions (p ≤ 0.003).

Discussion: Evidently, due to the loss of the ankle plantar flexors, gait imposes a high demand on the flexor muscle group of the residual limb. This study highlights how the elevated cost of gait in this population manifests in muscle recruitment. To enhance functionality, it is critical to consider the mechanical demand on the hip flexors and to develop rehabilitation interventions accordingly.
New trends in diagnosing and treating ovarian cancer using nanotechnology
Authors: Zhang Juan , Ding Haigang , Zhang Feng , Xu Yan , Liang Wenqing , Huang Liping
Published: April 2023

Ovarian cancer stands as the fifth most prevalent cancer among women, causing more mortalities than any other disease of the female reproductive system. There are numerous histological subtypes of ovarian cancer, each of which has distinct clinical characteristics, risk factors, cell origins, molecular compositions, and therapeutic options. Typically, it is identified at a late stage, and there is no efficient screening method. Standard therapies for newly diagnosed cancer are cytoreductive surgery and platinum-based chemotherapy. The difficulties of traditional therapeutic procedures encourage researchers to search for other approaches, such as nanotechnology. Due to the unique characteristics of matter at the nanoscale, nanomedicine has emerged as a potent tool for creating novel drug carriers that are more effective and have fewer adverse effects than traditional treatments. Nanocarriers including liposomes, dendrimers, polymer nanoparticles, and polymer micelles have unique properties in surface chemistry, morphology, and mechanism of action that can distinguish between malignant and normal cells, paving the way for targeted drug delivery. In contrast to their non-functionalized counterparts, the development of functionalized nano-formulations with specific ligands permits selective targeting of ovarian cancers and ultimately increases the therapeutic potential. This review focuses on the application of various nanomaterials to the treatment and diagnosis of ovarian cancer, their advantages over conventional treatment methods, and the effective role of controlled drug delivery systems in the therapy of ovarian cancer.
Epidemiological characteristics of respiratory viruses in hospitalized children during the COVID-19 pandemic in southwestern China
Authors: Zhu Lin , Luo Tingting , Yuan Yining , Yang Shu , Niu Chao , Gong Ting , Wang Xueer , Xie Xiaohong , Luo Jian , Liu Enmei , Fu Zhou , Tian Daiyin
Published: April 2023

Background

Multinational studies have reported that the implementation of nonpharmaceutical interventions (NPIs) to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission coincided with the decline of other respiratory viruses, such as influenza viruses and respiratory syncytial virus.

Objective

To investigate the prevalence of common respiratory viruses during the coronavirus disease 2019 (COVID-19) pandemic.

Methods

Respiratory specimens of children with lower respiratory tract infections (LRTIs) hospitalized at the Children’s Hospital of Chongqing Medical University from January 1, 2018 to December 31, 2021 were collected. Seven common pathogens, including respiratory syncytial virus (RSV), adenovirus (ADV), influenza virus A and B (Flu A, Flu B), and parainfluenza virus types 1–3 (PIV1–3), were detected by a multiplex direct immunofluorescence assay (DFA). Demographic data and laboratory test results were analyzed.

Results

1) A total of 31,113 children with LRTIs were enrolled, including 8141 in 2018, 8681 in 2019, 6252 in 2020, and 8059 in 2021.The overall detection rates decreased in 2020 and 2021 (P < 0.001). The detection rates of RSV, ADV, Flu A, PIV-1, and PIV-3 decreased when NPIs were active from February to August 2020, with Flu A decreasing most predominantly, from 2.7% to 0.3% (P < 0.05). The detection rates of RSV and PIV-1 resurged and even surpassed the historical level of 2018–2019, while Flu A continued decreasing when NPIs were lifted (P < 0.05). 2) Seasonal patterns of Flu A completely disappeared in 2020 and 2021. The Flu B epidemic was observed until October 2021 after a long period of low detection in 2020. RSV decreased sharply after January 2020 and stayed in a nearly dormant state during the next seven months. Nevertheless, the detection rates of RSV were abnormally higher than 10% in the summer of 2021. PIV-3 decreased significantly after the COVID-19 pandemic; however, it atypically surged from August to November 2020.

Conclusion

The NPIs implemented during the COVID-19 pandemic affected the prevalence and seasonal patterns of certain viruses such as RSV, PIV-3, and influenza viruses. We recommend continuous surveillance of the epidemiological and evolutionary dynamics of multiple respiratory pathogens, especially when NPIs are no longer necessary.
Are they still determining? Analysis of associations among ethnicity, gender, socioeconomic status, neighborhood factors, and COVID-19 vaccination
Authors: Kim Bokyung , Hong Seoyeon , Kim Sungwook
Published: April 2023

Introduction

This study explores associations among adult vaccination, ethnicity, gender, and socioeconomic variables such as educational attainment and income, as well as neighborhood factors.

Methods

A telephone quota sample of New Jersey adults (N = 1,984) was used to text associations among proposed predictors of vaccination behaviors.

Results

Our multivariate logistic regression analyses found that certain races/ethnicity, respondents' household income, and perceived safety of one's community were the strongest predictors of COVID-19 vaccination. The odds of COVID-19 vaccination were 52% lower for Black/African American respondents compared to white/Caucasian respondents (p = 0.001) and 44% lower for Hispanic/Latino respondents compared to white/Caucasian respondents (p = 0.001).

Discussion

The results add new insights to public health communication research and suggest careful interventions across racial groups, considering existing racial disparities in vaccination.
Epistemic and Existential, E2-sustainability. On the need to un-learn for re-learning in contemporary spaces
Authors: Bagga-Gupta Sangeeta
Published: April 2023

This paper contributes to a re-thinking, un-learning, and re-learning agenda by interrogating some core ideas and assumptions related to contemporary societal and planetary concerns, including concerns within the research enterprise. Transcending the first step that calls for pausing and re-thinking, this paper troubles universalizing vocabularies that naturalize conceptual framings and ways/waves-of-being in research and educational practices. Furthermore, it illuminates the ways in which scholarship has become complicit in re-cycling and re-creating reductionistic ideas that loop back into educational practices. Its overarching argument aligns with an emergent call within research and higher education for going beyond its universalizing monolithic ethos that has become naturalized in contemporary digital-analog entangled existence. Framed as alternative theorizing that is variously termed post/decolonial/southern thinking, these emergent perspectives are part of the introspection that is critically needed in mainstream academia, in particular in the Learning Sciences. This paper argues that this is needed to contribute to bothEpistemicandExistentialsustainability, i.e.,E2-sustainability. E2-sustainability enables transcending issues of environmental-, economic-, social-, and cultural-sustainability: E2-sustainability assumes and includes these. Marked by alternative conceptual framings and pushed by amobile gaze, this theoretical paper argues that major and minor shifts in thinking are needed for attending to contemporary societal and planetary challenges. E2-sustainability in the scholarly realm has relevance for transcending ethnocentrically framed biases and siloed framings of contemporary education and higher education, including teacher education. Troubling key, taken-for-granted universalizing truths and using the areas of language and educational scholarship as illustrative points of departure, this paper raises concerns regarding the outsourcing of important educational agendas to technologies, including digitalization on the one hand and concepts that build on contentious assumptions on the other hand. It is suchdefaultoutsourcing that is troubled through a curiosity-drivenmultiversalandglobal-centricmobile gaze wherein both northern and southern knowledge-regimes need to be privileged. The theorizing presented in this paper builds on a Second Wave of Southern Perspectives (SWaSP) framing that has relevance for both north-centric and south-centric scholarship, including writing research. Explicitly multi/inter/cross/trans-disciplinary, this work is relevant to Epistemic and Existential sustainability given its non-allegiance to the imaginaries of mono-disciplinarity, nation-state essences, or universalisms.
Predicting one-year left ventricular mass index regression following transcatheter aortic valve replacement in patients with severe aortic stenosis: A new era is coming
Authors: Asheghan Mohammad Mostafa , Javadikasgari Hoda , Attary Taraneh , Rouhollahi Amir , Straughan Ross , Willi James Noel , Awal Rabina , Sabe Ashraf , de la Cruz Kim I. , Nezami Farhad R.
Published: April 2023

Aortic stenosis (AS) is the most common valvular heart disease in the western world, particularly worrisome with an ever-aging population wherein postoperative outcome for aortic valve replacement is strongly related to the timing of surgery in the natural course of disease. Yet, guidelines for therapy planning overlook insightful, quantified measures from medical imaging to educate clinical decisions. Herein, we leverage statistical shape analysis (SSA) techniques combined with customized machine learning methods to extract latent information from segmented left ventricle (LV) shapes. This enabled us to predict left ventricular mass index (LVMI) regression a year after transcatheter aortic valve replacement (TAVR). LVMI regression is an expected phenomena in patients undergone aortic valve replacement reported to be tightly correlated with survival one and five year after the intervention. In brief, LV geometries were extracted from medical images of a cohort of AS patients using deep learning tools, and then analyzed to create a set of statistical shape models (SSMs). Then, the supervised shape features were extracted to feed a support vector regression (SVR) model to predict the LVMI regression. The average accuracy of the predictions was validated against clinical measurements calculating root mean square error and R2 score which yielded the satisfactory values of 0.28 and 0.67, respectively, on test data. Our work reveals the promising capability of advanced mathematical and bioinformatics approaches such as SSA and machine learning to improve medical output prediction and treatment planning.
Emerging data inputs for infectious diseases surveillance and decision making
Authors: Shausan Aminath , Nazarathy Yoni , Dyda Amalie
Published: April 2023

Infectious diseases create a significant health and social burden globally and can lead to outbreaks and epidemics. Timely surveillance for infectious diseases is required to inform both short and long term public responses and health policies. Novel data inputs for infectious disease surveillance and public health decision making are emerging, accelerated by the COVID-19 pandemic. These include the use of technology-enabled physiological measurements, crowd sourcing, field experiments, and artificial intelligence (AI). These technologies may provide benefits in relation to improved timeliness and reduced resource requirements in comparison to traditional methods. In this review paper, we describe current and emerging data inputs being used for infectious disease surveillance and summarize key benefits and limitations.
Maternal exposure to air pollution alters energy balance transiently according to gender and changes gut microbiota
Authors: Zordão Olivia Pizetta , Campolim Clara Machado , Yariwake Victor Yuji , Castro Gisele , Ferreira Clílton Kraüss de Oliveira , Santos Andrey , Norberto Sónia , Veras Mariana Matera , Saad Mario Jose Abdalla , Saldiva Paulo Hilário Nascimento , Kim Young-Bum , Prada Patricia Oliveira
Published: April 2023

Introduction

The timing of maternal exposure to air pollution is crucial to define metabolic changes in the offspring. Here we aimed to determine the most critical period of maternal exposure to particulate matter (PM2.5) that impairs offspring's energy metabolism and gut microbiota composition.

Methods

Unexposed female and male C57BL/6J mice were mated. PM2.5 or filtered air (FA) exposure occurred only in gestation (PM2.5/FA) or lactation (FA/PM2.5). We studied the offspring of both genders.

Results

PM2.5 exposure during gestation increased body weight (BW) at birth and from weaning to young in male adulthood. Leptin levels, food intake, Agrp, and Npy levels in the hypothalamus were also increased in young male offspring. Ikbke, Tnf increased in male PM2.5/FA. Males from FA/PM2.5 group were protected from these phenotypes showing higher O2 consumption and Ucp1 in the brown adipose tissue. In female offspring, we did not see changes in BW at weaning. However, adult females from PM2.5/FA displayed higher BW and leptin levels, despite increased energy expenditure and thermogenesis. This group showed a slight increase in food intake. In female offspring from FA/PM2.5, BW, and leptin levels were elevated. This group displayed higher energy expenditure and a mild increase in food intake. To determine if maternal exposure to PM2.5 could affect the offspring’s gut microbiota, we analyzed alpha diversity by Shannon and Simpson indexes and beta diversity by the Linear Discriminant Analysis (LDA) in offspring at 30 weeks. Unlike males, exposure during gestation led to higher adiposity and leptin maintenance in female offspring at this age. Gestation exposure was associated with decreased alpha diversity in the gut microbiota in both genders.

Discussion

Our data support that exposure to air pollution during gestation is more harmful to metabolism than exposure during lactation. Male offspring had an unfavorable metabolic phenotype at a young age. However, at an older age, only females kept more adiposity. Ultimately, our data highlight the importance of controlling air pollution, especially during gestation.
Influence of biological sex, age and smoking on Graves’ orbitopathy – a ten-year tertiary referral center analysis
Authors: Oeverhaus Michael , Winkler Luisa , Stähr Kerstin , Daser Anke , Bechrakis Nikolaos , Stöhr Mareile , Chen Ying , Eckstein Anja
Published: April 2023

Purpose

Severity of Graves’ orbitopathy (GO) shows wide individual differences. For optimal treatment, it is important to be able to predict the natural course of the disease as accurate as possible to counteract with anti-inflammatory and surgical treatment. Therefore, we aimed to further elucidate the impact of sex, age and smoking on GO.

Methods

We collected the clinical and demographic data of all patients of our tertiary referral center from January 2008 till December 2018 and analyzed it with descriptive statistics. Only patients with a complete data set were included in the further analysis. Odds ratio’s for moderate-to-severe and sight-threatening GO in relation to age, sex and smoking were calculated by means of multivariate logistic regression models.

Results

We evaluated the data of 4260 patient with GO and complete data sets. Most of these were women (83%). There were no significant differences between male and female patients regarding smoking habits and thyroid treatment. Men were significantly older at initial manifestation of TED (51.8 vs. 49.9y, p<0.01) and showed significant more often severe stages (61% vs. 53%, p<0.0001). Therefore, they needed significantly more intense treatment with steroids, irradiation, orbital decompression and muscle surgery. In multivariate logistic regression analyses age (OR 0.97, 95% CI:0.97-0.98, p<0.0001), male sex (OR 1.64, 95% CI:1.38-1.9, p<0.0001), smoking (OR 1.19, 95% CI:1.04-1.36, p=0.01), Grave’s disease (OR 1.55, 95% CI:1.26-1.90, p<0.0001) and history of radioiodine treatment (RAI) (OR 2.44, 95% CI:2.10-2.86, p<0.0001) showed an significant association with severe stages of GO.

Discussion

Our retrospective analysis showed once more that women are more often afflicted by GO. In contrast, men seem to be more severely afflicted and in need of anti-inflammatory and surgical treatments. This might be due to a different approach to the health system and resilience to GO specific symptoms, as well as previously described worse thyroid control. Estrogen mediated effects might also play a role as in other autoimmune diseases and should be subject of further trials. Besides the biological sex, smoking could again be confirmed as serious risk factor for severe GO. Of note, RAI was associated with more severe stages of GO, which should be subject to further investigation.
Long-term organoid culture of a small intestinal neuroendocrine tumor
Authors: D’Agosto Sabrina , Fiorini Elena , Pezzini Francesco , Delfino Pietro , Simbolo Michele , Vicentini Caterina , Andreani Silvia , Capelli Paola , Rusev Borislav , Lawlor Rita T. , Bassi Claudio , Landoni Luca , Pea Antonio , Luchini Claudio , Scarpa Aldo , Corbo Vincenzo
Published: April 2023

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and highly heterogeneous neoplasms whose incidence has markedly increased over the last decades. A grading system based on the tumor cells’ proliferation index predicts high-risk for G3 NETs. However, low-to-intermediate grade (G1/G2) NETs have an unpredictable clinical course that varies from indolent to highly malignant. Cultures of human cancer cells enable to perform functional perturbation analyses that are instrumental to enhance our understanding of cancer biology. To date, no tractable and reliable long-term culture of G1/G2 NET has been reported to permit disease modeling and pharmacological screens. Here, we report of the first long-term culture of a G2 metastatic small intestinal NET that preserves the main genetic drivers of the tumor and retains expression patterns of the endocrine cell lineage. Replicating the tissue, this long-term culture showed a low proliferation index, and yet it could be propagated continuously without dramatic changes in the karyotype. The model was readily available for pharmacological screens using targeted agents and as expected, showed low tumorigenic capacity in vivo. Overall, this is the first long-term culture of NETs to faithfully recapitulate many aspects of the original neuroendocrine tumor.
Dynamic equilibrium of cellular plasticity: The origin of diseases
Authors: Kwan Edmund K. , Flowers Jonathan , Ming Xue
Published: April 2023

Since its inception, cellular plasticity has undergone many iterations. Today we define it as the ability of mature, terminally differentiated cells to change their identity, meaning lineage change of the cells by transdifferentiation, dedifferentiation and reprogramming. This process does not involve a single DNA sequence change or a mutation. We now know that the behavior of a cell is profoundly affected by the surrounding environment. There is a perpetual pressure placed on the genetic expression of the cells. The external environment and specifically the microenvironment of the cells greatly influences the genotype. There is a never-ending dynamic interplay between the genotype and the phenotype. Incremental phenotypic adjustments are continuously occurring to yield improved cell survival. These changes are beneficial to the cells at a given moment. As the environmental condition declines, then more extensive phenotypic transformation (via transdifferentiation and dedifferentiation) can follow. When the cellular environment further deteriorates, cellular plasticity can trigger a pathologic sequence that eventually leads to cancers/diseases. These modifications are all part of an adaptive process that enhances the survival of the cells. They can offer short term advantages, but they can also lead to diseases. Oxygen level plays a pivotal role in the development of chronic diseases. Cellular response to hypoxia is mediated through hypoxia inducible factor (HIF). HIF is an oxygen sensor that is closely involved in the pathophysiologic adaptation to hypoxia. Our hypothesis centers on hypoxia as the major stressor initiating cellular plasticity and restoring normoxia is an essential step in the healing process. This theory could be tested using chronic pathological processes in animal models whereby achieving an adequate cellular oxygen level could improve or halt both plastic change and diseases.
Elevational patterns of soil nematode diversity, community structure and metabolic footprint in the Trikuta mountains of Northwestern Himalaya
Authors: Choudhary Fozia , Bhardwaj Anil , Sayeed Iqra , Rather Shabir Ahmad , Khan Mohammad Abdul Hannan , Shah Ali Asghar
Published: April 2023

Nematodes are an integral part of soil biodiversity and play a vital role in soil nutrient cycling. The Himalayan mountainous ecosystems are amongst the extreme environments in the world. Still little is known about the diversity and distribution patterns of soil nematodes along the elevation gradient in the region, thus limiting our ability in understanding and comparing the structural patterns of nematode communities across different regions. To address this knowledge gap, we aim to disentangle the elevational patterns of soil nematode community structure and trophic diversity by studying the abundance, composition, diversity and functional indices, and metabolic footprint of soil nematodes at four elevation classes (Elev1, Elev2, Elev3, and Elev4 each being 400 m) along an altitudinal gradient (1,000–2,600 m) in the Trikuta mountain range of Pir-Panjal to Shivalik Himalaya. Overall, a total of 55 genera were found in the study region. The diversity and richness of soil nematodes varied significantly among the elevation classes, and exhibit a decreasing trend with elevation. Also, the nematode community composition varied significantly among the elevation classes along the elevational gradient. The bacterivores were the dominant trophic group at each elevation class. Further, the soil properties played a key role in explaining the changes in the nematode community composition across the elevation classes. Moreover, the total nematode, bacterivore and herbivore abundances showed an increasing trend, while as that of fungivores and predators exhibit a negative trend with elevation. In addition, a declining pattern in the overall maturity and metabolic footprint with elevation was observed, thus depicting the lower sustenance of k-strategic nematodes and their relatively lower contribution to belowground carbon cycling at higher elevations. The finding of our study could enhance our understanding of the overall community structure and diversity patterns of soil nematode along the elevation gradient, and the response of soil nematodes to ongoing climate change in the rapidly warming Himalayas.
Resistance to thyroid hormone due to a novel mutation in the thyroid beta receptor (THRβ) gene coexisting with autoimmune thyroid disease—A case report
Authors: Skowrońska-Jóźwiak Elżbieta , Gach Agnieszka , Cyniak-Magierska Anna , Nykel Anna , Jurkowska Monika , Lewiński Andrzej
Published: April 2023

Resistance to thyroid hormone (RTH) is a syndrome characterized by impaired responsiveness of target tissues to thyroid hormones. The relationship between RTHβ and thyroid autoimmunity has been under research. In this study, we demonstrate a case report of a woman with a novel mutation in THRβ gene coexisting with autoimmune thyroid disease (AITD). The 36-year-old woman has been treated since childhood for a thyroid disease. Based on high levels of thyroid hormones (THs) and elevated concentrations of thyroperoxidase and thyroglobulin antibodies (TPOAb and TgAb, respectively), she received unnecessary long-term treatment with methimazole and finally underwent subtotal thyroidectomy. After the surgery, her TSH level remained significantly elevated, despite the treatment with 150 + 15 µg of thyroxine and triiodothyronine. A sequence analysis of the THRβ gene revealed a novel dinucleotide substitution affecting codon 453, resulting in the replacement of the normal proline with an asparagine (c.1357_1358delinsAA, p.(Pro453Asn)). The mutation has not been described in the literature yet; however, THRβ codon 453 represents a mutational hot spot, frequently altered in the TH receptor ß gene. After establishing the diagnosis of RTH, the patient was treated with 300 µg of thyroxine, which showed clinical improvement and normalization of TSH. The coexistence of RTHβ and AITD may additionally impede establishment of a proper diagnosis, leading to unnecessary therapy and delayed correct treatment. The presented case encourages a closer cooperation between clinical endocrinologists and geneticists.
MulCNN: An efficient and accurate deep learning method based on gene embedding for cell type identification in single-cell RNA-seq data
Authors: Jiao Linfang , Ren Yongqi , Wang Lulu , Gao Changnan , Wang Shuang , Song Tao
Published: April 2023

Advancements in single-cell sequencing research have revolutionized our understanding of cellular heterogeneity and functional diversity through the analysis of single-cell transcriptomes and genomes. A crucial step in single-cell RNA sequencing (scRNA-seq) analysis is identifying cell types. However, scRNA-seq data are often high dimensional and sparse, and manual cell type identification can be time-consuming, subjective, and lack reproducibility. Consequently, analyzing scRNA-seq data remains a computational challenge. With the increasing availability of well-annotated scRNA-seq datasets, advanced methods are emerging to aid in cell type identification by leveraging this information. Deep learning neural networks have great potential for analyzing single-cell data. This paper proposes MulCNN, a multi-level convolutional neural network that uses a unique cell type-specific gene expression feature extraction method. This method extracts critical features through multi-scale convolution while filtering noise. Extensive testing using datasets from various species and comparisons with popular classification methods show that MulCNN has outstanding performance and offers a new and scalable direction for scRNA-seq analysis.
Construction of a novel anoikis-related prognostic model and analysis of its correlation with infiltration of immune cells in neuroblastoma
Authors: Chen Ji , Sun Mengjiao , Chen Chuqin , Kang Meiyun , Qian Bo , Sun Jing , Ma Xiaopeng , Zhou Jianfeng , Huang Lei , Jiang Bin , Fang Yongjun
Published: April 2023

Background

Anoikis resistance (AR) plays an important role in the process of metastasis, which is an important factor affecting the risk stage of neuroblastoma (NB). This study aims to construct an anoikis-related prognostic model and analyze the characteristics of hub genes, important pathways and tumor microenvironment of anoikis-related subtypes of NB, so as to provide help for the clinical diagnosis, treatment and research of NB.

Methods

We combined transcriptome data of GSE49710 and E-MTAB-8248, screened anoikis-related genes (Args) closely related to the prognosis of NB by univariate cox regression analysis, and divided the samples into anoikis-related subtypes by consistent cluster analysis. WGCNA was used to screen hub genes, GSVA and GSEA were used to analyze the differentially enriched pathways between anoikis-related subtypes. We analyzed the infiltration levels of immune cells between different groups by SsGSEA and CIBERSORT. Lasso and multivariate regression analyses were used to construct a prognostic model. Finally, we analyzed drug sensitivity through the GDSC database.

Results

721 cases and 283 Args were included in this study. All samples were grouped into two subtypes with different prognoses. The analyses of WGCNA, GSVA and GSEA suggested the existence of differentially expressed hub genes and important pathways in the two subtypes. We further constructed an anoikis-related prognostic model, in which 15 Args participated. This model had more advantages in evaluating the prognoses of NB than other commonly used clinical indicators. The infiltration levels of 9 immune cells were significantly different between different risk groups, and 13 Args involved in the model construction were correlated with the infiltration levels of immune cells. There was a relationship between the infiltration levels of 6 immune cells and riskscores. Finally, we screened 15 drugs with more obvious effects on NB in high-risk group.

Conclusion

There are two anoikis-related subtypes with different prognoses in the population of NB. The anoikis-related prognostic model constructed in this study can accurately predict the prognoses of children with NB, and has a good guiding significance for clinical diagnosis, treatment and research of NB.
Maternal imprinting and determinants of neonates’ immune function in the SEPAGES mother-child cohort
Authors: Manches Olivier , Um Khémary , Boudier Anne , Maddouri Yasmina , Lyon-Caen Sarah , Bayat Sam , Slama Rémy , Philippat Claire , Siroux Valérie , Chaperot Laurence
Published: April 2023

Introduction

Immune function in pregnancy is influenced by host-specific and environmental factors. This may impact fetal immune development, but the link between maternal and neonatal immune function is still poorly characterized. Here, we investigate the relationship between maternal and neonatal immune function, and identify factors affecting the association between maternal and child cytokine secretion.

Methods

In the French prospective cohort SEPAGES, blood samples were obtained from pregnant women (n=322) at gestational week 20 ± 4 and from their child at birth (n=156). Maternal and cord blood cytokine and chemokine (CK) levels were measured at baseline in all subjects and after T cell or dendritic cell activation with phytohemagglutinin or R848 (in total 29 and 27 measures in maternal and cord blood samples, respectively). Associations between environmental, individual factors and CK level were estimated by linear regression modeling. The maternal-cord blood CK relations were assessed by Pearson correlation and regression models.

Results

We observed that pregnant women and neonates displayed specific CK secretion profiles in the innate and adaptive compartments at baseline and upon activation. Activation of T cells in cord blood induced high levels of IL-2, but low levels of IFNγ, IL-13 or IL-10, in comparison to maternal blood samples. Elsewhere, neonatal innate immune responses were characterized by low production of IFNα, while productions of IL-1β, IL-6, IL-8, IL-10 and TNFα were higher than maternal responses. Strong correlations were observed between most CK after activation in maternal and cord blood samples. Strikingly, a statistical association between global mother and child cytokine profiles was evidenced. Correlations were observed between some individual CK of pregnant women and their children, both at baseline (MCP1, RANTES) and after activation with R848 (IL-6, IL-8 and IL-10). We looked for factors which could influence cytokine secretion in maternal or cord blood, and found that leucocyte counts, maternal age, pre-conception BMI, smoking and season were associated with the levels of several CK in mothers or children.

Discussion

Our study reveals in utero immune imprinting influencing immune responses in infants, opening the way to investigate the mechanisms responsible for this imprinting. Whether such influences have long lasting effects on children health warrants further investigation.
Shaping of the alveolar landscape by respiratory infections and long-term consequences for lung immunity
Authors: Rodriguez-Rodriguez Lucia , Gillet Laurent , Machiels Bénédicte
Published: April 2023

Respiratory infections and especially viral infections, along with other extrinsic environmental factors, have been shown to profoundly affect macrophage populations in the lung. In particular, alveolar macrophages (AMs) are important sentinels during respiratory infections and their disappearance opens a niche for recruited monocytes (MOs) to differentiate into resident macrophages. Although this topic is still the focus of intense debate, the phenotype and function of AMs that recolonize the niche after an inflammatory insult, such as an infection, appear to be dictated in part by their origin, but also by local and/or systemic changes that may be imprinted at the epigenetic level. Phenotypic alterations following respiratory infections have the potential to shape lung immunity for the long-term, leading to beneficial responses such as protection against allergic airway inflammation or against other infections, but also to detrimental responses when associated with the development of immunopathologies. This review reports the persistence of virus-induced functional alterations in lung macrophages, and discusses the importance of this imprinting in explaining inter-individual and lifetime immune variation.
The aryl hydrocarbon receptor regulates lipid mediator production in alveolar macrophages
Authors: Maier Ann-Marie , Huth Karsten , Alessandrini Francesca , Henkel Fiona , Schnautz Benjamin , Arifovic Anela , Riols Fabien , Haid Mark , Koegler Anja , Sameith Katrin , Schmidt-Weber Carsten B. , Esser-von-Bieren Julia , Ohnmacht Caspar
Published: April 2023

Allergic inflammation of the airways such as allergic asthma is a major health problem with growing incidence world-wide. One cardinal feature in severe type 2-dominated airway inflammation is the release of lipid mediators of the eicosanoid family that can either promote or dampen allergic inflammation. Macrophages are key producers of prostaglandins and leukotrienes which play diverse roles in allergic airway inflammation and thus require tight control. Using RNA- and ATAC-sequencing, liquid chromatography coupled to mass spectrometry (LC-MS/MS), enzyme immunoassays (EIA), gene expression analysis and in vivo models, we show that the aryl hydrocarbon receptor (AhR) contributes to this control via transcriptional regulation of lipid mediator synthesis enzymes in bone marrow-derived as well as in primary alveolar macrophages. In the absence or inhibition of AhR activity, multiple genes of both the prostaglandin and the leukotriene pathway were downregulated, resulting in lower synthesis of prostanoids, such as prostaglandin E2 (PGE2), and cysteinyl leukotrienes, e.g., Leukotriene C4 (LTC4). These AhR-dependent genes include PTGS1 encoding for the enzyme cyclooxygenase 1 (COX1) and ALOX5 encoding for the arachidonate 5-lipoxygenase (5-LO) both of which major upstream regulators of the prostanoid and leukotriene pathway, respectively. This regulation is independent of the activation stimulus and partially also detectable in unstimulated macrophages suggesting an important role of basal AhR activity for eicosanoid production in steady state macrophages. Lastly, we demonstrate that AhR deficiency in hematopoietic but not epithelial cells aggravates house dust mite induced allergic airway inflammation. These results suggest an essential role for AhR-dependent eicosanoid regulation in macrophages during homeostasis and inflammation.
Advances in the role of STAT3 in macrophage polarization
Authors: Xia Tingting , Zhang Meng , Lei Wei , Yang Ruilin , Fu Shengping , Fan Zhenhai , Yang Ying , Zhang Tao
Published: April 2023

The physiological processes of cell growth, proliferation, differentiation, and apoptosis are closely related to STAT3, and it has been demonstrated that aberrant STAT3 expression has an impact on the onset and progression of a number of inflammatory immunological disorders, fibrotic diseases, and malignancies. In order to produce the necessary biological effects, macrophages (M0) can be polarized into pro-inflammatory (M1) and anti-inflammatory (M2) types in response to various microenvironmental stimuli. STAT3 signaling is involved in macrophage polarization, and the research of the effect of STAT3 on macrophage polarization has gained attention in recent years. In order to provide references for the treatment and investigation of disorders related to macrophage polarization, this review compiles the pertinent signaling pathways associated with STAT3 and macrophage polarization from many fundamental studies.
Reducing scratching behavior in atopic dermatitis patients using the EMDR treatment protocol for urge: A pilot study
Authors: de Veer Mathijs R. , Waalboer-Spuij Rick , Hijnen Dirk Jan , Doeksen Do , Busschbach Jan J. , Kranenburg Leonieke W.
Published: April 2023

Background

Itch, and thereby the scratching behavior, is a common complaint in atopic dermatitis. Scratching damages the skin, which in turn worsens the itch. This itch-scratch cycle perpetuates the skin condition and has a major impact on the patient's quality of life. In addition to pharmacological treatment, psychological interventions show promising results in reducing scratching behavior.

Objectives

To investigate the effect of treatment according the EMDR treatment protocol for urge on scratching behavior of atopic dermatitis patients in a controlled study.

Methods

This study applies a multiple baseline across subjects design. Six patients were randomly allocated to different baseline lengths and all of them started registration of scratching behavior at the same day, using a mobile phone application. Nocturnal scratching was registered by a smart watch application. The total study duration was 46 days and was equal for all patients. Treatment consisted of two sessions using the EMDR treatment protocol for urge. Furthermore, standardized measures were used to assess disease activity, quality of life, and self-control. The nonoverlap of all pairs effect size was calculated for the daily measure data.

Results

One patient dropped out. Visual inspection suggests that the scratching behavior decreased over time in all patients. Furthermore, a moderate effect size of the treatment is found. During the baseline phase, scratching behavior fluctuated considerably and showed a slight negative trend. Outcomes of disease activity decreased over time and patients' self-control and quality of life improved after treatment. Nocturnal scratching behavior did not change after the intervention.

Conclusion

The results of the visual analysis of day time scratching behavior, disease activity, quality of life, and self-control seem promising. These findings pave the way for future research into the effect of the new intervention on other skin conditions suffering from scratching behavior, such as prurigo nodularis.
Integrated gene network analysis sheds light on understanding the progression of Osteosarcoma
Authors: Dey Hrituraj , Vasudevan Karthick , Doss C. George Priya , Kumar S. Udhaya , El Allali Achraf , Alsamman Alsamman M. , Zayed Hatem
Published: April 2023

Introduction

Osteosarcoma is a rare disorder among cancer, but the most frequently occurring among sarcomas in children and adolescents. It has been reported to possess the relapsing capability as well as accompanying collateral adverse effects which hinder the development process of an effective treatment plan. Using networks of omics data to identify cancer biomarkers could revolutionize the field in understanding the cancer. Cancer biomarkers and the molecular mechanisms behind it can both be understood by studying the biological networks underpinning the etiology of the disease.

Methods

In our study, we aimed to highlight the hub genes involved in gene-gene interaction network to understand their interaction and how they affect the various biological processes and signaling pathways involved in Osteosarcoma. Gene interaction network provides a comprehensive overview of functional gene analysis by providing insight into how genes cooperatively interact to elicit a response. Because gene interaction networks serve as a nexus to many biological problems, their employment of it to identify the hub genes that can serve as potential biomarkers remain widely unexplored. A dynamic framework provides a clear understanding of biological complexity and a pathway from the gene level to interaction networks.

Results

Our study revealed various hub genes viz. TP53, CCND1, CDK4, STAT3, and VEGFA by analyzing various topological parameters of the network, such as highest number of interactions, average shortest path length, high cluster density, etc. Their involvement in key signaling pathways, such as the FOXM1 transcription factor network, FAK-mediated signaling events, and the ATM pathway, makes them significant candidates for studying the disease. The study also highlighted significant enrichment in GO terms (Biological Processes, Molecular Function, and Cellular Processes), such as cell cycle signal transduction, cell communication, kinase binding, transcription factor activity, nucleoplasm, PML body, nuclear body, etc.

Conclusion

To develop better therapeutics, a specific approach toward the disease targeting the hub genes involved in various signaling pathways must have opted to unravel the complexity of the disease. Our study has highlighted the candidate hub genes viz. TP53, CCND1 CDK4, STAT3, VEGFA. Their involvement in the major signaling pathways of Osteosarcoma makes them potential candidates to be targeted for drug development. The highly enriched signaling pathways include FOXM1 transcription pathway, ATM signal-ling pathway, FAK mediated signaling events, Arf6 signaling events, mTOR signaling pathway, and Integrin family cell surface interactions. Targeting the hub genes and their associated functional partners which we have reported in our studies may be efficacious in developing novel therapeutic targets.