bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the 21-gene expression assay on treatment decisions and clinical outcomes in breast cancer with one to three positive lymph nodes
Authors: Li Guan-Qiao , Xie Shang-Jin , Wu San-Gang , He Zhen-Yu
Published: February 2023

Background

To assess the practice patterns of the recurrence score (RS) based on the 21-gene expression assay on adjuvant chemotherapy recommendations and survival outcomes in estrogen receptor-positive (ER+)/HER2- breast cancer (BC) with one to three positive lymph nodes (N1).

Methods

We included patients with T1-2N1M0 and ER+/HER2- BC diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and End Results Oncotype DX Database. Breast cancer-specific survival (BCSS) and overall survival (OS) were assessed.

Results

We included 35,137 patients in this study. There were 21.2% of patients who had RS testing in 2010, which was significantly increased to 36.8% in 2015 (P < 0.001). Performance of the 21-gene testing was associated with older age, lower tumor grade, T1 stage, lower number of positive lymph nodes, and progesterone receptor-positive disease (all P < 0.05). In those without 21-gene testing, age was the main factor significantly related to the receipt of chemotherapy, whereas RS was the main factor significantly related to chemotherapy receipt in those with 21-gene testing. The probability of chemotherapy receipt in those without 21-gene testing was 64.1% and was decreased to 30.8% in those with 21-gene testing. On multivariate prognostic analysis, the performance of 21-gene testing was associated with better BCSS (P < 0.001) and OS (P < 0.001) compared with those without 21-gene testing. Similar results were found after propensity score matching.

Conclusions

The 21-gene expression assay is frequently and increasingly used for chemotherapy decision-making in ER+/HER2- BC with N1 disease. Performance of the 21-gene testing is associated with improved survival outcomes. Our study supports the routine use of 21-gene testing in the clinical practice of this population.
The association between renal accumulation of pancreatic amyloid-forming amylin and renal hypoxia
Authors: Verma Nirmal , Despa Florin
Published: February 2023

Chronic kidney disease (CKD) is increasing worldwide and is associated with diabetic states (obesity, prediabetes and type-2 diabetes mellitus). The kidney is intrinsically susceptible to low oxygen (hypoxia) and renal hypoxia plays a vital role in the progression of CKD. Recent studies suggest an association between CKD and renal deposition of amyloid-forming amylin secreted from the pancreas. Renal accumulation of amyloid-forming amylin is associated with hypertension, mitochondrial dysfunction, increased production of reactive oxygen species (ROS) and activation of hypoxia signaling in the kidney. In this review we will discuss potential associations between renal amylin amyloid accumulation, hypertension, and mechanism of hypoxia-induced kidney dysfunction, including activation of hypoxia-inducible factors (HIFs) and mitochondrial dysfunction.
Serum glycoprotein non-metastatic melanoma protein B (GPNMB) level as a potential biomarker for diabetes mellitus-related cataract: A cross-sectional study
Authors: Huo Da , Liu Yuan-Yuan , Zhang Chi , Zeng Lv-Tao , Fan Guo-Qing , Zhang Li-Qun , Pang Jing , Wang Yao , Shen Tao , Li Xue-Fei , Li Chuan-Bao , Zhang Tie-Mei , Cai Jian-Ping , Cui Ju
Published: February 2023

Background

Diabetes mellitus (DM), a metabolic disease that has attracted significant research and clinical attention over the years, can affect the eye structure and induce cataract in patients diagnosed with DM. Recent studies have indicated the relationship between glycoprotein non-metastatic melanoma protein B (GPNMB) and DM and DM-related renal dysfunction. However, the role of circulating GPNMB in DM-associated cataract is still unknown. In this study, we explored the potential of serum GPNMB as a biomarker for DM and DM-associated cataract.

Methods

A total of 406 subjects were enrolled, including 60 and 346 subjects with and without DM, respectively. The presence of cataract was evaluated and serum GPNMB levels were measured using a commercial enzyme-linked immunosorbent assay kit.

Results

Serum GPNMB levels were higher in diabetic individuals and subjects with cataract than in those without DM or cataract. Subjects in the highest GPNMB tertile group were more likely to have metabolic disorder, cataract, and DM. Analysis performed in subjects with DM elucidated the correlation between serum GPNMB levels and cataract. Receiver operating characteristic (ROC) curve analysis also indicated that GPNMB could be used to diagnose DM and cataract. Multivariable logistic regression analysis illustrated that GPNMB levels were independently associated with DM and cataract. DM was also found to be an independent risk factor for cataract. Further surveys revealed the combination of serum GPNMB levels and presence of DM was associated with a more precise identification of cataract than either factor alone.

Conclusions

Increased circulating GPNMB levels are associated with DM and cataract and can be used as a biomarker of DM-associated cataract.
Development and validation of a nomogram for evaluating the incident risk of carotid atherosclerosis in patients with type 2 diabetes
Authors: Feng Xiao , Ren Liying , Xiang Yuping , Xu Yancheng
Published: February 2023

Introduction

The purpose of this study was to evaluate the clinical characteristics of carotid atherosclerotic disease in patients with type 2 diabetes mellitus, investigate its risk factors, and develop and validate an easy-to-use nomogram.

Methods

1049 patients diagnosed with type 2 diabetes were enrolled and randomly assigned to the training and validation cohorts. Multivariate logistic regression analysis identified independent risk factors. A method combining least absolute shrinkage and selection operator with 10-fold cross-validation was used to screen for characteristic variables associated with carotid atherosclerosis. A nomogram was used to visually display the risk prediction model. Nomogram performance was evaluated using the C index, the area under the receiver operating characteristic curve, and calibration curves. Clinical utility was assessed by decision curve analysis.

Results

Age, nonalcoholic fatty liver disease, and OGTT3H were independent risk factors associated with carotid atherosclerosis in patients with diabetes. Age, nonalcoholic fatty liver disease, smoke, HDL-C, and LDL-C were characteristic variables used to develop the nomogram. The area under the curve for the discriminative power of the nomogram was 0.763 for the training cohort and 0.717 for the validation cohort. The calibration curves showed that the predicted probability matched the actual likelihood. The results of the decision curve analysis indicated that the nomograms were clinically useful.

Discussion

A new nomogram was developed and validated for assessing the incident risk of carotid atherosclerotic in patients with diabetes; this nomogram may act as a clinical tool to assist clinicians in making treatment recommendations.
A robust optimal dispatching strategy of distribution networks considering fast charging stations integrated with photovoltaic and energy storage
Authors: Zhang Cong , Peng Ke , Zhang Xinhui , Jiang Yan , Liu Yuxin , Cai Yuanxin
Published: February 2023

With the increasing number of electric vehicles, a large number of charging loads connected to the power system will have an impact on the economic and safe operation of the power system. In this paper a day-ahead optimal dispatching method for distribution network (DN) with fast charging station (FCS) integrated with photovoltaic (PV) and energy storage (ES) is proposed to deal with the negative impact of FCS on DN. By adjusting the load distribution of DN through the optimization decision of ES and soft open points (SOP), the operation level of DN is improved. Firstly, based on the historical vehicle travel data, Monte Carlo simulation method (MCSM) is applied to realize the simulation of fast charging load. Secondly, the uncertainties of PV power is addressed via a robust optimization model of the economic operation level of DN. Based on the second order cone relaxation and duality theory, a two-stage optimal dispatching model of DN is proposed. The optimization model is divided into main problem (MP) and sub problem (SP). For MP, the access position of FCS is adjusted based on SOP. And the charging and discharging power of ES is adjusted. The load distribution is optimized. For SP, based on the uncertainty of PV, the worst scenario of DN is calculated. The robustness of the proposed strategy is guaranteed. Finally, the proposed is verified based on the IEEE 33 bus system and a road network with 34 nodes. The simulation results show that the proposed method can effectively relieve line congestion of DN. The operating range of the voltage is better optimized. And the operation cost of DN is reduced significantly.
Intrusion detection in smart meters data using machine learning algorithms: A research report
Authors: Ravinder M. , Kulkarni Vikram
Published: February 2023

The intrusion detection in network traffic for crucial smart metering applications based on radio sensor networks is becoming very important in the Smart Grid area. The network’s structure for smart meters under investigation should consider important security factors. The potential of both passive and active cyber-attacks affecting the functioning of advanced metering infrastructure is studied and a novel method is proposed in this article. The proposed method for anomaly identification is efficient and rapid. In the beginning, Cook’s distance was employed to recognize and eliminate outlier observations. After observations are made three statistical models Brown’s, Holt’s, and winter’s models were used for exponential smoothing and were estimated using the provided data. Bollinger Bands with the appropriate parameters were employed to estimate potential changes in the forecasts produced by the models that were put into operation. The estimated traffic model’s statistical relationships with its actual variations were then investigated to spot any unusual behaviour that would point to a cyber-attack effort. Additionally, a method for updating common models in the event of substantial fluctuations in real network traffic was suggested. The findings confirmed the effectiveness of the proposed method and the precision of the selection of the appropriate statistical model for the under-study time series. The outcomes validated the effectiveness of the proposed approach and the precision in choosing a suitable statistical model for the time series under investigation.
Exposure to war and conflict: The individual and inherited epigenetic effects on health, with a focus on post-traumatic stress disorder
Authors: Raza Zara , Hussain Syeda F. , Foster Victoria S. , Wall Joseph , Coffey Peter J. , Martin John F. , Gomes Renata S. M.
Published: February 2023

War and conflict are global phenomena, identified as stress-inducing triggers for epigenetic modifications. In this state-of-the-science narrative review based on systematic principles, we summarise existing data to explore the outcomes of these exposures especially in veterans and show that they may result in an increased likelihood of developing gastrointestinal, auditory, metabolic and circadian issues, as well as post-traumatic stress disorder (PTSD). We also note that, despite a potential “healthy soldier effect”, both veterans and civilians with PTSD exhibit the altered DNA methylation status in hypothalamic–pituitary–adrenal (HPA) axis regulatory genes such as NR3C1. Genes associated with sleep (PAX8; LHX1) are seen to be differentially methylated in veterans. A limited number of studies also revealed hereditary effects of war exposure across groups: decreased cortisol levels and a heightened (sex-linked) mortality risk in offspring. Future large-scale studies further identifying the heritable risks of war, as well as any potential differences between military and civilian populations, would be valuable to inform future healthcare directives.
Citizen science can enhance strategies to detect and manage invasive forest pests and pathogens
Authors: Hulbert Joseph M. , Hallett Richard A. , Roy Helen E. , Cleary Michelle
Published: February 2023

Incorporating a citizen science approach into biological invasion management strategies can enhance biosecurity. Many citizen science projects exist to strengthen the management of forest pest and pathogen invasions within both pre- and post-border scenarios. Besides the value of citizen science initiatives for early detection and monitoring, they also contribute widely to raising awareness, informing decisions about eradication and containment efforts to minimize pest and pathogen spread, and even finding resistant plant material for restoration of landscapes degraded by disease. Overall, many projects actively engage citizens in the different stages of forest pest and pathogen invasions, but it is unclear how they work together across all stages of the entire biological invasion process to enhance biosecurity. Here we provide examples of citizen science projects for each stage of the biological invasion process, discuss options for developing a citizen science program to enhance biosecurity, and suggest approaches for integrating citizen science into biosecurity measures to help safeguard forest resources in the future.
Origin-country gender norms, individual work experience, and employment among immigrant women in Sweden
Authors: Tibajev Andrey , Nygård Olav
Published: February 2023

Many Western countries are built on a dual-earner model and have high levels of female labor force participation. Increasing the labor market activity of immigrant women is therefore seen as a key part of immigrant integration. However, female labor force participation (LFP) differs substantially between countries, reflecting differences in work-related gender norms that can continue to influence preferences and behaviors after migration. In this study, we investigate how origin-country gender norms and migrant selection interact to produce post-migration outcomes. Our data shows that immigrant women in Sweden have a higher level of pre-migration work experience than expected based on origin-country female LFP, indicating positive selection. Furthermore, the association between origin-country LFP and post-migration employment varied with work experience. For women without origin-country work experience, origin-country LFP was positively associated with employment in Sweden. For women with origin-country work experience, origin-country LFP however was not associated with higher likelihood of employment in Sweden. Though our focus is on immigrant women, we also include immigrant men in our analysis to test our prediction more thoroughly. For men without origin-country work experience, origin-country LFP was negatively associated with employment in Sweden, while we found no association for men with origin-country work experience. Our results show that migrant selection is a crucial factor in understanding the relationship between origin-country LFP and post-migration labor market outcomes, and that these patterns vary with gender. Policy interventions targeting immigrant women from countries with low female LFP should therefore not assume that women arrive socialized with gender-norms that hinder labor market activity.
Case report: HLA-haploidentical HSCT rescued with donor lymphocytes infusions in a patient with X-linked chronic granulomatous disease
Authors: Scheiermann Julia , Künkele Annette , von Stackelberg Arend , Eggert Angelika , Lang Peter , Zirngibl Felix , Martin Luise , Schulte Johannes Hubertus , von Bernuth Horst
Published: February 2023

Chronic granulomatous disease is an inborn error of immunity due to disrupted function of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. This results in impaired respiratory burst of phagocytes and insufficient killing of bacteria and fungi. Patients with chronic granulomatous disease are at increased risk for infections, autoinflammation and autoimmunity. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only widely available curative therapy. While HSCT from human leukocyte antigen (HLA) matched siblings or unrelated donors are standard of care, transplantation from HLA-haploidentical donors or gene therapy are considered alternative options. We describe a 14-month-old male with X-linked chronic granulomatous disease who underwent a paternal HLA-haploidentical HSCT using T-cell receptor (TCR) alpha/beta+/CD19+ depleted peripheral blood stem cells followed by mycophenolate graft versus host disease prophylaxis. Decreasing donor fraction of CD3+ T cells was overcome by repeated infusions of donor lymphocytes from the paternal HLA-haploidentical donor. The patient achieved normalized respiratory burst and full donor chimerism. He remained disease-free off any antibiotic prophylaxis for more than three years after HLA-haploidentical HSCT. In patients with x-linked chronic granulomatous disease without a matched donor paternal HLA-haploidentical HSCT is a treatment option worth to consider. Administration of donor lymphocytes can prevent imminent graft failure.
Immunological priming of mesenchymal stromal/stem cells and their extracellular vesicles augments their therapeutic benefits in experimental graft-versus-host disease via engagement of PD-1 ligands
Authors: Hackel Alexander , Vollmer Sebastian , Bruderek Kirsten , Lang Stephan , Brandau Sven
Published: February 2023

Mesenchymal stromal cells (MSCs) and their extracellular vesicles (EVs) exert profound anti-inflammatory and regenerative effects in inflammation and tissue damage, which makes them an attractive tool for cellular therapies. In this study we have assessed the inducible immunoregulatory properties of MSCs and their EVs upon stimulation with different combinations of cytokines. First, we found that MSCs primed with IFN-γ, TNF-α and IL-1β, upregulate the expression of PD-1 ligands, as crucial mediators of their immunomodulatory activity. Further, primed MSCs and MSC-EVs, compared to unstimulated MSCs and MSC-EVs, had increased immunosuppressive effects on activated T cells and mediated an enhanced induction of regulatory T cells, in a PD-1 dependent manner. Importantly, EVs derived from primed MSCs reduced the clinical score and prolonged the survival of mice in a model of graft-versus-host disease. These effects could be reversed in vitro and in vivo by adding neutralizing antibodies directed against PD-L1 and PD-L2 to both, MSCs and their EVs. In conclusion, our data reveal a priming strategy that potentiates the immunoregulatory function of MSCs and their EVs. This concept also provides new opportunities to improve the clinical applicability and efficiency of cellular or EV-based therapeutic MSC products.
Immunotherapy for hepatocellular carcinoma recurrence after liver transplantation, can we harness the power of immune checkpoint inhibitors?
Authors: Jiang Jingyu , Huang Haitao , Chen Ruihan , Lin Yimou , Ling Qi
Published: February 2023

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death globally and liver transplantation (LT) can serve as the best curative treatment option. However, HCC recurrence after LT remains the major obstacle to the long-term survival of recipients. Recently, immune checkpoint inhibitors (ICIs) have revolutionized the treatment of many cancers and provided a new treatment strategy for post-LT HCC recurrence. Evidence has been accumulated with the real-world application of ICIs in patients with post-LT HCC recurrence. Notably, the use of these agents as immunity boosters in recipients treated with immunosuppressors is still controversial. In this review, we summarized the immunotherapy for post-LT HCC recurrence and conducted an efficacy and safety evaluation based on the current experience of ICIs for post-LT HCC recurrence. In addition, we further discussed the potential mechanism of ICIs and immunosuppressive agents in regulating the balance between immune immunosuppression and lasting anti-tumor immunity.
Regulatory T cell enhancement in adults with cystic fibrosis receiving Elexacaftor/Tezacaftor/Ivacaftor therapy
Authors: Westhölter Dirk , Raspe Jonas , Uebner Hendrik , Pipping Johannes , Schmitz Mona , Straßburg Svenja , Sutharsan Sivagurunathan , Welsner Matthias , Taube Christian , Reuter Sebastian
Published: February 2023

Introduction

Cystic fibrosis (CF), especially CF lung disease, is characterized by chronic infection, immune dysfunction including impairment of regulatory T cells (Tregs) and an exaggerated inflammatory response. CF transmembrane conductance regulator (CFTR) modulators have shown to improve clinical outcomes in people with CF (PwCF) with a wide range of CFTR mutations. However, it remains unclear whether CFTR modulator therapy also affects CF-associated inflammation. We aimed to examine the effect of elexacaftor/tezacaftor/ivacaftor therapy on lymphocyte subsets and systemic cytokines in PwCF.

Methods

Peripheral blood mononuclear cells and plasma were collected before and at three and six months after the initiation of elexacaftor/tezacaftor/ivacaftor therapy; lymphocyte subsets and systemic cytokines were determined using flow cytometry.

Results

Elexacaftor/tezacaftor/ivacaftor treatment was initiated in 77 PwCF and improved percent predicted FEV1 by 12.5 points (p<0.001) at 3 months. During elexacaftor/tezacaftor/ivacaftor therapy, percentages of Tregs were enhanced (+18.7%, p<0.001), with an increased proportion of Tregs expressing CD39 as a marker of stability (+14.4%, p<0.001). Treg enhancement was more pronounced in PwCF clearing Pseudomonas aeruginosa infection. Only minor, non-significant shifts were observed among Th1-, Th2- and Th17-expressing effector T helper cells. These results were stable at 3- and 6-month follow-up. Cytokine measurements showed a significant decrease in interleukin-6 levels during treatment with elexacaftor/tezacaftor/ivacaftor (–50.2%, p<0.001).

Conclusion

Treatment with elexacaftor/tezacaftor/ivacaftor was associated with an increased percentage of Tregs, especially in PwCF clearing Pseudomonas aeruginosa infection. Targeting Treg homeostasis is a therapeutic option for PwCF with persistent Treg impairment.
Development and validation of a radiomics-based nomogram for predicting a major pathological response to neoadjuvant immunochemotherapy for patients with potentially resectable non-small cell lung cancer
Authors: Liu Chaoyuan , Zhao Wei , Xie Junpeng , Lin Huashan , Hu Xingsheng , Li Chang , Shang Youlan , Wang Yapeng , Jiang Yingjia , Ding Mengge , Peng Muyun , Xu Tian , Hu Ao’ran , Huang Yuda , Gao Yuan , Liu Xianling , Liu Jun , Ma Fang
Published: February 2023

Introduction

The treatment response to neoadjuvant immunochemotherapy varies among patients with potentially resectable non-small cell lung cancers (NSCLC) and may have severe immune-related adverse effects. We are currently unable to accurately predict therapeutic response. We aimed to develop a radiomics-based nomogram to predict a major pathological response (MPR) of potentially resectable NSCLC to neoadjuvant immunochemotherapy using pretreatment computed tomography (CT) images and clinical characteristics.

Methods

A total of 89 eligible participants were included and randomly divided into training (N=64) and validation (N=25) sets. Radiomic features were extracted from tumor volumes of interest in pretreatment CT images. Following data dimension reduction, feature selection, and radiomic signature building, a radiomics-clinical combined nomogram was developed using logistic regression analysis.

Results

The radiomics-clinical combined model achieved excellent discriminative performance, with AUCs of 0.84 (95% CI, 0.74-0.93) and 0.81(95% CI, 0.63-0.98) and accuracies of 80% and 80% in the training and validation sets, respectively. Decision curves analysis (DCA) indicated that the radiomics-clinical combined nomogram was clinically valuable.

Discussion

The constructed nomogram was able to predict MPR to neoadjuvant immunochemotherapy with a high degree of accuracy and robustness, suggesting that it is a convenient tool for assisting with the individualized management of patients with potentially resectable NSCLC.
Effects of hepatitis B virus infection and strategies for preventing mother-to-child transmission on maternal and fetal T-cell immunity
Authors: Lu Huihui , Cao Weihua , Zhang Luxue , Yang Liu , Bi Xiaoyue , Lin Yanjie , Deng Wen , Jiang Tingting , Sun Fangfang , Zeng Zhan , Lu Yao , Zhang Lu , Liu Ruyu , Gao Yuanjiao , Wu Shuling , Hao Hongxiao , Chen Xiaoxue , Hu Leiping , Xu Mengjiao , Xiong Qiqiu , Dong Jianping , Song Rui , Li Minghui , Xie Yao
Published: February 2023

One of the most common routes of chronic hepatitis B virus (HBV) infection is mother-to-child transmission (MTCT). Approximately 6.4 million children under the age of five have chronic HBV infections worldwide. HBV DNA high level, HBeAg positivity, placental barrier failure, and immaturity of the fetal immune are the possible causes of chronic HBV infection. The passive-active immune program for children, which consists of the hepatitis B vaccine and hepatitis B immunoglobulin, and antiviral therapy for pregnant women who have a high HBV DNA load (greater than 2 × 105IU/ml), are currently two of the most important ways to prevent the transmission of HBV from mother to child. Unfortunately, some infants still have chronic HBV infections. Some studies have also found that some supplementation during pregnancy can increase cytokine levels and then affect the level of HBsAb in infants. For example, IL-4 can mediate the beneficial effect on infants’ HBsAb levels when maternal folic acid supplementation. In addition, new research has indicated that HBV infection in the mother may also be linked to unfavorable outcomes such as gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and premature rupture of membranes. The changes in the immune environment during pregnancy and the hepatotropic nature of HBV may be the main reasons for the adverse maternal outcomes. It is interesting to note that after delivery, the women who had a chronic HBV infection may spontaneously achieve HBeAg seroconversion and HBsAg seroclearance. The maternal and fetal T-cell immunity in HBV infection is important because adaptive immune responses, especially virus-specific CD8 T-cell responses, are largely responsible for viral clearance and disease pathogenesis during HBV infection. Meanwhile, HBV humoral and T-cell responses are important for the durability of protection after fetal vaccination. This article reviews the literature on immunological characteristics of chronic HBV-infected patients during pregnancy and postpartum, blocking mother-to-child transmissions and related immune mechanisms, hoping to provide new insights for the prevention of HBV MTCT and antiviral intervention during pregnancy and postpartum.
Immunoglobulin M-degrading enzyme of Streptococcus suis (IdeSsuis) impairs porcine B cell signaling
Authors: Breitfelder Annika Katharina , Schrödl Wieland , Rungelrath Viktoria , Baums Christoph Georg , Alber Gottfried , Schütze Nicole , Müller Uwe
Published: February 2023

Streptococcus suis (S. suis) is an important porcine pathogen, causing severe disease like meningitis and septicemia primarily in piglets. Previous work showed that the IgM-degrading enzyme of S. suis (IdeSsuis) specifically cleaves soluble porcine IgM and is involved in complement evasion. The objective of this study was to investigate IdeSsuis cleavage of the IgM B cell receptor and subsequent changes in B cell receptor mediated signaling. Flow cytometry analysis revealed cleavage of the IgM B cell receptor by recombinant (r) IdeSsuis_homologue as well as IdeSsuis derived from culture supernatants of S. suis serotype 2 on porcine PBMCs and mandibular lymph node cells. Point-mutated rIdeSsuis_homologue_C195S did not cleave the IgM B cell receptor. After receptor cleavage by rIdeSsuis_homologue, it took at least 20 h for mandibular lymph node cells to restore the IgM B cell receptor to levels comparable to cells previously treated with rIdeSsuis_homologue_C195S. B cell receptor mediated signaling after specific stimulation via the F(ab’)2 portion was significantly inhibited by rIdeSsuis_homologue receptor cleavage in IgM+ B cells, but not in IgG+ B cells. Within IgM+ cells, CD21+ B2 cells and CD21- B1-like cells were equally impaired in their signaling capacity upon rIdeSsuis_homologue B cell receptor cleavage. In comparison, intracellular B cell receptor independent stimulation with tyrosine phosphatase inhibitor pervanadate increased signaling in all investigated B cell types. In conclusion, this study demonstrates IdeSsuis cleavage efficacy on the IgM B cell receptor and its consequences for B cell signaling.
A natural goldmine of binding proteins and soluble receptors simplified their translation to blockbuster drugs, all in one decade
Authors: Novick Daniela
Published: February 2023

Human urinary proteins are a goldmine of natural proteins a feature that simplifies their translation to biologics. Combining this goldmine together with the ligand-affinity-chromatography (LAC) purification method, proved a winning formula in their isolation. LAC specificity, efficiency, simplicity and inherent indispensability in the search for predictable and unpredictable proteins, is superior to other separation techniques. Unlimited amounts of recombinant cytokines and monoclonal antibodies (mAb) accelerated the “triumph”. My approach concluded 35 years of worldwide pursuit for Type I IFN receptor (IFNAR2) and advanced the understanding of the signal transduction of this Type of IFN. TNF, IFNγ and IL-6 as baits enabled the isolation of their corresponding soluble receptors and N-terminal amino acid sequence of the isolated proteins facilitated the cloning of their cell surface counterparts. IL-18, IL-32, and heparanase as the baits yielded the corresponding unpredictable proteins: the antidote IL-18 Binding Protein (IL-18BP), the enzyme Proteinase 3 (PR3) and the hormone Resistin. IFNβ proved beneficial in Multiple Sclerosis and is a blockbuster drug, Rebif®. TNF mAbs translated into Remicade® to treat Crohn’s disease. Enbrel® based on TBPII is for Rheumatoid Arthritis. Both are blockbusters. Tadekinig alfa™, a recombinant IL-18BP, is in phase III clinical study for inflammatory and autoimmune diseases. Seven years of continuous compassionate use of Tadekinig alfa™ in children born with mutations (NLRC4, XIAP) proved life-saving and is an example of tailored made medicine. IL-18 is a checkpoint biomarker in cancer and IL-18BP is planned recently to target cytokine storms resulting from CAR-T treatment and in COVID 19.
Morphological characteristics of retinal vessels in eyes with high myopia: Ultra-wide field images analyzed by artificial intelligence using a transfer learning system
Authors: Mao Jianbo , Deng Xinyi , Ye Yu , Liu Hui , Fang Yuyan , Zhang Zhengxi , Chen Nuo , Sun Mingzhai , Shen Lijun
Published: February 2023

Purpose

The purpose of this study is to investigate the retinal vascular morphological characteristics in high myopia patients of different severity.

Methods

317 eyes of high myopia patients and 104 eyes of healthy control subjects were included in this study. The severity of high myopia patients is classified into C0–C4 according to the Meta Analysis of the Pathologic Myopia (META-PM) classification and their vascular morphological characteristics in ultra-wide field imaging were analyzed using transfer learning methods and RU-net. Correlation with axial length (AL), best corrected visual acuity (BCVA) and age was analyzed. In addition, the vascular morphological characteristics of myopic choroidal neovascularization (mCNV) patients and their matched high myopia patients were compared.

Results

The RU-net and transfer learning system of blood vessel segmentation had an accuracy of 98.24%, a sensitivity of 71.42%, a specificity of 99.37%, a precision of 73.68% and a F1 score of 72.29. Compared with healthy control group, high myopia group had smaller vessel angle (31.12 ± 2.27 vs. 32.33 ± 2.14), smaller fractal dimension (Df) (1.383 ± 0.060 vs. 1.424 ± 0.038), smaller vessel density (2.57 ± 0.96 vs. 3.92 ± 0.93) and fewer vascular branches (201.87 ± 75.92 vs. 271.31 ± 67.37), all P < 0.001. With the increase of myopia maculopathy severity, vessel angle, Df, vessel density and vascular branches significantly decreased (all P < 0.001). There were significant correlations of these characteristics with AL, BCVA and age. Patients with mCNV tended to have larger vessel density (P < 0.001) and more vascular branches (P = 0.045).

Conclusion

The RU-net and transfer learning technology used in this study has an accuracy of 98.24%, thus has good performance in quantitative analysis of vascular morphological characteristics in Ultra-wide field images. Along with the increase of myopic maculopathy severity and the elongation of eyeball, vessel angle, Df, vessel density and vascular branches decreased. Myopic CNV patients have larger vessel density and more vascular branches.
Serum cotinine as a predictor of lipid-related indices in Turkish immigrants with type 2 diabetes: A clinic-based cross-sectional study
Authors: Sukhram Shiryn D. , Zarini Gustavo G. , Shaban Lemia H. , Vaccaro Joan A. , Sukhram Avinash R. , Huffman Fatma G.
Published: February 2023

Background

Turkish immigrants form the largest ethnic minority group in the Netherlands and show a higher prevalence of (i) cardiovascular disease (CVD), (ii) cigarette smoking, and (iii) type 2 diabetes (T2D) as compared to the native Dutch. This study examines the association of CVD risk factors: serum cotinine, as an indicator of cigarette smoke, and lipid-related indices among first-generation (foreign-born) Turkish immigrants with T2D living in deprived neighbourhoods in the Netherlands.

Methods

A total of 110 participants, physician-diagnosed with T2D, aged 30 years and older, were recruited by convenience sampling from the Schilderswijk neighbourhood of The Hague in a clinic-based cross-sectional design. Serum cotinine (independent variable) was measured with a solid-phase competitive chemiluminescent immunoassay. Serum lipids/lipoproteins (dependent variables) were determined by enzymatic assays and included: total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG). The Castelli Risk Index-I (CRI-I), and Atherogenic Coefficient (AC) were calculated using standardised formulas and assessed as dependent variables in multiple linear regression (MLR) models. Log-transformation of HDL-c, TG, CRI-I, and AC values were performed to account for the extreme right skewness of the data. Statistical analyses included descriptive characteristics and MLR models were adjusted for all major confounders of cotinine and lipids.

Results

The sample size had a mean age of 52.5 years [standard deviation (SD) = 9.21]. The geometric mean of serum cotinine level was 236.63 ng/mL [confidence interval (CI) = 175.89 ± 318.36]. The MLR models indicated that high serum cotinine levels (≥10 ng/mL) was positively associated with HDL-c (P = 0.04), CRI-I (P = 0.03), and AC (P = 0.03) in the age, gender, WC, diabetes medications, and statins-adjusted models (n = 32).

Conclusion

This study indicated that lipid ratios of HDL-c, CRI-I and AC are dependent determinants of serum cotinine and higher serum cotinine levels (≥10 ng/mL) are associated with worse HDL-c, CRI-I and AC values in participants with T2D. Clinical comprehension of these biochemical indicators (lipids/lipoproteins) and symptomatic results (CVD risk) in individuals with T2D will aid in the intervention (smoking) approach for this vulnerable cohort (Turkish immigrants). Therapy that is targetted to modify this behavioural risk factor may improve cardiovascular health outcomes and prevent comorbidities in Turkish immigrants with T2D living in deprived neighbourhoods in the Netherlands. In the meantime, this report contributes to a growing body of information and provides essential guidance to researchers and clinicians.
Prevalence and determinants of opportunistic infections among HIV-infected adults receiving antiretroviral therapy in Ethiopia: A systematic review and meta-analysis
Authors: Woldegeorgis Beshada Zerfu , Zekarias Zewdineh , Adem Bulcha Guye , Obsa Mohammed Suleiman , Kerbo Amene Abebe
Published: February 2023

Background

Reliable data on the burden of opportunistic infections (OIs) after the initiation of antiretroviral therapy (ART) is critical for planning health services and reducing OI-related morbidity and mortality. Nevertheless, there has been no nationally representative information on the prevalence of OIs in our country. Therefore, we have undertaken this comprehensive systematic review and meta-analysis to estimate the pooled prevalence, and identify factors associated with the development of OIs in Human Immunodeficiency Virus (HIV)-infected adults receiving ART in Ethiopia.

Methods

Articles were searched in international electronic databases. A standardized Microsoft Excel spreadsheet and STATA software version 16 were used for data extraction and analysis, respectively. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist was used to write this report. The random-effect meta-analysis model was used to estimate the pooled effect. The statistical heterogeneity of the meta-analysis was checked. Subgroup and sensitivity analyses were also performed. Publication bias was examined in funnel plots and the nonparametric rank correlation test of Begg and the regression-based test of Egger. Association was expressed through a pooled odds ratio (OR) with a 95% Confidence Interval (CI).

Results

A total of 12 studies with 6,163 study participants were included. The pooled prevalence of OIs was 43.97% [95% CI (38.59, 49.34)]. Poor adherence to ART [OR, 5.90, 95% CI (3.05, 11.40)], under nutrition [OR, 3.70, 95% CI (2.01, 6.80)], CD4 T lymphocyte count <200 cells /μL [OR, 3.23 95% CI (2.06, 5.07)], and advanced World Health Organization (WHO) HIV clinical stages [OR, 4.84 95% CI (1.83, 12.82)] were determinants of OIs.

Conclusion

The pooled prevalence of OIs among adults taking ART is high. Poor adherence to ART, under nutrition, a CD4 T lymphocyte count <200 cells /μL, and advanced WHO HIV clinical stages were factors associated with the development of OIs.
Biopesticides as a promising alternative to synthetic pesticides: A case for microbial pesticides, phytopesticides, and nanobiopesticides
Authors: Ayilara Modupe S. , Adeleke Bartholomew S. , Akinola Saheed A. , Fayose Chris A. , Adeyemi Uswat T. , Gbadegesin Lanre A. , Omole Richard K. , Johnson Remilekun M. , Uthman Qudus O. , Babalola Olubukola O.
Published: February 2023

Over the years, synthetic pesticides like herbicides, algicides, miticides, bactericides, fumigants, termiticides, repellents, insecticides, molluscicides, nematicides, and pheromones have been used to improve crop yield. When pesticides are used, the over-application and excess discharge into water bodies during rainfall often lead to death of fish and other aquatic life. Even when the fishes still live, their consumption by humans may lead to the biomagnification of chemicals in the body system and can cause deadly diseases, such as cancer, kidney diseases, diabetes, liver dysfunction, eczema, neurological destruction, cardiovascular diseases, and so on. Equally, synthetic pesticides harm the soil texture, soil microbes, animals, and plants. The dangers associated with the use of synthetic pesticides have necessitated the need for alternative use of organic pesticides (biopesticides), which are cheaper, environment friendly, and sustainable. Biopesticides can be sourced from microbes (e.g., metabolites), plants (e.g., from their exudates, essential oil, and extracts from bark, root, and leaves), and nanoparticles of biological origin (e.g., silver and gold nanoparticles). Unlike synthetic pesticides, microbial pesticides are specific in action, can be easily sourced without the need for expensive chemicals, and are environmentally sustainable without residual effects. Phytopesticides have myriad of phytochemical compounds that make them exhibit various mechanisms of action, likewise, they are not associated with the release of greenhouse gases and are of lesser risks to human health compared to the available synthetic pesticides. Nanobiopesticides have higher pesticidal activity, targeted or controlled release with top-notch biocompatibility and biodegradability. In this review, we examined the different types of pesticides, the merits, and demerits of synthetic pesticides and biopesticides, but more importantly, we x-rayed appropriate and sustainable approaches to improve the acceptability and commercial usage of microbial pesticides, phytopesticides, and nanobiopesticides for plant nutrition, crop protection/yield, animal/human health promotion, and their possible incorporation into the integrated pest management system.
Salinity pretreatment synergies heat shock toxicity in cyanobacterium Anabaena PCC7120
Authors: Srivastava Rupanshee , Kanda Tripti , Yadav Sadhana , Singh Nidhi , Yadav Shivam , Prajapati Rajesh , Kesari Vigya , Atri Neelam
Published: February 2023

This study was undertaken to bridge the knowledge gap pertaining to cyanobacteria’s response to pretreatment. The result elucidates the synergistic effect of pretreatment toxicity in cyanobacterium Anabaena PCC7120 on morphological and biochemical attributes. Chemical (salt) and physical (heat) stress-pretreated cells exhibited significant and reproducible changes in terms of growth pattern, morphology, pigments, lipid peroxidation, and antioxidant activity. Salinity pretreatment showed more than a five-fold decrease in the phycocyanin content but a six-fold and five-fold increase in carotenoid, lipid peroxidation (MDA content), and antioxidant activity (SOD and CAT) at 1 h and on 3rd day of treatment, respectively, giving the impression of stress-induced free radicals that are scavenged by antioxidants when compared to heat shock pretreatment. Furthermore, quantitative analysis of transcript (qRT-PCR) for FeSOD and MnSOD displayed a 3.6- and 1.8-fold increase in salt-pretreated (S-H) samples. The upregulation of transcript corresponding to salt pretreatment suggests a toxic role of salinity in synergizing heat shock. However, heat pretreatment suggests a protective role in mitigating salt toxicity. It could be inferred that pretreatment enhances the deleterious effect. However, it further showed that salinity (chemical stress) augments the damaging effect of heat shock (physical stress) more profoundly than physical stress on chemical stress possibly by modulating redox balance via activation of antioxidant responses. Our study reveals that upon pretreatment of heat, the negative effect of salt can be mitigated in filamentous cyanobacteria, thus providing a foundation for improved cyanobacterial tolerance to salt stress.
Rhizobacterial compositions and their relationships with soil properties and medicinal bioactive ingredients in Cinnamomum migao
Authors: Li Lixia , Yang Xuedong , Tong Bingli , Wang Deng , Tian Xiu , Liu Jiming , Chen Jingzhong , Xiao Xuefeng , Wang Shu
Published: February 2023

Introduction

Rhizobacterial communities and their metabolites can affect plant growth, development, and stress resistance, as well as the biosynthesis and accumulation of bioactive compounds in medicinal plants. This relationship has been well-characterized in many medicinal herbs, although much less commonly in medicinal trees.

Methods

Here, we analyzed the composition and structure of Cinnamomum migao rhizobacterial communities across nine growing regions in Yunnan, Guizhou and Guangxi, China, as well as differences in soil properties and fruit bioactive compounds.

Results

Results showed that the C. migao rhizobacterial communities exhibited high species richness, but location-specific differences in structure. Site-specific differences in soil properties and bioactive compounds were also observed. Furthermore, rhizobacterial community compositions were correlated with both soil properties and fruit bioactive compounds, metabolism-related functions were most common in C. migao rhizobacteria.

Discussion

Several bacterial genera, including Acidothermus, Acidibacter, Bryobacter, Candidatus_Solibacter, and Acidimicrobiales, potentially promote the biosynthesis and accumulation of 1,8-cineole, cypressene, limonene, and α-terpineol, Nitrospira and Alphaproteobacteria may play an inhibitory role. Finally, our results emphasized the critical role that soil pH and nitrogen levels play in driving rhizobacterial community structure, and specific functional bacteria can also counteract with soil properties, Acidibacter and Nitrospira can affect soil pH and nitrogen effectiveness. Overall, this study provides additional insight into the complex correlation of rhizosphere microorganisms with bioactive ingredients and soil properties of medicinal plants.
Paraburkholderia sabiae administration alters zebrafish anxiety-like behavior via gut microbial taurine metabolism
Authors: Ichikawa Shunsuke , Abe Reimi , Fujimoto Haruka , Higashi Koushi , Zang Liqing , Nakayama Hiroko , Matsuoka Izumi , Shimada Yasuhito
Published: February 2023

Interventions to the gut microbiome manipulate the gut–brain axis and could be useful in the treatment of anxiety and depression. In this study, we demonstrated that administration of the bacterium Paraburkholderia sabiae reduces anxiety-like behavior in adult zebrafish. P. sabiae administration increased the diversity of the zebrafish gut microbiome. Linear discriminant analysis Effect Size (LEfSe) analysis revealed that the populations of Actinomycetales including Nocardiaceae, Nocardia, Gordoniaceae, Gordonia, Nakamurellaceae, and Aeromonadaceae were reduced, whereas those of Rhizobiales including Xanthobacteraceae, Bradyrhizobiaceae, Rhodospirillaceae, and Pirellulaceae were increased in the gut microbiome. Functional analysis using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) predicted that P. sabiae administration altered taurine metabolism in the zebrafish gut, and we demonstrated that P. sabiae administration increased the taurine concentration in the brain. Since taurine functions as an antidepressant neurotransmitter in vertebrates, our results suggest that P. sabiae could improve anxiety-like behavior in zebrafish via the gut-brain axis.