bluuebunny/crossref_metadata_2025 huggingface dataset:
The clinical application of metagenomic next-generation sequencing in infectious diseases at a tertiary hospital in China
Authors: Wang Chuwen , Yan Danying , Huang Jiajia , Yang Naibin , Shi Jiejun , Pan Shou , Lin Gaoqiang , Liu Ying , Zhang Yingying , Bian Xueyan , Song Qifa , Qian Guoqing
Published: December 2022

Background

Compared with traditional diagnostic methods (TDMs), rapid diagnostic methods for infectious diseases (IDs) are urgently needed. Metagenomic next-generation sequencing (mNGS) has emerged as a promising diagnostic technology for clinical infections.

Methods

This retrospective observational study was performed at a tertiary hospital in China between May 2019 and August 2022. The chi-square test was used to compare the sensitivity and specificity of mNGS and TDMs. We also performed a subgroup analysis of the different pathogens and samples.

Results

A total of 435 patients with clinical suspicion of infection were enrolled and 372 (85.5%) patients were finally categorized as the ID group. The overall sensitivity of mNGS was significantly higher than that of the TDMs (59.7% vs. 30.1%, P < 0.05). However, there was no significant difference in the overall specificity between the two methods (83.3% vs. 89.6%, P = 0.37). In patients with identified pathogens, the positive rates of mNGS for detecting bacteria (88.7%), fungi (87.9%), viruses (96.9%), and Nontuberculous mycobacteria (NTM; 100%) were significantly higher than those of TDMs (P < 0.05). The positive rate of mNGS for detecting Mycobacterium tuberculosis was not superior to that of TDMs (77.3% vs. 54.5%, P = 0.11). The sensitivity rates of mNGS for pathogen identification in bronchoalveolar lavage fluid, blood, cerebrospinal fluid, pleural fluid, and tissue were 72.6%, 39.3%, 37.5%, 35.0% and 80.0%, respectively.

Conclusion

With the potential for screening multiple clinical samples, mNGS has an overall advantage over TDMs. It can effectively identify pathogens, especially those that are difficult to identify using TDMs, such as NTM, chlamydia, and parasites.
Enhanced utility of AI/ML methods during lead optimization by inclusion of 3D ligand information
Authors: Bleicher Leo S. , van Daelen Ton , Honeycutt J. Dana , Hassan Moises , Chandrasekhar Jayaraman , Shirley William , Tsui Vickie , Schmitz Uli
Published: December 2022

AI/ML methods in drug discovery are maturing and their utility and impact is likely to permeate many aspects of drug discovery including lead finding and lead optimization. Typical methods utilize ML-models for structure-property prediction with simple 2D-based chemical representations of the small molecules. Further, limited data, especially pertaining to novel targets, make it difficult to build effective structure-activity ML-models. Here we describe our recent work using the BIOVIA Generative Therapeutics Design (GTD) application, which is equipped to take advantage of 3D structural models of ligand protein interaction, i.e., pharmacophoric representation of desired features. Using an SAR data set pertaining to the discovery of SYK inhibitors entospletinib and lanraplenib in addition to two unrelated clinical SYK inhibitors, we show how several common problems in lead finding and lead optimization can be effectively addressed with GTD. This includes an effort to retrospectively re-identify drug candidate molecules based on data from an intermediate stage of the project using chemical space constraints and the application of evolutionary pressure within GTD. Additionally, studies of how the GTD platform can be configured to generate molecules incorporating features from multiple unrelated molecule series show how the GTD methods apply AI/ML to drug discovery.
Thermal structure and sediment bulk density of the MV420 mud volcano on the continental slope of the Canadian Beaufort Sea and its implications for the plumbing system
Authors: Kim Young-Gyun , Jin Young Keun , Hong Jong Kuk , Paull Charles , Caress David , Jang ChanHee , So Byung-Dal
Published: December 2022

The shallow migration path of mudflow of the mud volcano MV420 on the continental slope of the Canadian Beaufort Sea is investigated in terms of thermal and geotechnical characteristics. MV420 is a nearly flat topped active mud volcano that emits methane and fluidized mud. Its top is at a depth of water of 420 m, within the gas hydrate stability zone. During the summer 2017 IBRVAraonexpedition, several measurements of marine heat flow were conducted in the area of juvenile mud mound/pond morphologies identified by multibeam bathymetry and backscatter intensity images obtained by the Monterey Bay Aquarium Research Institute’s autonomous underwater vehicle. The heat probe (a gravity corer with temperature, pressure, and tilt sensors) appeared to penetrate to a depth of >70 m below the seafloor. The sediment bulk density in the mudflow migration path of MV420, estimated by pressure change with controlled stretches of a winch cable, was 1.56 g/cm3. The subsurface temperature reaches up to 18°C and profiles show that the maximum local temperature occurs from 20 to 40 m below the seafloor, implying substantial vertical variability of geothermal gradients. Our finding of large positive and small negative geothermal gradients above and below the depth of the local temperature maximum may represent stagnant hot mud along the mudflow migration path, indicating a pulsative eruption of the mudflow. Gas hydrate is stable only within a few meter thick layer near the seafloor above the path because of the cold bottom water (0.4°C) covering the top of the mud volcano. Furthermore, the thermal conductivity of 0.939 W/m/K and the marine heat flow of 22.5 mW/m2at a control site outside MV420 is estimated as the background heat flow in the slope, for which little data exists.
COVID-19 and thyroid function: What do we know so far?
Authors: Rossetti Camila Lüdke , Cazarin Juliana , Hecht Fabio , Beltrão Fabyan Esberard de Lima , Ferreira Andrea Cláudia Freitas , Fortunato Rodrigo Soares , Ramos Helton Estrela , de Carvalho Denise Pires
Published: December 2022

Coronavirus disease 2019 (COVID-19) was characterized as a pandemic in March, 2020 by the World Health Organization. COVID-19 is a respiratory syndrome that can progress to acute respiratory distress syndrome, multiorgan dysfunction, and eventually death. Despite being considered a respiratory disease, it is known that other organs and systems can be affected in COVID-19, including the thyroid gland. Thyroid gland, as well as hypothalamus and pituitary, which regulate the functioning of most endocrine glands, express angiotensin-converting enzyme 2 (ACE2), the main protein that functions as a receptor to which SARS-CoV-2 binds to enter host cells. In addition, thyroid gland is extremely sensitive to changes in body homeostasis and metabolism. Immune system cells are targets for thyroid hormones and T3 and T4 modulate specific immune responses, including cell-mediated immunity, natural killer cell activity, the antiviral action of interferon (IFN) and proliferation of T- and B-lymphocytes. However, studies show that patients with controlled hypothyroidism and hyperthyroidism do not have a higher prevalence of COVID-19, nor do they have a worse prognosis when infected with the virus. On the other hand, retrospective observational studies, prospective studies, and case reports published in the last two years reported abnormal thyroid function related to acute SARS-CoV-2 infection or even several weeks after its resolution. Indeed, a variety of thyroid disorders have been documented in COVID-19 patients, including non-thyroidal illness syndrome (NTIS), subacute thyroiditis and thyrotoxicosis. In addition, thyroid disease has already been reported as a consequence of the administration of vaccines against SARS-CoV-2. Overall, the data revealed that abnormal thyroid function may occur during and in the convalescence post-COVID condition phase. Although the cellular and molecular mechanisms are not completely understood, the evidence suggests that the “cytokine storm” is an important mediator in this context. Thus, future studies are needed to better investigate the pathophysiology of thyroid dysfunction induced by COVID-19 at both molecular and clinical levels.
Well-controlled gestational diabetes mellitus without pharmacologic therapy decelerates weight gain in infancy
Authors: Li Chao , Cai Yixi , Li Yinying , Peng Bin , Liu Yongfang , Wang Zhenming , Yang Ting , Hu Yirong , Fu Yajun , Shi Tingmei , Peng Hong , Zhang Yue , Chen Jie , Li Tingyu , Chen Li
Published: December 2022

Aim

There are no prospective longitudinal studies on the association between well-controlled gestational diabetes mellitus (GDM) without pharmacologic therapy and the physical growth of offspring in infancy. We aimed to identify the trajectories in physical growth (from 0–12 months of age) in the offspring of mothers with well-controlled GDM without pharmacologic therapy in a prospective cohort in China.

Methods

This study included 236 offspring of mothers with GDM and 369 offspring of mothers without GDM. Mothers with GDM were not on pharmacologic therapy. The length and weight of infants were measured at 0, 1, 3, 6, and 12 months. Linear mixed-effect models and linear mixed-effect models were applied.

Results

The fully adjusted model showed that the weight-for-age z-score (WAZ), length-for-age z-score (LAZ), and BMI-for-age z-score (BMIZ) were similar at birth for the GDM and control groups. However, subsequent increases in WAZ and BMIZ for the GDM group lagged the increases for the control group at the subsequent periods of observation, 0–1, 0–6, and 0–12 months.

Conclusions

Well-controlled GDM without pharmacologic therapy may normalize physical growth of offspring at birth and decelerate their weight gain in infancy. Whether glycemic control can mitigate the long-term effects of GDM on the growth trajectory in offspring remains unclear.
Progression of metabolic syndrome and associated cardiometabolic risk factors from prepuberty to puberty in children: The PUBMEP study
Authors: de Lamas Carmela , Kalén Anton , Anguita-Ruiz Augusto , Pérez-Ferreirós Alexandra , Picáns-Leis Rosaura , Flores Katherine , Moreno Luis A. , Bueno Gloria , Gil Ángel , Gil-Campos Mercedes , Aguilera Concepción M. , Leis Rosaura
Published: December 2022

Introduction

Metabolic syndrome (MetS) is a cluster of clinical and metabolic alterations related to the risk of cardiovascular diseases (CVD). Metabolic changes occurring during puberty, especially in children with overweight and obesity, can influence the risk of developing chronic diseases, especially CVD.

Methods

Longitudinal study based on the follow-up until puberty of a cohort of 191 prepubertal Spanish boys and girls without congenital, chronic, or inflammatory diseases: undernutrition: or intake of any drug that could alter blood glucose, blood pressure, or lipid metabolism. The following parameters were used to determine the presence of MetS: obesity, hypertension, hyperglycemia, hypertriglyceridemia, and low HDL-c.

Results

A total of 75·5% of participants stayed in the same BMI category from prepuberty to puberty, whereas 6·3% increased by at least one category. The prevalence of MetS was 9·1% (prepubertal stage) and 11·9% (pubertal stage). The risk of presenting alterations in puberty for systolic blood pressure (SBP), plasma triacylglycerols, HDL cholesterol (HDL-c), and HOMA-IR was significantly higher in those participants who had the same alterations in prepuberty. MetS prevalence in puberty was predicted by sex and levels of HOMA-IR, BMI-z, and waist circumference in the prepubertal stage, in the whole sample: in puberty, the predictors were levels of HOMA-IR, BMI-z, and diastolic blood pressure in participants with obesity. Two fast-and-frugal decision trees were built to predict the risk of MetS in puberty based on prepuberty HOMA-IR (cutoff 2·5), SBP (cutoff 106 mm of Hg), and TAG (cutoff 53 mg/dl).

Discussion

Controlling obesity and cardiometabolic risk factors, especially HOMA-IR and blood pressure, in children during the prepubertal stage appears critical to preventing pubertal MetS effectively.
Replacement control of Mikania micrantha in orchards and its eco-physiological mechanism
Authors: Jia Pu , Wang Jiayi , Liang Haolin , Wu Zhuo-hui , Li Fenglin , Li Weihua
Published: December 2022

Mikania micrantha is one of the most notorious invasive weeds in south China, especially in orchard habitats. Based on the principle of niche competition, screening plants with strong competitiveness and managing vacant niches through natural alternative methods (replacement control) were expected to achieve sustainable ecological management of invasive species. To this end, two legumes, Desmodium heterocarpon and Senna tora, were selected to conduct field competition experiments with M. micrantha to investigate the interspecific competitiveness of these two legumes and M. micrantha from the aspects of adaptability to low light and response to drought stress. We found that the relative interaction indexes of D. heterocarpon and S. tora to M. micrantha were both negative and the competitive inhibition of S. tora on M. micrantha was higher than that of D. heterocarpon. Compared with M. micrantha, D. heterocarpon and S. tora have higher photosynthetic efficiency and lower dark respiration efficiency under low-light conditions, thus maintaining positive plant carbon balance capacity in the low-light understory and becoming more shade-tolerant. Besides, the water stress experiment found that M. micrantha had the lowest tolerance to drought stress, followed by S. tora, and D. heterocarpon was the most drought tolerant. These results showed that D. heterocarpon and S. tora can effectively prevent and control M. micrantha, mainly due to their higher competitiveness, shade tolerance, and drought tolerance. The control effect of D. heterocarpon is better than that of S. tora which is an alien species. Therefore, we believed that the replacement control of the invasive weed M. micrantha by D. heterocarpon is expected to be a sustainable ecological management strategy for M. micrantha biocontrol in the dryland orchard habitat. These findings provide a theoretical basis for the selection of species for alternative control in the future and provide new ideas for solving the problem of repeated regeneration in the existing M. micrantha control process.
Construction of prediction model of inflammation related genes in idiopathic pulmonary fibrosis and its correlation with immune microenvironment
Authors: Yin Ying-Qiu , Peng Feng , Situ Hui-Jing , Xie Jun-Ling , Tan Liming , Wei Jie , Jiang Fang-fang , Zhang Shan-Qiang , Liu Jun
Published: December 2022

Background

The role of inflammation in the formation of idiopathic pulmonary fibrosis (IPF) has gained a lot of attention recently. However, the involvement of genes related to inflammation and immune exchange environment status in the prognosis of IPF remains to be further clarified. The objective of this research is to establish a new model for the prediction of the overall survival (OS) rate of inflammation-related IPF.

Methods

Gene Expression Omnibus (GEO) was employed to obtain the three expression microarrays of IPF, including two from alveolar lavage fluid cells and one from peripheral blood mononuclear cells. To construct the risk assessment model of inflammation-linked genes, least absolute shrinkage and selection operator (lasso), univariate cox and multivariate stepwise regression, and random forest method were used. The proportion of immune cell infiltration was evaluated by single sample Gene Set Enrichment Analysis (ssGSEA) algorithm.

Results

The value of genes linked with inflammation in the prognosis of IPF was analyzed, and a four-genes risk model was constructed, including tpbg, Myc, ffar2, and CCL2. It was highlighted by Kaplan Meier (K-M) survival analysis that patients with high-risk scores had worse overall survival time in all training and validation sets, and univariate and multivariate analysis highlighted that it has the potential to act as an independent risk indicator for poor prognosis. ROC analysis showed that the prediction efficiency of 1-, 3-, and 5-year OS time in the training set reached 0.784, 0.835, and 0.921, respectively. Immune infiltration analysis showed that Myeloid-Derived Suppressor Cells (MDSC), macrophages, regulatory T cells, cd4+ t cells, neutrophils, and dendritic cells were more infiltrated in the high-risk group than in the low-risk group.

Conclusion

Inflammation-related genes can be well used to evaluate the IPF prognosis and impart a new idea for the treatment and follow-up management of IPF patients.
Reverse causal relationship between periodontitis and shortened telomere length: Bidirectional two-sample Mendelian random analysis
Authors: Hu Jiaxin , Song Jukun , Chen Zhu , Yang Jing , Shi Qianhui , Jin Fuqian , Pang Qiyuan , Chang Xingtao , Tian Yuan , Luo Yi , Chen Liming
Published: December 2022

Background

Observational studies have demonstrated a link between shortened telomere lengths(TL) and chronic periodontitis. However, whether the shortened TL is the cause or the result of periodontitis is unknown.Therefore, our objective was to investigate a bidirectional causal relationship between periodontitis and TL using a two-sample Mendel randomized (MR) study.

Methods

A two-sample bidirectional MR analysis using publicly available genome-wide association study (GWAS) data was used. As the primary analysis, inverse variance weighting (IVW) was employed. To identify pleiotropy, we used leave-one-out analysis, MR-Egger, Weighted median, Simple mode, Weighted mode, and MR pleiotropy residual sum and outlier (MR-PRESSO).

Results

In reverse MR results, a genetic prediction of short TL was causally associated with a higher risk of periodontitis (IVW: odds ratio [OR]: 1.0601, 95% confidence interval [CI]: 1.0213 to 1.1002; P =0.0021) and other complementary MR methods. In the forward MR analysis, periodontitis was shown to have no significant effect on TL (IVW: p = 0.7242), with consistent results for the remaining complementary MR. No pleiotropy was detected in sensitivity analysis (all P>0.05).

Conclusion

Our MR studies showed a reverse causal relationship, with shorten TL being linked to a higher risk of periodontitis, rather than periodontitis shorten that TL. Future research is needed to investigate the relationship between cell senescence and the disease.
Reversal of splicing infidelity is a pre-activation step in B cell differentiation
Authors: O’Grady Tina M. , Baddoo Melody , Flemington Samuel A. , Ishaq Eman Y. , Ungerleider Nathan A. , Flemington Erik K.
Published: December 2022

Introduction

B cell activation and differentiation is central to the adaptive immune response. Changes in exon usage can have major impacts on cellular signaling and differentiation but have not been systematically explored in differentiating B cells.

Methods

We analyzed exon usage and intron retention in RNA-Seq data from subsets of human B cells at various stages of differentiation, and in an in vitro laboratory model of B cell activation and differentiation (Epstein Barr virus infection).

Results

Blood naïve B cells were found to have an unusual splicing profile, with unannotated splicing events in over 30% of expressed genes. Splicing changed substantially upon naïve B cell entry into secondary lymphoid tissue and before activation, involving significant increases in exon commitment and reductions in intron retention. These changes preferentially involved short introns with weak splice sites and were likely mediated by an overall increase in splicing efficiency induced by the lymphoid environment. The majority of transcripts affected by splicing changes showed restoration of encoded conserved protein domains and/or reduced targeting to the nonsense-mediated decay pathway. Affected genes were enriched in functionally important immune cell activation pathways such as antigen-mediated signaling, cell cycle control and mRNA processing and splicing.

Discussion

Functional observations from donor B cell subsets in progressive states of differentiation and from timecourse experiments using the in vitro model suggest that these widespread changes in mRNA splicing play a role in preparing naïve B cells for the decisive step of antigen-mediated activation and differentiation.
TGF-β: A novel predictor and target for anti-PD-1/PD-L1 therapy
Authors: Yi Ming , Li Tianye , Niu Mengke , Wu Yuze , Zhao Zhenyu , Wu Kongming
Published: December 2022

Transforming growth factor-β (TGF-β) signaling regulates multiple physiological processes, such as cell proliferation, differentiation, immune homeostasis, and wound healing. Besides, TGF-β plays a vital role in diseases, including cancer. Accumulating evidence indicates that TGF-β controls the composition and behavior of immune components in the tumor microenvironment (TME). Advanced cancers leverage TGF-β to reshape the TME and escape immune surveillance. TGF-β-mediated immune evasion is an unfavorable factor for cancer immunotherapy, especially immune checkpoint inhibitors (ICI). Numerous preclinical and clinical studies have demonstrated that hyperactive TGF-β signaling is closely associated with ICI resistance. It has been validated that TGF-β blockade synergizes with ICI and overcomes treatment resistance. TGF-β-targeted therapies, including trap and bispecific antibodies, have shown immense potential for cancer immunotherapy. In this review, we summarized the predictive value of TGF-β signaling and the prospects of TGF-β-targeted therapies for cancer immunotherapy.
Radiomic models based on magnetic resonance imaging predict the spatial distribution of CD8+ tumor-infiltrating lymphocytes in breast cancer
Authors: Jeon Seung Hyuck , Kim So-Woon , Na Kiyong , Seo Mirinae , Sohn Yu-Mee , Lim Yu Jin
Published: December 2022

Infiltration of CD8+ T cells and their spatial contexture, represented by immunophenotype, predict the prognosis and therapeutic response in breast cancer. However, a non-surgical method using radiomics to evaluate breast cancer immunophenotype has not been explored. Here, we assessed the CD8+ T cell-based immunophenotype in patients with breast cancer undergoing upfront surgery (n = 182). We extracted radiomic features from the four phases of dynamic contrast-enhanced magnetic resonance imaging, and randomly divided the patients into training (n = 137) and validation (n = 45) cohorts. For predicting the immunophenotypes, radiomic models (RMs) that combined the four phases demonstrated superior performance to those derived from a single phase. For discriminating the inflamed tumor from the non-inflamed tumor, the feature-based combination model from the whole tumor (RM-wholeFC) showed high performance in both training (area under the receiver operating characteristic curve [AUC] = 0.973) and validation cohorts (AUC = 0.985). Similarly, the feature-based combination model from the peripheral tumor (RM-periFC) discriminated between immune-desert and excluded tumors with high performance in both training (AUC = 0.993) and validation cohorts (AUC = 0.984). Both RM-wholeFC and RM-periFC demonstrated good to excellent performance for every molecular subtype. Furthermore, in patients who underwent neoadjuvant chemotherapy (n = 64), pre-treatment images showed that tumors exhibiting complete response to neoadjuvant chemotherapy had significantly higher scores from RM-wholeFC and lower scores from RM-periFC. Our RMs predicted the immunophenotype of breast cancer based on the spatial distribution of CD8+ T cells with high accuracy. This approach can be used to stratify patients non-invasively based on the status of the tumor-immune microenvironment.
Dublin’s saltmarshes contain climate-relevant carbon pools
Authors: Burke Shannon A. , Manahan Jane , Eichelmann Elke , Cott Grace M.
Published: December 2022

Wetland ecosystems, particularly coastal vegetated ecosystems, play a vital role in climate mitigation and adaptation. Coastal vegetated habitats (including coastal wetlands such as seagrass meadows, saltmarshes, and mangroves) are some of the most efficient ecosystems for storing carbon on a per hectare basis, retaining organic carbon for centuries to millennia. We conducted carbon stock assessments, to a depth of 1 m, across four young saltmarsh sites and the adjacent mudflats in Dublin, Ireland. Soil cores and vegetation samples were taken across each site in order to analyze the carbon content of each carbon pool. The carbon density of Dublin’s saltmarshes was 112.1 ± 10.1 Mg Corg ha−1. The dominant plant species were Spartina anglica, Plantago maritima, and Atriplex portulacoides. The soil carbon pool of these saltmarshes contributes 87% to the total carbon stock, with living plant biomass contributing the remaining 13%. Saltmarshes are important ecosystems for climate mitigation and can provide nature-based solutions to reduce net carbon emissions; however, their degradation will lead to the loss of climate-relevant carbon pools.
Tensile strain-hardening cementitious composites and its practical exploration without reinforcement: A review
Authors: Jiang Fangming , Long Xiong , Tian Likang , Tan Yan , Yu Jiangtao
Published: December 2022

Steel is widely used as reinforcement for brittle structural materials such as concrete structure and unreinforced masonry structure (URM). However, the job wasted in steel reinforcement installation and the following corrosion hinder the development of construction industry. The emergence of strain-hardening cement composites (SHCC) provides an opportunity for steel-free construction. This paper provides a comprehensive review of the properties of SHCC and the corresponding practical exploration without reinforcement. The authors herein begin with a discussion on the superior properties of SHCC and its structural applications on the RC structure. Following this, the application of SHCC to retrofit URM is reviewed. Finally, we presents the advances of SHCC used in 3D concrete printing (3DCP) technology, and discuss the feasibility of SHCC structures without reinforcements in the future. When these explorations are coupled with appropriate theoretical models, true values for auto-construction without steel reinforcement will emerge.
A survival prediction model and nomogram based on immune-related gene expression in chronic lymphocytic leukemia cells
Authors: Huang Han-ying , Wang Yun , Herold Tobias , Gale Robert Peter , Wang Jing-zi , Li Liang , Lin Huan-xin , Liang Yang
Published: December 2022

Introduction

There are many different chronic lymphoblastic leukemia (CLL) survival prediction models and scores. But none provide information on expression of immune-related genes in the CLL cells.

Methods

We interrogated data from the Gene Expression Omnibus database (GEO, GSE22762; Number = 151; training) and International Cancer Genome Consortium database (ICGC, CLLE-ES; Number = 491; validation) to develop an immune risk score (IRS) using Least absolute shrinkage and selection operator (LASSO) Cox regression analyses based on expression of immune-related genes in CLL cells. The accuracy of the predicted nomogram we developed using the IRS, Binet stage, and del(17p) cytogenetic data was subsequently assessed using calibration curves.

Results

A survival model based on expression of 5 immune-related genes was constructed. Areas under the curve (AUC) for 1-year survivals were 0.90 (95% confidence interval, 0.78, 0.99) and 0.75 (0.54, 0.87) in the training and validation datasets, respectively. 5-year survivals of low- and high-risk subjects were 89% (83, 95%) vs. 6% (0, 17%; p < 0.001) and 98% (95, 100%) vs. 92% (88, 96%; p < 0.001) in two datasets. The IRS was an independent survival predictor of both datasets. A calibration curve showed good performance of the nomogram. In vitro, the high expression of CDKN2A and SREBF2 in the bone marrow of patients with CLL was verified by immunohistochemistry analysis (IHC), which were associated with poor prognosis and may play an important role in the complex bone marrow immune environment.

Conclusion

The IRS is an accurate independent survival predictor with a high C-statistic. A combined nomogram had good survival prediction accuracy in calibration curves. These data demonstrate the potential impact of immune related genes on survival in CLL.
Coastal water bacteriophages infect various sets of Vibrio parahaemolyticus sequence types
Authors: Brossard Stoos Kari A. , Ren Jennifer , Shields-Cutler Robin R. , Sams Kelly L. , Caldwell Shannon , Ho Marvin B. , Rivara Gregg , Whistler Cheryl A. , Jones Stephen H. , Wiedmann Martin , DeMent Jamie , Getchell Rodman G. , Marquis Hélène
Published: December 2022

Introduction

Gastrointestinal illnesses associated with the consumption of shellfish contaminated with Vibrio parahaemolyticus have a negative impact on the shellfish industry due to recalls and loss of consumer confidence in products. This bacterial pathogen is very diverse and specific sequence types (STs), ST631 and ST36, have emerged as prevalent causes of Vibrio foodborne disease outbreaks in the US, though other STs have been implicated in sporadic cases. We investigated whether bacteriophages could be used as a proxy to monitor for the presence of distinct V. parahaemolyticus STs in coastal waters.

Methods

For this purpose, bacteriophages infecting V. parahaemolyticus were isolated from water samples collected on the Northeast Atlantic coast. The isolated phages were tested against a collection of 29 V. parahaemolyticus isolates representing 18 STs, including six clonal complexes (CC). Four distinct phages were identified based on their ability to infect different sets of V. parahaemolyticus isolates.

Results and Discussion

Overall, the 29 bacterial isolates segregated into one of eight patterns of susceptibility, ranging from resistance to all four phages to susceptibility to any number of phages. STs represented by more than one bacterial isolate segregated within the same pattern of susceptibility except for one V. parahaemolyticus ST. Other patterns of susceptibility included exclusively clinical isolates represented by distinct STs. Overall, this study suggests that phages populating coastal waters could be exploited to monitor for the presence of V. parahaemolyticus STs known to cause foodborne outbreaks.
Streptococcus pneumoniae promotes migration and invasion of A549 cells in vitro by activating mTORC2/AKT through up-regulation of DDIT4 expression
Authors: Song Xiaojie , Liu Baohong , Zhao Guanghui , Pu Xiaoxin , Liu Baoyi , Ding Meiling , Xue Yuwen
Published: December 2022

Introduction

Dysbiosis of the lower airway flora is associated with lung cancer, of which the relationship between Streptococcus, especially pathogenic Streptococcus pneumoniae (S. pneumoniae), and the progression of lung cancer are unclear.

Methods

Bronchoalveolar lavage fluid (BALF) samples were prospectively collected from patients with pulmonary nodules during diagnostic bronchoscopy, and finally included 70 patients diagnosed with primary lung cancer and 20 patients with benign pulmonary nodules as the disease control group. The differential flora was screened by 16S ribosomal RNA (rRNA) gene amplicon sequencing. An in vitro infection model of lung adenocarcinoma (LUAD) cells exposed to S.pneumoniae was established to observe its effects on cell migration and invasion ability. Exploring the molecular mechanisms downstream of DDIT4 through its loss- and gain-of-function experiments.

Results

16S rRNA sequencing analysis showed that the abundance of Streptococcus in the lower airway flora of lung cancer patients was significantly increased. After exposure to S. pneumoniae, A549 and H1299 cells significantly enhanced their cell migration and invasion ability. The results of DDIT4 loss- and gain-of-function experiments in A549 cells suggest that up-regulation of DDIT4 activates the mTORC2/Akt signaling pathway, thereby enhancing the migration and invasion of A549 cells while not affecting mTORC1. Immunofluorescence (IF) and fluorescence in situ hybridization (FISH) showed that S. pneumoniae was enriched in LUAD tissues, and DDIT4 expression was significantly higher in cancer tissues than in non-cancerous tissues. The increased expression of DDIT4 was also related to the poor prognosis of patients with LUAD.

Discussion

The data provided by this study show that S. pneumoniae enriched in the lower airway of patients with lung cancer can up-regulate DDIT4 expression and subsequently activate the mTORC2/AKT signal pathway, thereby increasing the migration and invasion abilities of A549 cells. Our study provides a potential new mechanism for targeted therapy of LUAD.
Gut microbiota of endangered Australian sea lion pups is unchanged by topical ivermectin treatment for endemic hookworm infection
Authors: Fulham Mariel , Power Michelle , Gray Rachael
Published: December 2022

The gut microbiota is essential for the development and maintenance of the hosts’ immune system. Disturbances to the gut microbiota in early life stages can result in long-lasting impacts on host health. This study aimed to determine if topical ivermectin treatment for endemic hookworm (Uncinaria sanguinis) infection in endangered Australian sea lion (Neophoca cinerea) pups resulted in gut microbial changes. The gut microbiota was characterised for untreated (control) (n = 23) and treated (n = 23) Australian sea lion pups sampled during the 2019 and 2020/21 breeding seasons at Seal Bay, Kangaroo Island. Samples were collected pre- and post-treatment on up to four occasions over a four-to-five-month period. The gut microbiota of untreated (control) and treated pups in both seasons was dominated by five bacterial phyla, Fusobacteria, Firmicutes, Proteobacteria, Actinobacteria and Bacteroidetes. A significant difference in alpha diversity between treatment groups was seen in pups sampled during the 2020/21 breeding season (p = 0.008), with higher richness and diversity in treated pups. Modelling the impact of individual pup identification (ID), capture, pup weight (kg), standard length (cm), age and sex on beta diversity revealed that pup ID accounted for most of the variation (35% in 2019 and 42% in 2020/21), with pup ID, capture, and age being the only significant contributors to microbial variation (p < 0.05). There were no statistically significant differences in the composition of the microbiota between treatment groups in both the 2019 and 2020/21 breeding seasons, indicating that topical ivermectin treatment did not alter the composition of the gut microbiota. To our knowledge, this is the first study to characterise the gut microbiota of free-ranging Australian pinniped pups, compare the composition across multiple time points, and to consider the impact of parasitic treatment on overall diversity and microbial composition of the gut microbiota. Importantly, the lack of compositional changes in the gut microbiota with treatment support the utility of topical ivermectin as a safe and minimally invasive management strategy to enhance pup survival in this endangered species.
Overexpressing GRE3 in Saccharomyces cerevisiae enables high ethanol production from different lignocellulose hydrolysates
Authors: Wang Haijie , Cao Limin , Li Qi , Wijayawardene Nalin N. , Zhao Jian , Cheng Min , Li Qi-Rui , Li Xiaobin , Promputtha Itthayakorn , Kang Ying-Qian
Published: December 2022

The efficiently renewable bioethanol can help to alleviate energy crisis and environmental pollution. Genetically modified strains for efficient use of xylose and developing lignocellulosic hydrolysates play an essential role in facilitating cellulosic ethanol production. Here we present a promising strain GRE3OE via GRE3 overexpressed in a previously reported Saccharomyces cerevisiae strain WXY70. A comprehensive evaluation of the fermentation level of GRE3OE in alkaline-distilled sweet sorghum bagasse, sorghum straw and xylose mother liquor hydrolysate. Under simulated corn stover hydrolysate, GRE3OE produced 53.39 g/L ethanol within 48 h. GRE3OE produced about 0.498 g/g total sugar in sorghum straw hydrolysate solution. Moreover, GRE3OE consumed more xylose than WXY70 in the high-concentration xylose mother liquor. Taken together, GRE3OE could be a candidate strain for industrial ethanol development, which is due to its remarkable fermentation efficiency during different lignocellulosic hydrolysates.
Cloud-based process design in a digital twin framework with integrated and coupled technology models for blisk milling
Authors: Rudel Viktor , Kienast Pascal , Vinogradov Georg , Ganser Philipp , Bergs Thomas
Published: December 2022

In this publication, the application of an implemented Digital Twin (DT) framework is presented by orchestration of CAM-integrated and containerized technology models carrying out FEM-coupled simulations for the finishing process of a simplified blade integrated disk (blisk) demonstrator. As a case study, the continuous acquisition, processing and usage of virtual process planning and simulation data as well as real machine and sensor data along the value chain is presented. The use case demonstrates the successful application of the underlying DT framework implementation for the prediction of the continuously changing dynamic behavior of the workpiece and according stable spindle speeds in the process planning phase as well as their validation in the actual manufacturing phase.
Indirect revascularization vs. non-surgical treatment for Moyamoya disease and Moyamoya syndrome: A comparative effectiveness study
Authors: Wang Yixuan , Li Miao , Wang Jie
Published: December 2022

Background

The efficacy of indirect revascularization vs. non-surgical treatment in adults with Moyamoya disease (MMD) and Moyamoya syndrome (MMS) remains controversial.

Objective

To compare the clinical outcomes of indirect revascularization and non-surgical treatments in adult patients with MMD and MMS.

Methods

We collected medical records and follow-up results of adult patients with MMD and MMS who received treatment in the China-Japan Union Hospital of Jilin University between January 2019 and December 2021. A Shapiro–Wilk test, independent sample t-test or Mann-Whitney U-test, and Pearson chi-square test were used to compare baseline variables. The propensity-score analysis was used to compare clinical outcomes of patients with MMD and MMS who underwent indirect revascularization and non-surgical treatments. The color-coded digital subtraction angiography (CC-DSA) was used to quantitatively analyzed the preoperative and postoperative (at 6-month follow-up) images of patients in the surgical group.

Results

A total of 144 patients were included in this study, of whom 37 received indirect revascularization treatment and 107 received non-surgical treatment. The average age of the patients was 58.3 ± 13.4 years. Perioperative complications were observed in eight of the operations. During the follow-up period, a total of 35 stroke events occurred, including two cases (5.4%) in the surgery group and 33 cases (30.8%) in the non-surgery group (p < 0.05). The preoperative mean transit time (MTT) of bypass vessel (superficial temporal artery, STA) was 0.26 ± 0.07, and the postoperative MTT of bypass vessel was 3.0 ± 0.25, and there was no statistical difference between the subgroups.

Conclusion

Indirect revascularization surgery can significantly reduce the recurrent stroke incidence of MMD and MMS patients.
Pregnancy and antibody-mediated CNS disorders: What do we know and what should we know?
Authors: Cortese Rosa , Mariotto Sara , Mancinelli Chiara Rosa , Tortorella Carla
Published: December 2022

Antibody-mediated central nervous system (CNS) disorders including those associated with aquaporin-4 or myelin oligodendrocyte glycoprotein IgG and autoimmune encephalitis often affect women of childbearing age. Pathogenic antibodies of these diseases can potentially alter reproductive functions and influence fetal development. Hormonal changes occurring during pregnancy may modify the course of autoimmune diseases by influencing relapse risk, attack severity, and affect the delivery and postpartum period. Moreover, balancing treatment related safety issues with the risk of potentially disabling relapses during pregnancy and breastfeeding are major challenges. Intentional prenatal, gestational, and post-partum counseling is paramount to address these issues and mitigate these risks. Fortunately, new insights on risk factors for adverse pregnancy outcomes and possible preventive strategies are emerging. This review aims to summarize the interplay between antibody-mediated CNS disorders and pregnancy during the prenatal, gestational, and postpartum periods, highlight current treatment recommendations, and discuss future areas of research.
Electro-acupuncture on Vascular Parkinsonism with multiple sleep disorders: A Case Report
Authors: Yan Mingyue , Fan Jingqi , Li Yingjia , Liu Xin , Yu Zhengmiao , Zhuang Lixing
Published: December 2022

Vascular Parkinsonism (VP) is a kind of rare secondary Parkinsonism caused by vascular lesions. Patients with VP experience not only movement disorders but also sleep disorders. But treatment options are limited and often associated with undesirable adverse effects. Electro-acupuncture (EA) is a safe, rapid work, easy operation, and convenient complementary replacement therapy. We report a case of a 51-year-old man who presented with VP and multiple sleep disorders. Based on clinical evaluation and nocturnal hospital-based polysomnography (PSG), the patient had severe PLMD (PSG showed severe periodic leg movements), excessive daytime sleepiness (EDS, the score of the ESS is 16), and probable rapid eye movement sleep disorder (RBD). Parkinson's disease sleep scale (PDSS) score, Pittsburgh sleep quality index (PSQI), and periodic leg movements index were 93, 11, and 135.2, respectively. After 8 weeks of EA treatment, the patient reported that the symptoms of subjective and objective sleep disturbance were significantly alleviated without any discomfort. This case report may provide a new alternative and complementary therapy for VP patients with sleep disturbance but more definitive and robust evidence is needed to support its efficacy.
Toward a fully implantable ecosystem for adaptive neuromodulation in humans: Preliminary experience with the CorTec BrainInterchange device in a canine model
Authors: Schalk Gerwin , Worrell Samuel , Mivalt Filip , Belsten Alexander , Kim Inyong , Morris Jonathan M. , Hermes Dora , Klassen Bryan T. , Staff Nathan P. , Messina Steven , Kaufmann Timothy , Rickert Jörn , Brunner Peter , Worrell Gregory A. , Miller Kai J.
Published: December 2022

This article describes initial work toward an ecosystem for adaptive neuromodulation in humans by documenting the experience of implanting CorTec's BrainInterchange (BIC) device in a beagle canine and using the BCI2000 environment to interact with the BIC device. It begins with laying out the substantial opportunity presented by a useful, easy-to-use, and widely available hardware/software ecosystem in the current landscape of the field of adaptive neuromodulation, and then describes experience with implantation, software integration, and post-surgical validation of recording of brain signals and implant parameters. Initial experience suggests that the hardware capabilities of the BIC device are fully supported by BCI2000, and that the BIC/BCI2000 device can record and process brain signals during free behavior. With further development and validation, the BIC/BCI2000 ecosystem could become an important tool for research into new adaptive neuromodulation protocols in humans.
Recent advances in PET-MRI for cardiac sarcoidosis
Authors: Munoz Camila , Schneider Alina , Botnar René M. , Prieto Claudia
Published: December 2022

The diagnosis of cardiac sarcoidosis (CS) remains challenging. While only a small fraction of patients with systemic sarcoidosis present with clinically symptomatic CS, cardiac involvement has been associated with adverse outcomes, such as ventricular arrhythmia, heart block, heart failure and sudden cardiac death. Despite the clinical relevance of having an early and accurate diagnosis of CS, there is no gold-standard technique available for the assessment of CS. Non-invasive PET and MR imaging have shown promise in the detection of different histopathological features of CS. More recently, the introduction of hybrid PET-MR scanners has enabled the acquisition of these hallmarks in a single scan, demonstrating higher sensitivity and specificity for CS detection and risk stratification than with either imaging modality alone. This article describes recent developments in hybrid PET-MR imaging for improving the diagnosis of CS and discusses areas of future development that could make cardiac PET-MRI the preferred diagnostic tool for the comprehensive assessment of CS.
Identification of characteristic aroma and bacteria related to aroma evolution during long-term storage of compressed white tea
Authors: Wang Zhihui , Wang Zhihua , Dai Haomin , Wu Shaoling , Song Bo , Lin Fuming , Huang Yan , Lin Xingchen , Sun Weijiang
Published: December 2022

Compressed white tea (CWT) is a reprocessed tea of white tea. Long-term storage has greatly changed its aroma characteristics, but the material basis and transformation mechanism of its unique aroma are still unclear. In this study, flavor wheel, headspace gas chromatography ion mobility spectroscopy, chemometrics, and microbiomics were applied to study the flavor evolution and important aroma components during long-term storage of CWT, and core functional bacteria were screened. During long-term storage, the aroma of CWT gradually changed from sweet, fruity and floral to stale flavor, woody and herbal. A total of 56 volatile organic compounds (VOCs) were identified, 54 of which were significantly differences during storage. The alcohols content was the highest during 1–5 years of storage, the esters content was the highest during 7–13 years of storage, and the aldehydes content was the highest during 16 years of storage. Twenty-nine VOCs were identified as important aroma components, which were significantly correlated with 6 aroma sub-attributes (P < 0.05). The functional prediction of bacterial community reminded that bacterial community could participate in the transformation of VOCs during storage of CWT. Twenty-four core functional bacteria were screened, which were significantly associated with 29 VOCs. Finally, 23 characteristic differential VOCs were excavated, which could be used to identify CWT in different storage years. Taken together, these findings provided new insights into the changes in aroma characteristics during storage of CWT and increased the understanding of the mechanism of characteristic aroma formation during storage.
Comparison of McKeown Minimally Invasive Esophagectomy vs sweet esophagectomy for esophageal squamous cell carcinoma: A retrospective study
Authors: Yu Fan , Zhang Yaozhong , Xu Haidi , Li Kuankuan , Gheng Jingge , Lin Chenxi , Li Lei , Wang Na , Wang Lei
Published: December 2022

There are two most widely used transthoracic esophagectomy methods: the McKeown Minimally Invasive esophagectomy (McKeown MIE) and the Sweet Esophagectomy. We evaluated and compared the therapeutic effects of these two methods to determine the appropriate method for the treatment of middle and lower third esophageal cancer patients who received neoadjuvant chemotherapy combined with immunotherapy (NACI). We retrospectively analyzed 43 sweet esophagectomy cases received NACI and 167 cases with McKeown MIE in the fourth hospital of Hebei Medical University from December 2019 to May 2022. This retrospective observational study showed that Sweet esophagectomy and McKeown MIE after NACI therapy for resectable ESCC patients appeared to be safe with low operative mortality and morbidity rate in the current population. In addition, sweet esophagectomy was associated with a lower incidence of severe complications and shorter hospital stay for patients over 70 years of age compared with McKeown MIE. There were no differences were found in length of stay, mortality and complication incidence rate between the two groups. The Sweet approach has advantage in hospital stay for the treatment of the elderly NACI patients with middle or lower third esophageal squamous cell carcinoma. In conclusion, Sweet esophagectomy and McKeown MIE are both safe, effective, and worthwhile approaches for ESCC patients in immunotherapy age.