bluuebunny/crossref_metadata_2025 huggingface dataset:
Youth agency in times of crisis: Exploring education and conflict in Mali through participatory visual approaches with youth
Authors: Mitchell Claudia , Lussier Kattie , Keita Fatoumata
Published: September 2022

Education in Mali is constrained by a multi-dimensional crisis that restricts education and makes life difficult. Young people are particularly affected. In this article, we use the preliminary findings of the Participatory Research on Education and Agency in Mali (PREAM) project that was implemented in the conflict-affected regions of Mopti and Segou, to discuss youth agency in situations of crisis and how participatory visual methods can be used both as a way of ascertaining adolescents’ perception of their agency and also to contribute to the development of youth agency. More specifically, we use data from six workshops using participatory visual methods (PVMs) to illustrate that young people have something valuable to say about education, agency, and conflict and that PVMs can be an effective way of engaging adolescents in dealing with such topics. Preliminary findings from the research suggest that although participating young people are in an asymmetrical position in relation to power with the adults around them, they nonetheless have a good understanding of their situation and demonstrate agentic behavior that is both adaptative and projective. Girls illustrated how generational order from child to grandmother and gender social norms can constrain agency. At the same time, they used their agency to expose and contest, in the cellphilms they produced, the unfair division of labor in their society. During the workshops, young people were eager to share their stories and wanted their artwork to communicate their concerns to the adults around them. In this article, we argue that it is important for adolescents in Mali to have a voice on questions of education and agency and we discuss why education actors and policy makers should pay attention to the perspectives of young people even (and especially) in times of crisis.
The safety of sotagliflozin in the therapy of diabetes mellitus type 1 and type 2: A meta-analysis of randomized trials
Authors: Zhou Feifei , Du Nannan , Zhou Lulin , Wang Chenxi , Ren He , Sun Qiang
Published: September 2022

Background

Diabetes mellitus (DM) is a global health problem, and it has become a shocking threat in the contemporary era. The objective of this study was to analyze the safety of sotagliflozin in patients with DM systematically and intuitively.

Methods

On November 15, 2021, literature retrieval was performed on PubMed, Web of Science, EBSCO, and Cochrane libraries. The meta-analysis results included genital mycotic infection, related-to-acidosis events, and other related adverse events, including diarrhea, severe nocturnal hypoglycemia event, and volume depletion. In addition, a subgroup analysis was also conducted based on different doses of sotagliflozin. Moreover, the patient-treated years analyzed in the study were 12 weeks, 24 weeks, and 52 weeks, respectively, for type 1 diabetes, and were 12 weeks, 22 weeks, and 52 weeks, respectively, for type 2 diabetes.

Results

The results of this meta-analysis illustrated that sotagliflozin could increase the risk of genital mycotic infection for patients with T1D and T2D (RR: 3.49, 95% Cl: 2.54-4.79, p < 0.001; RR: 2.83, 95% Cl: 2.04-3.93, p < 0.001; respectively). In addition, the subgroup analysis showed that the drug doses that could increase the risk of genital mycotic infection were 400 mg and 200 mg (RR: 3.63, 95% Cl: 2.46-5.36, p < 0.001; RR: 3.21, 95% Cl: 1.84-5.62, p < 0.001; respectively) in T1D. Moreover, sotagliflozin could increase the risk of events related to acidosis in the patients of T1D, including acidosis-related adverse events, positively adjudicated diabetic ketoacidosis, acidosis-related event, and diabetic ketoacidosis (RR: 7.49, 95% Cl: 3.20-17.52, p < 0.001; RR: 6.05, 95% Cl: 2.56-14.30, p < 0.001; RR: 4.83, 95% Cl: 3.13-7.45, p < 0.001; RR: 8.12, 95% Cl: 3.06-21.52, p < 0.001; respectively). In the patients of T2D, sotagliflozin could not increase the risk of DKA (RR: 1.30, 95% Cl: 0.34-4.99, p = 0.70). About serious of acidosis-related adverse events, positively adjudicated diabetic ketoacidosis (DKA) and acidosis-related event, the included studies were not reported for T2D patients. As for the other related adverse events, sotagliflozin was found to be a risk factor for diarrhea and volume depletion in T1D patients (RR: 1.44, 95% Cl: 1.09-1.90, p = 0.01; RR: 2.50, 95% Cl: 1.33-4.69, p < 0.01; respectively) and T2D patients (RR: 1.44, 95% Cl: 1.26-1.64, p < 0.001; RR: 1.25, 95% Cl: 1.07-1.45, p < 0.01; respectively).

Conclusions

This meta-analysis showed that the adverse events of sotagliflozin were tolerable to patients with DM, in terms of the incidence of genital mycotic infection, related-to-acidosis events, diarrhea, volume depletion, and severe nocturnal hypoglycemia events. In addition, the subgroup analysis of sotagliflozin dosage is considered to have great clinical significance for future guidance of sotagliflozin application in patients with DM.
Health risks associated with radon concentrations in carbonate and evaporite sequences of the uranium-rich district Karak, Pakistan
Authors: Khan Mumtaz Ali , Khattak Nimat Ullah , Hanif Muhammad , Al-Ansari Nadhir , Khan Muhammad Bashir , Ehsan Muhsan , Elbeltagi Ahmed
Published: September 2022

The present research was carried out to investigate the behavior of radon (222Rn) concentrations over the carbonate and evaporite sequences and to assess the related health hazards. A total of 50 points from three different stratigraphic units, namely, the Bahadurkhel Salt, Jatta Gypsum, and the Kohat Formation of the Eocene age, were analyzed for radon concentrations in the district of Karak, Khyber Pakhtunkhwa, Pakistan. Measurements for radon levels were made by using RAD7 of Durridge, United States. The highest average 222Rn concentration (16.5 Bq/L) was found in the limestone unit of the Kohat Formation of the Eocene age. However, the lowest radon levels were observed in the salt-bearing strata of the Bahadurkhel Salt of the Eocene age. The study revealed that the average radon concentration in all the lithologies varied in the order of RnLimestone > RnSalt > RnGypsum. The findings of the current research suggest that the study area is safe from radon-related health hazards.
Rio (1992) to Glasgow (2021): Three decades of inadequate mitigation of climate change and its slow onset effects
Authors: Stavi Ilan
Published: September 2022

This study reviews the global increase in atmospheric greenhouse gas (GHG) concentrations, including carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O), alongside the accelerated climatic change and its slow onset effects (or events) between 1992 and 2021. The establishment of the United Nations Framework Convention on Climate Change (UNFCCC) in 1992, and the simultaneous UN Earth Summit in Rio de Janeiro, generated the international efforts to tackle climatic change. Over the years, the UNFCCC-Conference of the Parties (COP) has led the efforts in climate change mitigation and adaptation, with many sequential meetings across the world. Three decades later, at the COP26 meeting in Glasgow in 2021, it is evident that climate change impacts have substantially worsened. Despite some uncertainties, it seems that over the last three decades, the climate change slow onset events, including 1) increasing temperatures, 2) glacial retreat, 3) sea level rise, 4) ocean acidification, 5) soil salinization, 6) land and forest degradation, 7) loss of biodiversity, and 8) desertification, have substantially exacerbated. Simultaneously, other (non-GHGs related) anthropogenic impacts, including habitat fragmentation, land-use and sea-use change and misuse, species overexploitation, environmental pollution, infrastructure constructions, and urbanization, have considerably increased. With the aim of achieving the Shared Socio-Economic Pathways 1.9 (SSP1-1.9) or SSP1-2.6 ultimate goals—keeping global warming in 2,100 below 1.5°C or 2.0°C, respectively, compared to preindustrial levels—it may still be possible to avoid climate change’s irreversible tipping points. To reach this target, policymaking must become more decisive and proactive, with continuous risks assessment, frequent monitoring of outcomes and their compatibility to goals, implementing practical legislation tools, and assigning specific financial instruments, aimed at effectively tackling climate change slow onset events and related environmental issues. Substantial efforts should be invested in boosting climate change mitigation, while simultaneously targeting effective climatic change adaptation measures and promoting environmental conservation and restoration. Relying on tools such as the UN Sustainable Development Goals (SDGs) will sustain provisioning, supporting, regulating, and cultural ecosystem services, thus improving water-, food-, environmental-, energy-, economic-, health-, and governance-security, while lessening the risks of social unrest, violent conflicts, mass migration, and other humanitarian catastrophes.
Fine mapping and characterization of RLL6 locus required for anti-silencing of a transgene and DNA demethylation in Arabidopsisthaliana
Authors: Wang Xiangyu , Wang Min , Dai Jie , Wang Qianqian , La Honggui
Published: September 2022

DNA methylation patterns in plants are dynamically shaped by the antagonistic actions of DNA methylation and demethylation pathways. Although the DNA methylation pathway has been well studied, the DNA demethylation pathway, however, are not fully understood so far. To gain deeper insights into the mechanisms of DNA demethylation pathway, we conducted a genetic screening for proteins that were involved in preventing epigenetic gene silencing, and then the ones, which were also implicated in DNA demethylation pathway, were used for further studies. Eventually, a mutant with low luciferase luminescence (low LUC luminescence) was recovered, and named reduced LUC luminescence 6–1 (rll6-1). Map-based cloning revealed that rll6-1 mutation was located on chromosome 4, and there were a total of 10 candidate genes residing within such a region. Analyses of genome-wide methylation patterns of rll6-1 mutant showed that mutation of RLL6 locus led to 3,863 hyper-DMRs (DMRs for differentially methylated regions) throughout five Arabidopsis chromosomes, and elevated DNA methylation level of 2 × 35S promoter, which was similar to that found in the ros1 (repressor of silencing 1) mutant. Further analysis demonstrated that there were 1,456 common hyper-DMRs shared by rll6-1 and ros1-7 mutants, suggesting that both proteins acted together in a synergistic manner to remove DNA methylation. Further investigations demonstrated that mutation of RLL6 locus did not affect the expression of the four genes of the DNA glycosylase/lyase family. Thus, our results demonstrate that RLL6 locus-encoded protein not only participates in transcriptional anti-silencing of a transgene, but is also involved in DNA demethylation pathway.
Identification of m6A-related long non-coding RNAs for predicting prognosis and immune characterizations in gastric cancer
Authors: Zhang Xianhui , Wang Changjing , Liu Zhongxin , Si Yuan
Published: September 2022

Background: N6-methyladenosine (m6A) mRNA modification triggers malignant behavior in tumor cells, which promotes malignant progression and migration of gastric cancer (GC). Nevertheless, studies on the prognostic value of m6A-related long non-coding RNA (MRlncRNA) in GC remain quite restricted. The study aimed to develop a reasonable predictive model to explore the prognostic potential of MRlncRNAs in predicting the prognosis of GC patients and monitoring the efficacy of immunotherapy.

Methods: Transcriptomic and clinical data for GC were derived from TCGA. Next, univariate Cox, LASSO and multivariate Cox regression analyses were next used to identify prognostic MRlncRNAs, calculate risk scores and build risk assessment models. The predictive power of the risk models was then validated by Kaplan-Meier analysis, ROC curves, DCA, C-index, and nomogram. We attempted to effectively differentiate between groups in terms of immune cell infiltration status, ICI-related genes, immunotherapy responses, and common anti-tumor drug sensitivity.

Results: A risk model based on 11 MRlncRNAs was developed with an AUC of 0.850, and the sensitivity and specificity of this model in predicting survival probability is satisfactory. The Kaplan-Meier analysis revealed that the low-risk group in the model had a significantly higher survival rate, and the model was highly associated with survival status, clinical features, and clinical stage. Furthermore, the model was verified to be an independent prognostic risk factor, and the low-risk group in the model had a remarkable positive correlation with a variety of immune cell infiltrates. The expression levels of ICI-related genes differed significantly between the different groups. Lastly, immunotherapy responses and common anti-tumor drug sensitivity also differed significantly between different groups.

Conclusion: The risk model on the basis of 11-MRlncRNAs can serve as independent predictors of GC prognosis and may be useful in developing personalized treatment strategies for patients.
Prognostic N6-methyladenosine (m6A)-related lncRNA patterns to aid therapy in pancreatic ductal adenocarcinoma
Authors: Wang Yuxin , Ji Yutian , Xu Qianhui , Huang Wen
Published: September 2022

Background: Mounting research studies have suggested the indispensable roles of N6-methyladenosine (m6A) RNA modification in carcinogenesis. Nevertheless, it was little known about the potential function of m6A-related lncRNAs in sample clustering, underlying mechanism, and anticancer immunity of pancreatic ductal adenocarcinoma (PDAC).

Methods: PDAC sample data were obtained from TCGA-PAAD project, and a total of 23 m6A regulators were employed based on published articles. Pearson correlation and univariate Cox regression were analyzed to determine m6A-related lncRNAs with prognostic significance to identify distinct m6A-related lncRNA subtypes by consensus clustering. Next, the least absolute shrinkage and selection operator (LASSO) algorithm was applied for constructing an m6A-related lncRNA scoring system, further quantifying the m6A-related lncRNA patterns in individual samples. Gene set variation analysis (GSVA) was employed to assign pathway activity estimates to individual samples. To decode the comprehensive landscape of TME, the CIBERSORT method and ESTIMATE algorithm were analyzed. The half-maximal inhibitory concentration (IC50) of chemotherapeutic agents was predicted with the R package pRRophetic. Finally, a quantitative real-time polymerase chain reaction was used to determine TRPC7-AS1 mRNA expression in PDAC.

Results: Two distinct m6A-related lncRNA patterns with different clinical outcomes, TEM features, and biological enrichment were identified based on 45 prognostic m6A-related lncRNAs. The identification of m6A-related lncRNA patterns within individual samples based on risk scores contributed to revealing biological signatures, clinical outcomes, TEM characterization, and chemotherapeutic effects. A prognostic risk-clinical nomogram was constructed and confirmed to estimate m6A-related lncRNA patterns in individual samples. Finally, the biological roles of TRPC7-AS1 were revealed in PDAC.

Conclusion: This work comprehensively elucidated that m6A-related lncRNA patterns served as an indispensable player in prognostic prediction and TEM features. Quantitative identification of m6A-related lncRNA patterns in individual tumors will contribute to sample stratification for further optimizing therapeutic strategies.
Clinical experience of noninvasive prenatal testing for rare chromosome abnormalities in singleton pregnancies
Authors: Hu Ting , Wang Jiamin , Zhu Qian , Zhang Zhu , Hu Rui , Xiao Like , Yang Yunyuan , Liao Na , Liu Sha , Wang He , Niu Xiaoyu , Liu Shanling
Published: September 2022

Objectives: The study aimed to investigate the clinical use of noninvasive prenatal testing (NIPT) for common fetal aneuploidies as a prenatal screening tool for the detection of rare chromosomal abnormalities (RCAs).

Methods: Gravidas with positive NIPT results for RCAs who subsequently underwent amniocentesis for a single nucleotide polymorphism array (SNP array) were recruited. The degrees of concordance between the NIPT and SNP array were classified into full concordance, partial concordance, and discordance. The positive predictive value (PPV) was used to evaluate the performance of NIPT.

Results: The screen-positivity rate of NIPT for RCAs was 0.5% (842/158,824). Of the 528 gravidas who underwent amniocentesis, 29.2% (154/528) were confirmed to have positive prenatal SNP array results. PPVs for rare autosomal trisomies (RATs) and segmental imbalances were 6.1% (7/115) and 21.1% (87/413), respectively. Regions of homozygosity/uniparental disomy (ROH/UPD) were identified in 9.5% (50/528) of gravidas. The PPV for clinically significant findings was 8.0% (42/528), including 7 cases with mosaic RATs, 30 with pathogenic/likely pathogenic copy number variants, and 5 with imprinting disorders.

Conclusion: NIPT for common fetal aneuploidies yielded low PPVs for RATs, moderate PPVs for segmental imbalances, and incidental findings for ROH/UPD. Due to the low PPV for clinically significant findings, NIPT for common fetal aneuploidies need to be noticed for RCAs.
Effect of metformin on the epigenetic age of peripheral blood in patients with diabetes mellitus
Authors: Li Man , Bao Litao , Zhu Ping , Wang Shuxia
Published: September 2022

Background: Metformin has been proven to have an antiaging effect. However, studies on how metformin affects global epigenetic regulation and its effect on the epigenetic clock in diabetes mellitus (DM) patients are limited. This study aims to investigate the impact of metformin on the epigenetic age in subjects with type 2 DM.

Results: We collected the peripheral blood of the metformin group and the no-metformin group of the 32 DM patients. Three previously established epigenetic clocks (Hannum, Horvath, and DNAmPhenoAge) were used to estimate the epigenetic age acceleration of the two groups. We defined biological age acceleration for each group by comparing the estimated biological age with the chronological age. Results were presented as follows: 1) all three epigenetic clocks were strongly correlated with chronological age. 2) We found a strong association between metformin intake and slower epigenetic aging by Horvath’s clock and Hannum’s clock.

Conclusions: Here, we found an association between metformin intake and slower epigenetic aging.
Mutant p53K120R expression enables a partial capacity to modulate metabolism
Authors: Monti Paola , Ravera Silvia , Speciale Andrea , Velkova Irena , Foggetti Giorgia , Degan Paolo , Fronza Gilberto , Menichini Paola
Published: September 2022

The TP53 tumor suppressor gene is one of the most studied gene in virtue of its ability to prevent cancer development by regulating apoptosis, cell cycle arrest, DNA repair, autophagy and senescence. Furthermore, the modulation of metabolism by P53 is fundamental for tumor suppressor activity. Studies in mouse models showed that mice carrying TP53 mutations affecting the acetylation in the DNA binding domain still retain the ability to transactivate genes involved in metabolism. Noteworthy, mice expressing the triple 3KR or the single K117R mutant do not show early on-set tumor development in contrast to TP53−/− mice. Interestingly, the mouse K117R mutation corresponds to the human tumor-derived K120R modification, which abrogates P53-dependent activation of apoptosis without affecting growth arrest. In this study, we investigated the property of the human P53 K120R mutant in the regulation of metabolism by analyzing the transcriptional specificity in yeast- and mammalian-based reporter assays, the metabolic phenotype associated to its expression in colon cancer HCT116TP53−/− cells and the induction of P53 targets and proteins involved in the antioxidant response. These properties were analyzed in comparison to wild type P53 protein, the human triple mutant corresponding to mouse 3KR and the cancer hot-spot R273H mutant. We confirm the selective functionality of P53 K120R mutant, which shows a transcriptional activity on cell cycle arrest but not on apoptotic targets. Interestingly, this mutant shows a partial transactivation activity on p53 response element belonging to the metabolic target TIGAR. Moreover, we observe a significant uncoupling between oxygen consumption and ATP production associated with higher lipid peroxidation level in all P53 mutants carrying cells with respect to wild type P53 expressing cells. Noteworthy, in the absence of a pro-oxidative challenge, cells expressing K120R mutant retain a partial capacity to modulate glucose metabolism, limiting lipid peroxidation with respect to the other P53 mutants carrying cells. Lastly, especially in presence of human 3KR mutant, a high expression of proteins involved in the antioxidant response is found. However, this response does not avoid the increased lipid peroxidation, confirming that only wild type P53 is able to completely counteract the oxidative stress and relative damages.
Comprehensive analysis of PTPN gene family revealing PTPN7 as a novel biomarker for immuno-hot tumors in breast cancer
Authors: Wang Fengxu , Wang Xuehai , Liu Lei , Deng Siyuan , Ji Wenqian , Liu Yang , Wang Xiangdong , Wang Rui , Zhao Xinyuan , Gao Erli
Published: September 2022

Background: The non-receptor protein tyrosine phosphatase (PTPN) gene family has been considered to be involved in the oncogenesis and development of multiple cancers. However, its prognostic utility and immunological relevance in breast cancer (BrCa) have not been clarified.

Methods: A transcriptional level interpretation of the expressions and prognostic values was analyzed using the data from The Cancer Genome Atlas (TCGA) cohort. In addition, GO and DAVID pinpoint the functional enrichment of PTPNs. Moreover, the immune correlations of PTPN7 in BrCa and pan-cancer were further investigated based on the TCGA cohort and were testified using the in-house and the Gene Expression Omnibus (GEO) cohorts.

Results: For systematic analysis of the PTPN family, we found that the expression levels of PTPN1, PTPN6, PTPN7, PTPN18, PTPN20, and PTPN22 was promoted in tumor tissues while comparing with paraneoplastic tissues during our study. We further investigated their functions and protein-protein interactions (PPI), and these results strongly suggested that PTPN family was associated with protein dephosphorylation. Next, we performed an immunological relevance analysis and found that PTPN7 was correlated with immune infiltration, suggesting a stronger association of PTPN7 with immuno-hot tumors in BrCa. In addition, results from the in-house cohort confirmed the positive correlation between PTPN7 and PD-L1. The pan-cancer analysis revealed that PTPN7 was related to PD-L1 and CTLA-4 expression in almost all cancer types. Finally, the predictive value of PTPN7 for immunotherapy was significant in two independent GEO cohorts.

Conclusion: In conclusion, this is the first extensive research on the correlation between PTPN family expression and immune characterization in BrCa. As results, PTPN7 expression is associated with immuno-hot tumors and could be a promising predictive biomarker for immunotherapy in not only BrCa but multiple cancers.
Transcriptional analysis of microRNAs related to unsaturated fatty acid synthesis by interfering bovine adipocyte ACSL1 gene
Authors: Li Xupeng , Bai Yanbin , Li Jingsheng , Chen Zongchang , Ma Yong , Shi Bingang , Han Xiangmin , Luo Yuzhu , Hu Jiang , Wang Jiqing , Liu Xiu , Li Shaobin , Zhao Zhidong
Published: September 2022

Long-chain fatty acyl-CoA synthase 1 (ACSL1) plays a vital role in the synthesis and metabolism of fatty acids. The proportion of highly unsaturated fatty acids in beef not only affects the flavor and improves the meat’s nutritional value. In this study, si-ACSL1 and NC-ACSL1 were transfected in bovine preadipocytes, respectively, collected cells were isolated on the fourth day of induction, and then RNA-Seq technology was used to screen miRNAs related to unsaturated fatty acid synthesis. A total of 1,075 miRNAs were characterized as differentially expressed miRNAs (DE-miRNAs), of which the expressions of 16 miRNAs were upregulated, and that of 12 were downregulated. Gene ontology analysis indicated that the target genes of DE-miRNAs were mainly involved in biological regulation and metabolic processes. Additionally, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis identified that the target genes of DE-miRNAs were mainly enriched in metabolic pathways, fatty acid metabolism, PI3K-Akt signaling pathway, glycerophospholipid metabolism, fatty acid elongation, and glucagon signaling pathway. Combined with the previous mRNA sequencing results, several key miRNA-mRNA targeting relationship pairs, i.e., novel-m0035-5p—ACSL1, novel-m0035-5p—ELOVL4, miR-9-X—ACSL1, bta-miR-677—ACSL1, miR-129-X—ELOVL4, and bta-miR-485—FADS2 were screened via the miRNA-mRNA interaction network. Thus, the results of this study provide a theoretical basis for further research on miRNA regulation of unsaturated fatty acid synthesis in bovine adipocytes.
Synthetic MRI in the detection and quantitative evaluation of sacroiliac joint lesions in axial spondyloarthritis
Authors: Zhang Ke , Liu Chaoran , Zhu Yunfei , Li Wenjuan , Li Ximeng , Zheng Jing , Hong Guobin
Published: September 2022

Objective

Our primary objective was to verify the hypothesis that synthetic magnetic resonance imaging (MRI) is similar to conventional MRI in detecting sacroiliac joint lesions in patients with axial spondyloarthritis (axSpA). A secondary objective was to assess the quantitative value of synthetic mapping in bone marrow edema (BME) and fat metaplasia.

Methods

A total of 132 axSpA patients who underwent synthetic and conventional MRI from October 2019 to March 2021 were included in this prospective study. Two independent readers visually evaluated active inflammatory (BME, capsulitis, enthesitis, and inflammation at site of erosion) and structural lesions (erosion, sclerosis, ankylosis, and fat metaplasia) of the sacroiliac joints on conventional and synthetic magnetic resonance (MR) images. In addition, T1, T2, and proton density (PD) values, which were generated by synthetic mapping, were used to further quantitatively evaluate BME and fat metaplasia. A McNemar test was used to compare the differences between the two methods in the detection of sacroiliac joint lesions. Intraclass correlation coefficients (ICCs) were used to assess the inter-reader consistency of quantitative values. Mann–Whitney tests were performed, and receiver operating characteristic (ROC) curves were created for all quantitative analyses.

Results

There were no statistical difference between synthetic and conventional MRI in the detection of sacroiliac joint lesions (all p-values > 0.05). A total of 103 images of BME and 111 images of fat metaplasia were quantitatively evaluated using T1, T2, and PD values. The consistency of quantitative values among readers was good (ICC 0.903–0.970). T1 and T2 values were consistently higher in BME than in normal marrow (p < 0.001), but PD values were not significantly different (p = 0.830). T2 and PD values were higher in fat metaplasia than in normal marrow, but T1 values were lower (p < 0.001). In the case of BME, T1 values had greater diagnostic efficiency [area under the curve (AUC) 0.99] than T2 values (AUC 0.78). There were no significant differences in the diagnostic efficiency of T1 (AUC 0.88), T2 (AUC 0.88), and PD (AUC 0.88) values in the case of fat metaplasia.

Conclusion

Synthetic MRI is as effective as conventional MRI in detecting sacroiliac joint lesions in patients with axSpA. Furthermore, synthetic mapping can accurately quantify BME and fat metaplasia.
A multi-faceted approach to sex and gender equity in solid organ transplantation: The Women in Transplantation Initiative of The Transplantation Society
Authors: Mannon Roslyn B. , Reed Elaine F. , Melk Anette , Vinson Amanda , Wong Germaine , Ahn Curie , Davidson Bianca , Foster Bethany , West Lori J. , Tait Katie , Chong Anita S.
Published: September 2022

The advancement of women’s careers in transplantation continues to be challenging. Academic careers in both basic and clinical disciplines in transplantation, such as surgery and management of end organ failure in medical specialties, have been underrepresented by diverse genders and ethnicities. Over the last decade, the Women in Transplantation Initiative (WIT) has solidified to becoming an internationally recognized organization with activities focused on diversity and inclusion in terms of the sexes. The WIT organization is divided into 3 pillars that address career advancement and networking (Pillar 1), scientific investigation and presentations on sex and gender in transplantation (Pillar 2) and investigating and facilitating equitable access to transplantation for women throughout the world (Pillar 3). By taking this multipronged approach of collaborating across continents, leveraging virtual platforms for information dissemination and discussion, and providing financial support for research, WIT has become a highly visible grass roots organization that aims to improve the experience of women as transplant professionals as well as transplant donors and recipients.
Organoids and microphysiological systems: Promising models for accelerating AAV gene therapy studies
Authors: Ramamurthy Ritu Mahesh , Atala Anthony , Porada Christopher D. , Almeida-Porada Graҫa
Published: September 2022

The FDA has predicted that at least 10-20 gene therapy products will be approved by 2025. The surge in the development of such therapies can be attributed to the advent of safe and effective gene delivery vectors such as adeno-associated virus (AAV). The enormous potential of AAV has been demonstrated by its use in over 100 clinical trials and the FDA’s approval of two AAV-based gene therapy products. Despite its demonstrated success in some clinical settings, AAV-based gene therapy is still plagued by issues related to host immunity, and recent studies have suggested that AAV vectors may actually integrate into the host cell genome, raising concerns over the potential for genotoxicity. To better understand these issues and develop means to overcome them, preclinical model systems that accurately recapitulate human physiology are needed. The objective of this review is to provide a brief overview of AAV gene therapy and its current hurdles, to discuss how 3D organoids, microphysiological systems, and body-on-a-chip platforms could serve as powerful models that could be adopted in the preclinical stage, and to provide some examples of the successful application of these models to answer critical questions regarding AAV biology and toxicity that could not have been answered using current animal models. Finally, technical considerations while adopting these models to study AAV gene therapy are also discussed.
Neoadjuvant therapy alters the immune microenvironment in pancreatic cancer
Authors: Zhang Huiru , Ye Longyun , Yu Xianjun , Jin Kaizhou , Wu Weiding
Published: September 2022

Pancreatic cancer has an exclusive inhibitory tumor microenvironment characterized by a dense mechanical barrier, profound infiltration of immunosuppressive cells, and a lack of penetration of effector T cells, which constitute an important cause for recurrence and metastasis, resistance to chemotherapy, and insensitivity to immunotherapy. Neoadjuvant therapy has been widely used in clinical practice due to its many benefits, including the ability to improve the R0 resection rate, eliminate tumor cell micrometastases, and identify highly malignant tumors that may not benefit from surgery. In this review, we summarize multiple aspects of the effect of neoadjuvant therapy on the immune microenvironment of pancreatic cancer, discuss possible mechanisms by which these changes occur, and generalize the theoretical basis of neoadjuvant chemoradiotherapy combined with immunotherapy, providing support for the development of more effective combination therapeutic strategies to induce potent immune responses to tumors.
Case Report: Successful engraftment of allogeneic hematopoietic stem cells using CAR-T cell therapy as the conditioning regimen in R/R Ph+ B cell acute lymphoblastic leukemia
Authors: Han Lu , Zhao Ran , Yang Jingyi , Zu Yingling , Liu Yanyan , Zhou Jian , Li Linlin , Huang Zhenghua , Zhang Jishuai , Gao Quanli , Song Yongping , Zhou Keshu
Published: September 2022

Background

Consolidative allogeneic hematopoietic stem cells (allo-HSCs) after chimeric antigen receptor T cells (CAR-T) therapy is an emerging modality in hematologic malignancies. Knowledge about the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CAR-T therapy without a conditioning regimen is limited.

Case presentation

We report a patient with relapsed/refractory (R/R) Ph+ B-cell acute lymphoblastic leukemia (ALL) who underwent anti-CD19 CAR-T immunotherapy. After 1 month of treatment, bone marrow hyperplasia remained reduced with no hematopoietic improvements. In line with this, allogeneic hematopoietic stem cells (HSCs) were extracted from an HLA-matched sibling donor and administered to the patient on day 33 after CAR-T cell therapy to support hematopoiesis. On day 40, the level of immature bone marrow lymphocytes was at 0% and minimal residual disease-negative, and the fusion gene BCR/ABL 190 was negative. Chimerism analysis showed full donor chimerism. Three months after CAR-T cells infusion, the patient was still in complete remission with full donor chimerism. However, decreased liver function with skin pigmentation and festering, indicative of acute graft versus host disease, was noted. The treatment was halted owing to financial reasons.

Conclusion

We report the successful engraftment of allogeneic HSCs using CAR-T cell therapy as a conditioning regimen for R/R B-ALL patients.
SARS-CoV-2 IgG spike protein antibody response in mRNA-1273 Moderna® vaccinated patients on maintenance immunoapheresis – a cohort study
Authors: Gaggl Martina , Aschauer Constantin , Aigner Christof , Bond Gregor , Vychytil Andreas , Strassl Robert , Wagner Ludwig , Sunder-Plassmann Gere , Schmidt Alice
Published: September 2022

Background

The SARS-CoV-2 pandemic increased mortality and morbidity among immunocompromised populations. Vaccination is the most important preventive measure, however, its effectiveness among patients depending on maintenance immunoglobulin G (IgG) apheresis to control autoimmune disease activity is unknown. We aimed to examine the humoral immune response after mRNA-1273 Moderna® vaccination in immunoapheresis patients.

Methods

We prospectively monitored SARS-CoV-2 IgG spike (S) protein antibody levels before and after each IgG (exposure) or lipid (LDL) apheresis (controls) over 12 weeks and once after 24 weeks. Primary outcome was the difference of change of SARS-CoV-2 IgG S antibody levels from vaccination until week 12, secondary outcome was the difference of change of SARS-CoV-2 IgG S antibody levels by apheresis treatments across groups.

Results

We included 6 IgG and 18 LDL apheresis patients. After 12 weeks the median SARS-CoV-2 IgG S antibody level was 115 (IQR: 0.74, 258) in the IgG and 1216 (IQR: 788, 2178) in the LDL group (p=0.03). Median SARS-CoV-2 IgG S antibody reduction by apheresis was 76.4 vs. 23.7% in the IgG and LDL group (p=0.04). The average post- vs. pre-treatment SARS-CoV-2 IgG S antibody rebound in the IgG group vs. the LDL group was 46.1 and 6.44%/week from prior until week 12 visit.

Conclusions

IgG apheresis patients had lower SARS-CoV-2 IgG S antibody levels compared to LDL apheresis patients, but recovered appropriately between treatment sessions. We believe that IgG apheresis itself probably has less effect on maintaining the immune response compared to concomitant immunosuppressive drugs. Immunization is recommended independent of apheresis treatment.
Communication is key: Innate immune cells regulate host protection to helminths
Authors: Peng Jianya , Federman Hannah G. , Hernandez Christina M. , Siracusa Mark C.
Published: September 2022

Parasitic helminth infections remain a significant global health issue and are responsible for devastating morbidity and economic hardships. During infection, helminths migrate through different host organs, which results in substantial tissue damage and the release of diverse effector molecules by both hematopoietic and non-hematopoietic cells. Thus, host protective responses to helminths must initiate mechanisms that help to promote worm clearance while simultaneously mitigating tissue injury. The specialized immunity that promotes these responses is termed type 2 inflammation and is initiated by the recruitment and activation of hematopoietic stem/progenitor cells, mast cells, basophils, eosinophils, dendritic cells, neutrophils, macrophages, myeloid-derived suppressor cells, and group 2 innate lymphoid cells. Recent work has also revealed the importance of neuron-derived signals in regulating type 2 inflammation and antihelminth immunity. These studies suggest that multiple body systems coordinate to promote optimal outcomes post-infection. In this review, we will describe the innate immune events that direct the scope and intensity of antihelminth immunity. Further, we will highlight the recent progress made in our understanding of the neuro-immune interactions that regulate these pathways and discuss the conceptual advances they promote.
Selective miRNA inhibition in CD8+ cytotoxic T lymphocytes enhances HIV-1 specific cytotoxic responses
Authors: Madrid-Elena Nadia , Serrano-Villar Sergio , Gutiérrez Carolina , Sastre Beatriz , Morín Matías , Luna Laura , Martín Laura , Santoyo-López Javier , López-Huertas María Rosa , Moreno Elena , García-Bermejo María Laura , Moreno-Pelayo Miguel Ángel , Moreno Santiago
Published: September 2022

miRNAs dictate relevant virus-host interactions, offering new avenues for interventions to achieve an HIV remission. We aimed to enhance HIV-specific cytotoxic responses—a hallmark of natural HIV control— by miRNA modulation in T cells. We recruited 12 participants six elite controllers and six patients with chronic HIV infection on long-term antiretroviral therapy ("progressors"). Elite controllers exhibited stronger HIV-specific cytotoxic responses than the progressors, and their CD8+T cells showed a miRNA (hsa-miR-10a-5p) significantly downregulated. When we transfected ex vivo CD8+ T cells from progressors with a synthetic miR-10a-5p inhibitor, miR-10a-5p levels decreased in 4 out of 6 progressors, correlating with an increase in HIV-specific cytotoxic responses. The effects of miR-10a-5p inhibition on HIV-specific CTL responses were modest, short-lived, and occurred before day seven after modulation. IL-4 and TNF-α levels strongly correlated with HIV-specific cytotoxic capacity. Thus, inhibition of miR-10a-5p enhanced HIV-specific CD8+ T cell capacity in progressors. Our pilot study proves the concept that miRNA modulation is a feasible strategy to combat HIV persistence by enhancing specific cytotoxic immune responses, which will inform new approaches for achieving an antiretroviral therapy-free HIV remission.
OECMs in marine capture fisheries: Key implementation issues of governance, management, and biodiversity
Authors: Garcia Serge Michel , Rice Jake , Himes-Cornell Amber , Friedman Kim Jerome , Charles Anthony , Diz Daniela , Appiott Joseph , Kaiser Michel J.
Published: September 2022

The ‘Other Effective Area-based Conservation Measure’ (OECM) concept was first introduced in 2010, by the Conference of the Parties of the Convention on Biological Diversity (CBD COP) in the CBD Strategic Plan for Biodiversity conservation 2011–2020. The concept acknowledged that a range of spatial measures other than protected areas were appropriate for reaching Aichi Target 11 spatial conservation coverage. The OECM definition was adopted in 2018 in CBD COP Decision 14/8, which calls on States to mainstream OECMs into economic sectors, to recognize the current biodiversity conservation benefits and co-benefits from their area-based management measures and enhance them as much as possible. In the marine capture fisheries sector, the identification of OECMs is a work in progress and the issues addressed in this paper are key implementation issues that States and fisheries authorities are or will be encountering regarding their governance, management, and biodiversity outcomes. The purpose of the paper is to draw attention to some key OECM implementation issues arising in marine capture fisheries and to suggest possible approaches to address them. The governance issues addressed relate to enabling frameworks, industrial fisheries, legitimate authorities, long-term commitments, cross-sectoral coordination and planning, and contribution to the Post-2020 Global Biodiversity Framework of the CBD. The management issues considered relate to effectiveness in achieving expected outcomes, costs and benefits of OECMs, spatial relations between OECMs and fisheries, and the role of OECMs in the Ecosystem Approach to Fisheries (EAF). Regarding the significant positive biodiversity outcomes expected from OECMs, issues relate to the type of outcomes expected, their current or intended nature, the level of evidence required, and their relationship to area-based conservation standards.
Distribution and ecological health risk assessment of dissolved trace metals in surface and bottom seawater of Yantai offshore, China
Authors: Liang Yan , Pan Dawei , Wang Chenchen , Lu Yuxi , Fan Xia
Published: September 2022

The biogeochemical cycle of trace metals plays an important role in the coastal zone. The distribution, interaction, and biogeochemical behavior of dissolved trace metals in surface and bottom seawater are still unclear. This study analyzed the distribution and performed an ecological health risk assessment of dissolved trace metals (Zn, Cd, Co, Pb and Cr) in surface and bottom seawater in the summer (August) of 2019 and 2020 in the seawater of the Yantai offshore area, China. Zinc (Zn), cadmium (Cd), cobalt (Co), lead (Pb) and chromium (Cr) ranged from 23.76–117.47 μg/L (42.67 μg/L ± 15.15), 0.21–0.51 μg/L (0.30 μg/L ± 0.05), 0.90–2.94 μg/L (1.09 μg/L ± 0.31), 0.13–1.06 μg/L (0.39 μg/L ± 0.17), and 2.00–9.9 μg/L (5.38 μg/L ± 2.99) in the summer of the two years. The average metal (Zn and Co) concentrations were slightly higher than the other Chinese coastal areas, while the major contamination pressures were from Zn and Pb. The largest contaminants were in the following order: Zn > Pb > Cd > Cr > Co. Correlation analysis, principal component analysis and hierarchical cluster were used to determine the potential origins and cause the spatial distribution of the multiple dissolved trace metals. The major sources of the trace metal contamination in study area were identified as external inputs from natural human and atmospheric settling and the natural release of the trace metals in sediments under external disturbances. Riverine inputs, the Lubei coastal current and aquaculture significantly influenced the multi-parameter horizontal distributions of the dissolved trace metals and dissolved organic carbon. Although the growth of phytoplankton was strong in summer, the uptake of Zn, Cd, Co and Pb was negligible compared with the exogenous input. The concentrations of Zn, Cd, Co and Pb were higher in the surface than those in the bottom. Monsoons, tides and wind waves also influence the migration, transformation and distribution of dissolved trace metals and dissolved organic carbon. This study provides important information on the biogeochemical cycle process (migration and conversion) and distribution of dissolved trace metals at different depths in coastal and marine pasture areas.
An overlook on the current registries for rare and complex connective tissue diseases and the future scenario of TogethERN ReCONNET
Authors: Bandeira Matilde , Di Cianni Federica , Marinello Diana , Arnaud Laurent , Cannizzo Sara , Carta Claudio , Cornet Alain , Barril Sara M. , Bulina Inita , Ferraris Alessandro , Fonseca João , Gaglioti Andrea , Limper Marteen , Lorenzoni Valentina , Majnik Judith , Matucci-Cerinic Marco , Palla Ilaria , Rednic Simona , Schneider Matthias , Smith Vanessa , Sulli Alberto , Søndergaard Klaus , Ticciati Simone , Tincani Angela , Turchetti Giuseppe , Talarico Rosaria , Cutolo Maurizio , Mosca Marta , Taruscio Domenica
Published: September 2022

Background

Patient registries play a crucial role in supporting clinical practice, healthcare planning and medical research, offering a real-world picture on rare and complex connective tissue diseases (rCTDs). ERN ReCONNET launched the first European Registry Infrastructure with the aim to plan, upgrade and link registries for rCTDs, with the final goal to promote a harmonized data collection approach all over Europe for rCTDs.

Methods

An online survey addressed to healthcare professionals and patients' representatives active in the field of rCTDs was integrated by an extensive database search in order to build a mapping of existing registries for rCTDs.

Findings

A total of 140 registries were found, 38 of which include multiple diseases. No disease-specific registry was identified for relapsing polychondritis, mixed connective tissue disease and undifferentiated connective tissue disease.

Discussion

This overview on the existing registries for rCTDs provides a useful starting point to identify the gaps and the strengths of registries on the coverage of rCTDs, and to develop a common data set and data collection approach for the establishment of the TogethERN ReCONNET Infrastructure.
Metabolic parameters on baseline 18F-FDG PET/CT are potential predictive biomarkers for immunotherapy in patients with head and neck squamous cell carcinoma
Authors: Kwon Hye Ryeong , Cho Junhun , Park Sehhoon , Lee Se-Hoon , Ahn Myung-Ju , Choi Joon Young , Lee Kyung-Han , Jung Hyun Ae , Moon Seung Hwan
Published: September 2022

Purpose

We evaluated baseline 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters for predicting prognosis in patients with head and neck squamous cell carcinoma (HNSCC) who were receiving immune checkpoint inhibitors (ICIs). In addition, we also investigated the relationships between immunohistochemical (IHC) biomarkers and metabolic parameters.

Materials and methods

A total of 39 patients with HNSCC who underwent 18F-FDG PET/CT prior to ICI therapy between November 2015 and December 2020 were enrolled. PET parameters of tumor lesions included standardized uptake values, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and spleen-to-liver ratio (SLR). Clinical variables, IHC markers, and derived neutrophil-to-lymphocyte ratio (dNLR) were also obtained. Analysis was performed using Cox proportional hazard model, Kaplan-Meier method with log-rank test, and Spearman's correlation.

Results

Total MTV (TMTV), total TLG (TTLG), and a combined parameter consisting of TMTV and dNLR were significant predictors for progression-free survival (PFS) in univariable analysis (TMTV, p = 0.018; TTLG, p = 0.027; combined parameter, p = 0.021). Above all, the combined parameter was an independent prognostic factor for PFS in multivariable analysis. The group with low TMTV and low dNLR had longer PFS than the group with high TMTV and high dNLR (p = 0.036). SLR was the only significant predictor for overall survival (p = 0.019). Additionally, there was a negative correlation between programmed cell death-ligand 1 expression (one of the IHC markers) and MTV in subgroup analysis.

Conclusion

PET parameters on baseline 18F-FDG PET/CT were predictive biomarkers for prognosis in patients with HNSCC undergoing ICI therapy. With dNLR, more accurate prognostic prediction could be possible.