bluuebunny/crossref_metadata_2025 huggingface dataset:
Polysaccharide-Bacteria Interactions From the Lens of Evolutionary Ecology
Authors: Sichert Andreas , Cordero Otto X.
Published: October 2021

Microbes have the unique ability to break down the complex polysaccharides that make up the bulk of organic matter, initiating a cascade of events that leads to their recycling. Traditionally, the rate of organic matter degradation is perceived to be limited by the chemical and physical structure of polymers. Recent advances in microbial ecology, however, suggest that polysaccharide persistence can result from non-linear growth dynamics created by the coexistence of alternate degradation strategies, metabolic roles as well as by ecological interactions between microbes. This complex “landscape” of degradation strategies and interspecific interactions present in natural microbial communities appears to be far from evolutionarily stable, as frequent gene gain and loss reshape enzymatic repertoires and metabolic roles. In this perspective, we discuss six challenges at the heart of this problem, ranging from the evolution of genetic repertoires, phenotypic heterogeneity in clonal populations, the development of a trait-based ecology, and the impact of metabolic interactions and microbial cooperation on degradation rates. We aim to reframe some of the key questions in the study of polysaccharide-bacteria interactions in the context of eco-evolutionary dynamics, highlighting possible research directions that, if pursued, would advance our understanding of polysaccharide degraders at the interface between biochemistry, ecology and evolution.
Insight Into Ecology, Metabolic Potential, and the Taxonomic Composition of Bacterial Communities in the Periodic Water Pond on King George Island (Antarctica)
Authors: Krucon Tomasz , Dziewit Lukasz , Drewniak Lukasz
Published: October 2021

Polar regions contain a wide variety of lentic ecosystems. These include periodic ponds that have a significant impact on carbon and nitrogen cycling in polar environments. This study was conducted to assess the taxonomic and metabolic diversity of bacteria found in Antarctic pond affected by penguins and sea elephants and to define their role in ongoing processes. Metabolic assays showed that of the 168 tested heterotrophic bacteria present in the Antarctic periodic pond, 96% are able to degrade lipids, 30% cellulose, 26% proteins, and 26% starch. The taxonomic classification of the obtained isolates differs from that based on the composition of the 16S rRNA relative abundances in the studied pond. The dominantActinobacteriaconstituting 45% of isolates represents a low proportion of the community, around 4%. With the addition of run-off, the proportions of inhabiting bacteria changed, including a significant decrease in the abundance ofCyanobacteria, from 2.38 to 0.33%, increase ofFirmicutesfrom 9.32 to 19.18%, and a decreasing richness (Chao1 index from 1299 to 889) and diversity (Shannon index from 4.73 to 4.20). Comparative studies of communities found in different Antarctic environments indicate a great role for penguins in shaping bacterial populations.
Isolation and Identification of Talaromyces sp. Strain Q2 and Its Biocontrol Mechanisms Involved in the Control of Fusarium Wilt
Authors: Tian Yehan , Zhao Yang , Fu Xuesong , Yu Chengming , Gao Kexiang , Liu Huixiang
Published: October 2021

Fusarium wilt is an important disease of many food crops and often causes serious damages to yield and food quality. Consequently, numerous studies mainly focused on exploring the control strategy for Fusarium oxysporum as well as the mechanism of interaction between the F. oxysporum and other beneficial soil microorganisms. In this study, we have screened and identified an efficient biocontrol strain from the soil with infection of F. oxysporum f. sp. momordica (referred to as Fom), Talaromyces purpurogenus Q2 (referred to as TpQ2), which could be effective to reduce relative abundance of the rhizospheric Fom, leading to a significant decrease of Fusarium wilt disease incidence in bitter gourd during the greenhouse and field trails. TpQ2 can reduce the relative abundance of rhizospheric Fom through inhibition of growth and development of Fom. During the co-cultivation of TpQ2 and Fom, we confirmed that TpQ2 could significantly suppress the growth and development of Fom through disturbing the normal hyphae shape and function of the cell walls of Fom via secreting cell wall–degrading enzymes and suppression of the expression of cell wall biosynthesis genes, such as FomCFEM. In the meantime, TpQ2 showed a strong negative correlation with F. oxysporum in soil and positive correlation with beneficial indigenous microorganisms that had significant negative correlation with Fusarium populations, such as Streptomycetes, Lysobacter, and Sphingobium. To summarize, TpQ2 has a good biocontrol efficacy on Fusarium wilt of bitter gourd. The biocontrol mechanisms of TpQ2 on Fusarium wilt are complex and diverse.
Prokaryotic Community Succession in Bulk and Rhizosphere Soils Along a High-Elevation Glacier Retreat Chronosequence on the Tibetan Plateau
Authors: Liu Jinbo , Kong Weidong , Xia Pinhua , Zhu Chunmao , Li Xiangzhen
Published: October 2021

Early colonization and succession of soil microbial communities are essential for soil development and nutrient accumulation. Herein we focused on the changes in pioneer prokaryotic communities in rhizosphere and bulk soils along the high-elevation glacier retreat chronosequence, the northern Himalayas, Tibetan Plateau. Rhizosphere soils showed substantially higher levels of total organic carbon, total nitrogen, ammonium, and nitrate than bulk soils. The dominant prokaryotes were Proteobacteria, Actinobacteria, Acidobacteria, Chloroflexi, Crenarchaeota, Bacteroidetes, and Planctomycetes, which totally accounted for more than 75% in relative abundance. The dominant genus Candidatus Nitrososphaera occurred at each stage of the microbial succession. The richness and evenness of soil prokaryotes displayed mild succession along chronosequene. Linear discriminant analysis effect size (LEfSe) analysis demonstrated that Proteobacteria (especially Alphaproteobacteria) and Actinobacteria were significantly enriched in rhizosphere soils compared with bulk soils. Actinobacteria, SHA_109, and Thermoleophilia; Betaproteobacteria and OP1.MSBL6; and Planctomycetia and Verrucomicrobia were separately enriched at each of the three sample sites. The compositions of prokaryotic communities were substantially changed with bulk and rhizosphere soils and sampling sites, indicating that the communities were dominantly driven by plants and habitat-specific effects in the deglaciated soils. Additionally, the distance to the glacier terminus also played a significant role in driving the change of prokaryotic communities in both bulk and rhizosphere soils. Soil C/N ratio exhibited a greater effect on prokaryotic communities in bulk soils than rhizosphere soils. These results indicate that plants, habitat, and glacier retreat chronosequence collectively control prokaryotic community composition and succession.
Combining CRISPR-Cas12a-Based Technology and Metagenomics Next Generation Sequencing: A New Paradigm for Rapid and Full-Scale Detection of Microbes in Infectious Diabetic Foot Samples
Authors: Chen Yixin , Shi Ya , Zhu Weifen , You Jiaxing , Yang Jie , Xie Yaping , Zhao Hanxin , Li Hongye , Fan Shunwu , Li Lin , Liu Chao
Published: October 2021

Introduction: Diabetic foot infections (DFIs) pose a huge challenge for clinicians. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is one of the most significant pathogens of DFI. Early pathogen identification will greatly benefit the diagnosis and treatment of the disease. However, existing diagnostic methods are not effective in early detection.

Methods: We developed an assay that coupled loop-mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeats (CRISPR) techniques to enable quick and specific detection of Staphylococcus aureus and differentiate MRSA in samples from patients with DFI. Furthermore, the results were compared using a reference culture, quantitative real-time polymerase chain reaction (qRT-PCR), and metagenomics next generation sequencing (mNGS).

Results: The CRISPR-LAMP assay targeting nuc and mecA successfully detected S. aureus strains and differentiated MRSA. The limit of detection (LoD) of the real-time LAMP for nuc and mecA was 20 copies per microliter reaction in comparison to two copies per μL reaction for the qRT-PCR assay. The specificity of the LAMP-CRISPR assay for nuc was 100%, without cross-reactions with non-S. aureus strains. Evaluating assay performance with 18 samples from DFI patients showed that the assay had 94.4% agreement (17/18 samples) with clinical culture results. The results of mNGS for 8/18 samples were consistent with those of the reference culture and LAMP-CRISPR assay.

Conclusion: The findings suggest that the LAMP-CRISPR assay could be promising for the point-of-care detection of S. aureus and the differentiation of MRSA in clinical samples. Furthermore, combining the LAMP-CRISPR assay and mNGS provides an advanced platform for molecular pathogen diagnosis of DFI.
Bacillus velezensis AP183 Inhibits Staphylococcus aureus Biofilm Formation and Proliferation in Murine and Bovine Disease Models
Authors: Afroj Sayma , Brannen Andrew D. , Nasrin Shamima , Al Mouslem Abdulaziz , Hathcock Terri , Maxwell Herris , Rasmussen-Ivey Cody R. , Sandage Mary J. , Davis Edward W. , Panizzi Peter , Wang Chengming , Liles Mark R.
Published: October 2021

The increasing frequency of S. aureus antimicrobial resistance has spurred interest in identifying alternative therapeutants. We investigated the S. aureus-inhibitory capacity of B. velezensis strains in mouse and bovine models. Among multiple B. velezensis strains that inhibited S. aureus growth in vitro, B. velezensis AP183 provided the most potent inhibition of S. aureus proliferation and bioluminescence in a mouse cutaneous wound (P = 0.02). Histology revealed abundant Gram-positive cocci in control wounds that were reduced in B. velezensis AP183-treated tissues. Experiments were then conducted to evaluate the ability of B. velezensis AP183 to prevent S. aureus biofilm formation on a tracheostomy tube substrate. B. velezensis AP183 could form a biofilm on a tracheostomy tube inner cannula substrate, and that this biofilm was antagonistic to S. aureus colonization. B. velezensis AP183 was also observed to inhibit the growth of S. aureus isolates originated from bovine mastitis cases. To evaluate the inflammatory response of mammary tissue to intramammary inoculation with B. velezensis AP183, we used high dose and low dose inocula in dairy cows. At the high dose, a significant increase in somatic cell count (SCC) and clinical mastitis was observed at all post-inoculation time points (P < 0.01), which resolved quickly compared to S. aureus-induced mastitis; in contrast, the lower dose of B. velezensis AP183 resulted in a slight increase of SCC and no clinical mastitis. In a subsequent experiment, all mammary quarters in four cows were induced to have grade 1 clinical mastitis by intramammary inoculation of a S. aureus mastitis isolate; following mastitis induction, eight quarters were treated with B. velezensis AP183 and milk samples were collected from pretreatment and post-treatment samples for 9 days. In groups treated with B. velezensis AP183, SCC and abundance of S. aureus decreased with significant reductions in S. aureus after 3 days post-inoculation with AP183 (P = 0.04). A milk microbiome analysis revealed significant reductions in S. aureus relative abundance in the AP183-treated group by 8 days post-inoculation (P = 0.02). These data indicate that B. velezensis AP183 can inhibit S. aureus biofilm formation and its proliferation in murine and bovine disease models.
Distribution of Peptidyl-Prolyl Isomerase (PPIase) in the Archaea
Authors: Anchal  , Kaushik Vineeta , Goel Manisha
Published: October 2021

Cis-trans isomerization of the peptide bond prior to proline is an intrinsically slow process but plays an essential role in protein folding. In vivo cis-trans isomerization reaction is catalyzed by Peptidyl-prolyl isomerase (PPIases), a category of proteins widely distributed among all the three domains of life. The present study is majorly focused on the distribution of different types of PPIases in the archaeal domain. All the three hitherto known families of PPIases (namely FKBP, Cyclophilin and parvulin) were studied to identify the evolutionary conservation across the phylum archaea. The basic function of cyclophilin, FKBP and parvulin has been conserved whereas the sequence alignment suggested variations in each clade. The conserved residues within the predicted motif of each family are unique. The available protein structures of different PPIase across various domains were aligned to ascertain the structural variation in the catalytic site. The structural alignment of native PPIase proteins among various groups suggested that the apo-protein may have variable conformations but when bound to their specific inhibitors, they attain similar active site configuration. This is the first study of its kind which explores the distribution of archaeal PPIases, along with detailed structural and functional analysis of each type of PPIase found in archaea.
Metabolic Engineering of Enterobacter aerogenes for Improved 2,3-Butanediol Production by Manipulating NADH Levels and Overexpressing the Small RNA RyhB
Authors: Wu Yan , Chu Wanying , Yang Jiayao , Xu Yudong , Shen Qi , Yang Haoning , Xu Fangxu , Liu Yefei , Lu Ping , Jiang Ke , Zhao Hongxin
Published: October 2021

Biotechnological production of 2,3-butanediol (2,3-BD), a versatile platform bio-chemical and a potential biofuel, is limited due to by-product toxicity. In this study, we aimed to redirect the metabolic flux toward 2,3-BD in Enterobacter aerogenes (E. aerogenes) by increasing the intracellular NADH pool. Increasing the NADH/NAD+ ratio by knocking out the NADH dehydrogenase genes (nuoC/nuoD) enhanced 2,3-BD production by up to 67% compared with wild-type E. aerogenes. When lactate dehydrogenase (ldh) was knocked out, the yield of 2,3-BD was increased by 71.2% compared to the wild type. Metabolic flux analysis revealed that upregulated expression of the sRNA RyhB led to a noteworthy shift in metabolism. The 2,3-BD titer of the best mutant Ea-2 was almost seven times higher than that of the parent strain in a 5-L fermenter. In this study, an effective metabolic engineering strategy for improved 2,3-BD production was implemented by increasing the NADH/NAD+ ratio and blocking competing pathways.
Weighted Gene Co-expression Network Analysis Identifies a Cancer-Associated Fibroblast Signature for Predicting Prognosis and Therapeutic Responses in Gastric Cancer
Authors: Zheng Hang , Liu Heshu , Li Huayu , Dou Weidong , Wang Xin
Published: October 2021

Background: Cancer-associated fibroblasts (CAFs) are the most prominent cellular components in gastric cancer (GC) stroma that contribute to GC progression, treatment resistance, and immunosuppression. This study aimed at exploring stromal CAF-related factors and developing a CAF-related classifier for predicting prognosis and therapeutic effects in GC.

Methods: We downloaded mRNA expression and clinical information of 431 GC samples from Gene Expression Omnibus (GEO) and 330 GC samples from The Cancer Genome Atlas (TCGA) databases. CAF infiltrations were quantified by the estimate the proportion of immune and cancer cells (EPIC) method, and stromal scores were calculated via the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm. Stromal CAF-related genes were identified by weighted gene co-expression network analysis (WGCNA). A CAF risk signature was then developed using the univariate and least absolute shrinkage and selection operator method (LASSO) Cox regression model. We applied the Spearman test to determine the correlation among CAF risk score, CAF markers, and CAF infiltrations (estimated via EPIC, xCell, microenvironment cell populations-counter (MCP-counter), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms). The TIDE algorithm was further used to assess immunotherapy response. Gene set enrichment analysis (GSEA) was applied to clarify the molecular mechanisms.

Results: The 4-gene (COL8A1, SPOCK1, AEBP1, and TIMP2) prognostic CAF model was constructed. GC patients were classified into high– and low–CAF-risk groups in accordance with their median CAF risk score, and patients in the high–CAF-risk group had significant worse prognosis. Spearman correlation analyses revealed the CAF risk score was strongly and positively correlated with stromal and CAF infiltrations, and the four model genes also exhibited positive correlations with CAF markers. Furthermore, TIDE analysis revealed high–CAF-risk patients were less likely to respond to immunotherapy. GSEA revealed that epithelial–mesenchymal transition (EMT), TGF-β signaling, hypoxia, and angiogenesis gene sets were significantly enriched in high–CAF-risk group patients.

Conclusion: The present four-gene prognostic CAF signature was not only reliable for predicting prognosis but also competent to estimate clinical immunotherapy response for GC patients, which might provide significant clinical implications for guiding tailored anti-CAF therapy in combination with immunotherapy for GC patients.
Sensory Transduction in Photoreceptors and Olfactory Sensory Neurons: Common Features and Distinct Characteristics
Authors: Genovese Federica , Reisert Johannes , Kefalov Vladimir J.
Published: October 2021

The past decades have seen tremendous progress in our understanding of the function of photoreceptors and olfactory sensory neurons, uncovering the mechanisms that determine their properties and, ultimately, our ability to see and smell. This progress has been driven to a large degree by the powerful combination of physiological experimental tools and genetic manipulations, which has enabled us to identify the main molecular players in the transduction cascades of these sensory neurons, how their properties affect the detection and discrimination of stimuli, and how diseases affect our senses of vision and smell. This review summarizes some of the common and unique features of photoreceptors and olfactory sensory neurons that make these cells so exciting to study.
Vitamin C and Metabolic Syndrome: A Meta-Analysis of Observational Studies
Authors: Guo Hongbin , Ding Jun , Liu Qi , Li Yusheng , Liang Jieyu , Zhang Yi
Published: October 2021

Background: The association between vitamin C and metabolic syndrome (MetS) has been evaluated in several epidemiological studies with conflicting results. This meta-analysis was therefore employed to further investigate the above issue.

Methods: The observational studies on the associations of dietary and circulating (serum and plasma) vitamin C levels with MetS were searched in the PubMed, Web of Science, and Embase database up to April 2021. The pooled relative risk (RR) of MetS for the highest vs. lowest dietary and circulating vitamin C levels and the standard mean difference (SMD) of dietary and circulating vitamin C levels for MetS vs. control subjects were calculated, respectively.

Results: A total of 28 observational studies were identified in this meta-analysis. Specifically, 23 studies were related to the dietary vitamin C level. The overall multivariable-adjusted RR demonstrated that the dietary vitamin C level was inversely associated with MetS (RR = 0.93, 95% CI: 0.88–0.97; P = 0.003). Moreover, the overall combined SMD showed that the dietary vitamin C level in MetS was lower than that in control subjects (SMD = −0.04, 95% CI: −0.08 to −0.01; P = 0.024). With regard to the circulating vitamin C level, 11 studies were included. The overall multivariable-adjusted RR demonstrated that the circulating vitamin C level was inversely associated with MetS (RR = 0.60, 95% CI: 0.49–0.74; P < 0.001). In addition, the overall combined SMD showed that the circulating vitamin C level in MetS was lower than that in control subjects (SMD=-0.82, 95%CI: −1.24 to −0.40; P < 0.001).

Conclusions: Current evidence suggests that both dietary and circulating vitamin C level is inversely associated with MetS. However, due to the limitation of the available evidence, more well-designed prospective studies are still needed.
Attenuating Effect of Chlorella Extract on NLRP3 Inflammasome Activation by Mitochondrial Reactive Oxygen Species
Authors: Nakashima Yuya , Gotoh Kazuhito , Mizuguchi Soichi , Setoyama Daiki , Takata Yurie , Kanno Toshihiro , Kang Dongchon
Published: October 2021

The NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome has been linked to the pathogenesis of a wide variety of human diseases. Although many drugs and inhibitors have been developed to treat NLRP3-associated diseases, only limited clinical data support their efficacy and safety. Chlorella, a unicellular green alga that is widely and safely used as a food supplement, contains various antioxidants. In this study, we obtained a fat-soluble extract from Chlorella (CE) and demonstrated that it reduced NLRP3 inflammasome activation by inhibiting mitochondrial reactive oxygen species and caspase-1 activation. In addition, CE supplementation attenuated lipopolysaccharide-induced interleukin 1β transcription through activation of hypoxia-inducible factor 1α in vitro and in vivo. As Chlorella is a safe and useful food supplement, it may be a practical pharmacological approach for treating NLRP3-driven diseases.
A Novel Prognostic Prediction Model for Colorectal Cancer Based on Nine Autophagy-Related Long Noncoding RNAs
Authors: Xu Guoqiang , Yang Mei , Wang Qiaoli , Zhao Liufang , Zhu Sijin , Zhu Lixiu , Xu Tianrui , Cao Ruixue , Li Cheng , Liu Qiuyan , Xiong Wei , Su Yan , Dong Jian
Published: October 2021

Introduction

Colorectal cancer (CRC) is the most common gastrointestinal cancer and has a low overall survival rate. Tumor–node–metastasis staging alone is insufficient to predict patient prognosis. Autophagy and long noncoding RNAs play important roles in regulating the biological behavior of CRC. Therefore, establishing an autophagy-related lncRNA (ARlncRNA)-based bioinformatics model is important for predicting survival and facilitating clinical treatment.

Methods

CRC data were retrieved from The Cancer Genome Atlas. The database was randomly divided into train set and validation set; then, univariate and multivariate Cox regression analyses were performed to screen prognosis-related ARlncRNAs for prediction model construction. Interactive network and Sankey diagrams of ARlncRNAs and messenger RNAs were plotted. We analyzed the survival rate of high- and low-risk patients and plotted survival curves and determined whether the risk score was an independent predictor of CRC. Receiver operating characteristic curves were used to evaluate model sensitivity and specificity. Then, the expression level of lncRNA was detected by quantitative real-time polymerase chain reaction, and the location of lncRNA was observed by fluorescence in situ hybridization. Additionally, the protein expression was detected by Western blot.

Results

A prognostic prediction model of CRC was built based on nine ARlncRNAs (NKILA, LINC00174, AC008760.1, LINC02041, PCAT6, AC156455.1, LINC01503, LINC00957, and CD27-AS1). The 5-year overall survival rate was significantly lower in the high-risk group than in the low-risk group among train set, validation set, and all patients (all p < 0.001). The model had high sensitivity and accuracy in predicting the 1-year overall survival rate (area under the curve = 0.717). The prediction model risk score was an independent predictor of CRC. LINC00174 and NKILA were expressed in the nucleus and cytoplasm of normal colonic epithelial cell line NCM460 and colorectal cancer cell lines HT29. Additionally, LINC00174 and NKILA were overexpressed in HT29 compared with NCM460. After autophagy activation, LINCC00174 expression was significantly downregulated both in NCM460 and HT29, while NKILA expression was significantly increased.

Conclusion

The new ARlncRNA-based model predicts CRC patient prognosis and provides new research ideas regarding potential mechanisms regulating the biological behavior of CRC. ARlncRNAs may play important roles in personalized cancer treatment.
Blood Supply of Cranial Nerves Passing Through the Cavernous Sinus: An Anatomical Study and Its Implications for Microsurgical and Endoscopic Cavernous Sinus Surgery
Authors: Najera Edinson , Ibrahim Bilal , Muhsen Baha’eddin A. , Ali Assad , Sanchez Clariza , Obrzut Michal , Borghei-Razavi Hamid , Adada Badih
Published: October 2021

Background

Despite improvements in surgical techniques, cranial nerve (CN) deficits remain the most frequent cause of disability following cavernous sinus (CS) surgery. The most common tumor affecting the CS is meningioma. They originate from lateral wall and have their blood supply from meningohypophyseal trunk (MHT) and inferolateral trunk (ILT). Pituitary adenomas commonly invade the CS through its medial wall and receive blood supply form medial branches of the internal carotid artery (ICA) (superior and inferior hypophyseal arteries). Some tumors may grow within the CS (e.g. trigeminal schwannomas, hemangiomas). These tumors are fed by all the intracavernous ICA branches. Tumors involving the CS may also displace the neurovascular structures, therefore, a better understanding of intracavernous neurovascular anatomy may reduce the postoperative morbidity associated with approaching CS tumors. In this anatomical study, the anatomic variations and their clinical implications of the intracavernous CNs’ blood supply were evaluated through transcranial and endonasal routes.

Methods

Twenty sides of ten adult cadaveric formalin-fixed, latex-injected specimens were dissected in stepwise fashion under microscopic and endoscopic magnification. The origin and course of the intracavernous ICA branches supplying the intracavernous CNs are studied.

Results

The proximal segment of the oculomotor nerve receives blood supply from the ILT in 85%, and the tentorial artery of the MHT in 15% of specimens. The distal segment is exclusively supplied by the ILT. The proximal trochlear nerve receives blood supply from the ILT (75%) and the tentorial artery (25%); the distal segment is exclusively supplied by the superior orbital branch. The proximal third of the abducens nerve receives its vascularity exclusively from the dorsal meningeal artery, and its middle and distal thirds from the ILT. The ophthalmic and proximal maxillary segments of the trigeminal nerve also receive blood supply from the ILT. The distal maxillary segment is supplied by the artery of the foramen rotundum. All ILT branches terminate on the inferomedial aspects of the intra-cavernous CNs. Extensive anastomoses are found between ILT branches and the branches arising from external carotid artery.

Conclusion

Understanding the anatomy of the intracavernous ICA’s branches is important to improving surgical outcomes with tumors involving the CS.
Association Between Serum Carcinoembryonic Antigen Levels at Different Perioperative Time Points and Colorectal Cancer Outcomes
Authors: Li Zhenhui , Zhang Dafu , Pang Xiaolin , Yan Shan , Lei Ming , Cheng Xianshuo , Song Qian , Cai Le , Wang Zhuozhong , You Dingyun
Published: October 2021

Background

Whether elevated postoperative serum carcinoembryonic antigen (CEA) levels are prognostic in patients with stage II colorectal cancer (CRC) remains controversial.

Patients and Methods

Primary and sensitivity analysis populations were obtained from a retrospective, multicenter longitudinal cohort including consecutive patients without neoadjuvant treatment undergoing curative resection for stage I–III CRC. Serum CEA levels before (CEApre-m1) and within 1 (CEApost-m1), 2–3 (CEApost-m2–3), and 4–6 months (CEApost-m4–6) after surgery were obtained, and their associations with recurrence-free survival (RFS) and overall survival (OS) were assessed using Cox regression. Sensitivity and subgroup analyses were performed.

Results

Primary and sensitivity analysis populations included 710 [415 men; age, 54.8 (11.6) years] and 1556 patients [941 men; age, 56.2 (11.8) years], respectively. Recurrence hazard ratios (HRs) in the elevated CEApre-m1, CEApost-m1, CEApost-m2–3, and CEApost-m4–6 groups were 1.30 (95% CI: 0.91–1.85), 1.53 (95% CI: 0.89–2.62), 1.88 (95% CI: 1.08–3.28), and 1.15 (95% CI: 0.91–1.85), respectively. The HRs of the elevated CEApre-m1, CEApost-m1, CEApost-m2–3, and CEApost-m4–6 groups for OS were 1.09 (95% CI: 0.60–1.97), 2.78 (95% CI: 1.34–5.79), 2.81 (95% CI: 1.25–6.30), and 3.30 (95% CI: 1.67–.536), respectively. Adjusted multivariate analyses showed that both in the primary and sensitivity analysis populations, elevated CEApost-m2–3, rather than CEApre-m1, CEApost-m1, and CEApost-m4–6, was an independent risk factor for recurrence, but not for OS. The RFS in the elevated and normal CEApost-m2–3 groups differed significantly among patients with stage II disease [n = 266; HR, 2.89; 95% CI, 1.02–8.24 (primary analysis); n = 612; HR, 2.69; 95% CI, 1.34–5.38 (sensitivity analysis)].

Conclusions

Elevated postoperative CEA levels are prognostic in patients with stage II CRC, with 2–3 months after surgery being the optimal timing for CEA measurement.
Identification of Candidate Biomarker ASXL2 and Its Predictive Value in Pancreatic Carcinoma
Authors: Wang Gaoming , Yang Ludi , Gao Jinli , Mu Huiling , Song Yanxiang , Jiang Xiaohua , Chen Bo , Cui Ran
Published: October 2021

Pancreatic adenocarcinoma is one of the most lethal diseases with a 5-year survival rate of about 8%. ASXL2 is an epigenetic regulator associated with various tumors including colorectal cancer, breast cancer, and myeloid leukemia. However, the role of ASXL2 in pancreatic cancer remains unclear. This is the first research focusing on the prognostic value of ASXL2 in pancreatic cancer. In this research, we aimed to explore the correlation between ASXL2 and the prognosis, as well as other features in PAAD. We obtained gene expression profiles of PAAD and normal tissues from TCGA, GEO, and Xena databases. TIMER and CIBERSORT algorithms were employed to investigate the effect of ASXL2 on tumor microenvironment. GSEA along with GO and KEGG enrichment analyses were conducted to uncover the biological functions of ASXL2. The response to various chemotherapeutic drugs was estimated by algorithms in R package “pRRophetic”, while the sensitivity to immunotherapy was quantified by TIDE score. We found that ASXL2 was upregulated in the PAAD samples and elevated expression of ASXL2 was linked to poor overall survival. ASXL2 DNA methylation contributed to ASXL2 expression. Functional annotation indicated that ASXL2 was mainly involved in inflammatory response and epithelial mesenchymal transition. Patients with high ASXL2 expression were more likely to benefit from immune checkpoint blockade, gemcitabine, and mitomycin-C. Finally, external datasets and biospecimens were used and the results further validated the aberrant expression of ASXL2 in PAAD samples. In summary, our results highlight that ASXL2 is a potential prognostic and predictive biomarker in pancreatic cancer.
Higher TOX Genes Expression Is Associated With Poor Overall Survival for Patients With Acute Myeloid Leukemia
Authors: Liang Chaofeng , Zhao Yujie , Chen Cunte , Huang Shuxin , Deng Tairan , Zeng Xiangbo , Tan Jiaxiong , Zha Xianfeng , Chen Shaohua , Li Yangqiu
Published: October 2021

Thymocyte selection-associated HMG box (TOX) is a transcription factor that belongs to the high mobility group box (HMG-box) superfamily, which includes four subfamily members: TOX, TOX2, TOX3, and TOX4. TOX is related to the formation of multiple malignancies and contributes to CD8+ T cell exhaustion in solid tumors. However, little is known about the role of TOX genes in hematological malignancies. In this study, we explored the prognostic value of TOX genes from 40 patients with de novo acute myeloid leukemia (AML) by quantitative real-time PCR (qRT-PCR) in a training cohort and validated the results using transcriptome data from 167 de novo AML patients from the Cancer Genome Atlas (TCGA) database. In the training cohort, higher expression of TOX and TOX4 was detected in the AML samples, whereas lower TOX3 expression was found. Moreover, both the training and validation results indicated that higher TOX2, TOX3, and TOX4 expression of AML patients (3-year OS: 0% vs. 37%, P = 0.036; 3-year OS: 4% vs. 61%, P < 0.001; 3-year OS: 0% vs. 32%, P = 0.010) and the AML patients with highly co-expressed TOX, TOX2, TOX4 genes (3-year OS: 0% vs. 25% vs. 75%, P = 0.001) were associated with poor overall survival (OS). Interestingly, TOX2 was positively correlated with CTLA-4, PD-1, TIGIT, and PDL-2 (rs = 0.43, P = 0.006; rs = 0.43, P = 0.006; rs = 0.56, P < 0.001; rs = 0.54, P < 0.001). In conclusion, higher expression of TOX genes was associated with poor OS for AML patients, which was related to the up-regulation of immune checkpoint genes. These data might provide novel predictors for AML outcome and direction for further investigation of the possibility of using TOX genes in novel targeted therapies for AML.
Case Report: Anlotinib Reverses Nivolumab Resistance in Advanced Primary Pulmonary Lymphoepithelioma-Like Carcinoma With FGFR3 Gene Amplification
Authors: Liu Yanyang , Long Lang , Liu Jiewei , Zhu Lingling , Luo Feng
Published: October 2021

Background

Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer (NSCLC). Currently, anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) has become an important treatment for NSCLC. Anti-human PD-1 monoclonal antibodies, such as nivolumab, significantly prolong the survival time of patients with advanced lung adenocarcinoma and lung squamous cell carcinoma. However, there are few reports on the therapeutic effect, drug resistance mechanism, and strategies to overcome resistance to anti-PD-1/PD-L1 treatment in advanced pulmonary LELC. We report the case of a patient with advanced pulmonary LELC harboring fibroblast growth factor receptor (FGFR)3 gene amplification that showed resistance to nivolumab. After treatment with anlotinib, a multi-targeted small-molecule tyrosine kinase inhibitor, the patient’s resistance to nivolumab was reversed. She achieved long-term disease remission with a combination of anlotinib and nivolumab treatment.

Case Presentation

A 68-year-old woman was diagnosed with stage IVA pulmonary LELC. After multiple-line chemotherapy, her disease progressed. Since the PD-L1 expression rate of the patient was 90%, nivolumab was administered. However, the therapeutic effect of nivolumab was not ideal; the disease continued to progress, and a new cervical lymph node metastasis appeared. FGFR3 gene amplification was detected in lymph node metastasis. Based on this gene abnormality, we added anlotinib to the treatment. After two cycles of anlotinib and nivolumab, the metastatic focus of the patient was significantly reduced. The patient continued to receive this combined treatment and achieved remission for more than 15 months.

Conclusion

Pulmonary LELC with FGFR3 gene amplification may not respond well to nivolumab monotherapy. The combination of anlotinib and nivolumab can reverse the resistance to nivolumab in pulmonary LELC with FGFR3 gene amplification.
Precision Interventional Brachytherapy: A Promising Strategy Toward Treatment of Malignant Tumors
Authors: He Pan , Guan Siwen , Ren En , Chen Hongwei , Chen Hu , Peng Yisheng , Luo Bin , Xiong Yongfu , Li Bo , Li Jingdong , Mao Jingsong , Liu Gang
Published: October 2021

Precision interventional brachytherapy is a radiotherapy technique that combines radiation therapy medicine with computer network technology, physics, etc. It can solve the limitations of conventional brachytherapy. Radioactive drugs and their carriers change with each passing day, and major research institutions and enterprises worldwide have conducted extensive research on them. In addition, the capabilities of interventional robotic systems are also rapidly developing to meet clinical needs for the precise delivery of radiopharmaceuticals in interventional radiotherapy. This study reviews the main radiopharmaceuticals, drug carriers, dispensing and fixation technologies, and interventional robotic precision delivery systems used in precision brachytherapy of malignant tumors. We then discuss the current needs in the field and future development prospects in high-precision interventional brachytherapy.
Use of 18F-FDG PET/CT to Differentiate Ectopic Adrenocorticotropic Hormone-Secreting Lung Tumors From Tumor-Like Pulmonary Infections in Patients With Ectopic Cushing Syndrome
Authors: Hou Guozhu , Jiang Yuanyuan , Li Fang , Cheng Xin
Published: October 2021

Background

Ectopic adrenocorticotropic hormone (ACTH)-secreting lung tumors represent the most common cause of ectopic Cushing syndrome (ECS). Pulmonary opportunistic infections are associated with ECS. The present study aimed to evaluate the usefulness of 18F-FDG PET/CT for differentiating ectopic ACTH-secreting lung tumors from tumor-like pulmonary infections in patients with ECS.

Methods

We retrospectively reviewed the imaging data of 24 patients with ECS who were suspected to have ACTH-secreting lung tumors and underwent 18F-FDG PET/CT between 2008 and 2019. Eleven patients with lung tumors and 4 with pulmonary infections also had additional somatostatin receptor imaging (99mTc-HYNIC-TOC SPECT/CT or 68Ga-DOTATATE PET/CT).

Results

In total, 18 patients had lung tumors and six had pulmonary infections. The primary source of ECS remained occult in the six patients with pulmonary infections. The maximum standardized uptake value (SUVmax) for pulmonary infections was significantly higher than that for tumors (P = 0.008). Receiver operating characteristic analysis revealed that a cut-off SUVmax of 4.95 helped in differentiating ACTH-secreting lung tumors from infections with 75% sensitivity and 94.4% specificity. For the 11 patients with ACTH-lung tumors, somatostatin receptor imaging (SRI) was positive in 6; while for the 4 with pulmonary infections, SRI was positive in 2. The sensitivity and specificity of somatostatin receptor imaging (SRI) for detecting ACTH-secreting lung tumor was 54.5% and 50%.

Conclusions

Our findings suggest that pulmonary infections exhibit significantly higher FDG uptake than ACTH-secreting lung tumors in 18F-FDG PET/CT. An SUVmax cut-off value of 4.95 may be useful for differentiating the two conditions. Our results also suggested that SRI may not be an effective tool for differentiating the two conditions given the relatively low specificity.
Preterm Birth Affects Early Motor Development in Pigs
Authors: Vanden Hole Charlotte , Ayuso Miriam , Aerts Peter , Van Cruchten Steven , Thymann Thomas , Sangild Per Torp , Van Ginneken Chris
Published: October 2021

Background: Preterm infants frequently show neuromotor dysfunctions, but it is not clear how reduced gestational age at birth may induce developmental coordination disorders. Advancing postnatal age, not only post-conceptional age, may determine neuromuscular development, and early interventions in preterm newborns may improve their later motor skills. An animal model of preterm birth that allows early postnatal detection of movement patterns may help to investigate this hypothesis.

Methods: Using pigs as a model for moderately preterm infants, preterm (106-day gestation, equivalent to 90% of normal gestation time; n = 38) and term (115-day gestation, equivalent to 99% of normal gestation time; n = 20) individuals were delivered by cesarean section and artificially reared until postnatal day 19 (preweaning period). The neuromotor skills of piglets were documented using spatiotemporal gait analyses on video recordings of locomotion at self-selected speed at postnatal age 3, 4, 5, 8, and 18 days. Results were controlled for effects of body weight and sex.

Results: Both preterm and term piglets reached mature neuromotor skills and performance between postnatal days 3–5. However, preterm pigs took shorter steps at a higher frequency, than term piglets, irrespective of their body size. Within preterm pigs, males and low birth weight individuals took the shortest steps, and with the highest frequency.

Conclusion: Postnatal development of motor skills and gait characteristics in pigs delivered in late gestation may show similarity to the compromised development of gait pattern in preterm infants. Relative to term pigs, the postnatal delay in gait development in preterm pigs was only few days, that is, much shorter than the 10-day reduction in gestation length. This indicates rapid postnatal adaptation of gait pattern after reduced gestational age at birth. Early-life physical training and medical interventions may support both short- and long-term gait development after preterm birth in both pigs and infants.
B Lymphocyte Subsets in Children With Steroid-Sensitive Nephrotic Syndrome: A Longitudinal Study
Authors: Ling Chen , Chen Zhi , Wang Xiaolin , Hua Lin , Gui Jingang , Liu Xiaorong
Published: October 2021

Background: B-cell subsets may be involved in the pathogenesis of childhood steroid-sensitive nephrotic syndrome (SSNS). Horizontal control studies have shown that homeostasis of B-cell subsets changes at different stages of the SSNS. However, there is a lack of longitudinal studies that have investigated dynamic changes in B cell subpopulations.

Methods: Blood samples were collected at the following time points from 15 children with SSNS treated at our hospital: before administration of steroid and after 3 days, 1 week, and 3, 6, 9, and 12 months. The proportions of circulating total B cells (CD19+), transitional B cells (CD19+CD24highCD38high), mature B cells (CD19+CD24lowCD38intermediate), and memory B cells (CD19+CD24highCD38−) were monitored by flow cytometry.

Results: The proportion of CD19+ B cells before steroid administration was significantly higher than that observed at any other time point or in the healthy control (HC) group (p < 0.001). However, this proportion was significantly lower than that in the HC group at 12 months (p = 0.031). Transitional B cells before (%BL 9.5 ± 4.4) and 3 days after steroid administration (%BL 10.6 ± 5.1) were significantly higher than at any other time point or in the HC group (p < 0.001). Although these cells declined after the 3rd day the percentage was still significantly lower than that of the HC group at 12 months (p = 0.029). Memory B cells increased gradually after steroid administration and decreased to the normal range after 9 months.

Conclusions: B cell subpopulations show dynamic changes in children with SSNS, suggesting that they are involved in the pathogenesis of the disorder. Further studies are required to determine whether this change can guide individualized treatment.
Parents' Experience and Satisfaction in Neonatal Intensive Care Units in Ethiopia: A Multicenter Cross-Sectional Study Using an Adapted Version of EMPATHIC-N
Authors: Gulo Berhanu , Miglierina Laura , Tognon Francesca , Panunzi Silvia , Tsegaye Ademe , Asnake Tina , Manenti Fabio , Dall'Oglio Immacolata
Published: October 2021

Background:In neonatal intensive care units (NICU) setting, parents' experience and satisfaction permit to evaluate clinical practice and improve the care of infants and parents. Little is known about this topic in low resource settings. The aim of this study was to (1) translate, adapt and validate the EMpowerment of PArents in THe Intensive Care-Neonatology (EMPHATIC-N) questionnaire in two languages in Ethiopia (2) explore parents' satisfaction with the care received in the NICUs in three hospitals; and, (3) explore socio-demographic characteristics and level of the NICU influence on the EMPATHIC-N domains.

Methods:This was a cross-sectional multicenter study. Participants were recruited from three different NICUs in Ethiopia upon discharge. We reduced the original EMPATHIC-N instrument to 38 items, culturally adapted and validated it in two local languages. Confirmatory Factor Analysis (CFA) was applied to verify the factor structure of the questionnaire, investigating the relationship between items and the five latent domains. Single item scores and the aggregate scores of the domains were investigated across NICUs and in the sample overall. Differences in the distribution of the domain scores were tested according to socio-demographic participants' characteristics. The scores of four general questions about overall experience and satisfaction were investigated in relation to the participant's characteristics and NICU levels. Qualitative data were collected using four open-ended questions and a synthesis of results was provided.

Results:Almost all the parents answered to the questionnaire (92%,n= 386). Questionnaire items on satisfaction on average scored more than four. The highest mean scores were obtained for Parental participation (median: 5.17; iqr: 4.67–5.62), while they were lower for Organization/Hospital environment (median: 4.67; iqr:4.33–5.17). Different levels of parent satisfaction were observed across the NICU levels showing a statistically higher satisfaction in level II NICU compared to the other levels. Education, place of residence and length of stay were associated with parental satisfaction and experience.

Conclusion:This study validated two Ethiopian versions of the EMPATHIC-N questionnaire to assess parents' experience and satisfaction during their child's stay in the NICU. The differences found across the three levels of NICU suggest the need to further investigate the determinants of satisfaction.
Clinical and Microbiological Characterization of Carbapenem-Resistant Enterobacteriales: A Prospective Cohort Study
Authors: Lin Qiuxia , Wu Menglu , Yu Hanbing , Jia Xiaojiong , Zou Hua , Ma Deyu , Niu Siqiang , Huang Shifeng
Published: October 2021

Aim: We aim to depict the clinicoepidemiological and molecular information of carbapenem-resistant Enterobacteriales (CRE) in Chongqing, China.

Methods: We performed a prospective, observational cohort study, recruiting inpatients diagnosed with CRE infections from June 1, 2018, to December 31, 2019. We carried out strain identification and molecular characterization of CRE. eBURST analysis was conducted to assess the relationships among the different isolates on the basis of their sequence types (STs) and associated epidemiological data using PHYLOViZ. Clinical parameters were compared between the carbapenemase-producing Enterobacteriales (CPE) and non-CPE group.

Findings: 128 unique CRE isolates from 128 patients were collected during the study period: 69 (53.9%) CPE and 59 (46.1%) non-CPE. The majority of CPE isolates were blaKPC-2 (56.5%), followed by blaNDM (39.1%) and blaIMP (5.8%). Klebsiella pneumoniae carbapenemase (KPC)–producing clonal group 11 Klebsiella pneumoniae (K. pneumoniae) was the most common CPE. Antibiotic resistance was more frequent in the CPE group than in the non-CPE group. Independent predictors for CPE infection were ICU admission and hepatobiliary system diseases. Although, there was no significant difference in desirability of outcome ranking (DOOR) outcomes between the two groups. At 30 days after index culture, 35 (27.3% ) of these patients had died.

Conclusion: CRE infections were related to high mortality and poor outcomes, regardless of CRE subgroups. CPE were associated with prolonged ICU stays and had different clinical and microbiological characteristics than non-CPE. The identification of CPE/non-CPE and CRE resistance mechanisms is essential for better guidance of the clinical administration of patients with CRE infections.