bluuebunny/crossref_metadata_2025 huggingface dataset:
CD4+TGFβ+ cells infiltrated the bursa of Fabricius following IBDV infection, and correlated with a delayed viral clearance, but did not correlate with disease severity, or immunosuppression
Authors: Nazki Salik , Reddy Vishwanatha R. A. P. , Kamble Nitin , Sadeyen Jean-Remy , Iqbal Munir , Behboudi Shahriar , Shelton Holly , Broadbent Andrew J.
Published: September 2023

Introduction

Infectious Bursal Disease Virus (IBDV) causes immunosuppression in chickens. While B-cell destruction is the main cause of humoral immunosuppression, bursal T cells from IBDV-infected birds have been reported to inhibit the mitogenic response of splenocytes, indicating that some T cell subsets in the infected bursa have immunomodulatory activities. CD4+CD25+TGFβ+ cells have been recently described in chickens that have immunoregulatory properties and play a role in the pathogenesis of Marek’s Disease Virus.

Methods

To evaluate if CD4+CD25+TGFβ+ cells infiltrated the bursa of Fabricius (BF) following IBDV infection, and influenced the outcome of infection, birds were inoculated at either 2 days or 2 weeks of age with vaccine strain (228E), classic field strain (F52/70), or PBS (mock), and bursal cell populations were quantified by flow cytometry.

Results

Both 228E and F52/70 led to atrophy of the BF, a significant reduction of Bu1+-B cells, and a significant increase in CD4+ and CD8α+ T cells in the BF, but only F52/70 caused suppression of immune responses to a test antigen in younger birds, and clinical signs in older birds. Virus was cleared from the BF more rapidly in younger birds than older birds. An infiltration of CD4+CD25+T cells into the BF, and elevated expression of bursal TGFβ-1+ mRNA was observed at all time points following infection, irrespective of the strain or age of the birds, but CD4+TGFβ+cells and CD4+CD25+TGFβ+ cells only appeared in the BF at 28 dpi in younger birds. In older birds, CD4+TGFβ+ cells and CD4+CD25+TGFβ+ cells were present at earlier time points, from 7dpi following 228E infection, and from 14 and 28 dpi following F52/70 infection, respectively.

Discussion

Our data suggest that an earlier infiltration of CD4+TGFβ+ cells into the BF correlated with a delayed clearance of virus. However, the influx of CD4+TGFβ+ cells and CD4+CD25+TGFβ+ into the BF did not correlate with increased pathogenicity, or immunosuppression.
The effect of Staphylococcus aureus on innate and adaptive immunity and potential immunotherapy for S. aureus-induced osteomyelitis
Authors: Chen Yingqi , Liu Zixian , Lin Zexin , Lu Mincheng , Fu Yong , Liu Guanqiao , Yu Bin
Published: September 2023

Osteomyelitis is a chronic inflammatory bone disease caused by infection of open fractures or post-operative implants. Particularly in patients with open fractures, the risk of osteomyelitis is greatly increased as the soft tissue damage and bacterial infection are often more severe. Staphylococcus aureus, one of the most common pathogens of osteomyelitis, disrupts the immune response through multiple mechanisms, such as biofilm formation, virulence factor secretion, and metabolic pattern alteration, which attenuates the effectiveness of antibiotics and surgical debridement toward osteomyelitis. In osteomyelitis, immune cells such as neutrophils, macrophages and T cells are activated in response to pathogenic bacteria invasion with excessive inflammatory factor secretion, immune checkpoint overexpression, and downregulation of immune pathway transcription factors, which enhances osteoclastogenesis and results in bone destruction. Therefore, the study of the mechanisms of abnormal immunity will be a new breakthrough in the treatment of osteomyelitis.
NETosis: an emerging therapeutic target in renal diseases
Authors: Juha Márk , Molnár Adél , Jakus Zoltán , Ledó Nóra
Published: September 2023

Introduction

Neutrophil extracellular traps (NETs) are web-like structures composed of nuclear and granular components. The primary role of NETS is to prevent the dissemination of microbes and facilitate their elimination. However, this process is accompanied by collateral proinflammatory adverse effects when the NET release becomes uncontrollable, or clearance is impaired. Although NET-induced organ damage is conducted primarily and indirectly via immune complexes and the subsequent release of cytokines, their direct effects on cells are also remarkable. NETosis plays a critical pathogenic role in several renal disorders, such as the early phase of acute tubular necrosis, anti-neutrophil cytoplasmic antibody-mediated renal vasculitis, lupus nephritis, thrombotic microangiopathies, anti-glomerular basement membrane disease, and diabetic nephropathy. Their substantial contribution in the course of these disorders makes them a desirable target in the therapeutic armamentarium. This article gives an in-depth review of the heterogeneous pathogenesis and physiological regulations of NETosis and its pivotal role in renal diseases. Based on the pathogenesis, the article also outlines the current therapeutic options and possible molecular targets in the treatment of NET-related renal disorders.

Methods

We carried out thorough literature research published in PubMed and Google Scholar, including a comprehensive review and analysis of the classification, pathomechanisms, and a broad spectrum of NET-related kidney disorders.

Conclusions

NETosis plays a pivotal role in certain renal diseases. It initiates and maintains inflammatory and autoimmune disorders, thus making it a desirable target for improving patient and renal outcomes. Better understanding and clinical translation of the pathogenesis are crucial aspects to treatment, for improving patient, and renal outcomes.
Identifying marine food web homogenization patterns
Authors: Xu Yan , Huo Xumeng , Jordán Ferenc , Zhou Mingliang , Cai Yanpeng , Sun Jun
Published: September 2023

Ecosystems become increasingly similar to each other, based on species composition. Despite the inevitability of homogenized ecosystems due to global change, few studies have specifically addressed the identification of homogeneous systems in food webs. This study focuses on identifying different patterns of marine food web homogenization by selecting 41 marine food webs and establishing an indicator system. The research classifies the food webs into seven main types based on three different homogenization processes (I, II, III, IV, V, VI, and VII), with approximately 60.1%, 46.3%, and 61% of the homogenization being structural, functional, and resource homogenization, respectively. It highlights the importance of homogenization processes in marine ecosystems, which are mainly driven by interactions between structural and resource homogenization. The research found that Type V exhibited universality in both temporal and spatial dimensions, while Type III also showed universality when the food webs were dominated by resource homogenization. On the other hand, Type I, which was associated with human activities, showed locality when the food web only manifested structural homogenization. Functional homogenization often occurred alongside structural homogenization, as seen in Type IV and Type VII. Yet, when the food web exhibited functional homogenization (Type II), it was directly linked to human activities over the past 20 years. The research aimed to improve the methodology in terms of (a) identifying different food web homogenization patterns; (b) establishing indicators system to quantify food web homogenization; and (c) clarifying the ecological significance of food web homogenization. The study provided a comprehensive understanding of food web homogenization and its associated risks, which could inform nature-based ecosystem management strategies to mitigate the impacts of future climate change.
An overview on spalling behavior, mechanism, residual strength and microstructure of fiber reinforced concrete under high temperatures
Authors: Gong Fang , Jiang Xi , Gamil Yaser , Iftikhar Bawar , Thomas Blessen Skariah
Published: September 2023

Recent research has shown that the incorporation of fibres, such as steel and polypropylene fibres, in concrete can significantly improve its resistance to spalling under high-temperature conditions. However, the reported outcomes of studies on the spalling performance of Fibre Reinforced Concrete (FRC) vary significantly due to differences in cementitious matrix and fibre types, mix design, and testing techniques. Existing review studies have struggled to systematically and precisely consolidate the diverse aspects of the literature. To address these limitations, this paper adopts the latest approach for mining, processing, and analyzing data to interpret bibliographic data on the fire resistance of FRC. The primary objective of this study is to comprehensively explore the viability of FRC as a fire-resistant and refractory material. In pursuit of this goal, the paper thoroughly reviews various aspects of FRC behavior at elevated temperatures, including pore pressure behaviors. Moreover, this review also discusses spalling behaviors, mechanisms, and residual mechanical properties under high temperatures. The microstructural analysis of FRC is also discussed comprehensively to gain an in-depth understanding of its behavior under elevated temperatures. By analyzing available data, this study aims to shed light on the potential of FRC as a suitable material for resisting spalling in high-temperature scenarios. Additionally, the research delves into prospects and challenges in achieving sustainable FRC with enhanced spalling resistance, considering both material and structural levels.
Therapeutic management of severe spinal cord decompression sickness in a hyperbaric center
Authors: Simonnet Benjamin , Roffi Romain , Lehot Henri , Morin Jean , Druelle Arnaud , Daubresse Lucille , Louge Pierre , Maistre Sébastien de , Gempp Emmanuel , Vallee Nicolas , Blatteau Jean-Eric
Published: September 2023

Introduction

Spinal cord decompression sickness (scDCS) unfortunately has a high rate of long-term sequelae. The purpose of this study was to determine the best therapeutic management in a hyperbaric center and, in particular, the influence of hyperbaric treatment performed according to tables at 4 atm (Comex 30) or 2.8 atm abs (USNT5 or T6 equivalent).

Methods

This was a retrospective study that included scDCS with objective sensory or motor deficit affecting the limbs and/or sphincter impairment seen at a single hyperbaric center from 2010 to 2020. Information on dive, time to recompression, and in-hospital management (hyperbaric and medical treatments such as lidocaine) were analyzed as predictor variables, as well as initial clinical severity and clinical deterioration in the first 24 h after initial recompression. The primary endpoint was the presence or absence of sequelae at discharge as assessed by the modified Japanese Orthopaedic Association score.

Results

102 divers (52 ± 16 years, 20 female) were included. In multivariate analysis, high initial clinical severity, deterioration in the first 24 h, and recompression tables at 4 atm versus 2.8 atm abs for both initial and additional recompression were associated with incomplete neurological recovery. Analysis of covariance comparing the effect of initial tables at 2.8 versus 4 atm abs as a function of initial clinical severity showed a significantly lower level of sequelae with tables at 2.8 atm. In studying correlations between exposure times to maximum or cumulative O2 dose and the degree of sequelae, the optimal initial treatment appears to be a balance between administration of a high partial pressure of O2 (2.8 atm) and a limited exposure duration that does not result in pulmonary oxygen toxicity. Further analysis suggests that additional tables in the first 24–48 h at 2.8 atm abs with a Heliox mixture may be beneficial, while the use of lidocaine does not appear to be relevant.

Conclusion

Our study shows that the risk of sequelae is related not only to initial severity but also to clinical deterioration in the first 24 h, suggesting the activation of biological cascades that can be mitigated by well-adapted initial and complementary hyperbaric treatment.
Role of sphingosine 1-phosphate (S1P) in sepsis-associated intestinal injury
Authors: Sun Gehui , Wang Bin , Zhu Hongquan , Ye Junming , Liu Xiaofeng
Published: September 2023

Sphingosine-1-phosphate (S1P) is a widespread lipid signaling molecule that binds to five sphingosine-1-phosphate receptors (S1PRs) to regulate downstream signaling pathways. Sepsis can cause intestinal injury and intestinal injury can aggravate sepsis. Thus, intestinal injury and sepsis are mutually interdependent. S1P is more abundant in intestinal tissues as compared to other tissues, exerts anti-inflammatory effects, promotes immune cell trafficking, and protects the intestinal barrier. Despite the clinical importance of S1P in inflammation, with a very well-defined mechanism in inflammatory bowel disease, their role in sepsis-induced intestinal injury has been relatively unexplored. In addition to regulating lymphocyte exit, the S1P-S1PR pathway has been implicated in the gut microbiota, intestinal epithelial cells (IECs), and immune cells in the lamina propria. This review mainly elaborates on the physiological role of S1P in sepsis, focusing on intestinal injury. We introduce the generation and metabolism of S1P, emphasize the maintenance of intestinal barrier homeostasis in sepsis, and the protective effect of S1P in the intestine. We also review the link between sepsis-induced intestinal injury and S1P-S1PRs signaling, as well as the underlying mechanisms of action. Finally, we discuss how S1PRs affect intestinal function and become targets for future drug development to improve the translational capacity of preclinical studies to the clinic.
Characterization of three rapidly growing novel Mycobacterium species with significant polycyclic aromatic hydrocarbon bioremediation potential
Authors: Deng Yang , Mou Tong , Wang Junhuan , Su Jing , Yan Yanchun , Zhang Yu-Qin
Published: September 2023

Mycobacterium species exhibit high bioremediation potential for the degradation of polycyclic aromatic hydrocarbons (PAHs) that are significant environmental pollutants. In this study, three Gram-positive, rapidly growing strains (YC-RL4T, MB418T, and HX176T) were isolated from petroleum-contaminated soils and were classified as Mycobacterium within the family Mycobacteriaceae. Genomic average nucleotide identity (ANI; < 95%) and digital DNA–DNA hybridization (dDDH; < 70%) values relative to other Mycobacterium spp. indicated that the strains represented novel species. The morphological, physiological, and chemotaxonomic characteristics of the isolates also supported their affiliation with Mycobacterium and their delineation as novel species. The strains were identified as Mycobacterium adipatum sp. nov. (type strain YC-RL4T = CPCC 205684T = CGMCC 1.62027T), Mycobacterium deserti sp. nov. (type strain MB418T = CPCC 205710T = KCTC 49782T), and Mycobacterium hippophais sp. nov. (type strain HX176T = CPCC 205372T = KCTC 49413T). Genes encoding enzymes involved in PAH degradation and metal resistance were present in the genomes of all three strains. Specifically, genes encoding alpha subunits of aromatic ring-hydroxylating dioxygenases were encoded by the genomes. The genes were also identified as core genes in a pangenomic analysis of the three strains along with 70 phylogenetically related mycobacterial strains that were previously classified as Mycolicibacterium. Notably, strain YC-RL4T could not only utilize phthalates as their sole carbon source for growth, but also convert di-(2-ethylhexyl) phthalate into phthalic acid. These results indicated that strains YC-RL4T, MB418T, and HX176T were important resources with significant bioremediation potential in soils contaminated by PAHs and heavy metals.
Bat STING drives IFN-beta production in anti-RNA virus innate immune response
Authors: Fu Feiyu , Shao Qi , Zhang Jianjian , Wang Jie , Wang Zhaofei , Ma Jingjiao , Yan Yaxian , Sun Jianhe , Cheng Yuqiang
Published: September 2023

The ability of stimulator of interferon genes (STING) to activate interferon (IFN) responses during RNA virus infection has been demonstrated in different mammalian cells. Despite being the host of numerous RNA viruses, the role of STING in bats during RNA virus infection has not been elucidated. In this study, we identified and cloned the STING gene of the Brazilian free-tailed bat Tadarida brasiliensis (T. brasiliensis) and tested its ability to induce IFN-β by overexpressing and knocking down bat STING (BatSTING) in T. brasiliensis 1 lung (TB1 Lu) cells. In addition, we used green fluorescent protein (GFP)-labeled vesicular stomatitis virus (VSV) VSV-GFP as a model to detect the antiviral activity of BatSTING. The results showed that overexpression of STING in TB1 Lu cells stimulated by cGAS significantly inhibited RNA virus replication, and the antiviral activities were associated with its ability to regulate basal expression of IFN-β and some IFN stimulated genes (ISGs). We also found that BatSTING was able to be activated after stimulation by diverse RNA viruses. The results of TB1 Lu cells with STING deficiency showed that knockdown of BatSTING severely hindered the IFN-β response triggered by VSV-GFP. Based on this, we confirm that BatSTING is required to induce IFN-β expression during RNA virus infection. In conclusion, our experimental data clearly show that STING in bat hosts plays an irreplaceable role in mediating IFN-β responses and anti-RNA virus infection.
Development of a specific MPXV antigen detection immunodiagnostic assay
Authors: Davis Ian , Payne Jackie M. , Olguin Victoria L. , Sanders Madison P. , Clements Tamara , Stefan Christopher P. , Williams Janice A. , Hooper Jay W. , Huggins John W. , Mucker Eric M. , Ricks Keersten M.
Published: September 2023

Human monkeypox (mpox) has recently become a global public health emergency; however, assays that detect mpox infection are not widely available, largely due to cross-reactivity within the Orthopoxvirus genus. Immunoassay development was largely confined to researchers who focus on biothreats and endemic areas (Central and West Africa) until the 2022 outbreak. As was noted in the COVID-19 pandemic, antigen detection assays, integrated with molecular assays, are necessary to help curb the spread of disease. Antigen-detecting immunoassays offer the advantage of providing results ranging from within min to h and in lateral flow formats; they can be deployed for point-of-care, home, or field use. This study reports the development of an mpox-specific antigen detection immunoassay developed on a multiplexed, magnetic-bead-based platform utilizing reagents from all research sectors (commercial, academic, and governmental). Two semi-quantitative assays were developed in parallel and standardized with infectious mpox virus (MPXV) cell culture fluid and MPXV-positive non-human primate (NHP) sera samples. These assays could detect viral antigens in serum, were highly specific toward MPXV as compared to other infectious orthopoxviruses (vaccinia virus, cowpox virus, and camelpox virus), and exhibited a correlation with quantitative PCR results from an NHP study. Access to a toolbox of assays for mpox detection will be key for identifying cases and ensuring proper treatment, as MPXV is currently a global traveler.
Argonaute protein-based nucleic acid detection technology
Authors: Wu Zhiyun , Yu Li , Shi Weifeng , Ma Jinhong
Published: September 2023

It is vital to diagnose pathogens quickly and effectively in the research and treatment of disease. Argonaute (Ago) proteins are recently discovered nucleases with nucleic acid shearing activity that exhibit specific recognition properties beyond CRISPR–Cas nucleases, which are highly researched but restricted PAM sequence recognition. Therefore, research on Ago protein-mediated nucleic acid detection technology has attracted significant attention from researchers in recent years. Using Ago proteins in developing nucleic acid detection platforms can enable efficient, convenient, and rapid nucleic acid detection and pathogen diagnosis, which is of great importance for human life and health and technological development. In this article, we introduce the structure and function of Argonaute proteins and discuss the latest advances in their use in nucleic acid detection.
Maternal stress is associated with higher protein-bound amino acid concentrations in human milk
Authors: Juncker Hannah G. , Naninck Eva F. G. , van Keulen Britt J. , Harinck Jolinda E. , Schipper Lidewij , Lucassen Paul J. , van Goudoever Johannes B. , de Rooij Susanne R. , Korosi Aniko
Published: September 2023

Background

Maternal stress in the postpartum period affects not only the mother but also her newborn child, who is at increased risk of developing metabolic and mental disorders later in life. The mechanisms by which stress is transmitted to the infant are not yet fully understood. Human milk (HM) is a potential candidate as maternal stress affects various components of HM, e.g., fat and immunoglobulin concentrations. To date, it is unknown whether maternal stress also affects the amino acids (AAs) in HM, even though this nutrient is of extreme importance to child health and development. This study aimed to investigate whether and how maternal stress is associated with the AA composition of HM.

Methods

In this observational cohort study (Amsterdam, The Netherlands), lactating women were recruited in two study groups: a high-stress (HS) group; women whose child was hospitalized (n = 24), and a control (CTL) group; women who gave birth to a healthy child (n = 73). HM was collected three times a day, on postpartum days 10, 17, and 24. Perceived psychological stress was measured using validated questionnaires, while biological stress measures were based on hair, saliva, and HM cortisol concentrations. HM protein-bound and free AAs were analyzed by liquid chromatography and compared between groups.

Results

Maternal perceived stress scores were higher in the HS group (p < 0.01). The concentrations of protein-bound AAs in HM were higher in the HS group compared to the CTL group (p = 0.028) and were positively associated with HM cortisol concentrations (p = 0.024). The concentrations of free AAs did not differ between study groups and were unrelated to cortisol concentrations.

Conclusion

Findings from this prospective cohort study suggest that maternal stress in the postpartum period is associated with an altered human milk amino acid composition, which could play a role in the transmission of maternal stress effects to her child. The physiological implications of these stress-induced changes for infant development await future research.
Evaluation of public submissions to the USDA for labeling of cell-cultured meat in the United States
Authors: Failla Morgan , Hopfer Helene , Wee Josephine
Published: September 2023

With the rapid advancement of cell-cultured meat processing technologies and regulations, commercialization of cell-cultured meat to market shelves requires the implementation of labeling that informs and protects consumers while ensuring economic competitiveness. In November 2022, the United States Food and Drug Administration (FDA) completed its first pre-market consultation of cell-cultured meat and did not question the safety of these products for human consumption. As of June 2023, commercialization of cell-cultured meat products has become a reality in the United States. To derive potential label terms and gain insight into how different stakeholders refer to these novel products, we analyzed 1,151 comments submitted to the 2021 U.S. Department of Agriculture’s Food Safety and Inspection Services (USDA-FSIS) call on the labeling of cell-cultured meat and poultry. Our first aim was to systematically assess the nature of comments with regards to their length, cited references, and supplemental materials. In addition, we aimed to identify the most used terms to refer to these products through text analysis. We also asked how these analyses would vary by affiliation category and economic interest. Using the listed organizations for each comment, we first determined financial ties: 77 (7%) comments came from those with an economic interest, 12 (1%) of the comments did not have an identifiable economic interest, while for the remaining 1,062 (92%) comments economic interest could not be determined. We then grouped comments into affiliation categories. Cell-cultured meat companies and animal welfare non-profits had the highest median word count, whereas comments from the unknown affiliation category had the lowest. We found across all comments the predominantly mentioned potential label terms, in descending order, to be cultured meat, lab-grown meat, cultivated meat, cell-cultured meat, clean meat, and cell-based meat. While all label terms were discussed throughout overall submissions, percentages of comments mentioning each term differed between affiliation categories. Our findings suggest differences in how affiliation categories are discussing cell-cultured meat products for the US market. As a next step, the perception and acceptance of these terms must be evaluated to identify the optimal label term regarding the information and protection provided to consumers while ensuring economic competitiveness.
Adherence to the Mediterranean diet and risk of gastric cancer: a systematic review and dose–response meta-analysis
Authors: Zhu Qin , Shu Long , Zhou Feng , Chen Li-Peng , Feng Yu-Liang
Published: September 2023

Background

Despite growing evidence for the association of adherence to the Mediterranean diet with gastric cancer risk, the results remain inconclusive. The purpose of this systematic review and meta-analysis was to summarize the evidence from previous observational studies and assess the potential association between adherence to the Mediterranean diet and risk of gastric cancer using a dose–response meta-analysis.

Methods

A comprehensive literature search for all observational studies published up to June 30, 2023 was conducted using the databases of PubMed, ISI Web of Science, EBSCO, China National Knowledge Infrastructure (CNKI) and Wanfang Data. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated for the highest versus the lowest categories of Mediterranean diet score in relation to gastric cancer risk, using random-effects models. The Cochran’s Q test and I-squared (I2) statistic were used to detect the sources of heterogeneity among the included studies.

Results

Overall, 11 studies (five cohort and six case–control studies) with a total number of 1,366,318 participants were included in the final analysis. Combining 14 effect sizes from 11 studies revealed that compared with the lowest category, the highest adherence to the Mediterranean diet was associated with a 29% reduction in the risk of gastric cancer (RR:0.71; 95%CI:0.59–0.84, p < 0.001). In addition, linear dose–response analysis showed that each 1-score increment in Mediterranean diet score was associated with a 5% lower risk of gastric cancer (RR:0.95; 95%CI: 0.94–0.96, p < 0.001). Stratified analysis showed a significant association between adherence to the Mediterranean diet and risk of gastric cancer in case–control studies (RR = 0.44;95%CI:0.32–0.61, p < 0.001), and a marginally significant association in prospective cohort studies (RR = 0.88; 95%CI: 0.79–0.98, p = 0.024), respectively. At the same time, a more significant association between Mediterranean diet and reduced risk of gastric cancer was observed in other countries (RR = 0.28; 95%CI:0.16–0.49, p < 0.001) than in Western countries (RR = 0.75; 95%CI:0.64–0.88, p = 0.001).

Conclusion

Our results demonstrate that high adherence to the Mediterranean diet is associated with 29% reduced risk of gastric cancer. Further large prospective studies and randomized controlled trials are warranted to confirm our findings.
Clinicopathological analysis of diffuse large B-cell lymphoma using molecular biomarkers: a retrospective analysis from 7 Hungarian centers
Authors: Balikó Anett , Szakács Zsolt , Kajtár Béla , Ritter Zsombor , Gyenesei Attila , Farkas Nelli , Kereskai László , Vályi-Nagy István , Alizadeh Hussain , Pajor László
Published: September 2023

Background

The clinical and genetic heterogeneity of diffuse large B-cell lymphoma (DLBCL) presents distinct challenges in predicting response to therapy and overall prognosis. The main objective of this study was to assess the application of the immunohistochemistry- and interphase fluorescence in situ hybridization (FISH)-based molecular markers in the diagnosis of DLBCL and its prognostic value in patients treated with rituximab-based immunochemotherapy.

Methods

This is a multicenter, retrospective study, which analyzed data from 7 Hungarian hematology centers. Eligible patients were adults, had a histologically confirmed diagnosis of DLBCL, were treated with rituximab-based immunochemotherapy in the first line, and had available clinicopathological data including International Prognostic Index (IPI). On the specimens, immunohistochemistry and FISH methods were performed. Germinal center B-cell like (GCB) and non-GCB subtypes were classified by the Hans algorithm. Outcomes included overall survival (OS), event-free survival (EFS), and EFS at 2 years (EFS24). For survival analysis, we used Kaplan-Meier curves with the log-rank test and multivariate Cox regression.

Results

A total of 247 DLBCL cases were included. Cases were positive for MYC, BCL2, BCL6, and MUM1 expression in 52.1%, 66.2%, 72.6%, and 77.8%, respectively. BCL6 translocation, BCL2 gene copy number (GCN) gain, IGH::MYC translocation, MYC GCN gain, IGH::BCL2 translocation, and BCL6 GCN gain were detected in 21.4%, 14.1%, 7.3%, 1.8%, 7.3%, and 0.9%, respectively. At a median follow-up of 52 months, 140 patients (56.7%) had disease progression or relapse. The Kaplan-Meier estimate for EFS24 was 56.2% (CI: 50.4–62.8%). In univariate analysis, only IPI and BCL6 expression were significant predictors of both OS and EFS, whereas MUM1 predicted EFS only. In multivariate analysis, the IPI score was a significant independent negative, whereas MIB-1 and BCL6 protein expressions were significant independent positive predictors of both OS and EFS.

Conclusion

In our study, we found that only IPI, BCL6 protein expression and MIB-1 protein expression are independent predictors of survival outcomes in DLBCL. We did not find any difference in survival by GCB vs. non-GCB subtypes. These findings may improve prognostication in DLBCL and can contribute to designing further research in the area.
Non-coding RNAs in lung cancer: molecular mechanisms and clinical applications
Authors: Liu Ying , Ding Wei , Wang Jianxun , Ao Xiang , Xue Junqiang
Published: September 2023

Lung cancer (LC) is a heterogeneous disease with high malignant degree, rapid growth, and early metastasis. The clinical outcomes of LC patients are generally poor due to the insufficient elucidation of pathological mechanisms, low efficiency of detection and assessment methods, and lack of individualized therapeutic strategies. Non-coding RNAs (ncRNAs), including microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA), are endogenous regulators that are widely involved in the modulation of almost all aspects of life activities, from organogenesis and aging to immunity and cancer. They commonly play vital roles in various biological processes by regulating gene expression via their interactions with DNA, RNA, or protein. An increasing amount of studies have demonstrated that ncRNAs are closely correlated with the initiation and development of LC. Their dysregulation promotes the progression of LC via distinct mechanisms, such as influencing protein activity, activating oncogenic signaling pathways, or altering specific gene expression. Furthermore, some ncRNAs present certain clinical values as biomarker candidates and therapeutic targets for LC patients. A complete understanding of their mechanisms in LC progression may be highly beneficial to developing ncRNA-based therapeutics for LC patients. This review mainly focuses on the intricate mechanisms of miRNA, lncRNA, and circRNA involved in LC progression and discuss their underlying applications in LC treatment.
Single domain Camelid antibody fragments for molecular imaging and therapy of cancer
Authors: Li Shulin , Hoefnagel Sanne Johanna Maria , Krishnadath Kausilia Krishnawatie
Published: September 2023

Despite innovations in cancer therapeutics, cancer remains associated with high mortality and is one of biggest health challenges worldwide. Therefore, developing precise cancer imaging and effective treatments is an unmet clinical need. A relatively novel type of therapeutics are heavy chain variable domain antibody fragments (VHHs) derived from llamas. Here, we explored the suitability of VHHs for cancer imaging and therapy through reviewing the existing literature. We searched the MEDLINE, EMBASE and Cochrane databases and identified 32 papers on molecular imaging and 41 papers on therapy that were suitable for comprehensive reviewing. We found that VHHs harbor a higher specificity and affinity compared to mAbs, which contributes to high-quality imaging and less side-effects on healthy cells. The employment of VHHs in cancer imaging showed remarkably shorter times between administration and imaging. Studies showed that 18F and 99mTc are two optimal radionuclides for imaging with VHHs and that site-specific labelling is the optimal conjugation modality for VHHs with radionuclide or fluorescent molecules. We found different solutions for reducing kidney retention and immunogenicity of VHHs. VHHs as anticancer therapeutics have been tested in photodynamic therapy, targeted radionuclide therapy, immunotherapy and molecular targeted therapy. These studies showed that VHHs target unique antigen epitopes, which are distinct from the ones recognized by mAbs. This advantage means that VHHs may be more effective for targeted anticancer therapy and can be combined with mAbs. We found that high cellular internalization and specificity of VHHs contributes to the effectiveness and safety of VHHs as anticancer therapeutics. Two clinical trials have confirmed that VHHs are effective and safe for cancer imaging and therapy. Together, VHHs seem to harbor several advantages compared to mAbs and show potential for application in personalized treatment for cancer patients. VHH-based imaging and therapy are promising options for improving outcomes of cancer patients.
Prospective study of the effect of auricular percutaneous electrical nerve field stimulation on quality of life in children with pain related disorders of gut-brain interaction
Authors: Chogle Ashish , Visnagra Kaajal , Janchoi Jamie , Tran Tammy , Davis Rachel , Callas Nicole , Ornelas Elisa
Published: September 2023

Background

Disorders of the Gut-Brain Interaction (DGBIs) account for 50% of pediatric gastrointestinal (GI) consultations. Children with DGBIs have worse quality of life (QoL) than those with organic GI disorders such as inflammatory bowel disease and gastroesophageal reflux disease. Pediatric DGBIs patients, especially those with chronic abdominal pain (AP), have impaired QoL and increased psychological distress in the form of anxiety and depression. Percutaneous Electrical Nerve Field Stimulation (PENFS) therapy has been shown to be effective in improving symptoms and functioning in children with DGBIs. The treatment's impact on these patients' QoL is unknown.

Methods

This prospective study evaluated changes in QoL, gastrointestinal symptoms, functional disability, somatization, global health, anxiety, and depression in patients aged 11–18 years who received PENFS therapy (IB-stim, NeurAxis, Versailles, IN) for treatment of pain related DGBIs, once a week for four consecutive weeks.

Results

This study included 31 patients with an average age of 15.7 years (SD = 2); 80.6% were female. After PENFS therapy, patients reported significant reductions in abdominal pain, nausea severity, functional disability, somatization, and anxiety from baseline to week 4 (p < 0.05). Parents reported significant improvement in their child's QoL regarding physical function, psychosocial function, and generic core scale scores (p < 0.05). Parents also noted reduced abdominal pain, functional disability, and somatization. Average scores on the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health scale significantly improved based on both patient and parent reports (p < 0.05). Our patients' QoL was significantly lower than healthy controls at baseline and after treatment (p < 0.05).

Conclusion

Our research demonstrates that PENFS significantly enhances the QoL of children suffering from pain-related DGBIs, in addition to improvement in GI symptoms, daily functioning, somatization, global health, and psychological comorbidities. These findings demonstrate the effectiveness of PENFS and its potential to alleviate the suffering of countless children.
Primary ciliary dyskinesia diagnosis and management and its implications in America: a mini review
Authors: Castillo M. , Freire E. , Romero V. I.
Published: September 2023

Introduction

Primary ciliary dyskinesia (PCD) is a rare genetic disorder that can result in significant morbidity and mortality if left untreated. Clinical manifestations of PCD include recurrent respiratory infections, laterality defects, and infertility, all of which arise from impaired or absent ciliary motility. Diagnostic approaches for PCD may include high-speed video microscopy, measurement of nasal nitric oxide levels, and genetic testing; however, no single definitive diagnostic test exists. The present study aims to highlight the lack of standardized diagnostic and treatment guidelines for PCD in Latin America (Central and South America, and the Caribbean). To this effect, we compared North American and European recommendations for the diagnosis and management of PCD and found that certain diagnostic tools and treatment options mentioned in these guidelines are not readily accessible in many Latin American countries.

Methods & Results

This review gathers disease information in North America, Europe, and Latin America organizing guideline results into tables for clarity and potential interventions. Management information for Latin America is inferred from case reports, as most findings are from North American recommendations and studies on PubMed, Google Scholar, and Scopus. Treatment and management information is based on North American and European standards.

Among 5,774 publications reviewed, only 15 articles met the inclusion criteria (focused on PCD management, peer-reviewed, and located in America). No clinical guideline for PCD in Latin America was found, but recommendations on respiratory management from Colombia and Chile were discovered. The lack of guidelines in Latin America may originate from limited resources and research on the disease in those countries.

Discussion

PCD lacks documentation, research, and recommendations regarding its prevalence in Latin America, likely due to unfavorable economic conditions. This disadvantage results in limited access to diagnostic tests available in North America and Europe. The PICADAR score, discussed in this review, can be used in low-income nations as a screening tool for the disorder.
Case report: Structural brain abnormalities in TUBA1A-tubulinopathies: a narrative review
Authors: Pavone Piero , Striano Pasquale , Cacciaguerra Giovanni , Marino Simona Domenica , Parano Enrico , Pappalardo Xena Giada , Falsaperla Raffaele , Ruggieri Martino
Published: September 2023

Introduction

Tubulin genes have been related to severe neurological complications and the term “tubulinopathy” now refers to a heterogeneous group of disorders involving an extensive family of tubulin genes with TUBA1A being the most common. A review was carried out on the complex and severe brain abnormalities associated with this genetic anomaly.

Methods

A literature review of the cases of TUBA1A-tubulopathy was performed to investigate the molecular findings linked with cerebral anomalies and to describe the clinical and neuroradiological features related to this genetic disorder.

Results

Clinical manifestations of TUBA1A-tubulinopathy patients are heterogeneous and severe ranging from craniofacial dysmorphism, notable developmental delay, and intellectual delay to early-onset seizures, neuroradiologically associated with complex abnormalities. TUBA1A-tubulinopathy may display various and complex cortical and subcortical malformations.

Discussion

A range of clinical manifestations related to different cerebral structures involved may be observed in patients with TUBA1A-tubulinopathy. Genotype–phenotype correlations are discussed here. Individuals with cortical and subcortical anomalies should be screened also for pathogenic variants in TUBA1A.
The avian taste system
Authors: Niknafs Shahram , Navarro Marta , Schneider Eve R. , Roura Eugeni
Published: September 2023

Taste or gustation is the sense evolving from the chemo-sensory system present in the oral cavity of avian species, which evolved to evaluate the nutritional value of foods by detecting relevant compounds including amino acids and peptides, carbohydrates, lipids, calcium, salts, and toxic or anti-nutritional compounds. In birds compared to mammals, due to the relatively low retention time of food in the oral cavity, the lack of taste papillae in the tongue, and an extremely limited secretion of saliva, the relevance of the avian taste system has been historically undermined. However, in recent years, novel data has emerged, facilitated partially by the advent of the genomic era, evidencing that the taste system is as crucial to avian species as is to mammals. Despite many similarities, there are also fundamental differences between avian and mammalian taste systems in terms of anatomy, distribution of taste buds, and the nature and molecular structure of taste receptors. Generally, birds have smaller oral cavities and a lower number of taste buds compared to mammals, and their distribution in the oral cavity appears to follow the swallowing pattern of foods. In addition, differences between bird species in the size, structure and distribution of taste buds seem to be associated with diet type and other ecological adaptations. Birds also seem to have a smaller repertoire of bitter taste receptors (T2Rs) and lack some taste receptors such as the T1R2 involved in sweet taste perception. This has opened new areas of research focusing on taste perception mechanisms independent of GPCR taste receptors and the discovery of evolutionary shifts in the molecular function of taste receptors adapting to ecological niches in birds. For example, recent discoveries have shown that the amino acid taste receptor dimer T1R1-T1R3 have mutated to sense simple sugars in almost half of the living bird species, or SGLT1 has been proposed as a part of a T1R2-independent sweet taste sensing in chicken. The aim of this review is to present the scientific data known to date related to the avian taste system across species and its impact on dietary choices including domestic and wild species.
Functional analysis of auxin derived from a symbiotic mycobiont
Authors: Chen Cheng-Yen , Selvaraj Poonguzhali , Naqvi Naweed I.
Published: September 2023

The biosynthesis of auxin or indole-3-acetic acid by microorganisms has a major impact on plant–microbe interactions. Several beneficial microbiota are known to produce auxin, which largely influences root development and growth in the host plants. Akin to findings in rhizobacteria, recent studies have confirmed the production of auxin by plant growth-promoting fungi too. Here, we show that Penicillium citrinum isolate B9 produces auxin as deduced by liquid chromatography tandem-mass spectrometry analysis. Such fungal auxin is secreted and contributes directly to enhanced root and shoot development and overall plant growth in Arabidopsis thaliana. Furthermore, auxin production by P. citrinum likely involves more than one tryptophan-dependent pathway. Using auxin biosynthesis inhibitor L-Kynurenine, we show that the indole-3-pyruvate pathway might be one of the key biosynthetic routes involved in such auxin production. Confocal microscopy of the DR5rev:GFP Arabidopsis reporter line helped demonstrate that P. citrunum B9-derived auxin is biologically active and is able to significantly enhance auxin signaling in roots during such improved root growth and plant development. Furthermore, the phenotypic growth defects arising from impaired auxin signaling in Arabidopsis taa1 mutant or upon L-Kynurenine treatment of wild-type Arabidopsis seedlings could be significantly alleviated by fungus B9-derived auxin, thus suggesting its positive role in plant growth promotion. Collectively, our results provide clear evidence that the production of auxin is one of the main mechanisms involved in induction of the beneficial plant growth by P. citrinum.
TaSPL17s act redundantly with TaSPL14s to control spike development and their elite haplotypes may improve wheat grain yield
Authors: Chen Hao , Zhang Xing , Xu Shuhao , Song Chengxiang , Mao Hailiang
Published: September 2023

Wheat is a staple crop for the world’s population, and there is constant pressure to improve grain yield, which is largely determined by plant architecture. SQUAMOSA promotor-binding protein-like (SPL) genes have been widely studied in rice, including their effects on plant architecture, grain development, and grain yield. However, the function of SPL homologous genes in wheat has not been well investigated. In this study, TaSPL14s and TaSPL17s, wheat’s closest orthologous of OsSPL14, were functionally investigated using gene-editing assays, revealing that these genes redundantly influence plant height, tiller number, spike length, and thousand-grain weight (TGW). Bract outgrowth was frequently observed in the hexa-mutant, occasionally in the quintuple mutant but never in the wild type. Transcriptome analysis revealed that the expression of many spike development-associated genes was altered in taspl14taspl17 hexa-mutants compared to that in the wild type. In addition, we analyzed the sequence polymorphisms of TaSPL14s and TaSPL17s among wheat germplasm and found superior haplotypes of TaSPL17-A and TaSPL17-D with significantly higher TGW, which had been positively selected during wheat breeding. Accordingly, dCAPS and KASP markers were developed for TaSPL17-A and TaSPL17-D, respectively, providing a novel insight for molecular marker-assisted breeding in wheat. Overall, our results highlight the role of TaSPLs in regulating plant architecture and their potential application for wheat grain yield improvement through molecular breeding.
Exploration of chlorophyll fluorescence characteristics gene regulatory in rice (Oryza sativa L.): a genome-wide association study
Authors: Liu Sicheng , Xiong Zhuang , Zhang Zuolin , Wei Youbo , Xiong Dongliang , Wang Fei , Huang Jianliang
Published: September 2023

Chlorophyll content and fluorescence parameters are crucial indicators to evaluate the light use efficiency in rice; however, the correlations among these parameters and the underlying genetic mechanisms remain poorly understood. Here, to clarify these issues, we conducted a genome-wide association study (GWAS) on 225 rice accessions. In the phenotypic and Mendelian randomization (MR) analysis, a weak negative correlation was observed between the chlorophyll content and actual quantum yield of photosystem II (ΦII). The phenotypic diversity observed in SPAD, NPQt, ΦNPQ, and Fv/Fm among accessions was affected by genetic background. Furthermore, the GWAS identified 78 SNPs and 17 candidate genes significantly associated with SPAD, NPQt, ΦII, ΦNPQ, qL and qP. Combining GWAS on 225 rice accessions with transcriptome analysis of two varieties exhibiting distinct fluorescence characteristics revealed two potential candidate genes (Os03g0583000 from ΦII & qP traits and Os06g0587200 from NPQt trait), which are respectively associated with peroxisomes, and protein kinase catalytic domains might involve in regulating the chlorophyll content and chlorophyll fluorescence. This study provides novel insights into the correlation among chlorophyll content and fluorescence parameters and the genetic mechanisms in rice, and offers valuable information for the breeding of rice with enhanced photosynthetic efficiency.