bluuebunny/crossref_metadata_2025 huggingface dataset:
Being and becoming instrumental musicians and teachers: A post-qualitative exploration
Authors: Southcott Jane , de Bruin Leon R.
Published: October 2022

In trying to understand the complex interplay between effective learning and personal experience in instrumental music education we look to our own histories of becoming instrumental performers trained in conservatoires. We seek a collective fusion of horizons of possibility to explore the relationships of musicians, both learners and teachers, with each other and their environments. We adopt the post-qualitative turn, as it offers space and place for simmering curiosities, introspections, evaluations, and yearnings. As pondering individuals, we question how we were pulled and prodded through the acquisition of instrumental expertise. We are a trumpeter and a clarinetist; we are performers. We are also music educators who both re-enact and resist what was given to us as gospel. We hope to find within our thick and layered experiences, understandings of the better teacher we hope to become. We look beyond our “training” to our becoming both musicians and pedagogues, a work that remains in progress. We offer this pathway to our students—how can we/they become the better music educator?
Impact of extracurricular factors on the academic performance of university students during the COVID-19 pandemic
Authors: Sanz Maria T. , López-Iñesta Emilia
Published: October 2022

This article aims to study the incidence of extracurricular factors relating to (a) personal work situation and place of residence; (b) family finances; and (c) access to the virtual environment on the academic results of university students during the COVID-19 pandemic. Regression models were used to determine the impact of the different factors on academic performance in a sample of 138 students of the Primary Education Teaching Degree at a Spanish Public University. The results show that students who devote themselves wholly to studying without having to work obtain better academic results than those who have to combine study and work. Furthermore, internet access affects academic results, with students having ADSL and Wi-Fi via smartphones reporting the highest grades.
The cAMP-signaling cancers: Clinically-divergent disorders with a common central pathway
Authors: Bolger Graeme B.
Published: October 2022

The cAMP-signaling cancers, which are defined by functionally-significant somatic mutations in one or more elements of the cAMP signaling pathway, have an unexpectedly wide range of cell origins, clinical manifestations, and potential therapeutic options. Mutations in at least 9 cAMP signaling pathway genes (TSHR, GPR101, GNAS, PDE8B, PDE11A, PRKARA1, PRKACA, PRKACB, and CREB) have been identified as driver mutations in human cancer. Although all cAMP-signaling pathway cancers are driven by mutation(s) that impinge on a single signaling pathway, the ultimate tumor phenotype reflects interactions between five critical variables: (1) the precise gene(s) that undergo mutation in each specific tumor type; (2) the effects of specific allele(s) in any given gene; (3) mutations in modifier genes (mutational “context”); (4) the tissue-specific expression of various cAMP signaling pathway elements in the tumor stem cell; and (5) and the precise biochemical regulation of the pathway components in tumor cells. These varying oncogenic mechanisms reveal novel and important targets for drug discovery. There is considerable diversity in the “druggability” of cAMP-signaling components, with some elements (GPCRs, cAMP-specific phosphodiesterases and kinases) appearing to be prime drug candidates, while other elements (transcription factors, protein-protein interactions) are currently refractory to robust drug-development efforts. Further refinement of the precise driver mutations in individual tumors will be essential for directing priorities in drug discovery efforts that target these mutations.
Modeling obesity in complex food systems: Systematic review
Authors: Bhatia Anita , Smetana Sergiy , Heinz Volker , Hertzberg Joachim
Published: October 2022

Obesity-related data derived from multiple complex systems spanning media, social, economic, food activity, health records, and infrastructure (sensors, smartphones, etc.) can assist us in understanding the relationship between obesity drivers for more efficient prevention and treatment. Reviewed literature shows a growing adaptation of the machine-learning model in recent years dealing with mechanisms and interventions in social influence, nutritional diet, eating behavior, physical activity, built environment, obesity prevalence prediction, distribution, and healthcare cost-related outcomes of obesity. Most models are designed to reflect through time and space at the individual level in a population, which indicates the need for a macro-level generalized population model. The model should consider all interconnected multi-system drivers to address obesity prevalence and intervention. This paper reviews existing computational models and datasets used to compute obesity outcomes to design a conceptual framework for establishing a macro-level generalized obesity model.
Identification of cuproptosis-related lncRNA prognostic signature for osteosarcoma
Authors: Liu Binfeng , Liu Zhongyue , Feng Chengyao , Li Chenbei , Zhang Haixia , Li Zhihong , Tu Chao , He Shasha
Published: October 2022

Background

Copper is an indispensably mineral element involved in various metabolic processes and functions in the active sites of many metalloproteins. Copper dysregulation is associated with cancers such as osteosarcoma (OS), the most common primary bone malignancy with invasiveness and metastasis. However, the causality between cuproptosis and OS remains elusive. We aim to identify cuproptosis-related long non-coding RNAs (lncRNAs) for osteosarcomatous prognosis, immune microenvironment response, and immunotherapy.

Methods

The Person correlation and differential expression analysis were used to identify differentially expressed cuproptosis-related lncRNAs (CRLs). The univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were performed to construct the CRL signature. The Kaplan–Meier (K-M) survival analysis, receiver operating characteristic (ROC) curve, internal validation, independent prognostic analysis, and nomograph were used to evaluate the prognostic value. The functional enrichment, tumor microenvironment, immunotherapy and chemotherapy response between the two distinct groups were further explored using a series of algorithms. The expression of signature CRLs was verified by real-time quantitative polymerase chain reaction (RT-qPCR) in OS cell lines.

Results

A novel CRL signature consisting of four CRLs were successfully identified. The K-M survival analysis indicated that the OS patients in the low-risk groups had a better prognosis than that in the high-risk group. Then, the ROC curve and subgroup survival analysis confirmed the prognostic evaluation performance of the signature. Equally, the independent prognostic analysis demonstrated that the CRL signature was an independently predicted factor for OS. Friends analysis determined the hub genes that played a critical role in differentially expressed genes between two distinct risk groups. In addition, the risk score was related to immunity status, immunotherapy response, and chemotherapeutic drug sensitivity. Finally, the expression of these signature CRLs detected by RT-qPCR was consistent with the bioinformatic analysis results.

Conclusion

In summary, our study confirmed that the novel CRL signature could effectively evaluate prognosis, tumor immune microenvironment, and immunotherapy response in OS. It may benefit for clinical decision-making and provide new insights for personalized therapeutics.
Serum levels of hormones regulating appetite in patients with cystic fibrosis − a single-center, cross-sectional study
Authors: Galiniak Sabina , Podgórski Rafał , Rachel Marta , Mazur Artur
Published: October 2022

Cystic fibrosis (CF), which is the most common inherited genetically determined disease caused by a mutation in the gene for the CF transmembrane conductance regulator protein. Pulmonary failure is the leading cause of death in this population, while the dysregulation of endocrine system creates significant disorders, including malnutrition, underweight, and CF-related diabetes. Therefore, the objective of our study was to determine the following hormones in the serum of patients with CF: ghrelin, putative peptide YY (PYY), Agouti-signaling protein (ASP), and alpha-melanocyte-stimulating hormone (α-MSH). To our knowledge, serum levels of PYY, ASP, and α-MSH have not yet been assessed in CF. For this purpose, we measured hormone levels using enzyme-linked immunosorbent assays in 38 patients from the local CF care center, as well as 16 sex- and age-matched healthy controls. Moreover, we estimated the correlations between the tested hormones and the parameters of the patients’ clinical status. In this study, we found sinificantly reduced serum levels of ghrelin and ASP in patients with CF (p<0.01). There was no difference in PYY and α-MSH levels between participants with CF and healthy subjects. Furthermore, there was no difference in hormone levels between females and males with CF. The type of gene mutation (homozygous or heterozygous for ΔF508) had no effect on hormone levels. Ghrelin was negatively correlated with age, body mass index, and C-reactive protein. PYY was negatively associated with the age of the patients. Hormone dysregulation in CF may contribute to decreased appetite, as well as many other disturbed processes. Therefore, ghrelin appears to play a key role in the regulation of energy management of CF. Future multicenter and multidisciplinary studies should focus on an unequivocal understanding of the role of these hormones in CF.
The role of teleconnection in the occurrence probability of extreme precipitation over China based on extreme value theory
Authors: Kang Xiaoping , Min Ruiying , Dai Juan , Gu Xihui
Published: October 2022

Non-stationarity of extreme climate events has been reported worldwide in recent decades, and traditional stationary analysis methods are no longer sufficient to properly reveal the occurrence probability of climate extremes. Based on the 0.25°C × 0.25°C gridded precipitation data (i.e., CN05.1), stationary and non-stationary models of generalized extreme value (GEV) and generalized Pareto (GP) distributions are adopted to estimate the occurrence probability of extreme precipitation over China during 1961–2018. Low-frequency oscillation (LFO) indices, such as El Niño-Southern Oscillation (ENSO), Indian Ocean Dipole (IOD), North Atlantic Oscillation (NAO), Southern Annular Mode (SAM), and Pacific Decadal Oscillation (PDO), are included as time-varying covariates in the non-stationary GEV and GP models. Results illustrate that the occurrence probability of extreme precipitation estimated from the stationary GEV and GP distributions shows a significant increasing trend in northwestern and southeastern China, and the opposite trend in southwestern, central, and northeastern China. In comparison with stationary model, the fitness of extreme precipitation series is improved for both the GEV and GP distributions if these LFO indices are used as time-varying covariates. Positive ENSO, IOD and PDO tend to cause negative anomalies in the occurrence probability of extreme precipitation in northeastern China and Tibet Plateau, and positive anomalies in southern China. Positive NAO and SAM phases mainly tend to cause positive anomalies in southern China. The circulation patterns of extreme precipitation anomalies associated with these LFO indices are discussed from aspects of precipitable water, vertical integrated moisture transport, 500-hPa geopotential height and 850-hPa wind field.
Meteorological factor contributions to the seesaw concentration pattern between PM2.5 and O3 in Shanghai
Authors: Sun Yongzhao , Wang Xiaoyan
Published: October 2022

With the implementation of various stringent emission reduction measures since 2013 in China, significant declines in fine particle (PM2.5) concentrations have occurred nationwide. However, China has suffered from increasing levels of ozone pollution in eastern urban areas. Many studies focus on the chemical interaction between PM2.5 and O3, but the meteorological mechanisms of the seesaw variation pattern between them are still unclear. Taking the megacity Shanghai (SH) as an example, we explored the meteorological causes of two types of PM2.5-O3 concentration variation seesaw events, i.e., high PM2.5 concentration with low O3 concentration (Type-one) events and low-PM-high-O3 (Type-two) seesaw events. The backward trajectories of the 144 Type-one events are divided into three clusters. Among the three clusters of Type-one seesaw events, the boundary layer height decreases by 20.53%–53.58%, and the wind speed decreases by 17.99%–28.29%, which is unfavorable for the diffusion of local air pollutants and contributes to the accumulation of PM2.5. Additionally, a backward air mass with a high content of PM2.5 plays an important role in the Type-one events, especially in the case of cluster one. In terms of cluster two, the increase in cloud cover, decrease in solar radiation and increase in relative humidity also promote the hygroscopic growth of aerosols and suppress the production of O3. As for cluster three, higher cloud cover and relative humidity contribute to the seesaw pattern of PM and O3. The 64 Type-two seesaw events are divided into two clusters. O3-rich air masses from the nearby east sea surface and remote northeast China increase the local O3 of SH. Moreover, in cluster one, high boundary layer depth and wet deposition contribute to the decrease in PM2.5 concentration. In cluster two, a obvious decrease in cloud cover and increase in solar radiation are also favorable for the photochemical production of ozone. The results will provide suggestions for the government to use to take measures to improve the air quality of SHs.
Yearly weather variation and surface temperature drives the spatiotemporal dynamics of a threatened butterfly and its host plant
Authors: Franzén Markus , Francioli Yannick , Askling John , Kindvall Oskar , Johansson Victor , Forsman Anders
Published: October 2022

It remains unclear to what extent yearly weather variation and spatial variation in microclimate influences the outcome of interacting plant-animal species and whether responses differ between life stages. We collected data over several years on 46 ha on File Hajdar, Gotland, Sweden, and executed a complete mapping of larva nests (n= 776) and imago (n= 5,952) of the marsh fritillary butterflyEuphydryas auriniaand its host plantSuccisa pratensis. The phenology of the butterflies and the major nectar plants visited varied among years. The duration of the adult flight period decreased with increasing ambient air temperatures. The density of butterflies, host plants, and host plant leaf size increased between years with increasing precipitation in the preceding year, and decreased with increasing average ambient air temperature in the preceding year. In 2021–2022 we deployed a unmanned aerial vehicle (UAV) with a high-resolution thermal sensor to measure spatial variation in surface temperatures in the study area. We found that survival from the egg to the larva stage increased with increasing surface temperature and host plant density. Host plants and larva nests generally occupied warmer microhabitats compared to imago butterflies. The results further suggested that the relationships linking surface temperature to the densities of imago, larva, host plants, and leaf size differed qualitatively between years. In 2017, larva nests and host plant density increased with increasing surface temperatures, and butterflies showed a non-linear response with a density peak at intermediate temperatures. As a result of the extreme drought in 2018 there was a reduction in maximum leaf size, and in the densities of plants, larvae, and butterflies. Moreover, the slopes of the relationships linking the density of larvae, butterflies, and plants to temperature shifted from linear positive to negative or curvilinear. Our findings demonstrate how yearly weather variation and heterogeneous surface temperatures can drive the spatiotemporal distribution and dynamics of butterflies and their host plants. The context specificity of the responses indicated by our results makes it challenging to project how climate change will affect the dynamics of ecological communities.
Borderline conditions for single or platooning operations in freight transport on expressways: Case study in Japan
Authors: Kawasaki Tomoya , Tagawa Hoshi , Lau Yui-yip
Published: October 2022

Truck platooning is defined as a convoy of freight vehicles operated using an electronic coupling system, and has several advantages, particularly in terms of cost savings for fuel consumption and labor. Platooning technology is introduced by discussing several issues: the distance between trucks, number of trucks convoyed, waiting time at the platooning center, and distance between the origin and destination, all of which are variables that influence the transport costs. Important is to identify the extent to which these factors affect borderline conditions for single or platooning freight transport operations. Therefore, this study aims to develop a cost function of platooning operations, compare transport costs between single and platooning operations, determine the factors that affect the transport costs and identify the borderline conditions for single or platooning operations. The cost functions in the hypothetical network were developed by considering the important factors that contribute to the transport costs in Japanese road freight transport. A scenario analysis was conducted to investigate the impact of the inter-vehicle distance and the number of platooned trucks on the borderline conditions. Our results revealed that the platooning operation would offer a comparative advantage with a shorter inter-vehicle distance. For example, for an inter-vehicle distance of 49 m and a distance of 800 km between the origin and destination, the platooning operation is not advantageous compared with manned driving unless the waiting time at the platooning center is less than 30 min. In addition, a platooning operation is feasible even with a travelling distance of 100 km if the trailing vehicles are unmanned. The highest cost contributor is the cost of labor, the reduction of which can significantly reduce the total transport costs.
Construction of a novel prognostic signature based on the composition of tumor-infiltrating immune cells in clear cell renal cell carcinoma
Authors: Yu Weiwei , Lu Jiahui , Wu Cen
Published: October 2022

Emerging evidence has uncovered that tumor-infiltrating immune cells (TIICs) play significant roles in regulating the tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC). However, the exact composition of TIICs and their prognostic values in ccRCC have not been well defined. A total of 534 ccRCC samples with survival information and TIIC data from The Cancer Genome Atlas (TCGA) dataset were included in our research. The ImmuCellAI tool was employed to estimate the abundance of 24 TIICs and further survival analysis explored the prognostic values of TIICs in ccRCC. In addition, the expression levels of immunosuppressive molecules (PDL1, PD1, LAG3, and CTLA4) in the high- and low-risk groups were explored. Various subtypes of TIICs had distinct infiltrating features and most TIICs exhibited dysregulated abundance between normal and tumor tissues. Moreover, specific kinds of TIICs had encouraging prognostic values in ccRCC. Further analysis constructed a 4-TIICs signature to evaluate the prognosis of ccRCC patients. Cox regression analyses confirmed the independent prognostic role of the signature in ccRCC. Moreover, immunosuppressive molecules, including PD1, LAG3, and CTLA4, were significantly upregulated in the high-risk group and predicted poor prognosis. However, PDL1 was not changed between high- and low-risk groups and could not predict poor prognosis. To sum up, our research explored the landscape of TIICs in ccRCC and established a novel 4-TIIC prognostic signature, which could effectively predict the prognosis for patients with ccRCC. Based on this signature, we also concluded that PDL1 may not predict prognosis in ccRCC.
Ethical challenges in genetic research among Philippine Indigenous Peoples: Insights from fieldwork in Zamboanga and the Sulu Archipelago
Authors: Rodriguez Jae Joseph Russell B. , Cuales John Meldwin D. , Herrera Michael James B. , Zubiri Louward Allen M. , Muallil Richard N. , Ishmael Altan I. , Jimenez Edlyn B. , Stoneking Mark , De Ungria Maria Corazon A.
Published: October 2022

The Philippines, with the recent discovery of an archaic hominin in Luzon and an extensive ethnolinguistic diversity of more than 100 Indigenous peoples, is crucial to understanding human evolution and population history in Island Southeast Asia. Advances in DNA sequencing technologies enable the rapid generation of genomic data to robustly address questions about origins, relatedness, and population movements. With the increased genetic sampling in the country, especially by international scientists, it is vital to revisit ethical rules and guidelines relevant to conducting research among Indigenous peoples. Our team led fieldwork expeditions between 2019 and February 2020 in Zamboanga and the Sulu Archipelago, a chain of islands connecting the Mindanao and Borneo landmasses. The trips concluded with a collection of 2,149 DNA samples from 104 field sites. We present our fieldwork experience among the mostly sea-oriented Sama-Bajaw and Tausug-speaking communities and propose recommendations to address the ethical challenges of conducting such research. This work contributes toward building an enabling research environment in the Philippines that respects the rights and autonomy of Indigenous peoples, who are the rightful owners of their DNA and all genetic information contained therein.
Sleep disturbances correlate with behavioral problems among individuals with Wiedemann-Steiner syndrome
Authors: Ng Rowena , Bjornsson Hans Tomas , Fahrner Jill A. , Harris Jacqueline
Published: October 2022

Wiedemann-Steiner syndrome (WSS) is a rare genetic disorder caused by mutation in KMT2A and characterized by neurodevelopmental delay. This study is the first prospective investigation to examine the sleep and behavioral phenotypes among those with WSS through parent-informant screening inventories. A total of 24 parents of children/adults with WSS (11F, Mean age = 12.71 years, SD = 8.17) completed the Strengths and Difficulties Questionnaire (SDQ) and 22 of these caregivers also completed the Modified Simonds and Parraga Sleep Questionnaire (MSPSQ). On average, the majority of those with WSS (83%) were rated to show borderline to clinical level of behavioral difficulties on the SDQ. Approximately 83% were rated in these ranges for hyperactivity, 63% for emotional problems, and 50% for conduct problems. When applying prior published clinical cut-off for risk of sleep disturbance among those with neurodevelopmental disorders, over 80% of our sample exceeded this limit on the MSPSQ. Largely, caregivers’ ratings suggested restless sleep, rigid bedtime rituals, sleep reluctance and breathing through the mouth in sleep were most consistent problems observed. Partial correlations between sleep and behavioral domains showed elevated emotional problems were associated with parasomnia characteristics after controlling for age. Daytime drowsiness and activity were associated with more hyperactivity. Those with more night waking problems and delayed sleep onset were rated to show more severe conduct problems. Overall, these findings suggest dysfunctional sleep behaviors, hyperactivity, and affective problems are part of the neurobehavioral phenotype of WSS. Routine clinical care for those affected by WSS should include close monitoring of sleep and overactive behaviors.
Construction of a ceRNA-based lncRNA–mRNA network to identify functional lncRNAs in premature ovarian insufficiency
Authors: Luo Chao , Zhang Jiakai , Bo Le , Wei Lun , Yang Guangzhao , Gao Shasha , Mao Caiping
Published: October 2022

Premature ovarian insufficiency, characterized by ovarian infertility and low fertility, has become a significant problem in developed countries due to its propensity for late delivery. It has been described that the vital role of lncRNA in the development and progression of POI. The aim of this work was to create a POI-based lncRNA–mRNA network (POILMN) to recognize key lncRNAs. Overall, differently expressed mRNAs (DEGs) and differently expressed lncRNAs (DELs) were achieved by using the AnnoProbe and limma R packages. POI-based lncRNA–mRNA network (POILMN) construction was carried out using the tinyarray R package and hypergeometric distribution. To identify key lncRNAs, we used CentiScaPe plug-in Cytoscape as a screening tool. In total, 244 differentially expressed lncRNAs (DELs) and 288 differentially expressed mRNAs (DEGs) were obtained in this study. Also, 177 lncRNA/mRNA pairs (including 39 lncRNAs and 86 mRNAs) were selected using the hypergeometric test. Finally, we identified four lncRNA (HCP5, NUTM2A-AS1, GABPB1-IT1, and SMIM25) intersections by topological analysis between two centralities (degree and betweenness), and we explored their subnetwork GO and KEGG pathway enrichment analysis. Here, we have provided strong evidence for a relationship with apoptosis, DNA repair damage, and energy metabolism terms and pathways in the key lncRNAs in our POI-based lncRNA–mRNA network. In addition, we evaluated the localization information of genes related to POI and found that genes were more distributed on chromosomes 15, 16, 17, and 19. However, more experiments are needed to confirm the functional significance of such predicted lncRNA/mRNA. In conclusion, our study identified four long non-coding RNA molecules that may be relevant to the progress of premature ovarian insufficiency.
IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury
Authors: Sun Qingyu , Hu Tingting , Zhang Yurui , Wang Xiaotong , Liu Jing , Chen Wen , Wei Chao , Liu Dianxin , Wu Weihua , Lan Ting , Ding Yumeng , Luo Zhaoli , Liu Meng , Shen Danmin , Xiao Zhongnan , Hu Liye , Pang Miaoyi , Ma Yiran , Shi Lei , Wang Peipei , Zhang Jiannan , Li Qian , Yang Fei
Published: October 2022

Inflammation plays an important role in the occurrence and development of neuropathic pain. Immune-responsive gene 1 (IRG1) decarboxylates cis-aconitate to produce itaconate in the mitochondria. Itaconate serves as an immunomodulator of macrophages and represses inflammation in infectious diseases. Recently, a study showed that an itaconate derivative inhibits neuroinflammation and reduces chronic pain in mice. However, the function and molecular mechanisms of endogenous itaconate in neuropathic pain have not been fullyelucidated. In this study, the content of itaconate in the ipsilateral spinal cord after nerve-injured mice was detected with mass spectrometry. The Irg1-/- mouse was constructed to determine the role of endogenous itaconate in the chronic constriction nerve injury (CCI) model. The analgesic effect of exogenous itaconate was assessed with intraperitoneal and intrathecal administration in both male and female CCI mice. The spinal application of 4-OI also reduced the evoked responses of wide dynamic range neurons in CCI mice. The potential analgesic mechanism of itaconate was explored through molecular biology experiments and verified in Interleukin (IL)-10-/- mice. We found the levels of itaconate and IRG1 in the spinal cord significantly increased after CCI. Irg1 deficiency aggravated the mechanical and heat hypersensitivity, while the exogenous administration of the itaconate derivative 4-OI alleviated the neuropathic pain in male and female CCI mice. Mechanistically, the treatment of 4-OI increased the level of IL-10 and activates STAT3/β-endorphin pathway in the spinal cord, and the analgesia effect of itaconate was impaired in IL-10-/- mice. Finally, we showed that the upregulation of IL-10 induced by 4-OI was mainly from spinal neurons through Nrf2 pathway. This study demonstrated the analgesic effect of endogenous and exogenous itaconate in the neuropathic pain model, suggesting that the spinal IL-10/STAT3/β-endorphin pathway might mediate the analgesia effect of itaconate.
Clinical characteristics of hepatitis flares during pregnancy and postpartum in Chinese chronic hepatitis B virus carriers—a prospective cohort study of 417 cases
Authors: Wang Xiaoxiao , Song Aixin , Lin Xiao , Lu Junfeng , Zheng Sujun , Ma Lina , Ren Shan , Zheng Yanhong , Chen Xinyue
Published: October 2022

Background

In China, it is common for pregnant women with a high load of hepatitis B virus (HBV) to take nucleos(t)ide analogue (NA) to prevent maternal-to-child transmission of HBV. However, the impact of NA intervention on virological and biochemical parameters in pregnant and postpartum women and the safety of drug cessation remain unclear. A prospective observational cohort was established in this study to analyze the clinical characteristics of hepatitis flares in pregnant and postpartum chronic HBV carriers, with or without NA intervention.

Methods

Pregnant women who were chronic HBV carriers were enrolled in this study and divided into an NA intervention group and a non-intervention group according to their preferences. Liver function, HBV DNA level, and HBV serological markers were regularly measured during pregnancy and at approximately 6 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks postpartum.

Results

A total of 417 patients were enrolled, including 303 in the NA intervention group and 114 in the non-intervention group. The incidence rates of postpartum hepatitis flares in both groups were higher than that of during pregnancy (45.7% vs 10.9%, p < 0.001; 41.2% vs 17.7%, p < 0.001). The second trimester was the peak of the incidence of flares during pregnancy and the incidence peak of postpartum flares was about 6 weeks postpartum. A total of 98% (145/148) of postpartum flares occurred within 24 weeks postpartum. After drug cessation, the incidence rate of flares was 34.1% (44/129).

Conclusion

In pregnant chronic HBV carriers, a certain proportion of hepatitis flares occurred during pregnancy and postpartum regardless of whether NA intervention was used, and the incidence of postpartum flares (44.6%) was significantly higher than that (12.8%) of during pregnancy. The flare incidence peaked at approximately 6 weeks postpartum, which may be the time period suitable for treatment. Since 98% of postpartum flares occurred within 24 weeks postpartum, the follow-up after drug cessation should be at least 24 weeks postpartum.
IL-22BP production is heterogeneously distributed in Crohn’s disease
Authors: Fantou Aurélie , Lagrue Eric , Laurent Thomas , Delbos Laurence , Blandin Stéphanie , Jarry Anne , Beriou Gaëlle , Braudeau Cécile , Salabert Nina , Marin Eros , Moreau Aurélie , Podevin Juliette , Bourreille Arnaud , Josien Régis , Martin Jérôme C.
Published: October 2022

Crohn’s disease (CD), a form of inflammatory bowel disease (IBD), is characterized by impaired epithelial barrier functions and dysregulated mucosal immune responses. IL-22 binding protein (IL-22BP) is a soluble inhibitor regulating IL-22 bioactivity, a cytokine proposed to play protective roles during CD. We and others have shown that IL-22BP is produced in IBD inflamed tissues, hence suggesting a role in CD. In this work, we extended the characterization of IL-22BP production and distribution in CD tissues by applying enzyme-linked immunosorbent assays to supernatants obtained from the culture of endoscopic biopsies of patients, and reverse transcription-quantitative polymerase chain reaction on sorted immune cell subsets. We reveal that IL-22BP levels are higher in inflamed ileums than colons. We observe that in a cell-intrinsic fashion, populations of mononuclear phagocytes and eosinophils express IL-22BP at the highest levels in comparison to other sources of T cells. We suggest the enrichment of intestinal eosinophils could explain higher IL-22BP levels in the ileum. In inflamed colon, we reveal the presence of increased IL-22/IL22BP ratios compared to controls, and a strong correlation between IL-22BP and CCL24. We identify monocyte-derived dendritic cells (moDC) as a cellular subtype co-expressing both cytokines and validate our finding using in vitro culture systems. We also show that retinoic acid induces the secretion of both IL-22BP and CCL24 by moDC. Finally, we report on higher IL-22BP levels in active smokers. In conclusion, our work provides new information relevant to therapeutic strategies modulating IL-22 bioactivity in CD, especially in the context of disease location.
Effects of microenvironment in osteosarcoma on chemoresistance and the promise of immunotherapy as an osteosarcoma therapeutic modality
Authors: Yu Lei , Zhang Jian , Li Yunfeng
Published: October 2022

Osteosarcoma (OS) is one of the most common primary malignant tumors originating in bones. Its high malignancy typically manifests in lung metastasis leading to high mortality. Although remarkable advances in surgical resection and neoadjuvant chemotherapy have lengthened life expectancy and greatly improved the survival rate among OS patients, no further breakthroughs have been achieved. It is challenging to treat patients with chemoresistant tumors and distant metastases. Recent studies have identified a compelling set of links between hypoxia and chemotherapy failure. Here, we review the evidence supporting the positive effects of hypoxia in the tumor microenvironment (TME). In addition, certain anticancer effects of immune checkpoint inhibitors have been demonstrated in OS preclinical models. Continued long-term observation in clinical trials is required. In the present review, we discuss the mutualistic effects of the TME in OS treatment and summarize the mechanisms of immunotherapy and their interaction with TME when used to treat OS. We also suggest that immunotherapy, a new comprehensive and potential antitumor approach that stimulates an immune response to eliminate tumor cells, may represent an innovative approach for the development of a novel treatment regimen for OS patients.
The TLR-NF-kB axis contributes to the monocytic inflammatory response against a virulent strain of Lichtheimia corymbifera, a causative agent of invasive mucormycosis
Authors: Montaño Dolly E. , Hartung Susann , Wich Melissa , Ali Rida , Jungnickel Berit , von Lilienfeld-Toal Marie , Voigt Kerstin
Published: October 2022

Invasive mucormycosis (IM) is a life-threatening infection caused by the fungal order Mucorales, its diagnosis is often delayed, and mortality rates range from 40-80% due to its rapid progression. Individuals suffering from hematological malignancies, diabetes mellitus, organ transplantations, and most recently COVID-19 are particularly susceptible to infection by Mucorales. Given the increase in the occurrence of these diseases, mucormycosis has emerged as one of the most common fungal infections in the last years. However, little is known about the host immune response to Mucorales. Therefore, we characterized the interaction among L. corymbifera—one of the most common causative agents of IM—and human monocytes, which are specialized phagocytes that play an instrumental role in the modulation of the inflammatory response against several pathogenic fungi. This study covered four relevant aspects of the host-pathogen interaction: i) The recognition of L. corymbifera by human monocytes. ii) The intracellular fate of L. corymbifera. iii) The inflammatory response by human monocytes against the most common causative agents of mucormycosis. iv) The main activated Pattern-Recognition Receptors (PRRs) inflammatory signaling cascades in response to L. corymbifera. Here, we demonstrate that L. corymbifera exhibits resistance to intracellular killing over 24 hours, does not germinate, and inflicts minimal damage to the host cell. Nonetheless, viable fungal spores of L. corymbifera induced early production of the pro-inflammatory cytokine IL-1β, and late release of TNF-α and IL-6 by human monocytes. Moreover, we revealed that IL-1β production predominantly depends on Toll-like receptors (TLRs) priming, especially via TLR4, while TNF-α is secreted via C-type lectin receptors (CTLs), and IL-6 is produced by synergistic activation of TLRs and CTLs. All these signaling pathways lead to the activation of NF-kB, a transcription factor that not only regulates the inflammatory response but also the apoptotic fate of monocytes during infection with L. corymbifera. Collectively, our findings provide new insights into the host-pathogen interactions, which may serve for future therapies to enhance the host inflammatory response to L. corymbifera.
The human milk proteome and allergy of mother and child: Exploring associations with protein abundances and protein network connectivity
Authors: Dekker Pieter M. , Azad Meghan B. , Boeren Sjef , Mandhane Piushkumar J. , Moraes Theo J. , Simons Elinor , Subbarao Padmaja , Turvey Stuart E. , Saccenti Edoardo , Hettinga Kasper A.
Published: October 2022

Background

The human milk proteome comprises a vast number of proteins with immunomodulatory functions, but it is not clear how this relates to allergy of the mother or allergy development in the breastfed infant. This study aimed to explore the relation between the human milk proteome and allergy of both mother and child.

Methods

Proteins were analyzed in milk samples from a subset of 300 mother-child dyads from the Canadian CHILD Cohort Study, selected based on maternal and child allergy phenotypes. For this selection, the definition of “allergy” included food allergy, eczema, allergic rhinitis, and asthma. Proteins were analyzed with non-targeted shotgun proteomics using filter-aided sample preparation (FASP) and nanoLC-Orbitrap-MS/MS. Protein abundances, based on label-free quantification, were compared using multiple statistical approaches, including univariate, multivariate, and network analyses.

Results

Using univariate analysis, we observed a trend that milk for infants who develop an allergy by 3 years of age contains higher abundances of immunoglobulin chains, irrespective of the allergy status of the mother. This observation suggests a difference in the milk’s immunological potential, which might be related to the development of the infant’s immune system. Furthermore, network analysis showed overall increased connectivity of proteins in the milk of allergic mothers and milk for infants who ultimately develop an allergy. This difference in connectivity was especially noted for proteins involved in the protein translation machinery and may be due to the physiological status of the mother, which is reflected in the interconnectedness of proteins in her milk. In addition, it was shown that network analysis complements the other methods for data analysis by revealing complex associations between the milk proteome and mother-child allergy status.

Conclusion

Together, these findings give new insights into how the human milk proteome, through differences in the abundance of individual proteins and protein-protein associations, relates to the allergy status of mother and child. In addition, these results inspire new research directions into the complex interplay of the mother-milk-infant triad and allergy.
FOXP3+ regulatory T cells and the immune escape in solid tumours
Authors: Qiu Yiran , Ke Shouyu , Chen Jieqiong , Qin Zhizhen , Zhang Wenle , Yuan Yaqin , Meng Dehua , Zhao Gang , Wu Kejin , Li Bin , Li Dan
Published: October 2022

FOXP3+ regulatory T (Treg) cells play critical roles in establishing the immunosuppressive tumour microenvironment, which is achieved and dynamically maintained with the contribution of various stromal and immune cell subsets. However, the dynamics of non-lymphoid FOXP3+ Treg cells and the mutual regulation of Treg cells and other cell types in solid tumour microenvironment remains largely unclear. In this review, we summarize the latest findings on the dynamic connections and reciprocal regulations of non-lymphoid Treg cell subsets in accordance with well-established and new emerging hallmarks of cancer, especially on the immune escape of tumour cells in solid tumours. Our comprehension of the interplay between FOXP3+ Treg cells and key hallmarks of cancer may provide new insights into the development of next-generation engineered T cell-based immune treatments for solid tumours.
Screening the Medicines for Malaria Venture (MMV) Pandemic Response Box chemical library on Caenorhabditis elegans identifies re-profiled candidate anthelmintic drug leads
Authors: Nick Marina , Partridge Frederick A. , Forman Ruth , Bataille Carole J. R. , Else Kathryn J. , Russell Angela J. , Sattelle David B.
Published: October 2022

The 3 major classes of soil transmitted helminths (whipworm, hookworm and Ascaris) affect 1.5 billion people worldwide mostly in poor countries, where they have adverse effects on child development, nutrition, and the work capacity of adults. Although there are drugs effective on Ascaris, notably the benzimidazoles, those same drugs show poor efficacy particularly against whipworm (Trichuris trichiura) and to a certain extent hookworm. Parasitic nematodes also infect farm livestock and companion animals. Resistance to currently deployed human and veterinary anthelmintic drugs is a growing problem. Therefore, new chemical anthelmintic lead compounds are urgently needed. One of the fastest routes to a novel therapeutic lead is to screen libraries of drugs which are either already approved for human use or have already been part of clinical trials. We have pursued this approach to anthelmintic lead discovery using an invertebrate automated phenotyping platform (INVAPP) for screening chemicals and the well-established nematode genetic model organism Caenorhabditis elegans. The 400 compound Medicines for Malaria Venture (MMV) Pandemic Response Box library was screened with each compound tested initially at 1.0x10-4 M. We identified 6 compounds (MMV1593515 (vorapaxar), MMV102270 (diphyllin), MMV1581032 (ABX464), MMV1580796 (rubitecan), MMV1580505 and MMV1593531) active in both an L1-L4 growth/motility assay and in an L4 motility assay. For vorapaxar, an EC50 of 5.7x10-7 M was observed, a value comparable to those of some commercial anthelmintics. Although not a parasite, the ease with which high-throughput screens can be pursued on the free-living nematode C. elegans makes this a useful approach to identify chemical leads and complements the often lower-throughput experiments on parasitic nematode models.
Immune characterization and expression analysis of a goose-type lysozyme gene from Pinctada fucata martensii
Authors: Guo Zhijie , Shen Chenghao , Liang Haiying , Zhang Meizhen , Liang Bidan , Zhang Bin
Published: October 2022

In the present study, a g-type lysozyme was successfully screened and cloned from Pinctada fucata martensii (designated as PmlysG). The cDNA has a length of 973 bp with an open reading frame (ORF) of 769 bp, encoding a protein of 255 amino acids. The PmlysG transcript was detected in multiple tissues by quantitative real-time PCR (qRT-PCR), with the highest expression being in the hepatopancreas. Additionally, the temporal expression of PmlysG mRNA in the hepatopancreas after in vivo stimulation with pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS), peptidoglycan (PGN) and polyinosinic acid (PolyI:C) was detected by qRT-PCR. Although PmlysG responded to all three stimulation modes, it rapidly responded to PGN stimulation. Meanwhile, the recombinant protein of g-type lysozyme of P.f. martensii (rPmlysG) was used for antibacterial function analysis, and the results showed that rPmlysG has antibacterial function against Vibrio parahaemolyticus, Aeromonas hydrophila, and Pseudomonas aeruginosa. Overall, these study results suggest that the identified PmlysG participates in the innate immune responses of P.f. martensii against pathogen infection.
Spatial and diel patterns of volatile organic compounds, DMSP-derived compounds, and planktonic microorganisms around a tropical scleractinian coral colony
Authors: Masdeu-Navarro Marta , Mangot Jean-François , Xue Lei , Cabrera-Brufau Miguel , Gardner Stephanie G. , Kieber David J. , González José M. , Simó Rafel
Published: October 2022

Volatile organic compounds (VOCs) are constituents of marine ecosystems including coral reefs, where they are sources of atmospheric reactivity, indicators of ecosystem state, components of defense strategies, and infochemicals. Most VOCs result from sunlight-related processes; however, their light-driven dynamics are still poorly understood. We studied the spatial variability of a suite of VOCs, including dimethylsulfide (DMS), and the other dimethylsulfoniopropionate-derived compounds (DMSPCs), namely, DMSP, acrylate, and dimethylsulfoxide (DMSO), in waters around colonies of two scleractinian corals (Acropora pulchra and Pocillopora sp.) and the brown seaweed Turbinaria ornata in Mo’orean reefs, French Polynesia. Concentration gradients indicated that the corals were sources of DMSPCs, but less or null sources of VOCs other than DMS, while the seaweed was a source of DMSPCs, carbonyl sulfide (COS), and poly-halomethanes. A focused study was conducted around an A. pulchra colony where VOC and DMSPC concentrations and free-living microorganism abundances were monitored every 6 h over 30 h. DMSPC concentrations near the polyps paralleled sunlight intensity, with large diurnal increases and nocturnal decrease. rDNA metabarcoding and metagenomics allowed the determination of microbial diversity and the relative abundance of target functional genes. Seawater near coral polyps was enriched in DMS as the only VOC, plus DMSP, acrylate, and DMSO, with a large increase during the day, coinciding with high abundances of symbiodiniacean sequences. Only 10 cm below, near the coral skeleton colonized by a turf alga, DMSPC concentrations were much lower and the microbial community was significantly different. Two meters down current from the coral, DMSPCs decreased further and the microbial community was more similar to that near the polyps than that near the turf alga. Several DMSP cycling genes were enriched in near-polyp with respect to down-current waters, namely, the eukaryotic DMS production and DMS oxidation encoding genes, attributed to the coral and the algal symbiont, and the prokaryotic DMS production gene dddD, harbored by coral-associated Gammaproteobacteria. Our results suggest that solar radiation-induced oxidative stress caused the release of DMSPCs by the coral holobiont, either directly or through symbiont expulsion. Strong chemical and biological gradients occurred in the water between the coral branches, which we attribute to layered hydrodynamics.