bluuebunny/crossref_metadata_2025 huggingface dataset:
Live and Live-Dead Intraspecific Morphometric Comparisons as Proxies for Seagrass Stability in Conservation Paleobiology
Authors: Anderson Laurie C. , Long-Fox Brooke L. , Paterson Audrey T. , Engel Annette S.
Published: July 2022

Comparisons of life and death assemblages are commonly conducted to detect environmental change, including when historical records of live occurrences are unavailable. Most live-dead comparisons focus on assemblage composition, but morphology can also vary in species with environmental variables. Although live-dead morphologic comparisons are less explored, their data could be useful as a proxy in conservation paleobiology. We tested the potential for geometric morphometric data from live-and dead-articulated Stewartia floridana (Bivalvia: Lucinidae) to serve as proxies for seagrass occurrence and stability. The study area is at the northern end of Pine Island in Charlotte Harbor, FL, United States, an estuarine system with substantial seagrass loss in the 20th century and subsequent partial recovery. The area sampled has had relatively stable seagrass occurrences since at least the early 2000s. Live and dead-articulated S. floridana samples were collected from two transects through a patchy seagrass meadow, with sampled sites ranging from bare sand to 100% seagrass cover. Dead-articulated specimens were also collected from three adjacent transects. Live S. floridana shape covaried significantly with seagrass taxonomic composition and percent cover at the time of collection based on two-block partial least squares analysis, although shape differences between seagrass end members (100% Halodule wrightii and 100% Syringodium filiforme) were not significant by multivariate analysis of variance (MANOVA). Instead, specimens from 100% H. wrightii had significantly greater Procrustes variance. Live S. floridana shape data placed in categories describing seagrass stability over 6 years prior to sampling (and reflecting sclerochronologic estimates of maximum longevity) differed significantly based on MANOVA. For live and dead S. floridana from the same transects, shape differed significantly, but allometric trends did not. In addition, patterns of morphologic variation tied to seagrass stability were detected in dead-articulated valve shape. Dead shells from adjacent transects differed significantly in shape and allometric trend from both live and dead specimens collected together. We infer that morphometric differences recorded fine-scale spatial and temporal patterns possibly tied to environmental change. Therefore, geometric morphometrics may be a powerful tool that allows for death assemblages to track seagrass distributions through time prior to systematic monitoring, including in areas under high anthropogenic stress.
Climate, Soil, and Plant Controls on Early-Stage Litter Decomposition in Moso Bamboo Stands at a Regional Scale
Authors: Orrego Marly , Ugawa Shin , Inoue Akio , Laplace Sophie , Kume Tomonori , Koga Shinya , Hishi Takuo , Enoki Tsutomu
Published: July 2022

Moso bamboo (Phyllostachys edulis) is currently distributed across a wide geographical area in East Asia. As a common bamboo species occurring along a broad environmental gradient, there is a need to understand how environmental and biotic drivers affect belowground processes at large scales. In this study, we investigated the influence of climate, soil properties, stand characteristics, and organic matter input parameters as potential drivers of the initial decomposition process in Moso bamboo stands at a regional scale. Using the Tea Bag Index method, we estimated the initial decomposition rate (k) and stabilization factor (S; potential long-term carbon storage) from standard litter incubated at 13 sites across southern Japan and Taiwan. We found that both decomposition parameters were strongly affected by the climate. The climatic conditions during the incubation period better explained the variance in k. In contrast, the long-term climate was more important for S. Notably, temperature and precipitation interactively affected the initial decomposition rates. This interaction showed that in warmer sites, precipitation increased k, whereas in cooler sites, precipitation had no effect or even decreased k. Soil parameters had no influence on k and only had minor effects on S. A structural equation model showed that the stabilization factor was indirectly affected by stand density, which suggests that higher bamboo densities could increase litter stabilization by increasing above-and below-ground organic matter input. Our study highlights the central role of climate in controlling decomposition processes in Moso bamboo stands on a broad scale. Moreover, differences in stand structure can indirectly affect potential soil carbon storage through changes in organic matter input and soil conditions.
Identifying Differential Expression Genes and Prognostic Signature Based on Subventricular Zone Involved Glioblastoma
Authors: Yuan Qing , Zuo Fu-Xing , Cai Hong-Qing , Qian Hai-Peng , Wan Jing-Hai
Published: July 2022

Background: Studies have suggested that glioblastoma (GBM) cells originate from the subventricular zone (SVZ) and that GBM contact with the SVZ correlated with worse prognosis and higher recurrence. However, research on differentially expressed genes (DEGs) between GBM and the SVZ is lacking.

Methods: We performed deep RNA sequencing on seven SVZ-involved GBMs and paired tumor-free SVZ tissues. DEGs and enrichment were assessed. We obtained GBM patient expression profiles and clinical data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. The least absolute shrinkage and selection operator Cox regression model was utilized to construct a multigene signature in the CGGA cohort. GBM patient data from TCGA cohort were used for validation.

Results: We identified 137 (97 up- and 40 down-regulated) DEGs between GBM and healthy SVZ samples. Enrichment analysis revealed that DEGs were mainly enriched in immune-related terms, including humoral immune response regulation, T cell differentiation, and response to tumor necrosis factor, and the MAPK, cAMP, PPAR, PI3K-Akt, and NF-κb signaling pathways. An eight-gene (BCAT1, HPX, NNMT, TBX5, RAB42, TNFRSF19, C16orf86, and TRPC5) signature was constructed. GBM patients were stratified into two risk groups. High-risk patients showed significantly reduced overall survival compared with low-risk patients. Univariate and multivariate regression analyses indicated that the risk score level represented an independent prognostic factor. High risk score of GBM patients negatively correlated with 1p19q codeletion and IDH1 mutation. Immune infiltration analysis further showed that the high risk score was negatively correlated with activated NK cell and monocyte counts, but positively correlated with macrophage and activated dendritic cell counts and higher PD-L1 mRNA expression.

Conclusion: Here, a novel gene signature based on DEGs between GBM and healthy SVZ was developed for determining GBM patient prognosis. Targeting these genes may be a therapeutic strategy for GBM.
Development and Validation of Diagnostic KASP Markers for Brown Planthopper Resistance in Rice
Authors: Ishwarya Lakshmi V. G. , Sreedhar M. , JhansiLakshmi V. , Gireesh C. , Rathod Santosha , Bohar Rajaguru , Deshpande Santosh , Laavanya R. , Kiranmayee K. N. S. Usha , Siddi Sreedhar , Vanisri S.
Published: July 2022

Rice (Oryza sativa L.) is an important source of nutrition for the world’s burgeoning population that often faces yield loss due to infestation by the brown planthopper (BPH, Nilaparvata lugens (Stål)). The development of rice cultivars with BPH resistance is one of the crucial precedences in rice breeding programs. Recent progress in high-throughput SNP-based genotyping technology has made it possible to develop markers linked to the BPH more quickly than ever before. With this view, a genome-wide association study was undertaken for deriving marker-trait associations with BPH damage scores and SNPs from genotyping-by-sequencing data of 391 multi-parent advanced generation inter-cross (MAGIC) lines. A total of 23 significant SNPs involved in stress resistance pathways were selected from a general linear model along with 31 SNPs reported from a FarmCPU model in previous studies. Of these 54 SNPs, 20 were selected in such a way to cover 13 stress-related genes. Kompetitive allele-specific PCR (KASP) assays were designed for the 20 selected SNPs and were subsequently used in validating the genotypes that were identified, six SNPs, viz, snpOS00912, snpOS00915, snpOS00922, snpOS00923, snpOS00927, and snpOS00929 as efficient in distinguishing the genotypes into BPH-resistant and susceptible clusters. Bph17 and Bph32 genes that are highly effective against the biotype 4 of the BPH have been validated by gene specific SNPs with favorable alleles in M201, M272, M344, RathuHeenati, and RathuHeenati accession. These identified genotypes could be useful as donors for transferring BPH resistance into popular varieties with marker-assisted selection using these diagnostic SNPs. The resistant lines and the significant SNPs unearthed from our study can be useful in developing BPH-resistant varieties after validating them in biparental populations with the potential usefulness of SNPs as causal markers.
Epigenetic Regulation in Knee Osteoarthritis
Authors: Cai Zhengyu , Long Teng , Zhao Yaochao , Lin Ruixin , Wang You
Published: July 2022

Osteoarthritis (OA) is a complicated disease with both hereditary and environmental causes. Despite an increase in reports of possible OA risk loci, it has become clear that genetics is not the sole cause of osteoarthritis. Epigenetics, which can be triggered by environmental influences and result in transcriptional alterations, may have a role in OA pathogenesis. The majority of recent research on the epigenetics of OA has been focused on DNA methylation, histone modification, and non-coding RNAs. However, this study will explore epigenetic regulation in OA at the present stage. How genetics, environmental variables, and epigenetics interact will be researched, shedding light for future studies. Their possible interaction and control processes open up new avenues for the development of innovative osteoarthritis treatment and diagnostic techniques.
Global Integrated Genomic and Transcriptomic Analyses of MYB Transcription Factor Superfamily in C3 Model Plant Oryza sativa (L.) Unravel Potential Candidates Involved in Abiotic Stress Signaling
Authors: Muthuramalingam Pandiyan , Jeyasri Rajendran , Selvaraj Anthonymuthu , Shin Hyunsuk , Chen Jen-Tsung , Satish Lakkakula , Wu Qiang-Sheng , Ramesh Manikandan
Published: July 2022

Plant transcription factors (TFs) are significant players in transcriptional regulations, signal transduction, and constitute an integral part of signaling networks. MYB TFs are major TF superfamilies that play pivotal roles in regulation of transcriptional reprogramming, physiological processes, and abiotic stress (AbS) responses. To explore the understanding of MYB TFs, genome and transcriptome-wide identification was performed in the C3 model plant, Oryza sativa (OsMYB). This study retrieved 114 OsMYB TFs that were computationally analyzed for their expression profiling, gene organization, cis-acting elements, and physicochemical properties. Based on the microarray datasets, six OsMYB genes which were sorted out and identified by a differential expression pattern were noted in various tissues. Systematic expression profiling of OsMYB TFs showed their meta-differential expression of different AbS treatments, spatio-temporal gene expression of various tissues and their growth in the field, and gene expression profiling in responses to phytohormones. In addition, the circular ideogram of OsMYB genes in related C4 grass plants conferred the gene synteny. Protein–protein interactions of these genes revealed the molecular crosstalk of OsMYB TFs. Transcriptional analysis (qPCR) of six OsMYB players in response to drought and salinity stress suggested the involvement in individual and combined AbS responses. To decipher how these OsMYB play functional roles in AbS dynamics, further research is a prerequisite.
Improving Menstrual Health Literacy Through Life-Skills Programming in Rural Ethiopia
Authors: Baird Sarah , Hamory Joan , Gezahegne Kiya , Pincock Kate , Woldehanna Tassew , Yadete Workneh , Jones Nicola
Published: July 2022

Despite its cultural and biological importance, limited knowledge about menstruation and cultural taboos in many contexts mean that menarche often brings fear and stigma. In Ethiopia, the context of this paper, lack of knowledge and the stigma around menstruation create challenges for adolescent girls related to menstrual hygiene management and their reproductive health more broadly. This paper uses a cluster-randomized controlled trial (cRCT), with 97 communities (kebeles) randomly assigned to treatment or control, to assess the impact of a gender-transformative life-skills intervention [Act With Her-Ethiopia (AWH-E)] on the menstrual health literacy of very young adolescent girls and boys (10–14) in two diverse regions of Ethiopia (South Gondar, Amhara and East Hararghe, Oromia). The evaluation employs a longitudinal mixed-methods design, with baseline data collected in late 2017/early 2018 and follow-up data collected in late 2019/early 2020. Quantitative surveys were undertaken with 2,492 very young adolescents and their primary caregivers, and complemented by qualitative interviews with 291 adolescents and their caregivers, as well as 96 key informants at community and district levels. Our quantitative findings highlight large and statistically significant improvements on norms around menstruation, knowledge about menstruation and biological function, and knowledge and behavior related to menstrual hygiene management, but with important differences by location and gender. Qualitative findings further unpack these gender and regional differences, highlighting the importance of adapting programming to the local context and, where possible, connecting to other health and gender initiatives. This analysis helps fill the evidence gap on “what works” to improve menstrual health literacy in rural low- and middle-income contexts.
Impact of Machine Perfusion on the Immune Response After Liver Transplantation – A Primary Treatment or Just a Delivery Tool
Authors: Panconesi Rebecca , Flores Carvalho Mauricio , Dondossola Daniele , Muiesan Paolo , Dutkowski Philipp , Schlegel Andrea
Published: July 2022

The frequent use of marginal livers forces transplant centres to explore novel technologies to improve organ quality and outcomes after implantation. Organ perfusion techniques are therefore frequently discussed with an ever-increasing number of experimental and clinical studies. Two main approaches, hypothermic and normothermic perfusion, are the leading strategies to be introduced in clinical practice in many western countries today. Despite this success, the number of studies, which provide robust data on the underlying mechanisms of protection conveyed through this technology remains scarce, particularly in context of different stages of ischemia-reperfusion-injury (IRI). Prior to a successful clinical implementation of machine perfusion, the concept of IRI and potential key molecules, which should be addressed to reduce IRI-associated inflammation, requires a better exploration. During ischemia, Krebs cycle metabolites, including succinate play a crucial role with their direct impact on the production of reactive oxygen species (ROS) at mitochondrial complex I upon reperfusion. Such features are even more pronounced under normothermic conditions and lead to even higher levels of downstream inflammation. The direct consequence appears with an activation of the innate immune system. The number of articles, which focus on the impact of machine perfusion with and without the use of specific perfusate additives to modulate the inflammatory cascade after transplantation is very small. This review describes first, the subcellular processes found in mitochondria, which instigate the IRI cascade together with proinflammatory downstream effects and their link to the innate immune system. Next, the impact of currently established machine perfusion strategies is described with a focus on protective mechanisms known for the different perfusion approaches. Finally, the role of such dynamic preservation techniques to deliver specific agents, which appear currently of interest to modulate this posttransplant inflammation, is discussed together with future aspects in this field.
Immune Response of the Monocytic Cell Line THP-1 Against Six Aeromonas spp.
Authors: Fernández-Bravo Ana , Figueras Maria José
Published: July 2022

Aeromonas are autochthonous bacteria of aquatic environments that are considered to be emerging pathogens to humans, producing diarrhea, bacteremia, and wound infections. Genetic identification shows that 95.4% of the strains associated with clinical cases correspond to the species Aeromonas caviae (37.26%), Aeromonas dhakensis (23.49%), Aeromonas veronii (21.54%), and Aeromonas hydrophila (13.07%). However, few studies have investigated the human immune response against some Aeromonas spp. such as A. hydrophila, Aeromonas salmonicida, and A. veronii. The present study aimed to increase the knowledge about the innate human immune response against six Aeromonas species, using, for the first time, an in vitro infection model with the monocytic human cell line THP-1, and to evaluate the intracellular survival, the cell damage, and the expression of 11 immune-related genes (TLR4, TNF-α, CCL2, CCL20, JUN, RELA, BAX, TP53, CASP3, NLRP3, and IL-1β). Transcriptional analysis showed an upregulated expression of a variety of the monocytic immune-related genes, with a variable response depending upon the Aeromonas species. The species that produced the highest cell damage, independently of the strain origin, coincidentally induced a higher expression of immune-related genes and corresponded to the more prevalent clinical species A. dhakensis, A. veronii, and A. caviae. Additionally, monocytic cells showed an overexpression of the apoptotic and pyroptotic genes involved in cell death after A. dhakensis, A. caviae, and Aeromonas media infection. However, the apoptosis route seemed to be the only way of producing cell damage and death in the case of the species Aeromonas piscicola and Aeromonas jandaei, while A. veronii apparently only used the pyroptosis route.
Detection of SARS-CoV-2 Specific Antibodies in Saliva Samples
Authors: Yu Siyang , Zhang Peiyan , Liao Mingfeng , Zhang Juanjuan , Luo Suisui , Zhai Jinglei , Zhang Yaxi , Lin Jingyan , Yuan Jing , Zhang Zheng , Wang Fuxiang , Wei Lanlan
Published: July 2022

Molecular assays on nasopharyngeal swabs act as a confirmatory test in coronavirus disease (COVID-19) diagnosis. However, the technical requirements of nasopharyngeal sampling and molecular assays limit the testing capabilities. Recent studies suggest the use of saliva for the COVID-19 diagnostic test. In this study, 44 patients diagnosed with COVID-19 in The Third People’s Hospital of Shenzhen were enrolled. Saliva and serum specimens were obtained at different time points and the immunoglobulins against SARS-CoV-2 were measured. The results showed that saliva IgA presented a higher COI value than IgG and IgM. In matched saliva and serum samples, all saliva samples presented lower IgG levels than serum samples, and only one saliva sample presented a higher IgM level. The conversion rates of saliva IgA and the detection of viral nucleic acids were analyzed in the first and second weeks after hospitalization. The positive rates increased when combining saliva IgA and viral nucleic acid detection. In conclusion, our results provide evidence that saliva IgA could serve as a useful index for the early diagnosis of COVID-19.
γδ T Cells in the Tumor Microenvironment—Interactions With Other Immune Cells
Authors: Chan Kok Fei , Duarte Jessica Da Gama , Ostrouska Simone , Behren Andreas
Published: July 2022

A growing number of studies have shown that γδ T cells play a pivotal role in mediating the clearance of tumors and pathogen-infected cells with their potent cytotoxic, cytolytic, and unique immune-modulating functions. Unlike the more abundant αβ T cells, γδ T cells can recognize a broad range of tumors and infected cells without the requirement of antigen presentationviamajor histocompatibility complex (MHC) molecules. Our group has recently demonstrated parts of the mechanisms of T-cell receptor (TCR)-dependent activation of Vγ9Vδ2+T cells by tumors following the presentation of phosphoantigens, intermediates of the mevalonate pathway. This process is mediated through the B7 immunoglobulin family-like butyrophilin 2A1 (BTN2A1) and BTN3A1 complexes. Such recognition results in activation, a robust immunosurveillance process, and elicits rapid γδ T-cell immune responses. These include targeted cell killing, and the ability to produce copious quantities of cytokines and chemokines to exert immune-modulating properties and to interact with other immune cells. This immune cell network includes αβ T cells, B cells, dendritic cells, macrophages, monocytes, natural killer cells, and neutrophils, hence heavily influencing the outcome of immune responses. This key role in orchestrating immune cells and their natural tropism for tumor microenvironment makes γδ T cells an attractive target for cancer immunotherapy. Here, we review the current understanding of these important interactions and highlight the implications of the crosstalk between γδ T cells and other immune cells in the context of anti-tumor immunity.
Clinical Patterns, Survival, Comorbidities, and Treatment Regimens in 149 Patients With Pemphigus in Tuscany (Italy): A 12-Year Hospital-Based Study
Authors: Quintarelli Lavinia , Coi Alessio , Maglie Roberto , Corrà Alberto , Mariotti Elena Biancamaria , Aimo Cristina , Ruffo di Calabria Valentina , Verdelli Alice , Bianchi Beatrice , Del Bianco Elena , Antiga Emiliano , Caproni Marzia
Published: July 2022

Introduction

Pemphigus encompasses a group of muco-cutaneous autoimmune bullous diseases characterized by the loss of adhesion between keratinocytes. The disease is associated with increased morbidity and mortality.

Materials and Methods

We characterized clinical patterns, survival, comorbidities, and drug prescriptions in patients with pemphigus referred to the Section of Dermatology of the University of Florence from January 2010 to December 2021.

Results

A total of 149 patients were identified (female/male sex ratio = 2.0). Median age at diagnosis was 57.7 ± 17.2 years; 108 patients were diagnosed with pemphigus vulgaris (PV) (72.5%) and 35 (23.5%) with pemphigus foliaceus (PF). Paraneoplastic pemphigus (PNP) and IgA-pemphigus accounted for three patients each. The overall survival rate was 86.9%. Accordingly, 14 (9%) patients died during the study period. The average age at death was 77.8 ± 9.3. Age at diagnosis was a risk factor for death in patients with pemphigus. Average concentration of Dsg3-IgG and Dsg1-IgG was 85.6 ± 68.8 and 75.9 ± 68.4, respectively. The most serious comorbid diseases included cerebro- and cardiovascular accidents and malignancies. Regarding the treatment regimen, we found a substantially stable use of systemic steroids in the 2010–2018 period; the prevalence of use of mycophenolic acid increased, whereas that of azathioprine decreased. The use of rituximab showed the highest increase in the 2013–2018 period. Proton-pump inhibitors and antibiotics were the most frequently prescribed non-immunomodulating drugs.

Conclusions

In this large series of the patients, patients with pemphigus showed a high incidence of serious comorbid diseases, highlighting the importance of a multidisciplinary approach for a proper management of the patients. Rituximab was the immunomodulating drug showing the highest increase in use over time, reflecting the growing evidence of its efficacy as a first-line treatment in pemphigus.
The Dynamic Role of FOXP3+ Tregs and Their Potential Therapeutic Applications During SARS-CoV-2 Infection
Authors: Xu Zhan , Jiang Xue , Dai Xueyu , Li Bin
Published: July 2022

Coronavirus disease 2019 (COVID-19) has been raging all around the world since the beginning of 2020, and leads to acute respiratory distress syndrome (ARDS) with strong cytokine storm which contributes to widespread tissue damage and even death in severe patients. Over-activated immune response becomes one of the characteristics of severe COVID-19 patients. Regulatory T cells (Treg) play an essential role in maintaining the immune homeostasis, which restrain excessive inflammation response. So FOXP3+Tregs might participate in the suppression of inflammation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Besides suppressive function, tissue resident Tregs are also responsible for tissue repair. In this review, we mainly summarize the latest research focusing on the change of FOXP3+Tregs in the COVID-19 patients, discuss the relationship between disease severity and number change of Tregs and speculate the potential role of FOXP3+Tregs during SARS-CoV-2 infection. Furthermore, we introduce some potential Treg-based therapies to improve patients’ outcomes, which include small molecular drugs, antibody drugs, CAR-Treg and cytokine treatment. We hope to reduce tissue damage of severe COVID-19 patients and offer better prognosis through Treg-based therapy.
Thymus Reconstitution in Young and Aged Mice Is Facilitated by In Vitro-Generated Progenitor T Cells
Authors: Mohtashami Mahmood , Li Yue Ru , Lee Christina R. , Zúñiga-Pflücker Juan Carlos
Published: July 2022

The prolonged lag in T cell recovery seen in older patients undergoing hematopoietic stem cell transplant (HSCT), after chemo-/radiotherapy, can lead to immune dysfunction. As a result, recovering patients may experience a relapse in malignancies and opportunistic infections, leading to high mortality rates. The delay in T cell recovery is partly due to thymic involution, a natural collapse in the size and function of the thymus, as individuals age, and partly due to the damage sustained by the thymic stromal cells through exposure to chemo-/radiotherapy. There is a clear need for new strategies to accelerate intrathymic T cell reconstitution when treating aged patients to counter the effects of involution and cancer therapy regimens. Adoptive transfer of human progenitor T (proT) cells has been shown to accelerate T cell regeneration in radiation-treated young mice and to restore thymic architecture in immunodeficient mice. Here, we demonstrate that the adoptive transfer of in vitro-generated proT cells in aged mice (18-24 months) accelerated thymic reconstitution after treatment with chemotherapy and gamma irradiation compared to HSCT alone. We noted that aged mice appeared to have a more limited expansion of CD4-CD8- thymocytes and slower temporal kinetics in the development of donor proT cells into mature T cells, when compared to younger mice, despite following the same chemo/radiation regimen. This suggests a greater resilience of the young thymus compared to the aged thymus. Nevertheless, newly generated T cells from proT cell engrafted aged and young mice were readily present in the periphery accelerating the reappearance of new naïve T cells. Accelerated T cell recovery was also observed in both aged and young mice receiving both proT cells and HSCT. The strategy of transferring proT cells can potentially be used as an effective cellular therapy in aged patients to improve immune recovery and reduce the risk of opportunistic infections post-HSCT.
Relationship Between Serum Complement C3 Levels and Outcomes Among Patients With Anti-GBM Disease
Authors: Zhu Mengyue , Wang Jingjing , Le Weibo , Xu Feng , Jin Ying , Jiao Chenfeng , Zhang Haitao
Published: July 2022

Background

IgG and complement 3 (C3) are generally found to be deposited along the glomerular basement membrane (GBM) in human anti-GBM disease. The pathogenic role of complement activation in kidney damage of anti-GBM disease has been explored in recent years. Therefore, we investigated the relationship between serum C3 and outcomes among patients with anti-GBM disease in this study.

Methods

Ninety-four anti-GBM disease patients between January 2004 and December 2020 at the National Clinical Research Center of Kidney Diseases Jinling Hospital were retrospectively analyzed, and were divided into the low C3 group and the normal C3 group according to serum C3 levels at diagnosis. Fifty-six patients had undergone renal biopsy. We analyzed the clinical manifestations, laboratory tests, kidney pathology, treatment, and outcomes between the two groups. The primary endpoint was kidney failure. Cox regression and smooth curve fitting of generalized additive mixed model analysis were used to explore the correlation between serum C3 and kidney failure. The outcomes of the two groups were compared by the Kaplan–Meier curve.

Results

A total of 94 patients (aged 43.6 ± 16.2; male patients, 46%) with anti-GBM disease were enrolled. There were 26 patients with low C3 levels and 68 patients with normal C3 levels. Compared with the normal C3 group, patients in the low C3 group have a higher proportion of glomerular sclerosis progressing to kidney failure. Multivariate Cox regression analysis suggested that C3 is associated with kidney outcomes in patients with anti-GBM disease (HR = 0.782, 95% CI = 0.673–0.907,p= 0.001). Smooth curve fitting of generalized additive mixed model analysis indicated that the level of C3 had a linear relationship with the changing trend of kidney failure. The Kaplan–Meier curve showed that there was a statistical difference between the two groups in terms of kidney failure (p= 0.033).

Conclusion

The kidney outcomes of anti-GBM disease in the low C3 group were poorer than those in the normal C3 group. The influence of C3 on the kidney outcomes of patients with anti-GBM disease may be of clinical relevance.
Photobiomodulation Improves Serum Cytokine Response in Mild to Moderate COVID-19: The First Randomized, Double-Blind, Placebo Controlled, Pilot Study
Authors: Marashian Seyed Mehran , Hashemian Mohammadreza , Pourabdollah Mihan , Nasseri Mansour , Mahmoudian Saeed , Reinhart Florian , Eslaminejad Alireza
Published: July 2022

Background

Because the major event in COVID-19 is the release of pre- and inflammatory cytokines, finding a reliable therapeutic strategy to inhibit this release, help patients manage organ damage and avoid ICU admission or severe disease progression is of paramount importance. Photobiomodulation (PBM), based on numerous studies, may help in this regard, and the present study sought to evaluate the effects of said technology on cytokine reduction.

Methods

This study was conducted in the 2nd half of 2021. The current study included 52 mild-to-moderately ill COVID-19, hospitalized patients. They were divided in two groups: a Placebo group and a PBM group, treated with PBM (620-635 nm light via 8 LEDs that provide an energy density of 45.40 J/cm2 and a power density of 0.12 W/cm2), twice daily for three days, along with classical approved treatment. 28 patients were in Placebo group and 24 in PBM group. In both groups, blood samples were taken four times in three days and serum IL-6, IL-8, IL-10, and TNF-α levels were determined.

Results

During the study period, in PBM group, there was a significant decrease in serum levels of IL-6 (-82.5% +/- 4, P<0.001), IL-8 (-54.4% ± 8, P<0.001), and TNF-α (-82.4% ± 8, P<0.001), although we did not detect a significant change in IL-10 during the study. The IL-6/IL-10 Ratio also improved in PBM group. The Placebo group showed no decrease or even an increase in these parameters. There were no reported complications or sequelae due to PBM therapy throughout the study.

Conclusion

The major cytokines in COVID-19 pathophysiology, including IL-6, IL-8, and TNF-α, responded positively to PBM therapy and opened a new window for inhibiting and managing a cytokine storm within only 3-10 days.
Age-Related Alterations in Macrophage Distribution and Function Are Associated With Delayed Cutaneous Wound Healing
Authors: Dube Christabel Thembela , Ong Yasmin Hui Binn , Wemyss Kelly , Krishnan Siddharth , Tan Tiak Ju , Janela Baptiste , Grainger John R. , Ronshaugen Matthew , Mace Kimberly A. , Lim Chin Yan
Published: July 2022

Ageing-related delays and dysregulated inflammation in wound healing are well-documented in both human and animal models. However, cellular and molecular changes underlying this impairment in healing progression are not fully understood. In this study, we characterised ageing-associated changes to macrophages in wounds of young and aged mice and investigated transcriptomic differences that may impact the progression of wound healing. Full-thickness wounds created on the dorsum of C57BL/6J young and aged mice were excised on Days 3 and 7 post-wounding for analysis by immunohistochemistry, flow cytometry, and RNA sequencing. Our data revealed that macrophages were significantly reduced in aged wounds in comparison to young. Functional transcriptomic analyses showed that macrophages from aged wounds exhibited significantly reduced expression of cell cycle, DNA replication, and repair pathway genes. Furthermore, we uncovered an elevated pro-inflammatory gene expression program in the aged macrophages correlated with poor inflammation resolution and excessive tissue damage observed in aged wounds. Altogether, our work provides insights into how poorly healing aged wounds are phenotypically defined by the presence of macrophages with reduced proliferative capacity and an exacerbated inflammatory response, both of which are pathways that can be targeted to improve healing in the elderly.
PD-1 Inhibitor Combined With Radiotherapy and GM-CSF (PRaG) in Patients With Metastatic Solid Tumors: An Open-Label Phase II Study
Authors: Kong Yuehong , Zhao Xiangrong , Xu Meiling , Pan Jie , Ma Yifu , Zou Li , Peng Qiliang , Zhang Junjun , Su Cunjin , Xu Zhi , Zhou Wei , Peng Yong , Yang Jiabao , Zhou Chengliang , Li Yujia , Guo Qiuchen , Chen Guangqiang , Wu Hongya , Xing Pengfei , Zhang Liyuan
Published: July 2022

Patients with metastatic cancer refractory to standard systemic therapies have a poor prognosis and few therapeutic options. Radiotherapy can shape the tumor microenvironment (TME) by inducing immunogenic cell death and promoting tumor recognition by natural killer cells and T lymphocytes. Granulocyte macrophage-colony stimulating factor (GM-CSF) was known to promote dendric cell maturation and function, and might also induce the macrophage polarization with anti-tumor capabilities. A phase II trial (ChiCTR1900026175) was conducted to assess the clinical efficacy and safety of radiotherapy, PD-1 inhibitor and GM-CSF (PRaG regimen). This trial was registered at http://www.chictr.org.cn/index.aspx. A PRaG cycle consisted of 3 fractions of 5 or 8 Gy delivered for one metastatic lesion from day 1, followed by 200 μg subcutaneous injection of GM-CSF once daily for 2 weeks, and intravenous infusion of PD-1 inhibitor once within one week after completion of radiotherapy. The PRaG regimen was repeated every 21 days for at least two cycles. Once the PRaG therapy was completed, the patient continued PD-1 inhibitor monotherapy until confirmed disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). A total of 54 patients were enrolled with a median follow-up time of 16.4 months. The ORR was 16.7%, and the disease control rate was 46.3% in intent-to-treat patients. Median progression-free survival was 4.0 months (95% confidence interval [CI], 3.3 to 4.8), and median overall survival was 10.5 months (95% CI, 8.7 to 12.2). Grade 3 treatment-related adverse events occurred in five patients (10.0%) and grade 4 in one patient (2.0%). Therefore, the PRaG regimen was well tolerated with acceptable toxicity and may represent a promising salvage treatment for patients with chemotherapy-refractory solid tumors. It is likely that PRaG acts via heating upthe TME with radiotherapy and GM-CSF, which was further boosted by PD-1 inhibitors.
The Outbreak of Human Monkeypox in 2022: A Changing Epidemiology or an Impending Aftereffect of Smallpox Eradication?
Authors: Al-Tammemi Ala’a B. , Albakri Rana , Alabsi Suhib
Published: July 2022

This article presents a concise mini review about human monkeypox (MPX), in response to the current outbreak in non-endemic countries. MPX is one of the viral zoonotic diseases which is attributed to monkeypox virus (MPXV) and causes a smallpox-like disease. Despite its ability to infect various mammals, the animal reservoir for MPXV is still unconfirmed. The disease usually lasts for an average of 2-4 weeks before complete recovery. The incubation period for MPXV ranges from 5-21 days and the illness starts with prodromal phase, which is characterized by fever, chills, muscle pain, back pain, general malaise, lymph node enlargement, and headache, followed by rash. MPX is a self-limited illness with spontaneous recovery in most cases. In the middle of May 2022, an outbreak of human MPX has been declared by the World Health Organization (WHO) across various WHO regions, and in countries that are not endemic for the disease. As of June 08, 2022, the number of confirmed MPX cases that were reported across 18 countries of European Union/European Economic Area (EU/EEA) has reached 704 cases. Worldwide, and as of June 08, 2022, a total of 1285 confirmed MPX cases were reported in non-endemic countries across four WHO regions. Exportation of MPXV from Africa to other continents has been increasingly reported. Lacking travel connections to Africa among most current reported cases in 2022 raises an alarm about the changing epidemiology of the disease which warrants a stringent epidemiological surveillance to prevent further escalation of the current outbreak in non-endemic countries.
Novel Epigenetic Clock Biomarkers of Age-Related Macular Degeneration
Authors: Mallik Saurav , Grodstein Fran , Bennett David A. , Vavvas Demetrios G. , Lemos Bernardo
Published: July 2022

Age-Related Macular Degeneration (AMD) is a bilateral ocular condition resulting in irreversible vision impairment caused by the progressive loss of photoreceptors in the macula, a region at the center of the retina. The progressive loss of photoreceptor is a key feature of dry AMD but not always wet AMD, though both forms of AMD can lead to loss of vision. Regression-based biological age clocks are one of the most promising biomarkers of aging but have not yet been used in AMD. Here we conducted analyses to identify regression-based biological age clocks for the retina and explored their use in AMD using transcriptomic data consisting of a total of 453 retina samples including 105 Minnesota Grading System (MGS) level 1 samples, 175 MGS level 2, 112 MGS level 3 and 61 MGS level 4 samples, as well as 167 fibroblast samples. The clocks yielded good separation among AMD samples with increasing severity score viz., MGS1-4, regardless of whether clocks were trained in retina tissue, dermal fibroblasts, or in combined datasets. Clock application to cultured fibroblasts, embryonic stem cells, and induced Pluripotent Stem Cells (iPSCs) were consistent with age reprograming in iPSCs. Moreover, clock application to in vitro neuronal differentiation suggests broader applications. Interesting, many of the age clock genes identified include known targets mechanistically linked to AMD and aging, such as GDF11, C16ORF72, and FBN2. This study provides new observations for retina age clocks and suggests new applications for monitoring in vitro neuronal differentiation. These clocks could provide useful markers for AMD monitoring and possible intervention, as well as potential targets for in vitro screens.
Ferroptosis in Intrahepatic Cholangiocarcinoma: IDH1105GGT Single Nucleotide Polymorphism Is Associated With Its Activation and Better Prognosis
Authors: Sarcognato Samantha , Sacchi Diana , Fabris Luca , Zanus Giacomo , Gringeri Enrico , Niero Monia , Gallina Giovanna , Guido Maria
Published: July 2022

Objectives

Intrahepatic cholangiocarcinoma (ICC) has a dismal prognosis and often demonstrates an anti-apoptotic landscape, which is a key step to chemotherapy resistance. Isocitrate dehydrogenase 1 or 2 (IDH1-2)-mutated ICCs have been described and associated with better prognosis. Ferroptosis is a regulated iron-mediated cell death induced by glutathione peroxidase 4 (GPX4) inhibition, and may be triggered pharmacologically. GPX4 is overexpressed in aggressive cancers, while its expression is inhibited by IDH1R132C mutation in cell lines. We investigated tissue expression of ferroptosis activation markers in ICC and its correlation with clinical-pathological features and IDH1-2 status.

Materials and Methods

We enrolled 112 patients who underwent hepatic resection or diagnostic liver biopsy for ICC. Immunostaining for transferrin-receptor 1 and GPX4, and Pearls’ stain for iron deposits were performed to evaluate ferroptosis activation. Immunostaining for STAT3 was performed to study pro-inflammatory and anti-apoptotic landscape. Main IDH1-2 mutations were investigated in 90 cases by real-time polymerase chain reaction.

Results

GPX4 overexpression was seen in 79.5% of cases and related to poor histological prognostic factors (grading and perineural and vascular invasion; p < 0.005 for all) and worse prognosis (OS p = 0.03; DFS p = 0.01). STAT3 was expressed in 95.5% of cases, confirming the inflammation-related anti-apoptotic milieu in ICC, and directly related to GPX4 expression (p < 0.0001). A high STAT3 expression correlated to a worse prognosis (OS p = 0.02; DFS p = 0.001). Nearly 12% of cases showed IDH1105GGT single nucleotide polymorphism, which was never described in ICC up to now, and was related to lower tumor grade (p < 0.0001), longer overall survival (p = 0.04), and lower GPX4 levels (p = 0.001).

Conclusion

Our study demonstrates for the first time that in most inflammatory ICCs ferroptosis is not active, and its triggering is related to IDH1-2 status. This supports the possible therapeutic role of ferroptosis-inducer drugs in ICC patients, especially in drug-resistant cases.
Advances in COVID-19 Vaccines and New Coronavirus Variants
Authors: Liu Mengchen , Li Yunqiao
Published: July 2022

With the successful development of the Corona Virus Disease 2019 (COVID-19) vaccines and increased vaccination coverage, great progress in global outbreak control has been made in several countries. However, new coronavirus variants emerge and their rapid spread, causing a new wave of economic and social upheaval worldwide. The spread of new coronavirus variants poses a new and enormous challenge to vaccination and pandemic control, so further studies to explore and develop vaccines for the prevention and control virus infection are warranted. In this review, we provide an overview of the most prevalent variants including Omicron, and explore the effectiveness of COVID-19 vaccines against related variants to better understand existing vaccines and to facilitate improved research into new vaccines. In addition, this review discusses existing strategies to increase vaccine efficacy and introduces novel vaccines by the non-injection route.
Making Visible HTLV Infection in a Non-endemic Area of Argentina
Authors: Simioli Federico R. , Bouzas Maria B. , Mijalovsky Dana , Pineda Maria V. , Mammana Lilia , Mangano Andrea , Orduna Tomas A.
Published: July 2022

In Argentina, the human T-cell lymphotropic virus type 1 (HTLV-1) infection has been documented mainly among blood banks with a prevalence of ~0.02–0.046% for Buenos Aires city, 0.8% for the northeast, and 1% for the northwest; both areas are considered endemic for HTLV-2 and 1, respectively. Policies and specific guidelines for testing blood donors for HTLV are included since 2005. Screening for antibodies is performed at blood banks and confirmatory testing is performed at reference laboratories. There are no specific recommendations for the assistance of communities and individuals affected, nor referral to specialized clinics on the HTLV infection. In 2016, as a strategy of intervention, we opened a specialized clinical attendance in a referral infectious diseases public hospital for the comprehensive approach to patients with HTLV, offering follow-up and counseling for patients and their families for the early diagnosis of HTLV-1/2 and related diseases. During the study, 124 patients with presumptive HTLV positive diagnosis from blood bank, symptomatic patients (SPs), relatives, and descendants visited the unit. A total of 46 patients were HTLV positive (38 HTLV-1 and 8 HTLV-2). There were nine SPs (2 adult T-cell leukemia/lymphoma [ATL] and 7 HTLV-1-associated myelopathy/tropical spastic paraparesis [HAM/TSP]). All patients with HTLV-1 and−2 were offered to study their relatives. Two out of 37 (5.4%) descendants tested were positive for HTLV-1. Sexual partners were studied; among 6 out of 11 couples (54.5%) were found positive (5 HTLV-1 and 1 HTLV-2). Other relatives, such as mothers (1/2) and siblings (1/6), were positive for HTLV-1. According to the place of birth among HTLV-1 carriers, 58% were born in an endemic area or in countries where HTLV infection is considered endemic while for HTLV-2 carriers, 12.5% were born in an endemic area of Argentina. The proviral load (pVL) was measured in all, patients with HTLV-1 being higher in symptomatic compared with asymptomatic carriers. In addition, two pregnant women were early diagnosed during their puerperium and breastmilk replacement by formula was indicated. Inhibition of lactation was also indicated. Our study provides tools for a multidisciplinary approach to the infection and reinforces the importance of having specialized clinical units in neglected diseases, such as HTLV for counseling, clinical and laboratory follow-up, and providing useful information for patients for self-care and that of their families.
Efficacy of Red Blood Cell Exchange as Adjunctive Treatment for Hypoxemia and Survival Rate of Patients With Severe Coronavirus-2 Disease: An Open-Labeled Phase 2 Randomized Clinical Trial
Authors: Aminianfar Mohammad , Soleiman-Meigooni Saeed , Hamidi-Farahani Ramin , Darvishi Mohammad , Hoseini-Shokouh Seyyed Javad , Asgari Ali , Faraji-Hormozi Syrous , Asli Maryam
Published: July 2022

Background

Severe acute respiratory syndrome (SARS) coronavirus-2 may infect red blood cells (RBCs) and impact oxygenation. We aimed to evaluate the efficacy of RBC exchange as an adjunctive treatment for hypoxemia and the survival rate of patients with severe coronavirus disease 2019 (COVID-19).

Methods

In a randomized clinical trial, we divided sixty patients with severe COVID-19 into two groups. The intervention group received the standard treatment of severe COVID-19 with RBC exchange three to four times in 2 days. The control group only received the standard treatment. Our primary outcomes were improving hypoxemia in 7 days, recovery or discharge, and death in 28 days. We conducted Chi-square test, independent samples t-test, and Fisher’s exact test to analyze the results. The ethical committee of Aja University of Medical Sciences approved the study (IR.AJAUMS.REC.1399.054), and the Iranian clinical trial registration organization registered it (IRCT20160316027081N2).

Results

Twenty-nine men and thirty-one women with a mean age of 67.5 years entered the study. The frequency of hypertension and diabetes mellitus was 86.7 and 68.3%, respectively. The most common symptoms of severe COVID-19 were dyspnea (91.6%), cough (75%), and fever (66.6%). Our results showed that hypoxemia improved in 21 of the 30 patients (70%) in the intervention group and 10 of the 30 patients (33.3%) in the control group (P < 0.004). The recovery and discharge rates were 19 of 30 patients (63.3%) in the intervention group and 2 of 30 patients (6.7%) in the control group (P < 0.001).

Conclusion

The RBC exchange improved the oxygenation and survival rate in patients with severe COVID-19.