bluuebunny/crossref_metadata_2025 huggingface dataset:
Atopic Dermatitis: The Need for a Sub-Saharan Perspective
Authors: Paul Richard , Sakuntabhai Anavaj
Published: October 2022

Atopic dermatitis (AD) is one of the most common non-infectious diseases in the world. For over two decades there has been considerable mobilisation to create a robust framework to address this global problem (the International Study of Asthma and Allergies in Childhood [ISAAC] consortium). However, information about Sub-Saharan Africa remains sparse, likely reflecting the increased focus placed on infectious diseases. However, this region harbours the greatest environmental and genetic diversity and thus offers enormous potential for understanding the differential environmental impact on human populations predisposed to allergic diseases. Moreover, it is increasingly clear that many pathologies share the same genetic determinants and this spans both non-infectious and infectious diseases. In this review, we discuss the comparative genetics of the allergic diseases and then expand into infectious diseases, notably malaria. We discuss the considerable overlap in the identified genetic determinants of AD and malaria and develop a hypothesis based on the importance of saliva from mosquito bites, arguably the most prevalent allergen in the region. Following the completion of the first phase of the African Genome project, we stress the significance of more focus on allergic diseases in the region, which will certainly generate an abundance of novel insight into the environmental and genetic determinants of allergy and may also contribute to our understanding of arthropod-borne infectious diseases.
Improving Diagnosis: The Next Frontier in Hereditary Angioedema Management
Authors: Bamanikar Arvind
Published: October 2022

Drug allergy, in clinical practice, includes a wide spectrum of immunologically-mediated hypersensitivity reactions, also called drug hypersensitivity reactions (DHRs). It can present with diverse clinical manifestations and can have various underlying pathophysiological mechanisms. Drug allergies often require a number of investigations and this can sometimes lead to a delay in treatment of the original disease. Drug allergy can affect quality of life too. It does contribute to significant morbidity and even mortality which is largely avoidable. Meticulous relevant details in history and clinical examination are often rewarding in arriving at the correct diagnosis. Patients with underlying chronic airways diseases such as asthma may benefit from skin tests and graded allergen challenges. Procedures to induce drug tolerance are sometimes helpful in the drug allergy management. Likelihood of cross-reactivity among drugs should be taken into account while choosing alternative medication. Measures for drug allergy reactions are mostly supportive and usually include topical corticosteroids and oral antihistamines. However, systemic corticosteroids may be required in severe DHRs along with adrenaline in the event of anaphylaxis. The most effective approach towards the problem of ‘drug allergy’ is discontinuing or avoiding the offending culprit. Procedures to induce drug tolerance may be considered as a temporary measure toward tolerance to the offending drug if there is no alternative available.

This article aims to provide a simple clinical review of drug allergy and plan of action for the diagnosis as well as management of some of the most common DHRs, such as allergies to acetylsalicylic acid, non-steroidal anti-inflammatory drugs, penicillins, sulpha drugs, cephalosporin, contrast media in imaging procedures, anaesthetic agents, and vaccines.
Edge-to-Edge Repair After Prior Left-Sided Pneumonectomy
Authors: Abdel-Hadi Mohammed Nasser , Staszewicz Pawel , Bayer Matthias , Moscoso-Ludueña Martin , Abt Bernd , Fischer Dieter , Nef Holger , Rastan Ardawan Julian
Published: October 2022

Cardiac surgery procedures for patients following previous pneumonectomy are challenging because of anaesthetic and cardio-surgical technical difficulties. Here, the case of a patient who had received a left-sided pneumectomy 13 years prior as a result of nonsmall cell lung cancer is presented. A mitral edge-to-edge clipping was applied with excellent success in treating severe mitral regurgitation attributable to flail of the posterior mitral valve leaflet (fibroelastic deficiency). Because the heart was severely left-displaced, the use of transoesophageal echo during the preinterventional screening was challenging but feasible, and imaging quality was good. The absence of left pulmonary veins demanded a guide catheter and clip delivery system to be introduced during the procedure through the use of a spiral, preshaped, stiff guidewire. The procedure was performed under general anaesthesia with the patient extubated on a table. No complications arose during the periprocedural period and hospital stay, and after 3 months’ follow-up the patient showed significant functional improvement.
Raiders of the Lost Wire
Authors: Salazar Carlos H. , Tirado Gabriela , Mclnerney Angela , Nombela-Franco Luis , Nuñez-Gil Ivan
Published: October 2022

Introduction: An angiographic guidewire is a basic, yet essential piece of equipment in the interventional cardiologist’s armamentarium. Complications associated with angiographic guidewires can be catastrophic to the safe completion of a coronary procedure. In this article, the authors report a case of angiography guidewire fracture and explore the options for management of this rare but serious complication.

Case presentation: A 77-year-old man with multiple cardiovascular risk factors was admitted with an anterior ST segment elevation myocardial infarction. Diagnostic angiography was performed via right radial access and revealed a subocclusive stenosis of the mid and distal left anterior descending artery (LAD) with thrombolysis in myocardial infarction 1 flow and a 70% stenosis of the proximal diagonal branch. Primary percutaneous coronary intervention was attempted and a HI-TORQUE Balance Middle Weight Universal II guidewire (Abbott Vascular Inc., Santa Clara, California, USA) was chosen. Guidewire manipulation was difficult because of significant calcification and tortuosity of the LAD. Consequently, the guidewire fractured and became trapped in the mid-LAD. The complication was ultimately resolved by stenting across the fractured guidewire and the patient was not afflicted by any adverse sequelae.

Discussion: This case highlights a rare but potentially serious complication of coronary intervention. Proposed management varies from leaving the fractured wire in situ and stenting across it, to varying techniques for removing the fractured wire. However, no consensus exists as to the best strategy. The authors have therefore performed a review of the current literature and propose an algorithm for the management of this rare complication.
Continuing education as value creation
Authors: Schöni Walter
Published: October 2022

The continuing education sector explicitly regards itself as serving the goals of lifelong learning. In fact, however, it is oriented towards the market and measures its success according to the sales of its products. The article analyses this market orientation from the perspectives of educational sociology and discourse theory and illustrates its consequences using examples from the Swiss continuing education market. The author develops an alternative approach whereby continuing education is measured according to the value it creates for individuals and society. Here, a connection is made with economic value creation theory, enhanced by sociological dimensions of the recognition and valorisation of education. This enhanced value creation concept shows how continuing education generates values, where these values are recognised, in what contexts they are valorised and what players and discourses are involved. The author also outlines a procedure for value creation analysis and, using two continuing education programmes as examples, illustrates the findings that value creation analysis can generate. On this basis, the author calls for a reorientation of continuing education that transcends the limitations of market logic.
Participation of older people in learning studies
Authors: Koski Jenni , Pihlainen Kaisa
Published: October 2022

The participation and meaningful engagement of older people are strongly supported because of their individual and communal benefits. Currently there is a lack of general understanding of how older people participate in research activities. The purpose of this review was to examine the ways older people participate in learning studies. A search of abstracts of empirical studies published in English was conducted in three databases between 2015 and 2019 using scoping review methodology. The results showed that most often older people did participate as study subjects in clinical studies. Other participant roles included informants, partners, and multiple roles. The review addressed a paucity in qualitative and participatory roles in older people’s learning studies. All participant roles are still needed to provide various standpoints for learning studies. Further studies are suggested to provide various meaningful and participatory ways for older people to get involved in research activities.
Effect of process mode, nitrogen source and temperature on L-malic acid production with Aspergillus oryzae DSM 1863 using acetate as carbon source
Authors: Kövilein Aline , Zadravec Lena , Hohmann Silja , Umpfenbach Julia , Ochsenreither Katrin
Published: October 2022

Malic acid, mainly used as acidulant and taste enhancer in the food industry, is currently produced from fossil resources. In this study, microbial L-malate production with the filamentous fungus A. oryzae using the carbon source acetate was evaluated. Acetate is for example contained in biomass-derived substrates such as lignocellulosic hydrolysates and condensates of fast pyrolysis, thus avoiding competition with food production. Since research on malic acid synthesis from acetate is limited and reported productivities and yields are low, this work aimed to improve the process. First, different cultivation temperatures were tested. This parameter was found to affect the ratio between malic and succinic acid, which is the major by-product of organic acid production with A. oryzae. At 32°C, the malate share was highest (53.7 ± 1.6%), while it was lowest at 38°C (43.3 ± 1.1%) whereas succinate represented the main product (51.5 ± 1.0%). Besides the temperature, the type of nitrogen source was also found to affect malate synthesis as well as biomass production. In the pre-culture, the biomass concentration was increased by a factor of 3.4–3.9, and germination started earlier with the complex nitrogen sources yeast extract, casein hydrolysate and peptone compared to the defined nitrogen source (NH4)2SO4. Especially with yeast extract, malate synthesis in the main culture was accelerated and the titer obtained after 48 h was about 2.6 times higher than that quantified with (NH4)2SO4. To reduce substrate inhibition in acetate medium, fed-batch and repeated-batch processes were evaluated using (NH4)2SO4 or yeast extract as nitrogen source. In the fed-batch process, the period of malate production was extended, and the maximum product concentration was increased to 11.49 ± 1.84 g/L with (NH4)2SO4 and 12.08 ± 1.25 g/L with yeast extract. In the repeated-batch process, the total acid production was highest within the first 240 h of fermentation, but optimization is required to maintain high production rates in later cycles. The lessons learned in this study will help in the development of further process strategies to maximize malate production using acetate as alternative substrate to the commonly used glucose.
Pharyngeal pathology in a mouse model of oculopharyngeal muscular dystrophy is associated with impaired basal autophagy in myoblasts
Authors: Zhang Yu , Zeuthen Christopher , Zhu Carol , Wu Fang , Mezzell Allison T. , Whitlow Thomas J. , Choo Hyojung J. , Vest Katherine E.
Published: October 2022

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset dominant disease that primarily affects craniofacial muscles. Despite the fact that the genetic cause of OPMD is known to be expansion mutations in the gene encoding the nuclear polyadenosine RNA binding protein PABPN1, the molecular mechanisms of pathology are unknown and no pharmacologic treatments are available. Due to the limited availability of patient tissues, several animal models have been employed to study the pathology of OPMD. However, none of these models have demonstrated functional deficits in the muscles of the pharynx, which are predominantly affected by OPMD. Here, we used a knock-in mouse model of OPMD,Pabpn1+/A17, that closely genocopies patients. InPabpn1+/A17mice, we detected impaired pharyngeal muscle function, and impaired pharyngeal satellite cell proliferation and fusion. Molecular studies revealed that basal autophagy, which is required for normal satellite cell function, is higher in pharynx-derived myoblasts than in myoblasts derived from limb muscles. Interestingly, basal autophagy is impaired in cells derived fromPabpn1+/A17mice.Pabpn1knockdown in pharyngeal myoblasts failed to recapitulate the autophagy defect detected inPabpn1+/A17myoblasts suggesting that loss of PABPN1 function does not contribute to the basal autophagy defect. Taken together, these studies provide the first evidence for pharyngeal muscle and satellite cell pathology in a mouse model of OPMD and suggest that aberrant gain of PABPN1 function contributes to the craniofacial pathology in OPMD.
Neutrophil infiltration and myocarditis in patients with severe COVID-19: A post-mortem study
Authors: Zhang Quanyu , Zhang Huarong , Yan Xiaowei , Ma Sicong , Yao Xiaohong , Shi Yu , Ping Yifang , Cao Mianfu , Peng Chengfei , Wang Shuai , Luo Min , Yan Chenghui , Zhang Shuyang , Han Yaling , Bian Xiuwu
Published: October 2022

Aims

To investigate cardiac pathology in critically ill patients with coronavirus disease 2019 (COVID-19) and identify associations between pathological changes and clinical characteristics.

Methods

The present autopsy cohort study included hearts from 26 deceased patients hospitalized in intensive care units due to COVID-19, and was conducted at four sites in Wuhan, China. Cases were divided into a neutrophil infiltration group and a no-neutrophil group based on the presence or absence of histopathologically identified neutrophilic infiltrates.

Results

Among the 26 patients, histopathological examination identified active myocarditis in four patients. All patients with myocarditis exhibited extensive accompanying neutrophil infiltration, and all patients without myocarditis did not. The neutrophil infiltration group exhibited significantly higher rates of detection of interleukin-6 (100 vs. 4.6%) and tumor necrosis factor-alpha (100 vs. 31.8%) than the no-neutrophil group (both p < 0.05). On admission, four patients with neutrophil infiltration in myocardium had significantly higher baseline levels of aspartate aminotransferase, D dimer, and high-sensitivity C reactive protein than the other 22 patients (all p < 0.05). During hospitalization, patients with neutrophil infiltration had significantly higher maximum creatine kinase-MB (median 280.0 IU/L vs. 38.7 IU/L, p = 0.04) and higher troponin I (median 1.112 ng/ml vs. 0.220 ng/ml, p = 0.56) than patients without neutrophil infiltration.

Conclusion

Active myocarditis was frequently associated with neutrophil infiltration in the hearts of deceased patients with severe COVID-19. Patients with neutrophil-infiltrated myocarditis had a series of severely abnormal laboratory test results on admission, and high maximum creatine kinase-MB during hospitalization. The role of neutrophils in severe heart injury and systemic conditions in patients with COVID-19 should be emphasized.
Case report: Unusual persistent hypotension and acute occlusion after peripheral paclitaxel balloon angioplasty
Authors: Yang Lin , Liu Jianlin , Liu Chao
Published: October 2022

Background

Paclitaxel-coated balloon (PCB) angioplasty is a mainstream treatment for peripheral artery disease; however, the safety of PCB remains controversial.

Case presentation

We confirmed acute occlusion during PCB angioplasty in a patient with femoropopliteal artery occlusion. The occluded vessels were revascularized completely after endovascular medical therapy and bailout stenting angioplasty. Then, the patient experienced persistent post-procedure orthostatic hypotension (30 days) and received hydration and vasoactive agents with a target mean arterial blood pressure of 75–85 mmHg. The patient's blood pressure gradually recovered over the 30 days after the procedure, and there was no recurrence of symptomatic hypotension during the follow-up.

Conclusions

This rare complication is helpful to evaluate the safety of the PCB device.
Massive pleural effusion following high-power and short-duration radiofrequency ablation for treatment of atrial fibrillation: A case report and review of the literature
Authors: He Miaomiao , Qiu Jie , Bai Yang , Wang Yan , Chen Guangzhi
Published: October 2022

Postpericardial injury syndrome (PPIS) is defined as pericarditis or pericardial effusion that results from recent myocardial infarction or intracardiac interventions. These symptoms typically include fever, leukocytosis, a high erythrocyte sedimentation rate, and elevated C-reactive protein levels. Additionally, pericardial effusion and pleural effusion may be present. It is considered to be a common complication in cardio-surgery with an occurrence of 3–30%. In the past 20 years, a high number of patients with atrial fibrillation have suffered from PPIS following radiofrequency catheter ablation. However, previous reports focused on identifying cardiac tamponade and pericardial effusion as their main clinical manifestations. Solitary pulmonary involvement following PPIS with the radiofrequency catheter ablation may occur. We report a case of PPIS that presented pleural effusion as the dominant feature soon after the operation and systematic review to illustrate the clinical characteristics of PPIS.
Effect of flocculation on turbidity currents
Authors: Ali W. , Enthoven D. , Kirichek A. , Chassagne C. , Helmons R.
Published: October 2022

Flocculation between inorganic sediment, salt ions and microscopic organic matter present in the marine environment might play an important role in the dynamics of turbidity currents. The ability to predict, understand, and potentially leverage the effect of flocculation on turbidity currents will help to minimize the impact of human interventions such as dredging, trenching, and deep-sea mining. To better characterize the effect of flocculation on the benthic turbidity currents generated by these activities, a series of laboratory experiments were performed. Turbidity currents were created by means of lock exchange experiments. The present work focuses on the flocculation of clays that are representative for abyssal regions where deep-sea mining is performed, but most of the conclusions of this work are generic and can be applied to other types of benthic flows, occuring in harbours and channels. The effect of salt and organic material as flocculant agent was investigated. Various concentrations of clay and organic flocculant were tested. Video analysis was used to determine the head velocity of the plume. Samples at different run-out lengths were collected at the end of the lock exchange experiments for particle size and settling velocity measurements. The velocities of the turbidity currents in fresh and saline water (when no organic matter was present) were found to be similar, which was expected considering the timescales of salt-induced flocculation (about 30 min or more compared to the duration of lock exchange experiment <60 s). It was however demonstrated that, in presence of organic matter, flocculation occurred during the short time (30–60 s) of the experiment, leading to a reduced current propagation and a significant change in floc sizes (from 20 to 1,000 µm) and settling velocities (from 1 to 60 mm s−1). Salt ions contributed to flocculation in the sense that flocculation with organic matter was improved in the presence of salt.
Analysis of factors influencing the clinical outcome after surgery and 131I therapy in patients with moderate-risk thyroid papillary carcinoma
Authors: Li Yixuan , Rao Maohua , Zheng Chenxi , Huang Jiahui , Fang Danzhou , Xiong Yalan , Yuan Gengbiao
Published: October 2022

Purpose

Generally, the prognosis for papillary thyroid cancer (PTC) is favorable. However, the moderate risk involved warrants further evaluation. Hence, we investigated the clinical outcomes in patients with moderate-risk PTC following surgery and the first 131I therapy, as well as the relevant factors that influence the therapeutic efficacy.

Methods

Retrospective analyses of 175 patients with medium-risk PTC who visited the Second Affiliated Hospital of Chongqing Medical University from September 2017 to April 2019 were conducted. In according with the 2015 American Thyroid Association (ATA) guideline treatment response evaluation system, the patients were categorized into the following groups: excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR), and structurally incomplete response (SIR), of which IDR, BIR, and SIR were collectively referred to as the NER group. To compare the general clinical features between the 2 groups of patients, 2 independent samples t-tests, χ2 test, and Mann–Whitney U-test were performed, followed by multivariate logistic regression analyses. With reference to the receiver operating characteristic (ROC) curve, the predicted value of ps-Tg to ER was evaluated, and the best cut-off value was determined. The subgroups with BRAFV600E test results were analyzed by χ2 test only.

Results

The treatment responses of 123 patients were ER, while those of 52 patients were NER. The differences in the maximum tumor diameter (U = 2495.50), the amount of metastatic lymph nodes (U = 2313.50), the size of metastatic lymph node (U = 2113.50), the metastatic lymph node ratio (U = 2111.50), metastatic lymph node location (χ2 = 9.20), and ps-Tg level (U = 1011.00) were statistically significant. Multivariate regression analysis revealed that ps-Tg (OR = 1.209, 95% CI: 1.120–1.305) was an independent variable affecting ER. The cut-off value of ps-Tg for predicting ER was 6.915 ug/L, while its sensitivity and specificity were 69.2% and 89.4%, respectively.

Conclusions

Patients with smaller tumor size, fewer lymph nodes, lower metastatic lymph node ratio, metastatic lymph nodes in the central region, smaller lymph node size, and ps-Tg <6.915 ug/L demonstrated better therapeutic effects after the initial treatment.
Dissecting the effect of sphingolipid metabolism gene in progression and microenvironment of osteosarcoma to develop a prognostic signature
Authors: Zhong Yujian , Zhang Yubiao , Wei Sixing , Chen Junwen , Zhong Changheng , Cai Wenxiang , Jin Wenyi , Peng Hao
Published: October 2022

Sphingolipid metabolism (SM) fuels tumorigenesis and the malignant progression of osteosarcoma (OS), which leads to an unfavorable prognosis. Elucidating the molecular mechanisms underlying SM in osteosarcoma and developing a SM-based prognostic signature could be beneficial in the clinical setting. This study included 88 frozen OS samples to recognize the vital SM-relevant genes in the development of OS utilizing univariate Cox regression. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was conducted on the SM- relevant genes to minimize the risk of overfitting. The prognostic signature was generate utilizing the multivariable Cox regression analysis and was verified in the validation cohort. Moreover, cellular and molecular mechanisms associated with SM have an unfavorable prognosis for OS patients and have been widely studied. Resultantly, an SM-based prognostic risk model was established according to critical prognostic genes (CBS, GLB1, and HACD1), which had an excellent ability to predict the prognosis of OS patients (AUC for the train cohort was 0.887 and AUC for validation cohort was 0.737). The high-risk OS patients identified based on this prognostic signature had significantly poor immune microenvironment, indicated by significantly low immune score (mean=216.290 ± 662.463), reduced infiltrations of 25 immune cells, including NK cells (LogFC= -0.3597), CD8+T cells ((LogFC=-0.2346), Cytolytic activity ((LogFC=-0.1998), etc. The immunosuppressive microenvironment could be due to dysregulated SM of glycolipids. Further, a nomogram was constructed by integrating the SM-based prognostic signature and clinical paraments to facilitate clinical application. The nomogram could accurately predict the prognosis of OS invalids. Collectively, this study clarified the function of SM in the development of OS and helped develop a tool for risk stratification based on SM-related genes with application in clinical settings. The results of our study will aid in identifying high-risk patients and provide individualized treatments.
Hypoxia-related tumor environment correlated with immune infiltration and therapeutic sensitivity in diffuse large B-cell lymphoma
Authors: Liu Chen , Liu Lin
Published: October 2022

Background: Due to the high heterogeneity of diffuse large B-cell lymphoma (DLBCL), traditional chemotherapy treatment ultimately failed in one-third of the patients. Big challenges existed in finding how to accurately predict prognosis and provide individualized treatment. Hypoxia, although being a key factor in the development and progression of DLBCL, plays its role in DLBCL prognosis, which has yet to be fully explored.

Methods: Data used in the current study were sourced from the Gene Expression Omnibus (GEO) database. DLBCL patients were divided according to different hypoxia-related subtypes based on the expressions of hypoxia-related genes (HRGs) relevant to survival. Differentially expressed genes (DEGs) between subtypes were identified using the limma package. Using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses, the prognostic signature was established to calculate risk scores. The tumor microenvironment (TME) in low- and high-risk groups was evaluated by single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE. The chemotherapeutic sensitivity in two groups was assessed by IC50 values.

Results: DLBCL patients were clustered into two hypoxia-related subtype groups according to different gene survival and expressions associated with increasing oxygen delivery and reducing oxygen consumption, and these two subtype groups were compared. Based on the differential expression, a risk model was established using univariate cox and LASSO regression analyses, FNDC1, ANTXR1, RARRES2, S100A9, and MT1M. The performance of the risk signature in predicting the prognosis of DLBCL patients was validated in the internal and external datasets, as evidenced by receiver operating characteristic (ROC) curves. In addition, we observed significant differences in the tumor microenvironment and chemotherapeutic response between low- and high-risk groups.

Conclusion: Our study developed novel hypoxia-related subtypes in DLBCL and identified five prognostic signatures for DLBCL patients. These findings may enrich our understanding of the role of hypoxia in DLBCL and help improve the treatment of DLBCL patients.
Construction and validation of a glycolysis-related lncRNA signature for prognosis prediction in Stomach Adenocarcinoma
Authors: Liao Tianyou , Lu Yan , Li Wangji , Wang Kang , Zhang Yanxiang , Luo Zhentao , Ju Yongle , Ouyang Manzhao
Published: October 2022

Background: Glycolysis is closely related to the occurrence and progression of gastric cancer (GC). Currently, there is no systematic study on using the glycolysis-related long non-coding RNA (lncRNA) as a model for predicting the survival time in patients with GC. Therefore, it was essential to develop a signature for predicting the survival based on glycolysis-related lncRNA in patients with GC.

Materials and methods: LncRNA expression profiles, containing 375 stomach adenocarcinoma (STAD) samples, were obtained from The Cancer Genome Atlas (TCGA) database. The co-expression network of lncRNA and glycolysis-related genes was used to identify the glycolysis-related lncRNAs. The Kaplan-Meier survival analysis and univariate Cox regression analysis were used to detect the glycolysis-related lncRNA with prognostic significance. Then, Bayesian Lasso-logistic and multivariate Cox regression analyses were performed to screen the glycolysis-related lncRNA with independent prognostic significance and to develop the risk model. Patients were assigned into the low- and high-risk cohorts according to their risk scores. A nomogram model was constructed based on clinical information and risk scores. Gene Set Enrichment Analysis (GSEA) was performed to visualize the functional and pathway enrichment analyses of the glycolysis-related lncRNA. Finally, the robustness of the results obtained was verified in an internal validation data set.

Results: Seven glycolysis-related lncRNAs (AL353804.1, AC010719.1, TNFRSF10A-AS1, AC005586.1, AL355574.1, AC009948.1, and AL161785.1) were obtained to construct a risk model for prognosis prediction in the STAD patients using Lasso regression and multivariate Cox regression analyses. The risk score was identified as an independent prognostic factor for the patients with STAD [HR = 1.315, 95% CI (1.056–1.130), p < 0.001] via multivariate Cox regression analysis. Receiver operating characteristic (ROC) curves were drawn and the area under curve (AUC) values of 1-, 3-, and 5-year overall survival (OS) were calculated to be 0.691, 0.717, and 0.723 respectively. Similar results were obtained in the validation data set. In addition, seven glycolysis-related lncRNAs were significantly enriched in the classical tumor processes and pathways including cell adhesion, positive regulation of vascular endothelial growth factor, leukocyte transendothelial migration, and JAK_STAT signaling pathway.

Conclusion: The prognostic prediction model constructed using seven glycolysis-related lncRNA could be used to predict the prognosis in patients with STAD, which might help clinicians in the clinical treatment for STAD.
Alteration of synonymous codon usage bias accompanies polyploidization in wheat
Authors: Tian Geng , Xiao Guilian , Wu Tong , Zhou Junzhi , Xu Wenjing , Wang Yanxia , Xia Guangmin , Wang Mengcheng
Published: October 2022

The diploidization of polyploid genomes is accompanied by genomic variation, including synonymous nucleotide substitutions that may lead to synonymous codon usage bias (SCUB). SCUB can mirror the evolutionary specialization of plants, but its effect on the formation of polyploidies is not well documented. We explored this issue here with hexaploid wheat and its progenitors. Synonymous codons (SCs) ending in either cytosine (NNC) or guanidine (NNG) were more frequent than those ending in either adenosine (NNA) or thymine (NNT), and the preference for NNC/G codons followed the increase in genome ploidy. The ratios between NNC/G and NNA/T codons gradually decreased in genes with more introns, and the difference in these ratios between wheat and its progenitors diminished with increasing ploidy. SCUB frequencies were heterogeneous among exons, and the bias preferred to NNA/T in more internal exons, especially for genes with more exons; while the preference did not appear to associate with ploidy. The SCUB alteration of the progenitors was different during the formation of hexaploid wheat, so that SCUB was the homogeneous among A, B and D subgenomes. DNA methylation-mediated conversion from cytosine to thymine weakened following the increase of genome ploidy, coinciding with the stronger bias for NNC/G SCs in the genome as a function of ploidy, suggesting that SCUB contribute to the epigenetic variation in hexaploid wheat. The patterns in SCUB mirrored the formation of hexaploid wheat, which provides new insight into genome shock-induced genetic variation during polyploidization. SCs representing non-neutral synonymous mutations can be used for genetic dissection and improvement of agricultural traits of wheat and other polyploidies.
Identifying potential microRNA biomarkers for colon cancer and colorectal cancer through bound nuclear norm regularization
Authors: Zhai Shengyong , Li Xiaoling , Wu Yan , Shi Xiaoli , Ji Binbin , Qiu Chun
Published: October 2022

Colon cancer and colorectal cancer are two common cancer-related deaths worldwide. Identification of potential biomarkers for the two cancers can help us to evaluate their initiation, progression and therapeutic response. In this study, we propose a new microRNA-disease association identification method, BNNRMDA, to discover potential microRNA biomarkers for the two cancers. BNNRMDA better combines disease semantic similarity and Gaussian Association Profile Kernel (GAPK) similarity, microRNA function similarity and GAPK similarity, and the bound nuclear norm regularization model. Compared to other five classical microRNA-disease association identification methods (MIDPE, MIDP, RLSMDA, GRNMF, AND LPLNS), BNNRMDA obtains the highest AUC of 0.9071, demonstrating its strong microRNA-disease association identification performance. BNNRMDA is applied to discover possible microRNA biomarkers for colon cancer and colorectal cancer. The results show that all 73 known microRNAs associated with colon cancer in the HMDD database have the highest association scores with colon cancer and are ranked as top 73. Among 137 known microRNAs associated with colorectal cancer in the HMDD database, 129 microRNAs have the highest association scores with colorectal cancer and are ranked as top 129. In addition, we predict that hsa-miR-103a could be a potential biomarker of colon cancer and hsa-mir-193b and hsa-mir-7days could be potential biomarkers of colorectal cancer.
Embryonic transcriptome unravels mechanisms and pathways underlying embryonic development with respect to muscle growth, egg production, and plumage formation in native and broiler chickens
Authors: Kanakachari M. , Ashwini R. , Chatterjee R. N. , Bhattacharya T. K.
Published: October 2022

Background: Muscle development, egg production, and plumage colors are different between native and broiler chickens. The study was designed to investigate why improved Aseel (PD4) is colorful, stronger, and grew slowly compared with the control broiler (CB).

Methods: A microarray was conducted using the 7th-day embryo (7EB) and 18th-day thigh muscle (18TM) of improved Aseel and broiler, respectively. Also, we have selected 24 Gallus gallus candidate reference genes from NCBI, and total RNA was isolated from the broiler, improved Aseel embryo tissues, and their expression profiles were studied by real-time quantitative PCR (qPCR). Furthermore, microarray data were validated with qPCR using improved Aseel and broiler embryo tissues.

Results: In the differential transcripts screening, all the transcripts obtained by microarray of slow and fast growth groups were screened by fold change ≥ 1 and false discovery rate (FDR) ≤ 0.05. In total, 8,069 transcripts were differentially expressed between the 7EB and 18TM of PD4 compared to the CB. A further analysis showed that a high number of transcripts are differentially regulated in the 7EB of PD4 (6,896) and fewer transcripts are differentially regulated (1,173) in the 18TM of PD4 compared to the CB. On the 7th- and 18th-day PD4 embryos, 3,890, 3,006, 745, and 428 transcripts were up- and downregulated, respectively. The commonly up- and downregulated transcripts are 91 and 44 between the 7th- and 18th-day of embryos. In addition, the best housekeeping gene was identified. Furthermore, we validated the differentially expressed genes (DEGs) related to muscle growth, myostatin signaling and development, and fatty acid metabolism genes in PD4 and CB embryo tissues by qPCR, and the results correlated with microarray expression data.

Conclusion: Our study identified DEGs that regulate the myostatin signaling and differentiation pathway; glycolysis and gluconeogenesis; fatty acid metabolism; Jak-STAT, mTOR, and TGF-β signaling pathways; tryptophan metabolism; and PI3K-Akt signaling pathways in PD4. The results revealed that the gene expression architecture is present in the improved Aseel exhibiting embryo growth that will help improve muscle development, differentiation, egg production, protein synthesis, and plumage formation in PD4 native chickens. Our findings may be used as a model for improving the growth in Aseel as well as optimizing the growth in the broiler.
Symptomatology during previous SARS-CoV-2 infection and serostatus before vaccination influence the immunogenicity of BNT162b2 COVID-19 mRNA vaccine
Authors: Nantel Sabryna , Bourdin Benoîte , Adams Kelsey , Carbonneau Julie , Rabezanahary Henintsoa , Hamelin Marie-Ève , McCormack Deirdre , Savard Patrice , Longtin Yves , Cheng Matthew P. , De Serres Gaston , Corbeil Jacques , Gilca Vladimir , Baz Mariana , Boivin Guy , Quach Caroline , Decaluwe Hélène
Published: October 2022

Public health vaccination recommendations for COVID-19 primary series and boosters in previously infected individuals differ worldwide. As infection with SARS-CoV-2 is often asymptomatic, it remains to be determined if vaccine immunogenicity is comparable in all previously infected subjects. This study presents detailed immunological evidence to clarify the requirements for one- or two-dose primary vaccination series for naturally primed individuals. The main objective was to evaluate the immune response to COVID-19 mRNA vaccination to establish the most appropriate vaccination regimen to induce robust immune responses in individuals with prior SARS-CoV-2 infection. The main outcome measure was a functional immunity score (zero to three) before and after vaccination, based on anti-RBD IgG levels, serum capacity to neutralize live virus and IFN-γ secretion capacity in response to SARS-CoV-2 peptide pools. One point was attributed for each of these three functional assays with response above the positivity threshold. The immunity score was compared based on subjects’ symptoms at diagnosis and/or serostatus prior to vaccination. None of the naïve participants (n=14) showed a maximal immunity score of three following one dose of vaccine compared to 84% of the previously infected participants (n=55). All recovered individuals who did not have an immunity score of three were seronegative prior to vaccination, and 67% had not reported symptoms resulting from their initial infection. Following one dose of vaccine, their immune responses were comparable to naïve individuals, with significantly weaker responses than individuals who were symptomatic during infection. These results indicate that the absence of symptoms during initial infection and negative serostatus prior to vaccination predict the strength of immune responses to COVID-19 mRNA vaccine. Altogether, these findings highlight the importance of administering the complete two-dose primary regimen and following boosters of mRNA vaccines to individuals who experienced asymptomatic SARS-CoV-2 infection.
Integrated analysis of single-cell and bulk RNA-sequencing identifies a signature based on T-cell marker genes to predict prognosis and therapeutic response in lung squamous cell carcinoma
Authors: Shi Xuezhong , Dong Ani , Jia Xiaocan , Zheng Guowei , Wang Nana , Wang Yuping , Yang Chaojun , Lu Jie , Yang Yongli
Published: October 2022

Cancer immunotherapy is an increasingly successful strategy for treating patients with advanced or conventionally drug-resistant cancers. T cells have been proved to play important roles in anti-tumor and tumor microenvironment shaping, while these roles have not been explained in lung squamous cell carcinoma (LUSC). In this study, we first performed a comprehensive analysis of single-cell RNA sequencing (scRNA-seq) data from the gene expression omnibus (GEO) database to identify 72 T-cell marker genes. Subsequently, we constructed a 5-gene prognostic signature in the training cohort based on the T-cell marker genes from the cancer genome atlas (TCGA) database, which was further validated in the testing cohort and GEO cohort. The areas under the receiver operating characteristic curve at 1-, 3-, and 5-years were 0.614, 0.713 and 0.702 in the training cohort, 0.669, 0.603 and 0.645 in the testing cohort, 0.661, 0.628 and 0.590 in the GEO cohort, respectively. Furthermore, we created a highly reliable nomogram to facilitate clinical application. Gene set enrichment analysis showed that immune-related pathways were mainly enriched in the high-risk group. Tumor immune microenvironment indicated that high-risk group exhibited higher immune score, stromal score, and immune cell infiltration levels. Moreover, genes of the immune checkpoints and human leukocyte antigen family were all overexpressed in high-risk group. Drug sensitivity revealed that low-risk group was sensitive to 8 chemotherapeutic drugs and high-risk group to 4 chemotherapeutic drugs. In short, our study reveals a novel prognostic signature based on T-cell marker genes, which provides a new target and theoretical support for LUSC patients.
Microbiome-metabolome analysis reveals alterations in the composition and metabolism of caecal microbiota and metabolites with dietary Enteromorpha polysaccharide and Yeast glycoprotein in chickens
Authors: Wassie Teketay , Cheng Bei , Zhou Tiantian , Gao Lumin , Lu Zhuang , Xie Chunyan , Wu Xin
Published: October 2022

The intestinal microbiome is responsible for the fermentation of complex carbohydrates and orchestrates the immune system through gut microbiota-derived metabolites. In our previous study, we reported that supplementation of Enteromorpha polysaccharide (EP) and yeast glycoprotein (YG) in combination synergistically improved antioxidant activities, serum lipid profile, and fatty acid metabolism in chicken. However, the mechanism of action of these polysaccharides remains elusive. The present study used an integrated 16S-rRNA sequencing technology and untargeted metabolomics technique to reveal the mechanism of action of EP+YG supplementation in broiler chickens fed basal diet or diets supplemented with EP+YG (200mg/kg EP + 200mg/kg YG). The results showed that EP+YG supplementation altered the overall structure of caecal microbiota as evidenced by β diversities analysis. Besides, EP+YG supplementation changed the microbiota composition by altering the community profile at the phylum and genus levels. Furthermore, Spearman correlation analysis indicated a significant correlation between altered microbiota genera vs serum cytokine levels and microbiota genera vs volatile fatty acids production. Predicted functional analysis showed that EP+YG supplementation significantly enriched amino acid metabolism, nucleotide metabolism, glycan biosynthesis and metabolism, energy metabolism, and carbohydrate metabolism. Metabolomics analysis confirmed that EP+YG supplementation modulates a myriad of caecal metabolites by increasing some metabolites, including pyruvic acid, pyridoxine, spermidine, spermine, and dopamine, and decreasing metabolites related to lipid metabolisms such as malonic acid, oleic acid, and docosahexaenoic acid. The quantitative enrichment analysis results further showed that glycolysis/gluconeogenesis, citric acid cycle, tyrosine metabolism, glycine, serine, and threonine metabolism, and cysteine and methionine metabolism were the most important enriched pathways identified with enrichment ratio >11, whereas, fatty acid biosynthesis and biosynthesis of unsaturated fatty acids pathways were suppressed. Together, the 16S-rRNA and untargeted metabolomics results uncovered that EP+YG supplementation modulates intestinal microbiota and their metabolites, thereby influencing the important metabolism pathways, suggesting a potential feed additive.
Hydrodynamical transport structure and lagrangian connectivity of circulations in the Pearl River Estuary
Authors: Chu Nanyang , Liu Guangliang , Xu Jie , Yao Peng , Du Yan , Liu Zhiqiang , Cai Zhongya
Published: October 2022

Using a three-dimensional (3D) hydrodynamic model, this study explored the seasonal hydrodynamic transport structure in the Pearl River Estuary and illustrated the intrinsic connectivity under multiscale motions from a Lagrangian perspective. Generally, the surface Lagrangian residual current (UL) is uniformly southwestward/southeastward in summer/winter, with a stronger intensity in the lower estuary. The bottom UL features in the southeastward direction in the upper estuary and northwest direction in the lower estuary. The fluvial–tide interaction line advances southeastward and northwestward in summer and winter, respectively. The UL captured the major transport processes and was in good agreement with the mean surface sediment transport patterns. In the transition region between Lantau Island and Neilingding Island, where it is largely affected by the interaction between the periodic tidal current and river discharge, the spatially averaged UL showed intensified intratidal variations and had a larger difference with the locally temporally averaged Eulerian residual current. The remarkable Lagrangian coherent structures that illustrated the transport paths and transport convergence regions were identified, which are generally consistent with the bottom sediment depocenters. Based on the Lagrangian connectivity analysis, it was revealed that a barrier between the western and eastern estuaries existed, which was weakened by the strong river discharge during summer. Two convergence regions near the Macau and Hong Kong waters were identified, where the sediment and pollutants easily settled. The study demonstrated the importance of the Lagrangian view in understanding the hydrodynamic process and transport structure in the estuary–shelf regions.
Molecular epidemiology of tuberculosis in the Somali region, eastern Ethiopia
Authors: Worku Getnet , Gumi Balako , Mohammedbirhan Binyam , Girma Musse , Sileshi Henok , Hailu Michael , Wondimu Amanuel , Ashagre Wondimu , Tschopp Rea , Carruth Lauren , Ameni Gobena
Published: October 2022

Background

Tuberculosis (TB) is one of the leading causes of morbidity and mortality in low-income countries like Ethiopia. However, because of the limited laboratory infrastructure there is a shortage of comprehensive data on the genotypes of clinical isolates of Mycobacterium tuberculosis (M. tuberculosis) complex (MTBC) in peripheral regions of Ethiopia. The objective of this study was to characterize MTBC isolates in the Somali region of eastern Ethiopia.

Methods

A cross-sectional study was conducted in three health institutions between October 2018 and December 2019 in the capital of Somali region. A total of 323 MTBC isolates (249 from pulmonary TB and 74 from extrapulmonary TB) were analyzed using regions of difference 9 (RD 9)-based polymerase chain reaction (PCR) and spoligotyping.

Results

Of the 323 MTBC isolates, 99.7% (95% CI: 99.1–100%) were M. tuberculosis while the remaining one isolate was M. bovis based on RD 9-based PCR. Spoligotyping identified 71 spoligotype patterns; 61 shared types and 10 orphans. A majority of the isolates were grouped in shared types while the remaining grouped in orphans. The M. tuberculosis lineages identified in this study were lineage 1, 2, 3, 4, and 7 with the percentages of 7.4, 2.2, 28.2, 60.4, and 0.6%, respectively. Most (87.9%) of the isolates were classified in clustered spoligotypes while the remaining 12.1% isolates were singletons. The predominant clustered spoligotypes identified were SIT 149, SIT 21, SIT 26, SIT 53, and SIT 52, each consisting of 17.6, 13.3, 8.4, 7.4, and 5%, respectively. Lineage 3 and lineage 4, as well as the age group (15–24), were associated significantly with clustering.

Conclusion

The MTBC isolated from TB patients in Somali region were highly diverse, with considerable spoligotype clustering which suggests active TB transmission. In addition, the Beijing spoligotype was isolated in relatively higher frequency than the frequencies of its isolation from the other regions of Ethiopia warranting the attention of the TB Control Program of the Somali region.