bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 antibody progression and neutralizing potential in mild symptomatic COVID-19 patients – a comparative long term post-infection study
Authors: Brehm Jessica , Spaeth Alexander , Dreßler Lars , Masetto Thomas , Dannenberg Rainer , Peter Christoph , Grimmler Matthias
Published: August 2022

Background

Since December 2019, SARS-CoV-2 has been keeping the world in suspense. Rapid tests, molecular diagnosis of acute infections, and vaccination campaigns with vaccines are building blocks of strategic pandemic control worldwide. For laboratory diagnostics, the quantification of the antibody titer of convalescents and vaccinated patients is thus increasingly coming to the fore.

Methods

Here we present an evaluation on the comparability of five serological tests on a cohort of 13 patients with mild COVID-19 disease. Also participants who were vaccinated after recovery were included in this study. All common immune methods (ELISA, CLIA, PETIA) and SARS-CoV-2 specific antigens (N-, S1- and RBD-) were specifically tracked and directly compared for up to 455 days. The titer of recovered participants was also set to the degree of symptoms during infection and the occurrence of Long-COVID. In addition, relative comparability of different serological tests, all standardized to WHO, was set in reference to the neutralizing potential of the corresponding participants.

Findings

The individual immune responses over 455 days after a mild SARS-CoV-2 infection remain stable, in contrast to vaccinated participants. All sero-tests reveal comparable performance and dynamics during the study and compared well to a surrogate neutralization test.

Conclusion

The information presented here will help clinicians in the daily laboratory work in the selection and evaluation of different serological tests offered. The data also will support in respect of a sero-test-based neutralization cutoff.
Modulation of dendritic cell metabolism by an MPLA-adjuvanted allergen product for specific immunotherapy
Authors: Zimmermann Jennifer , Goretzki Alexandra , Meier Clara , Wolfheimer Sonja , Lin Yen-Ju , Rainer Hannah , Krause Maren , Wedel Saskia , Spies Gerd , Führer Frank , Vieths Stefan , Scheurer Stephan , Schülke Stefan
Published: August 2022

Background

Recently, bacterial components were shown to enhance immune responses by shifting immune cell metabolism towards glycolysis and lactic acid production, also known as the Warburg Effect. Currently, the effect of allergen products for immunotherapy (AIT) and commercial vaccines on immune cell metabolism is mostly unknown.

Objective

To investigate the effect of AIT products (adjuvanted with either MPLA or Alum) on myeloid dendritic cell (mDC) metabolism and activation.

Methods

Bone marrow-derived mDCs were stimulated with five allergoid-based AIT products (one adjuvanted with MPLA, four adjuvanted with Alum) and two MPLA-adjuvanted vaccines and analyzed for their metabolic activation, expression of cell surface markers, and cytokine secretion by ELISA. mDCs were pre-incubated with either immunological or metabolic inhibitors or cultured in glucose- or glutamine-free culture media and subsequently stimulated with the MPLA-containing AIT product (AIT product 1). mDCs were co-cultured with allergen-specific CD4+ T cells to investigate the contribution of metabolic pathways to the T cell priming capacity of mDCs stimulated with AIT product 1.

Results

Both the MPLA-containing AIT product 1 and commercial vaccines, but not the Alum-adjuvanted AIT products, activated Warburg metabolism and TNF-α secretion in mDCs. Further experiments focused on AIT product 1. Metabolic analysis showed that AIT product 1 increased glycolytic activity while also inducing the secretion of IL-1β, IL-10, IL-12, and TNF-α. Both rapamycin (mTOR-inhibitor) and SP600125 (SAP/JNK MAPK-inhibitor) dose-dependently suppressed the AIT product 1-induced Warburg Effect, glucose consumption, IL-10-, and TNF-α secretion. Moreover, both glucose- and glutamine deficiency suppressed secretion of all investigated cytokines (IL-1β, IL-10, and TNF-α). Glucose metabolism in mDCs was also critical for the (Th1-biased) T cell priming capacity of AIT product 1-stimulated mDCs, as inhibition of mTOR signaling abrogated their ability to induce Th1-responses.

Conclusion

The AIT product and commercial vaccines containing the adjuvant MPLA were shown to modulate the induction of immune responses by changing the metabolic state of mDCs. Better understanding the mechanisms underlying the interactions between cell metabolism and immune responses will allow us to further improve vaccine development and AIT.
Investigating population-level immunosenescence: From bench to bedside
Authors: Cunha Lucas Leite , Valsecchi Victor Alexandre dos Santos , Ward Laura Sterian
Published: August 2022

The immune response is remodeled with aging in a process called immunosenescence. Some immunologists conceive immunosenescence as an adaptation of immunity to the aged immune-environment rather than a merely collapsed reactivity of immune cells against microbes and tumor cells. Others believe on an uninterrupted activation of the innate immune system with aging, leading to a low grade, sterile and chronic proinflammatory state called inflammaging. For instance, it is possible that chronic infection by cytomegalovirus leads to persistent production of viral load. This phenomenon offers periodic stimuli to the immune system that ultimately contribute to the remodeling of the immune response. If investigating immunosenescence at the cellular level is already a difficult task, considering the population level is much more complex. However, by studying immunosenescence at the population level, we can extract valuable results with viable applications. While studies with animal models allow scientists to deepen their understanding of the mechanisms of immunosenescence, studying large populations can bring practical innovations to medicine and the health system. Many researchers and funders have dedicated themselves to producing methods for the evaluation of immunosenescence on a large scale, aiming to elucidate new mechanisms by which diseases are established in the elderly. The description of how the immune response is remodeled with aging emerges as a new tool to identify the subset of subjects in which unhealthy aging is a matter of time, to help better individualize clinical management and select patients who may benefit. of early interventions. This review focuses on functional assays as valuable methods for measuring the remodeling of the immune response with aging and discuss their clinical impact. We also recall fundamental concepts for understanding the aging process of the immune response. In addition, we highlight future prospects for immunosenescence research.
Thioredoxin-interacting protein: A new therapeutic target in bone metabolism disorders?
Authors: Jiang Na , Liu Jinjin , Guan Conghui , Ma Chengxu , An Jinyang , Tang Xulei
Published: August 2022

Target identification is essential for developing novel therapeutic strategies in diseases. Thioredoxin-interacting protein (TXNIP), also known as thioredoxin-binding protein-2, is a member of the α-arrestin protein family and is regulated by several cellular stress factors. TXNIP overexpression coupled with thioredoxin inhibits its antioxidant functions, thereby increasing oxidative stress. TXNIP is directly involved in inflammatory activation by interacting with Nod-like receptor protein 3 inflammasome. Bone metabolic disorders are associated with aging, oxidative stress, and inflammation. They are characterized by an imbalance between bone formation involving osteoblasts and bone resorption by osteoclasts, and by chondrocyte destruction. The role of TXNIP in bone metabolic diseases has been extensively investigated. Here, we discuss the roles of TXNIP in the regulatory mechanisms of transcription and protein levels and summarize its involvement in bone metabolic disorders such as osteoporosis, osteoarthritis, and rheumatoid arthritis. TXNIP is expressed in osteoblasts, osteoclasts, and chondrocytes and affects the differentiation and functioning of skeletal cells through both redox-dependent and -independent regulatory mechanisms. Therefore, TXNIP is a potential regulatory and functional factor in bone metabolism and a possible new target for the treatment of bone metabolism-related diseases.
Key molecules associated with thyroid carcinoma prognosis: A study based on transcriptome sequencing and GEO datasets
Authors: Bai Miaoyu , Ke Shanjia , Yu Hongjun , Xu Yanan , Yu Yue , Lu Shounan , Wang Chaoqun , Huang Jingjing , Ma Yong , Dai Wenjie , Wu Yaohua
Published: August 2022

Background

Thyroid carcinoma (THCA) has a low mortality rate, but its incidence has been rising over the years. We need to pay attention to its progression and prognosis. In this study, a transcriptome sequencing analysis and bioinformatics methods were used to screen key genes associated with THCA development and analyse their clinical significance and diagnostic value.

Methods

We collected 10 pairs of THCA tissues and noncancerous tissues, these samples were used for transcriptome sequencing to identify disordered genes. The gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Comprehensive analysis of thyroid clinicopathological data using The Cancer Genome Atlas (TCGA). R software was used to carry out background correction, normalization and log2 conversion. We used quantitative real-time PCR (qRT–PCR) and Western blot to determine differentially expressed genes (DEGs) expression in samples. We integrated the DEGs expression, clinical features and progression-free interval (PFI). The related functions and immune infiltration degree were established by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and single-sample Gene Set Enrichment Analysis (ssGSEA). The UALCAN database was used to analyse the methylation level.

Results

We evaluated DEGs between normal tissue and cancer. Three genes were identified: regulator of G protein signaling 8 (RGS8), diacylglycerol kinase iota (DGKI) and oculocutaneous albinism II (OCA2). The mRNA and protein expression levels of RGS8, DGKI and OCA2 in normal tissues were higher than those in THCA tissues. Better survival outcomes were associated with higher expression of RGS8 (HR=0.38, P=0.001), DGKI (HR=0.52, P=0.022), and OCA2 (HR=0.41, P=0.003). The GO analysis, KEGG analysis and GSEA proved that the coexpressed genes of RGS8, DGKI and OCA2 were related to thyroid hormone production and peripheral downstream signal transduction effects. The expression levels of RGS8, DGKI and OCA2 were linked to the infiltration of immune cells such as DC cells. The DNA methylation level of OCA2 in cancer tissues was higher than that in the normal samples.

Conclusions

RGS8, DGKI and OCA2 might be promising prognostic molecular markers in patients with THCA and reveal the clinical significance of RGS8, DGKI and OCA2 in THCA.
Decitabine-primed tandem CD19/CD22 CAR-T therapy in relapsed/refractory diffuse large B-cell lymphoma patients
Authors: Qu Changju , Zou Rui , Wang Peng , Zhu Qian , Kang Liqing , Ping Nana , Xia Fan , Liu Hailing , Kong Danqing , Yu Lei , Wu Depei , Jin Zhengming
Published: August 2022

Chimeric antigen receptor T cell (CAR-T) therapy has emerged as highly effective in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but only about 40% patients have achieved sustained responses. Here, we conducted a phase II clinical trial testing efficacy and toxicities of CAR-T therapy in R/R non-Hodgkin’s lymphoma patients (NCT03196830). Among enrolled patients, 33 R/R DLBCL patients pretreated with DFC (decitabine, fludarabine plus cyclophosphamide) lymphodepletion chemotherapy and infused with tandem CD19-CD22 based CAR-T cells were drawn out for efficacy and toxicities of CAR-T therapy evaluation. With a median follow-up of 10.9(0.6-29.0) months, the best overall response and complete remission (CR) rates were 90.9% and 63.6%, respectively. The median progression-free survival (PFS) was 10.2 months and overall survival (OS) was undefined. The 2-year OS and PFS rates were 54.3% and 47.2%, respectively. No severe grade 4 cytokine release syndrome (CRS) was observed and grade 3 CRS was observed in only 7 patients; 3 patients developed mild immune effect or cell-associated neurotoxic syndrome. All toxicities were transient and reversible and no CAR-T-related mortality. Further subgroup analysis showed that achieving CR was an independent prognostic factor associated with favorable PFS and OS. The 2-year OS and PFS for patients who achieved CR within 3 months (undefined versus undefined P=0.021 and undefined versus undefined P=0.036) or during the follow-up period were significantly longer than those who did not (undefined versus 4.6 months P < 0.0001 and undefined versus 2.0months P<0.001). While severe CRS was also an independent prognostic factor but associated with inferior PFS and OS. The 2-year OS and PFS for patients with grade 3 CRS were significantly shorter than those with grade 0-2 CRS (4.1 months versus undefined P<0.0001 and 1.7 months versus undefined P=0.0002). This study indicated that CD19/CD22 dual-targeted CAR-T therapy under a decitabine-containing lymphodepletion regimen may be a safe, potent effective approach to R/R DLBCL patients.
The antitumor effect induced by an IL-2 ‘no-alpha’ mutein depends on changes in the CD8+ T lymphocyte/Treg cell balance
Authors: Carmenate Tania , Montalvo Galia , Lozada Sum Lai , Rodriguez Yaretnis , Ortiz Yaquelin , Díaz Claudia , Avellanet Janet , Kim Juhee , Surh Charles D. , Graça Luis , León Kalet
Published: August 2022

High doses of interleukin-2 (IL-2) have been used for the treatment of melanoma and renal cell carcinoma, but this therapy has limited efficacy, with a ~15% response rate. Remarkably, 7%–9% of patients achieve complete or long-lasting responses. Many patients treated with IL-2 experienced an expansion of regulatory T cells (Tregs), specifically the expansion of ICOS+ highly suppressive Tregs, which correlate with worse clinical outcomes. This partial efficacy together with the high toxicity associated with the therapy has limited the use of IL-2-based therapy. Taking into account the understanding of IL-2 structure, signaling, and in vivo functions, some efforts to improve the cytokine properties are currently under study. In previous work, we described an IL-2 mutein with higher antitumor activity and less toxicity than wtIL-2. Mutein was in silico designed for losing the binding capacity to CD25 and for preferential stimulation of effector cells CD8+ and NK cells but not Tregs. Mutein induces a higher anti-metastatic effect than wtIL-2, but the extent of the in vivo antitumor activity was still unexplored. In this work, it is shown that mutein induces a strong antitumor effect on four primary tumor models, being effective even in those models where wtIL-2 does not work. Furthermore, mutein can change the in vivo balance between Tregs and T CD8+ memory/activated cells toward immune activation, in both healthy and tumor-bearing mice. This change reaches the tumor microenvironment and seems to be the major explanation for mutein efficacy in vivo.
A Novel hepatocellular carcinoma specific hypoxic related signature for predicting prognosis and therapeutic responses
Authors: Cai Guangzhen , Zhu Jinghan , Ning Deng , Li Ganxun , Zhang Yuxin , Xiong Yixiao , Liang Junnan , Yu Chengpeng , Chen Xiaoping , Liang Huifang , Ding Zeyang
Published: August 2022

Hypoxia is an important feature of the tumor microenvironment(TME) and is closely associated with cancer metastasis, immune evasion, and drug resistance. However, the precise role of hypoxia in hepatocellular carcinoma(HCC), as well as its influence on the TME, and drug sensitivity remains unclear. We found the excellent survival prediction value of Hypoxia_DEGs_Score model. In hypoxic HCC, somatic mutation, copy number variation, and DNA methylation were closely related to hypoxic changes and affected tumorigenesis, progression, metastasis, and drug resistance. In HCC, aggravated hypoxic stress was found to be accompanied by an immune exclusion phenotype and increased infiltration of immunosuppressive cells. In the validation cohort, patients with high Hypoxia_DEGs_Score were found to have worse immunotherapeutic outcomes and prognoses, and may benefit from drugs against cell cycle signaling pathways rather than those inhibiting the PI3K/mTOR pathway. Hypoxia_DEGs_Score has an excellent predictive capability of changes in the TME, the efficacy of immunotherapy, and the response of drugs. Therefore, Hypoxia_DEGs_Score can help develop personalized immunotherapy regimens and improve the prognosis of HCC patients.
Chronic exposure to insecticides impairs honeybee optomotor behaviour
Authors: Parkinson Rachel H. , Fecher Caroline , Gray John R.
Published: August 2022

Honeybees use wide-field visual motion information to calculate the distance they have flown from the hive, and this information is communicated to conspecifics during the waggle dance. Seed treatment insecticides, including neonicotinoids and novel insecticides like sulfoxaflor, display detrimental effects on wild and managed bees, even when present at sublethal quantities. These effects include deficits in flight navigation and homing ability, and decreased survival of exposed worker bees. Neonicotinoid insecticides disrupt visual motion detection in the locust, resulting in impaired escape behaviors, but it had not previously been shown whether seed treatment insecticides disrupt wide-field motion detection in the honeybee. Here, we show that sublethal exposure to two commonly used insecticides, imidacloprid (a neonicotinoid) and sulfoxaflor, results in impaired optomotor behavior in the honeybee. This behavioral effect correlates with altered stress and detoxification gene expression in the brain. Exposure to sulfoxaflor led to sparse increases in neuronal apoptosis, localized primarily in the optic lobes, however there was no effect of imidacloprid. We propose that exposure to cholinergic insecticides disrupts the honeybee’s ability to accurately encode wide-field visual motion, resulting in impaired optomotor behaviors. These findings provide a novel explanation for previously described effects of neonicotinoid insecticides on navigation and link these effects to sulfoxaflor for which there is a gap in scientific knowledge.
An insight into the microstructures and composition of 2,700 m-depth deep-sea limpet shells
Authors: Ying Zhehan , Wang Shi , Wong Wai Chuen , Cai Xiangbin , Feng Xuemeng , Xiang Shengling , Cai Yuan , Qian Pei-Yuan , Wang Ning
Published: August 2022

Structural and physiochemical properties contribute to the biological adaptation of deep-sea animals to their harsh living environment but have hardly been investigated systematically. In the present study, we for the first time applied various material characterization techniques including transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and Fourier-transform infrared (FT-IR) spectroscopy to investigate the shell microstructures and chemical composition of a deep-sea limpet Eulepetopsis crystallina collected from the Tiancheng hydrothermal vent field at a depth of around 2,700 m in the Southwest Indian Ocean. Analyses of shell microstructural morphology and diffraction patterns of E. crystallina explicitly revealed the layered structures, exfoliation characteristics, and crystallographic orientation of each layer’s unit cell which was tilted at a small angle sequentially. In comparison with ordinary shallow-water limpet Cellana toreuma shells, E. crystallina shells showed a unique chemical composition and contained pure calcite of calcium carbonate polymorph and the trace of phosphate originated from regional phosphatic sediments of the Southwest Indian Ocean. The further microscopic analyses indicated that the shell of the deep-sea limpet E. crystallina features integrated and untruncated layer structures with a compressed width, possibly owning to the ultra-high hydrostatic pressure, which confirmed the effects of the living environment on the shell microstructure of deep-sea animals.
The gene expression profile of the glucocorticoid receptor 1 (gr1) but not gr2 is modulated in mucosal tissues of gilthead sea bream (Sparus aurata) exposed to acute air-exposure stress
Authors: Vallejos-Vidal Eva , Sanz-Milián Beatriz , Teles Mariana , Reyes-Cerpa Sebastián , Mancera Juan Miguel , Tort Lluis , Reyes-López Felipe E.
Published: August 2022

The perception of an acute stressor (short-duration; high-intensity) induces a physiological response that activates the hypothalamic-pituitary-interrenal (HPI) axis and the subsequent release of cortisol. Cortisol carries out its effect at the molecular level through its recognition by the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). Recently, we unveiled the nucleotide sequence of the glucocorticoid receptor 1 (gr1) and gr2 in gilthead sea bream (Sparus aurata). Importantly, GR1 and GR2 respond to different levels of cortisol concentration in fish and, consequently, play a differential role in the stress response. To date, and despite their relevance, no data describes the modulation of these receptors in response to an acute stressor in gilthead sea bream (S. aurata). In this study, we evaluated the kinetics of modulation of cortisol receptors expression (gr1, gr2, mr), and its similarity with the expression pattern of selected genes associated with stress (hsp70; enolase) and immune response (lysozyme; c3; il-1β; tnf-α; il-10; tgf-β1) in gilthead sea bream mucosal tissues (skin; gills; anterior gut). To do it, fish were acutely stressed by three-minute air exposure, and the expression profile was evaluated at zero, 1 h, 6 h, and 24 h post-stress (hps). The cortisol level in plasma and skin mucus peaked at 1 hps. All the mucosal tissues showed a time-dependent and tissue-specific upregulation of gr1 and mr. The immune-related genes showed the upregulation of il-1β at 6 hps (gills; anterior gut), and tnf-α and c3 at 24 hps (anterior gut). Taking together, our study concludes that fish subjected to three-minute air exposure modulated the expression of gr1 but not gr2 in mucosal tissues (skin; gills; anterior gut). Furthermore, our data reinforce the idea of a stimulatory effect induced in genes associated with the innate immune response after acute stress but focused at the mucosal level and in a time- and tissue-dependent manner.
Response of soil carbon fractions and enzyme activities to mowing management on in a coastal wetland of the yellow river delta
Authors: Cui Qian , Yang Hongjun , Wang Guangmei , Ma Jinzhao , Feng Lu , Liu Jingtao
Published: August 2022

Coastal wetlands are considered as important “blue carbon” sink, and mowing management induced by anthropogenic activities is anticipated to profoundly affect soil carbon stocks in coastal wetlands. However, the impacts of mowing management on soil organic carbon (SOC) and enzyme activities and the mechanisms responsible for associated changes in Phragmites australis wetland remain uncertain. We conducted a field mowing manipulation experiment [control (CK), mowing and returning straw in December (12MS), mowing and removing straw in December (12MR), mowing and returning straw in March (3MS), and mowing and removing straw in March (3MR)] in P. australis wetland of the Yellow River Delta and quantified their impacts on soil quality, SOC, SOC fractions, and enzyme activities. Results showed that mowing treatments led to overall increases in soil nutrients [total carbon (TC), total nitrogen (TN), total phosphorus (TP), NH4+, and NO3−] and decreases in soil C/N ratio. The effects of mowing treatments on soil nutrient content were pronounced on topsoil than deep soil, and the maximum value of TC, TN, and TP reached in the 12MR treatment. Compared with CK, the 12MS, 12MR, 3MS, and 3MR treatments at 0–10 cm depth significantly enhanced SOC content by 8.78%, 32.9%, 16.5%, and 30.1%, respectively, but only the 3MS treatment enhanced SOC by 16.5% at 10–20 cm depth. Mowing treatments increased dissolved organic carbon (DOC), microbial biomass carbon (MBC), particulate organic carbon (POC), and labile organic carbon (LOC) and the contents of DOC, MBC, POC, and LOC decreased with soil depth. Mowing treatments stimulated the activities of sucrase and urease in topsoil, but only the 3MR treatment improved alkaline phosphatase activity in topsoil. Path analysis indicated that mowing management dominantly modulates SOC by changing sucrase activity, alkaline phosphatase activity, TN, TP, NH4+, NO3−, DOC, and LOC in 0–10 cm depth. However, SOC was significantly controlled by sucrase activity, urease activity, TC, TN, TP, LOC, and POC in 10–20 cm depth. Collectively, our results indicate that the continuous mowing management is beneficial to enhance soil quality and carbon storage capacity of P. australis wetlands, which will contribute to enhance carbon sequestration and sink capacity of coastal wetlands.
Safety and anterior chamber structure of evolution implantable Collamer lens implantation with short white-to-white corneal diameters
Authors: Chen Xun , Chen Fang , Wang Xuanqi , Xu Yilin , Cheng Mingrui , Han Tian , Wang Xiaoying , Zhou Xingtao
Published: August 2022

Introduction

To evaluate the safety and anterior chamber structure of implantation of the Evolution (EVO) implantable Collamer lens (EVO-ICL) in patients with short white-to-white (WTW) corneal diameters.

Materials and methods

The study population was divided into two groups: the experimental group (34 eyes of 34 patients) with WTW corneal diameters of ≤10.6 mm and the control group (59 eyes of 59 patients) with WTW corneal diameters of >10.6 mm. The outcome measures included uncorrected distance visual acuity, corrected distance visual acuity, refractive power, intraocular pressure (IOP), anterior chamber angle, depth, volume, and vault.

Results

The safety indices of the experimental and control groups were 1.17 ± 0.30 and 1.12 ± 0.14, respectively (P > 0.05); the effectiveness indices were 1.16 ± 0.31 and 1.07 ± 0.17, respectively (P > 0.05). The simulation curves of the expected and actual corrections in the experimental and control groups were y = 0.9876x – 0.0927 and y = 0.9799x + 0.0343, respectively. There were no significant differences between the IOPs and anterior chamber structures of the two groups (P > 0.05). The average vaults of the experimental and control groups were 395.76 ± 155.32 and 389.49 ± 135.01 μm, respectively (P > 0.05).

Conclusion

EVO-ICL implantation in patients with short WTW corneal diameters (≤ 10.6 mm) was determined to be a safe, effective, and predictable method for correcting myopia. The changes in the anterior chamber structure were still within normal limits after the surgery, the IOP remained stable, and the ideal vault was achieved after the surgery.
Deep learning framework for prediction of infection severity of COVID-19
Authors: Yousefzadeh Mehdi , Hasanpour Masoud , Zolghadri Mozhdeh , Salimi Fatemeh , Yektaeian Vaziri Ava , Mahmoudi Aqeel Abadi Abolfazl , Jafari Ramezan , Esfahanian Parsa , Nazem-Zadeh Mohammad-Reza
Published: August 2022

With the onset of the COVID-19 pandemic, quantifying the condition of positively diagnosed patients is of paramount importance. Chest CT scans can be used to measure the severity of a lung infection and the isolate involvement sites in order to increase awareness of a patient's disease progression. In this work, we developed a deep learning framework for lung infection severity prediction. To this end, we collected a dataset of 232 chest CT scans and involved two public datasets with an additional 59 scans for our model's training and used two external test sets with 21 scans for evaluation. On an input chest Computer Tomography (CT) scan, our framework, in parallel, performs a lung lobe segmentation utilizing a pre-trained model and infection segmentation using three distinct trained SE-ResNet18 based U-Net models, one for each of the axial, coronal, and sagittal views. By having the lobe and infection segmentation masks, we calculate the infection severity percentage in each lobe and classify that percentage into 6 categories of infection severity score using a k-nearest neighbors (k-NN) model. The lobe segmentation model achieved a Dice Similarity Score (DSC) in the range of [0.918, 0.981] for different lung lobes and our infection segmentation models gained DSC scores of 0.7254 and 0.7105 on our two test sets, respectfully. Similarly, two resident radiologists were assigned the same infection segmentation tasks, for which they obtained a DSC score of 0.7281 and 0.6693 on the two test sets. At last, performance on infection severity score over the entire test datasets was calculated, for which the framework's resulted in a Mean Absolute Error (MAE) of 0.505 ± 0.029, while the resident radiologists' was 0.571 ± 0.039.
Point-of-care application of diaphragmatic ultrasonography in the emergency department for the prediction of development of respiratory failure in community-acquired pneumonia: A pilot study
Authors: Chu Sheng-En , Lu Jian-Xun , Chang Shi-Chuan , Hsu Kuang-Hung , Goh Zhong Ning Leonard , Seak Chen-Ken , Seak Joanna Chen-Yeen , Ng Chip-Jin , Seak Chen-June
Published: August 2022

Background

Early recognition of patients with community-acquired pneumonia (CAP) at risk of poor outcomes is crucial. However, there is no effective assessment tool for predicting the development of respiratory failure in patients with CAP. Diaphragmatic ultrasonography (DUS) is a novel technique developed for evaluating diaphragmatic functionviameasurements of the diaphragm thickening fraction (DTF) and diaphragm excursion (DE). This study evaluated the accuracy of DUS in predicting the development of respiratory failure in patients with CAP, as well as the feasibility of its use in the emergency department (ED) setting.

Materials and methods

This was a single-center prospective cohort study. We invited all patients with ED aged ≥ 20 years who were diagnosed with CAP of pneumonia severity index (PSI) SIe diagnosed with CAP of pneumonia severe with respiratory failure or septic shock were excluded. Two emergency physicians performed DUS to obtain DTF and DE measurements. Data were collected to calculate PSI, CURB-65 score, and Infectious Diseases Society of America/American Thoracic Society severity criteria. Study endpoints were taken at the development of respiratory failure or 30 days post-ED presentation. Continuous variables were analyzed usingT-tests, while categorical variables were analyzed using chi-square tests. Further logistic regression and receiver operating characteristic curve analyses were performed to examine the ability to predict the development of respiratory failure. Intra- and inter-rater reliability was examined with intraclass correlation coefficients (ICCs).

Results

In this study, 13 of 50 patients with CAP enrolled developed respiratory failure. DTF was found to be an independent predictor (OR: 0.939,p= 0.0416). At the optimal cut-off point of 23.95%, DTF had 69.23% of sensitivity, 83.78% of specificity, 88.57% of negative predictive value, and 80% of accuracy. Intra- and inter-rater analysis demonstrated good consistency (intra-rater ICC 0.817, 0.789; inter-rater ICC 0.774, 0.781).

Conclusion

DUS assessment of DTF may reliably predict the development of respiratory failure in patients with CAP presenting to the ED. Patients with DTF > 23.95% may be considered for outpatient management.
Acute decompensation events differentially impact the risk of nosocomial infections and short-term outcomes in patients with cirrhosis
Authors: Xu Xianbin , Yu Xia , Gong Kai , Tu Huilan , Yao Junjie , Lan Yan , Ye Shaoheng , Weng Haoda , Shi Yu , Sheng Jifang
Published: August 2022

Aims

This research aimed to evaluate the influence of acute decompensation (AD) events upon admission on the subsequent risk of nosocomial infections (NIs) and the synergy between AD and the following NIs on the short-term outcome.

Methods

A total of 419 hospitalized individuals with cirrhosis and AD participated in the current study. Various AD events at admission and outcomes in patients with or without NIs were compared. The logistic regression and Cox proportional hazards models were designed for NIs development and liver transplant (LT)-free mortality at 28 and 90 days, respectively.

Results

During hospitalization, 91 patients developed NIs. Notably, a higher proportion of patients with NIs had jaundice (52.7 vs. 30.5%; p < 0.001) and bacterial infections (37.4 vs. 20.7%; p = 0.001) at admission compared to patients without NIs, while a lower proportion suffered gastrointestinal hemorrhage (16.5 vs. 36.6%; p < 0.001). Multivariate analysis revealed that jaundice was independently linked with the development of NIs (OR, 2.732; 95% CI: 1.104–6.762). The 28-day (16.5 vs. 7.3%; p = 0.008) and 90-day (27.5 vs. 15.9%; p = 0.011) LT-free mortality rates of patients with NIs were significantly higher than those without NIs. According to the Cox proportional hazards model, jaundice remained an independent risk factor for 90-day death (HR, 5.775; 95% CI: 1.217–27.397). The connection between total bilirubin and 90-day mortality was nonlinear, and a 6 mg/mL threshold was proposed.

Conclusion

The types of AD events differentially predispose to risk of NIs. Presenting jaundice at admission is independently associated with NIs occurrence and increased 90-day mortality of patients with NIs. Antibiotic prophylaxis may benefit this specific subset of patients.
Pathomechanisms of bone loss in rheumatoid arthritis
Authors: Sakthiswary Rajalingham , Uma Veshaaliini Rajeswaran , Chin Kok-Yong , Das Srijit , Sirasanagandla Srinivasa Rao
Published: August 2022

Rheumatoid arthritis (RA) is an autoimmune disease, in which the inflammatory processes involve the skeletal system and there is marked destruction of the bones and the surrounding structures. In this review, we discuss the current concepts of osteoimmunology in RA, which represent the molecular crosstalk between the immune and skeletal systems, resulting in the disruption of bone remodeling. Bone loss in RA can be focal or generalized, leading to secondary osteoporosis. We have summarized the recent studies of bone loss in RA, which focused on the molecular aspects, such as cytokines, autoantibodies, receptor activator of nuclear kappa-β ligand (RANKL) and osteoprotegerin (OPG). Apart from the above molecules, the role of aryl hydrocarbon receptor (Ahr), which is a potential key mediator in this process through the generation of the Th17 cells, is discussed. Hence, this review highlights the key insights into molecular mechanisms of bone loss in RA.
In silico analysis reveals the co-existence of CRISPR-Cas type I-F1 and type I-F2 systems and its association with restricted phage invasion in Acinetobacter baumannii
Authors: Yadav Gulshan , Singh Ruchi
Published: August 2022

Introduction

Acinetobacter baumannii, an opportunistic pathogen, rapidly acquires antibiotic resistance, thus compelling researchers to develop alternative treatments at utmost priority. Phage-based therapies are of appreciable benefit; however, CRISPR-Cas systems are a major constraint in this approach. Hence for effective implementation and a promising future of phage-based therapies, a multifaceted understanding of the CRISPR-Cas systems is necessary.

Methods

This study investigated 4,977 RefSeq genomes of A. baumannii from the NCBI database to comprehend the distribution and association of CRISPR-Cas systems with genomic determinants.

Results

Approximately 13.84% (n = 689/4,977) isolates were found to carry the CRSIPR-Cas system, and a small fraction of isolates, 1.49% (n = 74/4,977), exhibited degenerated CRISPR-Cas systems. Of these CRISPR-Cas positive (+) isolates, 67.48% (465/689) isolates harbored type I-F1, 28.59% (197/689) had type I-F2, and 3.7% (26/689) had co-existence of both type I-F1 and type I-F2 systems. Co-existing type I-F1 and type I-F2 systems are located distantly (∼1.733 Mb). We found a strong association of CRISPR-Cas systems within STs for type I-F1 and type I-F2, whereas the type I-F1 + F2 was not confined to any particular ST. Isolates with type I-F1 + F2 exhibited a significantly high number of mean spacers (n = 164.58 ± 46.41) per isolate as compared to isolates with type I-F2 (n = 82.87 ± 36.14) and type I-F1 (n = 54.51 ± 26.27) with majority targeting the phages. Isolates with type I-F1 (p < 0.0001) and type I-F2 (p < 0.0115) displayed significantly larger genome sizes than type I-F1 + F2. A significantly reduced number of integrated phages in isolates with co-existence of type I-F1 + F2 compared with other counterparts was observed (p = 0.0041). In addition, the isolates carrying type I-F1 + F2 did not exhibit reduced resistance and virulence genes compared to CRISPR-Cas(–) and CRISPR-Cas (+) type I-F1 and type I-F2, except for bap, abaI, and abaR.

Conclusion

Our observation suggests that the co-existence of type I-F1 and F2 is more effective in constraining the horizontal gene transfer and phage invasion in A. baumannii than the isolates exhibiting only type I-F1 and only type I-F2 systems.
A review on effective soil health bio-indicators for ecosystem restoration and sustainability
Authors: Bhaduri Debarati , Sihi Debjani , Bhowmik Arnab , Verma Bibhash C. , Munda Sushmita , Dari Biswanath
Published: August 2022

Preventing degradation, facilitating restoration, and maintaining soil health is fundamental for achieving ecosystem stability and resilience. A healthy soil ecosystem is supported by favorable components in the soil that promote biological productivity and provide ecosystem services. Bio-indicators of soil health are measurable properties that define the biotic components in soil and could potentially be used as a metric in determining soil functionality over a wide range of ecological conditions. However, it has been a challenge to determine effective bio-indicators of soil health due to its temporal and spatial resolutions at ecosystem levels. The objective of this review is to compile a set of effective bio-indicators for developing a better understanding of ecosystem restoration capabilities. It addresses a set of potential bio-indicators including microbial biomass, respiration, enzymatic activity, molecular gene markers, microbial metabolic substances, and microbial community analysis that have been responsive to a wide range of ecosystem functions in agricultural soils, mine deposited soil, heavy metal contaminated soil, desert soil, radioactive polluted soil, pesticide polluted soil, and wetland soils. The importance of ecosystem restoration in the United Nations Sustainable Development Goals was also discussed. This review identifies key management strategies that can help in ecosystem restoration and maintain ecosystem stability.
Antibacterial properties of lactoferrin: A bibliometric analysis from 2000 to early 2022
Authors: Xu Yunling , Wang Yuji , He Jiaolong , Zhu Wanping
Published: August 2022

Background

Here, a bibliometric and knowledge map analysis are used to analyze the research hot spots and development trends regarding the antibacterial effect of lactoferrin (LF). By looking for research hot spots and new topics, we provide new clues and research directions for future research.

Methods

Articles and reviews regarding the antibacterial effect of LF were retrieved and from the Web of Science Core Collection (WoSCC) on 25 June 2022. CiteSpace and VOSviewer were used to conduct the bibliometric and knowledge map analysis.

Results

In total, 8,292 authors at 2,151 institutions from 86 countries published 1,923 articles in 770 academic journals. The United States was the leader regarding research on the antibacterial effects of LF, while the Netherlands was a pioneer in conducting research in this field. The University of California system contributed the most publications. Bolscher JGM published most articles, while Wayne Bellamy had most cocitations. However, there was insufficient cooperation among the various institutions and authors. BioMetals published most LF-antibacterial activity-related articles, whereas Infection and Immunity was most commonly cocited journal. The most influential research hot spots about the antibacterial effect of LF focused on antimicrobial peptides, casein, human milk, expression, and Escherichia coli-related research. The latest hot spots and research frontier included COVID-19, antibiofilm activity, and immune defense.

Conclusions

LF is a multifunctional protein with a broad spectrum of antimicrobial activities. The related field of antibacterial properties of LF will remain a research hot spot in future.
Layered and integrated medical countermeasures against Burkholderia pseudomallei infections in C57BL/6 mice
Authors: Klimko Christopher P. , Shoe Jennifer L. , Rill Nathaniel O. , Hunter Melissa , Dankmeyer Jennifer L. , Talyansky Yuli , Schmidt Lindsey K. , Orne Caitlyn E. , Fetterer David P. , Biryukov Sergei S. , Burtnick Mary N. , Brett Paul J. , DeShazer David , Cote Christopher K.
Published: August 2022

Burkholderia pseudomallei, the gram-negative bacterium that causes melioidosis, is notoriously difficult to treat with antibiotics. A significant effort has focused on identifying protective vaccine strategies to prevent melioidosis. However, when used as individual medical countermeasures both antibiotic treatments (therapeutics or post-exposure prophylaxes) and experimental vaccine strategies remain partially protective. Here we demonstrate that when used in combination, current vaccine strategies (recombinant protein subunits AhpC and/or Hcp1 plus capsular polysaccharide conjugated to CRM197 or the live attenuated vaccine strainB. pseudomallei668 ΔilvI) and co-trimoxazole regimens can result in near uniform protection in a mouse model of melioidosis due to apparent synergy associated with distinct medical countermeasures. Our results demonstrated significant improvement when examining several suboptimal antibiotic regimens (e.g., 7-day antibiotic course started early after infection or 21-day antibiotic course with delayed initiation). Importantly, this combinatorial strategy worked similarly when either protein subunit or live attenuated vaccines were evaluated. Layered and integrated medical countermeasures will provide novel treatment options for melioidosis as well as diseases caused by other pathogens that are refractory to individual strategies, particularly in the case of engineered, emerging, or re-emerging bacterial biothreat agents.
Gut microbiota and short-chain fatty acids may be new biomarkers for predicting neonatal necrotizing enterocolitis: A pilot study
Authors: Liu Xiao-Chen , Du Ting-Ting , Gao Xiong , Zhao Wen-Jing , Wang Zheng-Li , He Yu , Bao Lei , Li Lu-Quan
Published: August 2022

Background

Dysbacteriosis is thought to play an important role in the pathogenesis of necrotizing enterocolitis (NEC). We aimed to identify new biomarkers among gut microbiota and short-chain fatty acids (SCFAs) for the early prediction of NEC.

Materials and methods

Thirty-four preterm infants with gestational ages of ≤ 34 weeks who developed gastrointestinal symptoms were divided into the NEC group (n = 17) and non-NEC group (n = 17). In the NEC group, the gut microbiota and SCFAs in feces were assessed when the infants were enrolled (Group P) and when they were diagnosed with NEC (Group N). In the non-NEC group, samples were assessed when the infants were enrolled (Group C).

Results

The Ace and Chao1 indices were higher in Group P than in Group C (P < 0.05), and there was no difference between Groups C and N or between Groups P and N (P > 0.05). There was no significant difference in the Simpson and Shannon indices among Groups C, P and N (P > 0.05). The four main phyla showed no differences (P > 0.05) in composition, while at the genus level, compared with Group C, in Group P, Clostridioides, Blautia and Clostridium_sensu_stricto_1 were increased, while Lactobacillus and Bifidobacterium were decreased (P < 0.05). At the species level, Streptococcus salivarius and Rothia mucilaginosa increased, while Bifidobacterium animals subsp. lactis decreased (P < 0.05). In Group N, at the genus level, Stenotrophomonas, Streptococcus and Prevotella increased (P < 0.05). Compared with those in Group C, the levels of acetic acid, propanoic acid and butyric acid decreased significantly in Groups P and N (P < 0.05), and the areas under the curves (AUCs) of these three SCFAs between groups C and P were 0.73, 0.70, and 0.68, respectively.

Conclusion

The increase in Streptococcus salivarius and Rothia mucilaginosa and decrease in Bifidobacterium_animals_subsp._lactis, as well as the decrease in acetic, propionic and butyric acids, may help in the early prediction of NEC.
Study on the production of high 3HV content PHBV via an open fermentation with waste silkworm excrement as the carbon source by the haloarchaeon Haloferax mediterranei
Authors: Cai Shuangfeng , Wu Yaran , Liu Runjie , Jia Hongzhe , Qiu Yunxiao , Jiang Min , Ma Yuwen , Yang Xingxu , Zhang Siyu , Zhao Yan , Cai Lei
Published: August 2022

Silkworm excrement is hard to be degraded or bio-utilized by environmental microorganisms due to its high content of heavy metals and antimicrobial biomacromolecules in mulberry leaves. In traditional Chinese silk industry, the silkworm excrement results in environmental problems. In this study, the silkworm excrement after chlorophyll ethanol-extraction was researched. An open fermentation strategy was developed using the silkworm excrement as the sole or partial carbon source by haloarchaea to accumulate polyhydroxyalkanoates. As a haloarchaeon with strong carbon source utilization ability, Haloferax mediterranei was found to accumulate a certain amount of poly(3-hydroxybutyrate-co-3-hydroxyvalerate; PHBV) using waste silkworm excrement. The results showed that the addition of silkworm excrement into glucose based fermentation medium can significantly improve the production of PHBV. Using a mixture carbon source including the extract of silkworm excrement and glucose (with a 1:1 carbon content ratio), the yield of PHBV was 1.73 ± 0.12 g/l, which showed a 26% increase than that of fermentation without the silkworm excrement addition. When the NaCl content of medium was set to approximately 15%, fermentation without sterilization was performed using silkworm excrement as the carbon source. Moreover, the addition of the silkworm excrement extract could increase the 3-hydroxyvalerate (3 HV) content of PHBV regardless of the sterilization or non-sterilization fermentation conditions. When using silkworm excrement as the sole carbon source, the 3 HV content was as high as 16.37 ± 0.54 mol %. The real-time quantitative PCR results showed that the addition of the silkworm excrement could specifically enhance the expression of genes involved in the aspartate/2-ketobutyric acid pathway related to 3 HV synthesis in H. mediterranei, and further analysis of the amino acid of the silkworm excrement suggested that the high content of threonine in the silkworm excrement might be the reason for the increase of 3 HV content. Taken together, the success of non-sterile fermentation in hypersaline condition using haloarchaea implied a novel way to reuse the silkworm excrement, which not only reduces the production costs of PHBV, but also is conducive to environmental protection.