bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Pharmaceutical Compounds in the Bioremediation of Municipal Biosolids by the White-Rot-Fungi Trametes hirsuta
Authors: Saibi Sabrina , Haroune Lounès , Savary Olivier , Bellenger Jean-Philippe , Cabana Hubert
Published: January 2023

The potential of microorganisms for the treatment of municipal biosolids is continuously growing. The present studies evaluated the potency of Trametes hirsuta for the reduction in biosolid mass, production of extracellular enzymes, and removal of pharmaceutical compounds (PhACs) in biosolid slurry in the presence and absence of spiked PhACs [5 non-steroidal anti-inflammatories (NSAIs) and 2 psychoactive compounds (PACs)]. Toxicity after 35 days of fungal treatment was also assessed. Results showed that the growth of T. hirsuta is limited above 25% and wholly inhibited above 50% of biosolids in the slurry. At 12% of biosolid concentration, biosolid mass was reduced by 90%, NSAIs were entirely removed, but PACs' removal was only ~20%. Increasing biosolid content to 25% did not markedly affect biosolid reduction but significantly enhanced the removal of PACs (>50%). Results also showed that both PhACs and biosolids induced the production of oxidative enzymes. In 12% biosolids in the slurry, the oxidative potential measured by the ABTS assay (OABTS) reached 5,000 mM of OABTS in the presence of PhACs, and 2,500 mM of OABTS without PhACs, as compared to 1,200 mM of OABTS in control culture. Finally, we report that white rot fungi (WRF) treatment significantly decreased the toxicity of the biosolids.
Long Non Coding RNA Based Regulation of Cerebrovascular Endothelium
Authors: Mathew Samatha , Sivasubbu Sridhar
Published: January 2023

Graphical Abstract

Long non coding RNAs regulate the cerebrovascular endothelial processes.
Comparison of methods for donor-derived cell-free DNA quantification in plasma and urine from solid organ transplant recipients
Authors: Kueng Nicholas , Arcioni Séverine , Sandberg Fanny , Kuhn Christian , Banz Vanessa , Largiadèr Carlo R. , Sidler Daniel , Amstutz Ursula
Published: January 2023

In allograft monitoring of solid organ transplant recipients, liquid biopsy has emerged as a novel approach using quantification of donor-derived cell-free DNA (dd-cfDNA) in plasma. Despite early clinical implementation and analytical validation of techniques, direct comparisons of dd-cfDNA quantification methods are lacking. Furthermore, data on dd-cfDNA in urine is scarce and high-throughput sequencing-based methods so far have not leveraged unique molecular identifiers (UMIs) for absolute dd-cfDNA quantification. Different dd-cfDNA quantification approaches were compared in urine and plasma of kidney and liver recipients: A) Droplet digital PCR (ddPCR) using allele-specific detection of seven common HLA-DRB1 alleles and the Y chromosome; B) high-throughput sequencing (HTS) using a custom QIAseq DNA panel targeting 121 common polymorphisms; and C) a commercial dd-cfDNA quantification method (AlloSeq® cfDNA, CareDx). Dd-cfDNA was quantified as %dd-cfDNA, and for ddPCR and HTS using UMIs additionally as donor copies. In addition, relative and absolute dd-cfDNA levels in urine and plasma were compared in clinically stable recipients. The HTS method presented here showed a strong correlation of the %dd-cfDNA with ddPCR (R2 = 0.98) and AlloSeq® cfDNA (R2 = 0.99) displaying only minimal to no proportional bias. Absolute dd-cfDNA copies also correlated strongly (τ = 0.78) between HTS with UMI and ddPCR albeit with substantial proportional bias (slope: 0.25; 95%-CI: 0.19–0.26). Among 30 stable kidney transplant recipients, the median %dd-cfDNA in urine was 39.5% (interquartile range, IQR: 21.8–58.5%) with 36.6 copies/μmol urinary creatinine (IQR: 18.4–109) and 0.19% (IQR: 0.01–0.43%) with 5.0 copies/ml (IQR: 1.8–12.9) in plasma without any correlation between body fluids. The median %dd-cfDNA in plasma from eight stable liver recipients was 2.2% (IQR: 0.72–4.1%) with 120 copies/ml (IQR: 85.0–138) while the median dd-cfDNA copies/ml was below 0.1 in urine. This first head-to-head comparison of methods for absolute and relative quantification of dd-cfDNA in urine and plasma supports a method-independent %dd-cfDNA cutoff and indicates the suitability of the presented HTS method for absolute dd-cfDNA quantification using UMIs. To evaluate the utility of dd-cfDNA in urine for allograft surveillance, absolute levels instead of relative amounts will most likely be required given the extensive variability of %dd-cfDNA in stable kidney recipients.
Two novel variations in LRP2 cause Donnai-Barrow syndrome in a Chinese family with severe early-onset high myopia
Authors: Yuan Shiqin , Huang Xiaoyu , Zhang Shuang , Yang Shangying , Rui Xue , Qi Xiaolong , Wang Xuhui , Zheng Yali , Rong Weining , Sheng Xunlun
Published: January 2023

Donnai-Barrow syndrome (DBS) is a rare autosomal recessive disorder caused by mutation in the low density lipoprotein receptor-related protein 2 gene (LRP2). Defects in this protein may lead to clinical multiple organ malformations by affecting the development of organs such as the nervous system, eyes, ears, and kidneys. Although some variations on LRP2 have been found to be associated with DBS, early diagnosis and prevention of patients with atypical DBS remains a challenge for many physicians because of their clinical heterogeneity. The objective of this study is to explore the association between the clinical presentation and the genotype of a DBS patient who was initially diagnosed with early-onset high myopia (eoHM) from a healthy Chinese family. To this end, we tested the patient of this family via whole exome sequencing and further verified the results among other family members by Sanger sequencing. Comprehensive ophthalmic tests as well as other systemic examinations were also performed on participants with various genotypes. Genetic assessment revealed that two novel variations in LRP2, a de novo missense variation (c.9032G>A; p.Arg3011Lys) and a novel splicing variation (c.2909-2A>T) inherited from the father, were both carried by the proband in this family, and they are strongly associated with the typical clinical features of DBS patients. Therefore, in this paper we are the first to report two novel compound heterozygous variations in LPR2 causing DBS. Our study extends the genotypic spectrums for LPR2-DBS and better assists physicians in predicting, diagnosing, and conducting gene therapy for DBS.
Nanocell COVID-19 vaccine triggers a novel immune response pathway producing high-affinity antibodies which neutralize all variants of concern
Authors: Gao Steven Y. , Amaro-Mugridge Nancy B. , Madrid-Weiss Jocelyn , Petkovic Nikolina , Vanegas Natasha , Visvanathan Kumar , Williams Bryan R. G. , MacDiarmid Jennifer A. , Brahmbhatt Himanshu
Published: January 2023

Most current anti-viral vaccines elicit a humoral and cellular immune response via the pathway of phagocytic cell mediated viral antigen presentation to B and T cell surface receptors. However, this pathway results in reduced ability to neutralize S-protein Receptor Binding Domains (RBDs) from several Variants of Concern (VOC) and the rapid waning of memory B cell response requiring vaccine reformulation to cover dominant VOC S-proteins and multiple boosters. Here we show for the first time in mice and humans, that a bacterially derived, non-living, nanocell (EDV; EnGeneIC Dream Vector) packaged with plasmid expressed SARS-CoV-2 S-protein and α-galactosyl ceramide adjuvant (EDV-COVID-αGC), stimulates an alternate pathway due to dendritic cells (DC) displaying both S-polypeptides and αGC thereby recruiting and activating iNKT cells with release of IFNγ. This triggers DC activation/maturation, activation of follicular helper T cells (TFH), cognate help to B cells with secretion of a cytokine milieu promoting B cell maturation, somatic hypermutation in germinal centers to result in high affinity antibodies. Surrogate virus neutralization tests show 90-100% neutralization of ancestral and early VOC in mice and human trial volunteers. EDV-COVID-αGC as a third dose booster neutralized Omicron BA. 4/5. Serum and PBMC analyses reveal long lasting S-specific memory B and T cells. In contrast, control EDVs lacking αGC, did not engage the iNKT/DC pathway resulting in antibody responses unable to neutralize all VOCs and had a reduced B cell memory. The vaccine is lyophilized, stored and transported at room temperature with a shelf-life of over a year.
The association between serum complement C3a and severity in patients with community-acquired pneumonia
Authors: Xu Zheng , Hou Xue-Feng , Feng Chun-Mei , Zheng Ling , Xu De-Xiang , Zhao Hui , Fu Lin
Published: January 2023

Background

A few studies found that the complement system may be involved in the onset and progression of community-acquired pneumonia (CAP). However, the role of the complement system in CAP was obscure. The goal of this study was to analyze the association of serum complement C3a with CAP severity scores based on a cross-sectional study.

Methods

All 190 CAP patients and 95 control subjects were enrolled. Demographic information and clinical data were extracted. Peripheral blood samples were collected on admission.

Results

Serum complement C3a on admission was elevated in CAP patients compared with healthy subjects. The level of complement C3a was gradually elevated in parallel with CAP severity scores (CURB-65, CRB-65, PSI, SMART-COP, and CURXO). Complement C3a was positively correlated with blood routine parameters, renal function markers, and inflammatory cytokines in CAP patients. Furthermore, multivariate linear and logistic regression models found that serum complement C3a on admission was positively associated with CAP severity scores. Mechanistic research suggested that complement system inhibition alleviated Streptococcus pneumoniae-induced upregulation of IL-1β, TNF-α, IL-6, and CRP in MLE-12 cells.

Conclusions

Serum complement C3a on admission is positively associated with the severity of CAP patients. Inhibiting complement system attenuates S. pneumoniae-elevated secretion of inflammatory cytokines in pulmonary epithelial cells, indicating that complement C3a is involved in the pathophysiology of CAP. Serum complement C3a may serve as an earlier diagnostic biomarker for CAP.
Suppression of microRNA-222-3p ameliorates ulcerative colitis and colitis-associated colorectal cancer to protect against oxidative stress via targeting BRG1 to activate Nrf2/HO-1 signaling pathway
Authors: Wang Xue-jun , Zhang Dan , Yang Yan-ting , Li Xiao-ying , Li Hong-na , Zhang Xiao-peng , Long Jun-yi , Lu Yun-qiong , Liu Li , Yang Guang , Liu Jie , Hong Jue , Wu Huan-gan , Ma Xiao-peng
Published: January 2023

Oxidative stress is an important pathogenic factor in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC), further impairing the entire colon. Intestinal epithelial cells (IECs) are crucial components of innate immunity and play an important role in maintaining intestinal barrier function. Recent studies have indicated that microRNA-222-3p (miR-222-3p) is increased in colon of UC and colorectal cancer (CRC) patients, and miR-222-3p is a crucial regulator of oxidative stress. However, whether miR-222-3p influences IEC oxidative stress in UC and CAC remains unknown. This study investigated the effect of miR-222-3p on the regulation of IEC oxidative stress in UC and CAC. An in vitro inflammation model was established in NCM460 colonic cells, mouse UC and CAC models were established in vivo, and IECs were isolated. The biological role and mechanism of miR-222-3p-mediated oxidative stress in UC and CAC were determined. We demonstrated that miR-222-3p expression was notably increased in dextran sulfate sodium (DSS)-induced NCM460 cells and IECs from UC and CAC mice. In vitro, these results showed that the downregulation of miR-222-3p reduced oxidative stress, caspase-3 activity, IL-1β and TNF-α in DSS-induced NCM460 cells. We further identified BRG1 as the target gene of miR-222-3p, and downregulating miR-222-3p alleviated DSS-induced oxidative injury via promoting BRG1-mediated activation Nrf2/HO-1 signaling in NCM460 cells. The in vivo results demonstrated that inhibiting miR-222-3p in IECs significantly relieved oxidative stress and inflammation in the damaged colons of UC and CAC mice, as evidenced by decreases in ROS, MDA, IL-1β and TNF-α levels and increases in GSH-Px levels. Our study further demonstrated that inhibiting miR-222-3p in IECs attenuated oxidative damage by targeting BRG1 to activate the Nrf2/HO-1 signaling. In summary, inhibiting miR-222-3p in IECs attenuates oxidative stress by targeting BRG1 to activate the Nrf2/HO-1 signaling, thereby reducing colonic inflammation and tumorigenesis.
Follicle-like tertiary lymphoid structures: A potential biomarker for prognosis and immunotherapy response in patients with laryngeal squamous cell carcinoma
Authors: Liang Haifeng , Zhang Zhigang , Guan Zhong , Zheng Shibie , Lou Jintao , Liu Wei , Cai Qian , Si Yu
Published: January 2023

Background

The maturity and spatial distribution of tertiary lymphoid structures (TLSs) vary dynamically within and between cancers, leading to a controversial role in cancer. We aimed to develop a simple morphology-based approach to identify the maturity of TLSs in laryngeal squamous cell carcinoma and examine their clinically relevant functional role.

Methods

TLSs were identified based on morphological features via hematoxylin and eosin (H&E) staining, and the accuracy was verified by multi-immunohistochemical analysis. The density, maturity, spatial distribution and prognostic value of TLSs were separately analyzed in two human laryngeal cancer cohorts. The TLS profile was linked to RNA-seq data from the TCGA database to perform bioinformatics analysis.

Results

TLSs can be classified as early TLSs (E-TLSs), primary follicle-like TLSs (PFL-TLSs) and secondary follicle-like TLSs (SFL-TLSs). The three types of TLSs showed higher infiltration in the extratumoral region. XCL2 is a vital chemokine in the maturation and infiltration of TLSs. FL-TLS was an independent positive prognostic indicator in laryngeal cancer. The FL-TLS group had more abundant immune cell infiltration and a better response to immunotherapies than the non-FL-TLS group. Functional analysis showed that the non-FL-TLS group was enriched in tumor invasion, metastasis and immunosuppression pathways.

Conclusion

The maturity of TLSs can be accurately classified by H&E staining. FL-TLS is a potential mediator of antitumor immunity in human laryngeal cancer.
The COVID-19, tuberculosis and HIV/AIDS: Ménage à Trois
Authors: Udoakang Aniefiok John , Djomkam Zune Alexandra Lindsey , Tapela Kesego , Nganyewo Nora Nghochuzie , Olisaka Frances Ngozi , Anyigba Claudia Adzo , Tawiah-Eshun Sylvia , Owusu Irene Amoakoh , Paemka Lily , Awandare Gordon A. , Quashie Peter Kojo
Published: January 2023

In December 2019, a novel pneumonic condition, Coronavirus disease 2019 (COVID- 19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), broke out in China and spread globally. The presentation of COVID-19 is more severe in persons with underlying medical conditions such as Tuberculosis (TB), Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) and other pneumonic conditions. All three diseases are of global concern and can significantly affect the lungs with characteristic cytokine storm, immunosuppression, and respiratory failure. Co-infections of SARS-CoV-2 with HIV and Mycobacterium tuberculosis (Mtb) have been reported, which may influence their pathogenesis and disease progression. Pulmonary TB and HIV/AIDS patients could be more susceptible to SARS-CoV-2 infection leading to lethal synergy and disease severity. Therefore, the biological and epidemiological interactions of COVID-19, HIV/AIDS, and TB need to be understood holistically. While data is needed to predict the impact of the COVID-19 pandemic on these existing diseases, it is necessary to review the implications of the evolving COVID-19 management on HIV/AIDS and TB control, including therapy and funding. Also, the impact of long COVID on patients, who may have this co-infection. Thus, this review highlights the implications of COVID-19, HIV/AIDS, and TB co-infection compares disease mechanisms, addresses growing concerns, and suggests a direction for improved diagnosis and general management.
Hepcidin and ferritin levels as markers of immune cell activation during septic shock, severe COVID-19 and sterile inflammation
Authors: Hortová-Kohoutková Marcela , Skotáková Monika , Onyango Isaac G. , Slezáková Miriam , Panovský Roman , Opatřil Lukáš , Slanina Peter , De Zuani Marco , Mrkva Ondřej , Andrejčinová Ivana , Lázničková Petra , Dvončová Martina , Mýtniková Alexandra , Ostland Vaughn , Šitina Michal , Stokin Gorazd B. , Šrámek Vladimír , Vlková Marcela , Helán Martin , Frič Jan
Published: January 2023

Introduction

Major clinically relevant inflammatory events such as septic shock and severe COVID-19 trigger dynamic changes in the host immune system, presenting promising candidates for new biomarkers to improve precision diagnostics and patient stratification. Hepcidin, a master regulator of iron metabolism, has been intensively studied in many pathologies associated with immune system activation, however these data have never been compared to other clinical settings. Thus, we aimed to reveal the dynamics of iron regulation in various clinical settings and to determine the suitability of hepcidin and/or ferritin levels as biomarkers of inflammatory disease severity.

Cohorts

To investigate the overall predictive ability of hepcidin and ferritin, we enrolled the patients suffering with three different diagnoses – in detail 40 patients with COVID-19, 29 patients in septic shock and eight orthopedic patients who were compared to nine healthy donors and all cohorts to each other.

Results

We showed that increased hepcidin levels reflect overall immune cell activation driven by intrinsic stimuli, without requiring direct involvement of infection vectors. Contrary to hepcidin, ferritin levels were more strongly boosted by pathogen-induced inflammation – in septic shock more than four-fold and in COVID-19 six-fold in comparison to sterile inflammation. We also defined the predictive capacity of hepcidin-to-ferritin ratio with AUC=0.79 and P = 0.03.

Discussion

Our findings confirm that hepcidin is a potent marker of septic shock and other acute inflammation-associated pathologies and demonstrate the utility of the hepcidin-to-ferritin ratio as a predictor of mortality in septic shock, but not in COVID-19.
High aspect ratio nanomaterial-induced macrophage polarization is mediated by changes in miRNA levels
Authors: Erdem Johanna Samulin , Závodná Táňa , Ervik Torunn K. , Skare Øivind , Hron Tomáš , Anmarkrud Kristine H. , Kuśnierczyk Anna , Catalán Julia , Ellingsen Dag G. , Topinka Jan , Zienolddiny-Narui Shan
Published: January 2023

Introduction

Inhalation of nanomaterials may induce inflammation in the lung which if left unresolved can manifest in pulmonary fibrosis. In these processes, alveolar macrophages have an essential role and timely modulation of the macrophage phenotype is imperative in the onset and resolution of inflammatory responses. This study aimed to investigate, the immunomodulating properties of two industrially relevant high aspect ratio nanomaterials, namely nanocellulose and multiwalled carbon nanotubes (MWCNT), in an alveolar macrophage model.

Methods

MH-S alveolar macrophages were exposed at air-liquid interface to cellulose nanocrystals (CNC), cellulose nanofibers (CNF) and two MWCNT (NM-400 and NM-401). Following exposure, changes in macrophage polarization markers and secretion of inflammatory cytokines were analyzed. Furthermore, the potential contribution of epigenetic regulation in nanomaterial-induced macrophage polarization was investigated by assessing changes in epigenetic regulatory enzymes, miRNAs, and rRNA modifications.

Results

Our data illustrate that the investigated nanomaterials trigger phenotypic changes in alveolar macrophages, where CNF exposure leads to enhanced M1 phenotype and MWCNT promotes M2 phenotype. Furthermore, MWCNT exposure induced more prominent epigenetic regulatory events with changes in the expression of histone modification and DNA methylation enzymes as well as in miRNA transcript levels. MWCNT-enhanced changes in the macrophage phenotype were correlated with prominent downregulation of the histone methyltransferases Kmt2a and Smyd5 and histone deacetylases Hdac4, Hdac9 and Sirt1 indicating that both histone methylation and acetylation events may be critical in the Th2 responses to MWCNT. Furthermore, MWCNT as well as CNF exposure led to altered miRNA levels, where miR-155-5p, miR-16-1-3p, miR-25-3p, and miR-27a-5p were significantly regulated by both materials. PANTHER pathway analysis of the identified miRNA targets showed that both materials affected growth factor (PDGF, EGF and FGF), Ras/MAPKs, CCKR, GnRH-R, integrin, and endothelin signaling pathways. These pathways are important in inflammation or in the activation, polarization, migration, and regulation of phagocytic capacity of macrophages. In addition, pathways involved in interleukin, WNT and TGFB signaling were highly enriched following MWCNT exposure.

Conclusion

Together, these data support the importance of macrophage phenotypic changes in the onset and resolution of inflammation and identify epigenetic patterns in macrophages which may be critical in nanomaterial-induced inflammation and fibrosis.
Massive nutrients offshore transport off the Changjiang Estuary in flooding summer of 2020
Authors: Sun Qianwen , Li Dewang , Wang Bin , Xu Zhongsheng , Miao Yanyi , Lin Hua , Jin Haiyan , Jiang Zhibing , Zeng Jiangning , Zhou Feng , Chen Jianfang
Published: January 2023

Flood events significantly increase water discharges and terrigenous material inputs to coastal waters. Riverine nutrients in the Changjiang Estuary are transported by the dispersion of Changjiang Diluted Water (CDW) plumes and detached low-salinity water patches. However, the effects of flooding on nutrient offshore transports have not been well explored. Here, we present the nutrient conditions in the Changjiang Estuary and adjacent East China Sea in the historical flooding year 2020. Comparisons of nutrient distributions between flooding years, drought year and non-flooding years were also made. Our results showed that nitrate flux from the Changjiang River in August 2020 was 1.5 times that of the multi-year averaged flux in non-flooding years. Enormous riverine nutrient input resulted in much higher nutrient concentrations in the outer estuary than those in non-flooding years. In addition, a detached low-salinity water patch was observed, which made the salinity of the northern estuary even lower than that in the historical flooding year 1998. Surface dissolved inorganic nitrate (DIN) level in the low-salinity water patch was even ~16 times of that at nearby station in the drought year 2006. While phosphate (PO43−) concentrations were less than 0.1 μmol L−1 east of 123°E, which was probably caused by intensive biological uptake, as indicated by a high Chlorophyll a (Chl a) concentration (29.08 μg L−1). The depleted PO43− and high N/P of the low-salinity water patch suggested PO43− limitation even under flood conditions. A three end-member mixing model was adopted to identify the contributions of the CDW end-member (CDWend-member) and biological process to nutrient distributions. Our model results showed that the nutrient contribution of the CDWend-member to the estuary (122–124°E, 31–32.5°N) in flooding year 2020 was over double that in drought year 2006. Model-derived biological DIN uptake was as high as 24.65 μmol L−1 at the low-salinity water patch. Accordingly, the estimated net community production was 566–1131 mg C m−2 d−1 within the euphotic zone. The offshore transport of a low-salinity, high-DIN water patch during flooding could probably have a significant influence on biogeochemical cycles in the broad shelf, and even the adjacent Japan Sea.
Exposure to polychlorinated biphenyls (PCBs) affects the histology and antioxidant capability of the clam Cyclina sinensis
Authors: Liu Meimei , Fan Sishao , Rong Zhichao , Qiu Hao , Yan Susu , Ni Hongwei , Dong Zhiguo
Published: January 2023

Polychlorinated biphenyls (PCBs) are environmentally persistent and highly toxic organochlorine compounds that may cause toxic effects on aquatic animals. In this study we assess the toxic effect of PCBs on a bivalve used in aquaculture, the clam Cyclina sinensis. To this end, individuals of C. sinensis were exposed for 72 h at two PCB concentrations (1 ng/L and 10 ng/L) and control (absence of PCBs). At the end of the exposure, the hemolymph, hepatopancreas, and gills samples of C. sinensis were harvested for analysis of the enzyme activity and histology. The results showed that acute PCBs exposure decreased the survival rate of C. sinensis compared to the control. Acute PCBs exposure up-regulated the enzymatic activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) in the hemolymph of C. sinensis, while down-regulated the non-specific enzymatic activity of alkaline phosphatase (AKP). For the hepatopancreas, 1 ng/L PCBs exposure up-regulated the enzymatic activity of SOD while down-regulated the enzymatic activity of CAT of C. sinensis. In the gill, the enzymatic activity of CAT decreased significantly and the MDA content increased of C. sinensis after 10 ng/L PCBs exposure. Moreover, histological observations showed that acute exposure to PCBs caused loss of gill filaments and lateral cilia and shortening of their length, in the studied organism. The present study will provide valuable reference data for marine shellfish aquaculture and toxicology research.
Automated, high-accuracy classification of textured microstructures using a convolutional neural network
Authors: Khurjekar Ishan D. , Conry Bryan , Kesler Michael S. , Tonks Michael R. , Krause Amanda R. , Harley Joel B.
Published: January 2023

Crystallographic texture is an important descriptor of material properties but requires time-intensive electron backscatter diffraction (EBSD) for identifying grain orientations. While some metrics such as grain size or grain aspect ratio can distinguish textured microstructures from untextured microstructures after significant grain growth, such morphological differences are not always visually observable. This paper explores the use of deep learning to classify experimentally measured textured microstructures without knowledge of crystallographic orientation. A deep convolutional neural network is used to extract high-order morphological features from binary images to distinguish textured microstructures from untextured microstructures. The convolutional neural network results are compared with a statistical Kolmogorov–Smirnov tests with traditional morphological metrics for describing microstructures. Results show that the convolutional neural network achieves a significantly improved classification accuracy, particularly at early stages of grain growth, highlighting the capability of deep learning to identify the subtle morphological patterns resulting from texture. The results demonstrate the potential of a convolutional neural network as a tool for reliable and automated microstructure classification with minimal preprocessing.
Galaxy ASIST: A web-based platform for mapping and assessment of global standards of antimicrobial susceptibility: A case study in Acinetobacter baumannii genomes
Authors: Sharma Tina , Kumar Rakesh , Kalra Jasmeer Singh , Singh Shreya , Bhalla Gurpreet Singh , Bhardwaj Anshu
Published: January 2023

Introduction

Antimicrobial susceptibility testing (AST) is used to determine the susceptibility of an organism to antibiotics. The determination of susceptibility is based on MIC breakpoints and is provided by EUCAST and CLSI. Likewise, phenotypic classification criteria developed by CDC/ECDC are used for the classification of pathogens into susceptible, multidrug-resistant, extremely drug-resistant, or totally drug-resistant categories. Whole-genome sequencing (WGS)-based diagnosis is now supplementing existing gold-standard microbiology methods for rapid and more precise AST, and therefore, EUCAST recommended quality criteria to assess whole-genome sequence for reporting the same. In this study, these three global standards, MIC breakpoints, phenotypic classification, and genome quality, are applied to the largest publicly available data for Acinetobacter baumannii (AB), the most critical priority pathogen identified by WHO.

Materials and Methods

The drug sensitivity profile and genomes for isolates of AB were obtained from PATRIC and evaluated with respect to AST standards (CLSI and EUCAST). Whole genome quality assessment and antimicrobial resistance mapping is performed with QUAST and ABRicate, respectively. Four in-house methods are developed for mapping standards and are integrated into a Galaxy workflow based system, Galaxy-ASIST. Analysis of the extent of agreement between CLSI 2022 and EUCAST 2022 for antibiotics was carried out using Cohen’s kappa statistics.

Results and Discussion

An automated pipeline, Galaxy-ASIST, is designed and developed for the characterization of clinical isolates based on these standards. Evaluation of over 6,500 AB strains using Galaxy-ASIST indicated that only 10% of the publicly available datasets have metadata to implement these standards. Furthermore, given that CLSI and EUCAST have different MIC breakpoints, discrepancies are observed in the classification of resistant and susceptible isolates following these standards. It is, therefore, imperative that platforms are developed that allow the evaluation of ever increasing phenotypic and genome sequence datasets for AST. Galaxy-ASIST offers a centralized repository and a structured metadata architecture to provide a single globally acceptable framework for AST profiling of clinical isolates based on global standards. The platform also offers subsequent fine mapping of antimicrobial-resistant determinants. Galaxy-ASIST is freely available at https://ab-openlab.csir.res.in/asist.
Effects of magnesium-modified biochar on soil organic carbon mineralization in citrus orchard
Authors: Hu Lening , Huang Rui , Zhou Liming , Qin Rui , He Xunyang , Deng Hua , Li Ke
Published: January 2023

In order to investigate the carbon sequestration potential of biochar on soil, citrus orchard soils with a forest age of 5 years was taken as the research object, citrus peel biochar (OBC) and magnesium-modified citrus peel biochar (OBC-mg) were selected as additive materials, and organic carbon mineralization experiments were carried out in citrus orchard soil. OBC and OBC-Mg were applied to citrus orchard soils at four application rates (0, 1, 2, and 4%), and incubated at a constant temperature for 100 days. Compared with CK, the cumulative mineralization of soil organic carbon decreased by 5.11% with 1% OBC and 2.14% with 1% OBC-Mg. The application of OBC and OBC-Mg significantly increased the content of soil organic carbon fraction, while the content of soil organic carbon fraction was higher in OBC-Mg treated soil than in OBC treated soil. Meanwhile, the cumulative mineralization of soil organic carbon was significantly and positively correlated with the activities of soil catalase, urease and sucrase. The enzyme activities increased with the cumulative mineralization of organic carbon, and the enzyme activities of the OBC-Mg treated soil were significantly higher than those of the OBC treated soil. The results indicated that the OBC-Mg treatment inhibited the organic carbon mineralization in citrus orchard soils and was more favorable to the increase of soil organic carbon fraction. The Mg-modified approach improved the carbon sequestration potential of biochar for citrus orchard soils and provided favorable support for the theory of soil carbon sink in orchards.
Eastern Cooperative Oncology Group, β2-microglobulin, hemoglobin, and lactate dehydrogenase can predict early grade ≥ 3 infection in patients with newly diagnosed multiple myeloma: A real-world multicenter study
Authors: Lu Xinyi , Liu Wenhua , Zhang Lan , Chen Xinyue , Yang Liping , Yao Qiong , Zhao Jie , He Shaolong , Wei Jia , Tian Weiwei
Published: January 2023

Introduction

This research explored the clinical application of grade ≥ 3 infection predictive models for the newly diagnosed multiple myeloma (NDMM) population.

Methods

It evaluated 306 patients with NDMM based on three different predictive models. The relationship between the grade ≥ 3 infection rates in NDMM and the scores was analyzed retrospectively. The cumulative incidence of early grade ≥ 3 infection was estimated using the Kaplan–Meier method and log-rank test to assess the statistical significance of the difference. To compare the predictive performance in the prediction of infection, the Receiver Operating Characteristic Curve (ROC) curve was used to show the area under the curve (AUC), and DeLong’s test was used to analyze the difference in AUC.

Results

The incidence of grade ≥ 3 infection within the first 4 months of NDMM was 40.20%. Concerning the FIRST score (predictors: ECOG, β2-microglobulin, hemoglobin, and lactate dehydrogenase), GEM-PETHEMA score (predictors: albumin, male sex, ECOG, and non-IgA type MM), and Infection Risk model of Multiple Myeloma (IRMM) score (predictors: ECOG, serum β2-microglobulin, globulin, and hemoglobin), the probability of early grade ≥ 3 infection in the different groups showed statistically significant differences (low-risk vs. high-risk: 25.81% vs. 50.00%, p < 0.001; low-risk vs. moderate-risk vs. high-risk: 35.93% vs. 41.28% vs. 60.00%, p= 0.045; low-risk vs. moderate-risk vs. high-risk: 20.00% vs. 43.75% vs. 52.04%, p < 0.001). Statistical differences existed in the probability of early grade ≥ 3 infection among the different groups by the FIRST and IRMM scores but no statistical differences in the GEM-PETHEMA score (p < 0.001, p< 0.001, and p = 0.090, respectively). The FIRST score showed good discrimination and simple calculation with highest AUC. Further subgroup analysis showed that the FIRST score could still apply for patients treated with bortezomib-based regimen and frail patients.

Discussion

Our findings indicate that the FIRST score (consisting of ECOG, β2-microglobulin, hemoglobin, and lactate dehydrogenase) is a simple and robust infection stratification tool for patients with NDMM and could be used in routine clinical work.
Effects of “Taking the Waist as the Axis” Therapy on trunk postural control disorder after stroke: A randomized controlled trial
Authors: Cui Rong , Liu Hongtao , Li Meng , Wang Jie , Mao Junjie , Ni Weidong , Wang Furong , Pan Jingxian , Yu Long , Wang Yan , Wang Yanmin , Huang Pufeng , Li Gaiyan , Zhao Yi , Zhu Ning , Chen Chen , Pan Ziyang , Zhang Ying , Fu Weijie , Yang Jianzhong
Published: January 2023

Background

Sufficient attention to trunk rehabilitation after stroke is still lacking. Loss of trunk selective activity is considered to be the leading cause of trunk postural control disorder after stroke. “Taking the Waist as the Axis” Therapy (WAT) was developed as a combination of the concept of “Taking the Waist as the Axis” from Tai Chi and the rehabilitation of trunk dysfunction after stroke. The present clinical trial examined and assessed the effects of WAT on stroke patients.

Methods

A total of 43 stroke hemiplegic patients with trunk postural control disorder, whose Trunk Impairment Scale (TIS) scoring between 8 and 18, participated in the present study and were allocated randomly to the experimental (n = 23) or control groups (n = 20). The experimental group received WAT plus conventional therapy, and the control group received “Trunk Selective Activity” Therapy (TSAT) plus conventional therapy. Both groups received treatment once daily and 5 times per week for 3 weeks. The Trunk Impairment Scale (TIS), Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS), change of Intra-abdominal Pressure (IAP), static balance ability assessment, rapid ventilation lung function test and the Modified Barthel Index (MBI) were evaluated before and after intervention for both groups.

Results

The experimental group was superior to the control group in TIS [4 (2, 5) vs. 3 (1.25, 4), p = 0.030], change of IAP [−3 (−8, −1.33) vs. −0.02 (−3.08, 6), p = 0.011], FMA-upper extremity [10 (6, 18) vs. 1 (0, 3), p = 0.002], FMA-lower extremity [2 (1, 4) vs. 1 (0, 2), p = 0.009] and FMA [14 (7, 21) vs. 2 (0.25, 3.75), p = 0.001]. Within experimental group, forced vital capacity (FVC) [81.35 (63.30, 94.88) vs. 91.75 (79.40, 97.90), p = 0.02] was significantly improved.

Conclusion

WAT was an effective trunk treatment after stroke, which significantly improved the patients’ trunk posture control ability, motor function and forced vital capacity. However, the results still need to be interpreted with caution for the intervention only lasted for 3 weeks.
Gut-brain axis: Mechanisms and potential therapeutic strategies for ischemic stroke through immune functions
Authors: Zhou Sheng-Yu , Guo Zhen-Ni , Yang Yi , Qu Yang , Jin Hang
Published: January 2023

After an ischemic stroke (IS) occurs, immune cells begin traveling to the brain and immune system from the gut and gastrointestinal tract, where most of them typically reside. Because the majority of the body’s macrophages and more than 70% of the total immune cell pool are typically found within the gut and gastrointestinal tract, inflammation and immune responses in the brain and immune organs require the mobilization of a large number of immune cells. The bidirectional communication pathway between the brain and gut is often referred to as the gut-brain axis. IS usually leads to intestinal motility disorders, dysbiosis of intestinal microbiota, and a leaky gut, which are often associated with poor prognosis in patients with IS. In recent years, several studies have suggested that intestinal inflammation and immune responses play key roles in the development of IS, and thus may become potential therapeutic targets that can drive new therapeutic strategies. However, research on gut inflammation and immune responses after stroke remains in its infancy. A better understanding of gut inflammation and immune responses after stroke may be important for developing effective therapies. This review discusses the immune-related mechanisms of the gut-brain axis after IS and compiles potential therapeutic targets to provide new ideas and strategies for the future effective treatment of IS.
Inflammatory processes involved in the alteration of liver function biomarkers in adult hospitalized patients treated with parenteral nutrition
Authors: Llop Talaveron Josep M. , Suárez-Lledó Grande Ana , Leiva Badosa Elisabet , Bas Minguet Jordi , Climent Martí Joan , Poyatos Cantón Elisabet , Badia Tahull María B.
Published: January 2023

Introduction

Liver damage has been associated with the accumulation of phytosterols (PS) in patients treated with parenteral nutrition (PN). We aimed to study the association of inflammatory markers with liver function biomarker (LFB) alterations in patients treated with PN containing PS.

Materials and methods

Prospective observational study. Simple linear and stepwise multiple linear regression tests and interactions were performed.

Results

Nineteen patients were included. In the multivariable model, determinations based on LFBs as dependent and phytosterols (and their fractions) as independent variables showed an association between increases in gamma-glutamyltransferase (GGT) and lanosterol (p < 0.001), stigmasterol (p < 0.001), interleukin-10 (IL-10) × total phytosterols (Phyt) (p < 0.009), tumor necrosis factor-α (TNF-α) × Phyt (p < 0.002), IL-10 × sitosterol (p < 0.002), TNF-α × sitosterol (p < 0.001), IL-10 × campesterol (p < 0.033), IL-10 (p < 0.006 and p < 0.015), TNF-α (p < 0.048 and p < 0.027). Increases in alanine aminotransferase (ALT) were associated with Phyt (p < 0.006), lanosterol (p < 0.016), C-reactive protein (CRP) × campesterol (p < 0.001), interleukin-6 (IL-6) × stigmasterol (p < 0.030), CRP (p < 0.08), and IL-6 (p < 0.042). Alkaline phosphatase (AP) increases were associated with CRP (p < 0.002).

Discussion

Inflammation in the presence of plasmatic PS seems to have a synergistic effect in impairing liver function, mainly altering GGT but also ALT.
Transcriptomic profiling revealed FZD10 as a novel biomarker for nasopharyngeal carcinoma recurrence
Authors: Tulalamba Warut , Ngernsombat Chawalit , Larbcharoensub Noppadol , Janvilisri Tavan
Published: January 2023

Background

Nasopharyngeal carcinoma (NPC) is a type of cancers that develops in the nasopharynx, the very upper part of the throat behind the nose. NPC is typically diagnosed in later stages of the disease and has a high rate of recurrence due to the location of the tumor growth site. In this study, we compared the gene expression profiles of NPC tissues from patients with and without recurrence to identify potential molecular biomarkers of NPC recurrence.

Methods

Microarrays were used to analyze the expression of genes in 15 NPC tissues taken at the time of diagnosis and at the site of recurrence following therapeutic treatment. Pathway enrichment analysis was used to examine the biological interactions between the major differentially expressed genes. The target identified was then validated using immunohistochemistry on 86 NPC tissue samples.

Results

Our data showed that the Wnt signaling pathway was enhanced in NPC tissues with recurrence. FZD10, a component of the Wnt signaling pathway, was significantly expressed in NPC tissues, and was significantly associated with NPC recurrence.

Conclusion

Our study provides new insights into the pathogenesis of NPC and identifies FZD10 as a potential molecular biomarker for NPC recurrence. FZD10 may be a promising candidate for NPC recurrence and a potential therapeutic target.
BASP1 is a prognostic biomarker associated with immunotherapeutic response in head and neck squamous cell carcinoma
Authors: Pan Xue , Xu Xun , Wang Lixuan , Zhang Siyuan , Chen Yingyao , Yang Rongchun , Chen Xijuan , Cheng Bin , Xia Juan , Ren Xianyue
Published: January 2023

Backgrounds

Immunotherapy is effective in a subset of head and neck squamous cell carcinoma (HNSCC). However, the unfavorable response rate and inadequate biomarkers for stratifying patients have primarily limited its clinical application. Considering transcriptional factors (TFs) play essential roles in regulating immune activity during HNSCC progression, we comprehensively analyzed the expression alterations of TFs and their prognostic values.

Methods

Gene expression datasets and clinical information of HNSCC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repository. Then, Brain abundant membrane attached signal protein 1 (BASP1) was screened out of differentially expressed TFs by univariate and multivariate survival analysis. Tumor immune dysfunction and exclusion (TIDE) was applied to analyze the response to immunotherapy of BASP1high/low patients. Meanwhile, GO, KEGG and GSEA analyses were used to enrich the pathways between the BASP1high and BASP1low groups. Single-sample gene set enrichment analysis (ssGSEA), CIBERSORT, EPIC and quanTiseq algorithms were applied to explore immune infiltrations. Also, immune cycle analysis was conducted by ssGSEA. Additionally, lipid peroxidation, glutathione and reactive oxygen species were performed to detect the ferroptosis alternations.

Results

BASP1 was upregulated and associated with poor survival in HNSCC patients. BASP1high patients exhibited better response rates to anti-PD-1 immunotherapy and higher expressions of immune checkpoint inhibitors. GO, KEGG and GSEA analyses indicated that the expression of BASP1 was related to several immune-related pathways and immunogenic ferroptosis signature. The infiltration of activated CD8+ T cells was authenticated to be decreased in BASP1high patients. Furthermore, BASP1 was identified to be positively correlated with T cell dysfunction and immune escape. Moreover, silencing BASP1 triggered ferroptosis in HNSCC cells, representing as increased LDH, lipid peroxidation and ROS levels, and reduced glutathione synthesis

Conclusions

We demonstrated that BASP1 suppressed immunogenic ferroptosis to induce immunosuppressive tumor microenvironment. BASP1 plays a critical role in immune response, and might be a promising classifier for selecting HNSCC patients who benefit from current immunotherapy.
Review: Improving quality of life in patients with differentiated thyroid cancer
Authors: Pace-Asciak Pia , Russell Jonathon O. , Tufano Ralph P.
Published: January 2023

Well differentiated thyroid cancer is a common malignancy diagnosed in young patients. The prognosis tends to be excellent, so years of survivorship is expected with low risk disease. When making treatment decisions, physicians should consider long-term quality of life outcomes when guiding patients. The implications for treating indolent, slow growing tumors are immense and warrant careful consideration for the functioning years ahead. Surgery is the standard of care for most patients, however for a subset of patients, active surveillance is appropriate. For those wishing to treat their cancer in a more active way, novel remote access approaches have emerged to avoid a cervical incision. In the era of “doing less”, options have further expanded to include minimally invasive approaches, such as radiofrequency ablation that avoids an incision, time off work, a general anesthetic, and the possibility of post-treatment hypothyroidism. In this narrative review, we examine the health related quality of life effects that surgery has on patients with thyroid cancer, including some of the newer innovations that have been developed to address patient concerns. We also review the impact that less aggressive treatment has on patient care and overall wellbeing in terms of active surveillance, reduced doses of radioactive iodine (RAI) treatment, or minimally invasive techniques such as radiofrequency ablation (RFA) for low risk thyroid disease.
Cancer beliefs and screening behaviors: The impact of neighborhood and other social determinants of health
Authors: Layne Tracy M. , Agarwal Parul , Rapkin Bruce D. , Jandorf Lina H. , Bickell Nina A.
Published: January 2023

Background

Beliefs about cancer influence breast and colorectal cancer (CRC) screening behavior. Screening rates for these cancers differ in the contiguous neighborhoods of East Harlem (EH), Central Harlem (CH), and the Upper East Side (UES), which have distinct socio-demographic compositions. We assessed the belief-screening behavior relationship in these neighborhoods.

Methods

The 2019 Community Cancer Needs Survey included adults eligible for breast and/or colorectal cancer screening. Raking was used to generate neighborhood-specific distribution estimates. Categorical variables were compared using Chi-square tests. Stepwise logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between cancer beliefs and screening.

Results

Our weighted sample included 147,726 respondents. Screening was 75% in CH, 81% in EH, and 90% in the UES for breast cancer, and 71%, 76%, and 92% for CRC, respectively. The fatalistic belief “There’s not much you can do to lower your chances of getting cancer” differed by neighborhood with screening more likely in CH respondents (breast OR =1.45 and colorectal OR =1.11), but less likely in EH (OR= 0.77 and 0.37, respectively). UES ORs were not generated due to too few unscreened respondents.

Conclusions

Cancer beliefs were inconsistently associated with breast and CRC screening across three NYC neighborhoods. This suggests that a given belief may either motivate or deter screening, depending upon context or interpretation. Once access is addressed, efforts seeking to enhance screening rates should consider implications of communities’ varying beliefs.