bluuebunny/crossref_metadata_2025 huggingface dataset:
The Median Effective Analgesic Concentration of Ropivacaine in Sciatic Nerve Block Guided by Ultrasound After Arthroscopic Anterior Cruciate Ligament Reconstruction: A Double-Blind Up-Down Concentration-Finding Study
Authors: Xu Cheng , Gu Fei , Wang Chengyu , Liu Yang , Chen Rui , Zhou Quanhong , Lu Jie
Published: May 2022

Background

The median effective analgesic concentration (MEAC; EC50 = effective concentration in 50% patients) of ropivacaine in sciatic nerve block guided by ultrasound (US) required for effective postoperative analgesia following arthroscopic anterior cruciate ligament (ACL) reconstruction has not yet been found. This study aimed to determine the effectiveness of MEAC of 20 ml ropivacaine of postoperative anesthesia for patients after ACL reconstruction.

Methods

In total, 29 patients who underwent elective arthroscopic ACL reconstruction were enrolled in this study. All the subjects were given 20 ml of 0.2% ropivacaine for femoral nerve block. A concentration of 20 ml ropivacaine administered to the sciatic nerve was measured by applying the up-and-down sequential method (UDM). The starting concentration was 0.2% in the first patient, and the next patient received decremented 0.025% ropivacaine if the prior patient's postoperative visual analog pain score was <4 in the initial 8 h. Otherwise, the participant was given an incremental dose of 0.025% ropivacaine. The EC50 of ropivacaine was determined by using centered isotonic, linear-logarithmic, exponential regressions, and linear regression. The “goodness of fit” was compared among various models by calculating the residual standard errors.

Results

The concentration of ropivacaine administered ranged from 0.1 to 0.2%. The EC50 [95% confidence interval (CI)] determined by four statistical methods (centered isotonic, exponential regressions, linear-logarithmic, and linear regression) was 0.115, 0.113% (0.108, 0.343%), 0.142% (0.112, 0.347%), and 0.129% (0.103, 0.359%), respectively. Among all models, the residual standard error was the smallest for the exponential regression (0.2243).

Conclusion

The EC50 of ropivacaine in US-guided sciatic nerve block was 0.113–0.142%, and exponential regression model best matched the data.
Rapid Generation of In-House Serological Assays Is Comparable to Commercial Kits Critical for Early Response to Pandemics: A Case With SARS-CoV-2
Authors: Auerswald Heidi , Eng Chanreaksmey , Lay Sokchea , In Saraden , Eng Sokchea , Vo Hoa Thi My , Sith Charya , Cheng Sokleaph , Delvallez Gauthier , Mich Vann , Meng Ngy , Sovann Ly , Sidonn Kraing , Vanhomwegen Jessica , Cantaert Tineke , Dussart Philippe , Duong Veasna , Karlsson Erik A.
Published: May 2022

Introduction

Accurate and sensitive measurement of antibodies is critical to assess the prevalence of infection, especially asymptomatic infection, and to analyze the immune response to vaccination during outbreaks and pandemics. A broad variety of commercial and in-house serological assays are available to cater to different laboratory requirements; however direct comparison is necessary to understand utility.

Materials and Methods

We investigate the performance of six serological methods against SARS-CoV-2 to determine the antibody profile of 250 serum samples, including 234 RT-PCR-confirmed SARS-CoV-2 cases, the majority with asymptomatic presentation (87.2%) at 1–51 days post laboratory diagnosis. First, we compare to the performance of two in-house antibody assays: (i) an in-house IgG ELISA, utilizing UV-inactivated virus, and (ii) a live-virus neutralization assay (PRNT) using the same Cambodian isolate as the ELISA. In-house assays are then compared to standardized commercial anti-SARS-CoV-2 electrochemiluminescence immunoassays (Elecsys ECLIAs, Roche Diagnostics; targeting anti-N and anti-S antibodies) along with a flow cytometry based assay (FACS) that measures IgM and IgG against spike (S) protein and a multiplex microsphere-based immunoassay (MIA) determining the antibodies against various spike and nucleoprotein (N) antigens of SARS-CoV-2 and other coronaviruses (SARS-CoV-1, MERS-CoV, hCoVs 229E, NL63, HKU1).

Results

Overall, specificity of assays was 100%, except for the anti-S IgM flow cytometry based assay (96.2%), and the in-house IgG ELISA (94.2%). Sensitivity ranged from 97.3% for the anti-S ECLIA down to 76.3% for the anti-S IgG flow cytometry based assay. PRNT and in-house IgG ELISA performed similarly well when compared to the commercial ECLIA: sensitivity of ELISA and PRNT was 94.7 and 91.1%, respectively, compared to S- and N-targeting ECLIA with 97.3 and 96.8%, respectively. The MIA revealed cross-reactivity of antibodies from SARS-CoV-2-infected patients to the nucleocapsid of SARS-CoV-1, and the spike S1 domain of HKU1.

Conclusion

In-house serological assays, especially ELISA and PRNT, perform similarly to commercial assays, a critical factor in pandemic response. Selection of suitable immunoassays should be made based on available resources and diagnostic needs.
Anticholinergic Drug Exposure Increases the Risk of Delirium in Older Patients Undergoing Elective Surgery
Authors: Herrmann Matthias L. , Boden Cindy , Maurer Christoph , Kentischer Felix , Mennig Eva , Wagner Sören , Conzelmann Lars O. , Förstner Bernd R. , Rapp Michael A. , von Arnim Christine A. F. , Denkinger Michael , Eschweiler Gerhard W. , Thomas Christine
Published: May 2022

Introduction

Postoperative delirium (POD) is a common and serious adverse event of surgery in older people. Because of its great impact on patients' safety and quality of life, identification of modifiable risk factors could be useful. Although preoperative medication intake is assumed to be an important modifiable risk factor, the impact of anticholinergic drugs on the occurrence of POD seems underestimated in elective surgery. The aim of this study was to investigate the association between preoperative anticholinergic burden and POD. We hypothesized that a high preoperative anticholinergic burden is an independent, potentially modifiable predisposing and precipitating factor of POD in older people.

Methods

Between November 2017 and April 2019, 1,470 patients of 70 years and older undergoing elective orthopedic, general, cardiac, or vascular surgery were recruited in the randomized, prospective, multicenter PAWEL trial. Anticholinergic burden of a sub-cohort of 899 patients, who did not receive a multimodal intervention for preventing POD, was assessed by two different tools at hospital admission: The established Anticholinergic Risk Scale (ARS) and the recently developed Anticholinergic Burden Score (ABS). POD was detected by confusion assessment method (CAM) and a validated post discharge medical record review. Logistic regression analyses were performed to evaluate the association between anticholinergic burden and POD.

Results

POD was observed in 210 of 899 patients (23.4%). Both ARS and ABS were independently associated with POD. The association persisted after adjustment for relevant confounding factors such as age, sex, comorbidities, preoperative cognitive and physical status, number of prescribed drugs, surgery time, type of surgery and anesthesia, usage of heart-lung-machine, and treatment in intensive care unit. If a patient was taking one of the 56 drugs listed in the ABS, risk for POD was 2.7-fold higher (OR = 2.74, 95% CI = 1.55–4.94) and 1.5-fold higher per additional point on the ARS (OR = 1.54, 95% CI = 1.15–2.02).

Conclusion

Preoperative anticholinergic drug exposure measured by ARS or ABS was independently associated with POD in older patients undergoing elective surgery. Therefore, identification, discontinuation or substitution of anticholinergic medication prior to surgery may be a promising approach to reduce the risk of POD in older patients.
Blood HDAC4 Variation Links With Disease Activity and Response to Tumor Necrosis Factor Inhibitor and Regulates CD4+ T Cell Differentiation in Ankylosing Spondylitis
Authors: Dou Bin , Ma Fuzhe , Jiang Zhenyu , Zhao Ling
Published: May 2022

Purpose

Histone deacetylase 4 (HDAC4) regulates the progression of autoimmune diseases. This study aimed to further investigate the correlation between HDAC4 and Th cells, inflammation, disease activity, and treatment response in patients with ankylosing spondylitis (AS).

Methods

A total of 132 active patients with AS were enrolled, of whom 54 patients received TNF inhibitor (TNFi) and 78 patients received NSAID. Serum HDAC4 was measured by ELISA in patients with AS before treatment (W0) and at week (W)4, W8, and W12 after treatment. Meanwhile, serum HDAC4 was detected in 30 patients with osteoarthritis and in 30 healthy controls (HCs) by ELISA. Besides, naïve CD4+ T cells from patients with AS were isolated, followed by modulation of HDAC4 and then polarization toward Th1, Th2, and Th17.

Results

Histone deacetylase 4 was reduced in patients with AS compared with HCs and patients with osteoarthritis (both P < 0.01). In patients with AS, HDAC4 was negatively correlated with TNF (P < 0.001), IL-1β (P = 0.003), Th17 proportion (P = 0.008), C-reactive protein (P < 0.001), and ASDAS (P = 0.038), but not with IL-6, Th1 proportion, or other characteristics. Meanwhile, HDAC4 increased from W0 to W12 (P < 0.001); HDAC4 at W8 (P = 0.014) and W12 (P = 0.006) was raised in ASAS40-response patients than ASAS40-non-response patients; further subgroup analysis showed that HDAC4 at W12 was higher in ASAS40-response patients than ASAS40-non-response patients (P = 0.016) in the TNFi-treated group, but not in the NSAID-treated group. In addition, HDAC4 negatively regulated the polarization of naïve CD4+ T cells toward Th17 (P < 0.01), but not Th1 or Th2.

Conclusion

Histone deacetylase 4 is associated with lower inflammation, and the disease activity negatively regulates Th17 polarization, whose increment after treatment reflects favorable outcomes in patients with AS.
Effects of Co-application of Cadmium-Immobilizing Bacteria and Organic Fertilizers on Houttuynia cordata and Microbial Communities in a Cadmium-Contaminated Field
Authors: Yu Xiumei , Yan Min , Cui Yongliang , Liu Zhongyi , Liu Han , Zhou Jie , Liu Jiahao , Zeng Lan , Chen Qiang , Gu Yunfu , Zou Likou , Zhao Ke , Xiang Quanju , Ma Menggen , Li Shuangcheng
Published: May 2022

Cadmium pollution is a serious threat to the soil environment. The application of bio-based fertilizers in combination with beneficial microbial agents is a sustainable approach to solving Cd pollution in farm soil. The present study investigated the effects of co-application of a Cd-immobilizing bacterial agent and two fermented organic fertilizers (fermentative edible fungi residue; fermentative cow dung) on Houttuynia cordata and its microbial communities in a Cd-polluted field. It showed that both the application of the Cd-immobilizing bacterial agent alone and the combined application of bio-based soil amendments and the bacterial agent effectively reduced >20% of the uptake of Cd by the plant. Soil nitrogen level was significantly raised after the combined fertilization. The multivariate diversity analysis and co-occurrence network algorithm showed that a significant shift of microbial communities took place, in which the microbial populations tended to be homogeneous with reduced microbial richness and increased diversity after the co-application. The treatment of fermentative cow dung with the addition of the bacterial agent showed a significant increase in the microbial community dissimilarity (R = 0.996, p = 0.001) compared to that treated with cow dung alone. The co-application of the bacterial agent with both organic fertilizers significantly increased the abundance of Actinobacteria and Bacteroidetes. The FAPROTAX soil functional analysis revealed that the introduction of the microbial agent could potentially suppress human pathogenic microorganisms in the field fertilized with edible fungi residue. It also showed that the microbial agent can reduce the nitrite oxidation function in the soil when applied alone or with the organic fertilizers. Our study thus highlights the beneficial effects of the Cd-immobilizing bacterial inoculant on H. cordata and provides a better understanding of the microbial changes induced by the combined fertilization using the microbial agent and organic soil amendments in a Cd-contaminated field.
Probiotic Escherichia coli Nissle 1917 Expressing Elafin Protects Against Inflammation and Restores the Gut Microbiota
Authors: Teng Guigen , Liu Zilin , Liu Yun , Wu Ting , Dai Yun , Wang Huahong , Wang Weihong
Published: May 2022

Intestinal mucosal inflammation and epithelial barrier dysfunction have been implicated as pathological factors in inflammatory bowel disease (IBD). An emerging area of IBD research focuses on probiotics. The probiotic Escherichia coli Nissle 1917 (EcN) is an excellent choice for engineering therapeutic microbes. Elafin is an endogenous specific inhibitor of neutrophil elastase (NE) and proteinase 3, and we previously found Elafin can effectively suppress the development of colitis. Here, we genetically engineered EcN to deliver Elafin (EcN-Elafin) directly to the colonic mucosa and explored the protective effects of EcN-Elafin against colitis in mice. EcN-Elafin significantly alleviated dextran sodium sulfate (DSS) induced colitis. Compared with wild-type EcN, oral administration of EcN-Elafin displayed better effects on loss of weight, colon length shortening, elevated expression of myeloperoxidase (MPO), and proinflammatory cytokines and chemokine in colonic tissues. In addition, EcN-Elafin restored the expression and distribution of tight junction protein ZO-1 in colonic tissues back to normal. In a damaged colonic epithelial model utilizing Caco-2 cells stimulated with TNF-α, EcN-Elafin efficiently downregulated the activation level of NF-κB signaling. EcN-Elafin was also found to have restored the dysbiosis in gut caused by DSS administration. Moreover, EcN-Elafin significantly enhanced the concentrations of butyrate and valerate in the gut lumen. Thus, our findings demonstrated that EcN-Elafin enhanced the colonic epithelial barrier, promoted the resolution of inflammation, modulated the gut microbiota, and elevated concentrations of short-chain fatty acids (SCFAs) in the gut. EcN-Elafin may be a potential therapeutic method for IBD.
Clean and Safe Drinking Water Systems via Metagenomics Data and Artificial Intelligence: State-of-the-Art and Future Perspective
Authors: Mahajna Asala , Dinkla Inez J. T. , Euverink Gert Jan W. , Keesman Karel J. , Jayawardhana Bayu
Published: May 2022

The use of next-generation sequencing technologies in drinking water distribution systems (DWDS) has shed insight into the microbial communities’ composition, and interaction in the drinking water microbiome. For the past two decades, various studies have been conducted in which metagenomics data have been collected over extended periods and analyzed spatially and temporally to understand the dynamics of microbial communities in DWDS. In this literature review, we outline the findings which were reported in the literature on what kind of occupancy-abundance patterns are exhibited in the drinking water microbiome, how the drinking water microbiome dynamically evolves spatially and temporally in the distribution networks, how different microbial communities co-exist, and what kind of clusters exist in the drinking water ecosystem. While data analysis in the current literature concerns mainly with confirmatory and exploratory questions pertaining to the use of metagenomics data for the analysis of DWDS microbiome, we present also future perspectives and the potential role of artificial intelligence (AI) and mechanistic models to address the predictive and mechanistic questions. The integration of meta-omics, AI, and mechanistic models transcends metagenomics into functional metagenomics, enabling deterministic understanding and control of DWDS for clean and safe drinking water systems of the future.
FE-SEM/EDX Based Zinc Mobilization Analysis of Burkholderia cepacia and Pantoea rodasii and Their Functional Annotation in Crop Productivity, Soil Quality, and Zinc Biofortification of Paddy
Authors: Upadhayay Viabhav Kumar , Singh Ajay Veer , Khan Amir , Singh Jyoti , Pareek Navneet , Raghav Alok
Published: May 2022

The experimental study was contrived to characterize two zinc-solubilizing bacteria (ZSB), namely BMRR126 and BMAR64, and their role in zinc (Zn) biofortification of rice. These bacteria solubilized Zn profoundly, determined qualitatively by halo-zone formation on a solid medium and quantitatively in a liquid broth by AAS and SEM-EDX. The lowering of pH and contact angle assessment of the liquid broth unveiled the establishment of the acidic conditions in a medium suitable for Zn solubilization. The characterization of both isolates on the basis of 16S rRNA gene analysis was identified as Burkholderia cepacia and Pantoea rodasii, respectively. These strains were also found to have some plant probiotic traits namely phosphate solubilization, production of siderophore, indole acetic acid (IAA), exopolysaccharide (EPS), and ammonia. The field experiments were performed at two diverse locations and under all treatments; the simultaneous use of BMRR126 and BMAR64 with zinc oxide (ZnO) resulted in the highest growth and productivity of the paddy crop. The utmost Zn achievement in the grain was estimated in a treatment (T9) (25.07 mg/kg) containing a consortium of BMRR126 and BMAR64 along with ZnO for the Terai region. The treatment containing single ZSB bioinoculant BMRR126 (T7) showed an elevated Zn amount in the rice grain (33.25 mg/kg) for the Katchar region. The soil parameters (pH, EC, organic carbon, NPK, available Zn, and dehydrogenase activity) were also positively influenced under all bacterial treatments compared to the uninoculated control. Our study clearly accentuates the need for Zn solubilizing bacteria (ZSB) to provide the benefits of Zn-biofortification in different regions.
Antibacterial Activity of Two Metabolites Isolated From Endophytic Bacteria Bacillus velezensis Ea73 in Ageratina adenophora
Authors: Ren Zhihua , Xie Lei , Okyere Samuel Kumi , Wen Juan , Ran Yinan , Nong Xiang , Hu Yanchun
Published: May 2022

Ageratina adenophora, as an invasive and poisonous weed, seriously affects the ecological diversity and development of animal husbandry. Weed management practitioners have reported that it is very difficult to control A. adenophora invasion. In recent years, many researchers have focused on harnessing the endophytes of the plant as a useful resource for the development of pharmacological products for human and animal use. This study was performed to identify endophytes with antibacterial properties from A. adenophora. Agar well diffusion method and 16S rRNA gene sequencing technique were used to screen and identify endophytes with antibacterial activity. The response surface methodology and prep- high-performance liquid chromatography were used to determine the optimizing fermentation conditions and isolate secondary metabolites, respectively. UV-visible spectroscopy, infrared spectroscopy, nuclear magnetic resonance, and high-resolution mass spectrum were used to determine the structures of the isolated metabolites. From the experiment, we isolated a strain of Bacillus velezensis Ea73 (GenBank no. MZ540895) with broad-spectrum antibacterial activity. We also observed that the zone of inhibition of B. velezensis Ea73 against Staphylococcus aureus was the largest when fermentation broth contained 6.55 g/L yeast extract, 6.61 g/L peptone, 20.00 g/L NaCl at broth conditions of 7.95 pH, 51.04 h harvest time, and a temperature of 27.97°C. Two antibacterial peptides, Cyclo (L-Pro-L-Val) and Cyclo (L-Leu-L-Pro), were successfully extracted from B. velezensis Ea73. These two peptides exhibited mild inhibition against S. aureus and Escherichia coli. Therefore, we isolated B. velezensis Ea73 with antibacterial activity from A. adenophora. Hence, its metabolites, Cyclo (L-Pro-L-Val) and Cyclo (L-Leu-L-Pro), could further be developed as a substitute for human and animal antibiotics.
Formulation of Chemically Defined Media and Growth Evaluation of Ligilactobacillus salivarius ZJ614 and Limosilactobacillus reuteri ZJ625
Authors: Kwoji Iliya Dauda , Okpeku Moses , Adeleke Matthew Adekunle , Aiyegoro Olayinka Ayobami
Published: May 2022

Lactic acid bacteria are increasingly becoming important dietary supplements due to their health benefits when consumed in adequate quantity. The increasing attention on these important microbes has necessitated an in-depth understanding of their physiological processes, such as nutritional requirements and growth patterns, to better harness their probiotic potentials. This study was carried out to determine the nutritional requirements for the growth of L. salivarius ZJ614 and L. reuteri ZJ625 from a chemically defined medium and evaluate growth kinetics by fitting different sigmoidal growth models. The complete CDM contains 49 nutritional ingredients such as glucose, Tween 80®, mineral salts, buffers, amino acids, vitamins, and nucleotides at defined concentrations. In addition, the minimal nutritional requirements of the isolates were determined in a series of single-omission experiments (SOEs) to compose the MDM. Growth curve data were generated by culturing in an automated 96-well micro-plate reader at 37°C for 36 h, and photometric readings (optical density: OD600) were taken. The data were summarized in tables and charts using Microsoft Excel, while growth evaluation was carried out using open-source software (Curveball) on Python. The results revealed that omission of the amino acids, vitamins, and nucleotides groups resulted in 2.0, 20.17, and 60.24% (for L. salivarius ZJ614) and 0.95, 42.7, and 70.5% (for L. reuteri ZJ625) relative growths, respectively. Elimination of the individual CDM components also indicates varying levels of growth by the strains. The growth curve data revealed LogisticLag2 and Baranyi–Roberts models as the best fits for L. reuteri ZJ625 and L. salivarius ZJ614, respectively. All the strains showed appreciable growth on the CDM and MDM as observed in de Man–Rogosa–Sharpe (MRS) broth. We also described the growth kinetics of L. reuteri ZJ625 and L. salivarius ZJ614 in the CDM, and the best models revealed the estimated growth parameters.
Epidemiological Characteristics of COVID-19 Outbreak in Yangzhou, China, 2021
Authors: Zhang Yu-Dong , Chen Ding , Hu Lei , Shen Liang , Wu Ren-Yuan , Cao Fu-Ming , Xu Jian-Qiang , Wang Liang
Published: May 2022

Objective

Epidemiological characteristics of COVID-19 outbreak in Yangzhou city caused by the highly contagious Delta variant strain of SARS-CoV-2 virus were investigated in this retrospective descriptive study to provide prevention and control guidelines for outbreaks in the future.

Methods

All the epidemiological data used in this study were collected manually from the official website of the Yangzhou Municipal Health Committee from 28 July to 26 August 2021, and then were analyzed systematically and statistically in this study.

Results

A total of 570 COVID-19 cases were reported during the short-term outbreak in Yangzhou City. The ages of infected individuals ranged from 1 to 90 years with the average age at 49.47 ± 22.69 years. As for gender distributions, the ratio of male- to-female patients was 1:1.36 (242:328). Geographic analysis showed that 377 patients (66.1%) were in Hanjiang District while 188 patients (33.0%) were in Guangling District. Clinical diagnosis showed that 175 people (30.7%) had mild symptoms, 385 people were in moderate conditions (67.5%), and 10 people were in severe situations (1.8%). Significant age differences were found among the three groups (P < 0.001). However, no significant difference was identified in terms of gender ratio (P > 0.05). Based on the transmission chain formed by 6 generations of infected persons with a clear transmission relationship, the age showed a gradually decreasing trend, while the median time of diagnosis in 2 adjacent generations was 3 days. In addition, the estimated basic reproduction number R0 of the Delta variant was 3.3651 by the classical Susceptible, Infectious, and/or Recovered (SIR) model.

Conclusion

The Delta variant of SARS-CoV-2 was highly infectious and has obvious clustering characteristics during the Yangzhou outbreak in China.
Flagellar Motor Transformed: Biophysical Perspectives of the Myxococcus xanthus Gliding Mechanism
Authors: Chen Jing , Nan Beiyan
Published: May 2022

Many bacteria move on solid surfaces using gliding motility, without involvement of flagella or pili. Gliding of Myxococcus xanthus is powered by a proton channel homologous to the stators in the bacterial flagellar motor. Instead of being fixed in place and driving the rotation of a circular protein track like the flagellar basal body, the gliding machinery of M. xanthus travels the length of the cell along helical trajectories, while mechanically engaging with the substrate. Such movement entails a different molecular mechanism to generate propulsion on the cell. In this perspective, we will discuss the similarities and differences between the M. xanthus gliding machinery and bacterial flagellar motor, and use biophysical principles to generate hypotheses about the operating mechanism, efficiency, sensitivity to control, and mechanosensing of M. xanthus gliding.
Inferring the Significance of the Polyamine Metabolism in the Phytopathogenic Bacteria Pseudomonas syringae: A Meta-Analysis Approach
Authors: Solmi Leandro , Rosli Hernán G. , Pombo Marina A. , Stalder Santiago , Rossi Franco R. , Romero Fernando M. , Ruiz Oscar A. , Gárriz Andrés
Published: May 2022

To succeed in plant invasion, phytopathogenic bacteria rely on virulence mechanisms to subvert plant immunity and create favorable conditions for growth. This process requires a precise regulation in the production of important proteins and metabolites. Among them, the family of compounds known as polyamines have attracted considerable attention as they are involved in important cellular processes, but it is not known yet how phytopathogenic bacteria regulate polyamine homeostasis in the plant environment. In the present study, we performed a meta-analysis of publicly available transcriptomic data from experiments conducted on bacteria to begin delving into this topic and better understand the regulation of polyamine metabolism and its links to pathogenicity. We focused our research on Pseudomonas syringae, an important phytopathogen that causes disease in many economically valuable plant species. Our analysis discovered that polyamine synthesis, as well as general gene expression activation and energy production are induced in the early stages of the disease. On the contrary, synthesis of these compounds is inhibited whereas its transport is upregulated later in the process, which correlates with the induction of virulence genes and the metabolism of nitrogen and carboxylic acids. We also found that activation of plant defense mechanisms affects bacterial polyamine synthesis to some extent, which could reduce bacterial cell fitness in the plant environment. Furthermore, data suggest that a proper bacterial response to oxidative conditions requires a decrease in polyamine production. The implications of these findings are discussed.
A Tensorized Multitask Deep Learning Network for Progression Prediction of Alzheimer’s Disease
Authors: Tabarestani Solale , Eslami Mohammad , Cabrerizo Mercedes , Curiel Rosie E. , Barreto Armando , Rishe Naphtali , Vaillancourt David , DeKosky Steven T. , Loewenstein David A. , Duara Ranjan , Adjouadi Malek
Published: May 2022

With the advances in machine learning for the diagnosis of Alzheimer’s disease (AD), most studies have focused on either identifying the subject’s status through classification algorithms or on predicting their cognitive scores through regression methods, neglecting the potential association between these two tasks. Motivated by the need to enhance the prospects for early diagnosis along with the ability to predict future disease states, this study proposes a deep neural network based on modality fusion, kernelization, and tensorization that perform multiclass classification and longitudinal regression simultaneously within a unified multitask framework. This relationship between multiclass classification and longitudinal regression is found to boost the efficacy of the final model in dealing with both tasks. Different multimodality scenarios are investigated, and complementary aspects of the multimodal features are exploited to simultaneously delineate the subject’s label and predict related cognitive scores at future timepoints using baseline data. The main intent in this multitask framework is to consolidate the highest accuracy possible in terms of precision, sensitivity, F1 score, and area under the curve (AUC) in the multiclass classification task while maintaining the highest similarity in the MMSE score as measured through the correlation coefficient and the RMSE for all time points under the prediction task, with both tasks, run simultaneously under the same set of hyperparameters. The overall accuracy for multiclass classification of the proposed KTMnet method is 66.85 ± 3.77. The prediction results show an average RMSE of 2.32 ± 0.52 and a correlation of 0.71 ± 5.98 for predicting MMSE throughout the time points. These results are compared to state-of-the-art techniques reported in the literature. A discovery from the multitasking of this consolidated machine learning framework is that a set of hyperparameters that optimize the prediction results may not necessarily be the same as those that would optimize the multiclass classification. In other words, there is a breakpoint beyond which enhancing further the results of one process could lead to the downgrading in accuracy for the other.
Comparison of Long-Term Use of Low Dose Rituximab and Mycophenolate Mofetil in Chinese Patients With Neuromyelitis Optica Spectrum Disorder
Authors: Lin Jie , Xue Binbin , Li Jia , Zhu Ruofan , Pan Juyuan , Chen Zhibo , Zhang Xu , Li Xiang , Xia Junhui
Published: May 2022

Background

Several studies have reported the efficacy and safety of rituximab (RTX) and mycophenolate mofetil (MMF) in neuromyelitis optica spectrum disorder (NMOSD). This study aimed to evaluate the efficacy and safety of long-term use of low-dose RTX and MMF in Chinese patients with NMOSD.

Methods

We retrospectively reviewed data from patients with NMOSD in our hospital. The enrolled patients were administrated different immunosuppressive agents. We accessed annual relapse rate (ARR), neurological disability (Expanded Disability Status Scale, EDSS), time to the next relapse, and adverse events.

Results

EDSS and ARR were both reduced after RTX and MMF treatment. Kaplan-Meier analysis indicated that patients treated with RTX had a longer time to next relapse compared other immunosuppressive agents before RTX (log-rank test: p < 0.001). Furthermore, we evaluated the change of EDSS and ARR in RTX and MMF, and patients treated with RTX showed a better reduction. Eleven relapses from seven patients in group RTX and 20 relapses from 14 patients in group MMF were reported during follow-up.

Conclusion

Long-term using of low dose of RTX and MMF were effective and tolerable in Chinese patients with NMOSD. Compared with MMF, RTX showed a better way to reduce the ARR.
A Diffusion Tensor Imaging Study on the White Matter Structures Related to the Phonology in Cantonese–Mandarin Bilinguals
Authors: Xu Xiaoyu , Jin Yuying , Pan Ning , Cao Muqing , Jing Jin , Ma Jingwen , Fan Xiaoxuan , Tan Si , Song Xiaojing , Li Xiuhong
Published: May 2022

Cantonese and Mandarin are logographic languages, and the phonology is the main difference between the two languages. It is unclear whether the long-term experience of Cantonese–Mandarin bilingualism will shape different brain white matter structures related to phonological processing. A total of 30 Cantonese–Mandarin bilinguals and 30 Mandarin monolinguals completed diffusion-weighted imaging scan and phonological processing tasks. The tractography and tract-based spatial statistics were used to investigate the structural differences in the bilateral superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), and inferior fronto–occipital fasciculus (IFOF) between Cantonese–Mandarin bilinguals and Mandarin monolinguals. The post-hoc correlation analysis was conducted to investigate the relationship between the different structures with phonological processing skills. Compared to the Mandarin monolinguals, the Cantonese–Mandarin bilinguals had higher fractional anisotropy (FA) along the left ILFs higher mean diffusivity (MD) along the right IFOF and the temporoparietal segment of SLF (tSLF), higher axial diffusivity (AD) in the right IFOF and left ILF, and lower number of streamlines in the bilateral tSLF. The mean AD of the different voxels in the right IFOF and the mean FA of the different voxels in the left ILF were positively correlated with the inverse efficiency score (IES) of the Cantonese auditory and Mandarin visual rhyming judgment tasks, respectively, within the bilingual group. The correlation between FA and IES was different among the groups. The long-term experience of Cantonese–Mandarin bilinguals shapes the different brain white matter structures in tSLF, IFOF, and ILF. Compared to the monolinguals, the bilinguals’ white matter showed higher diffusivity, especially in the axonal direction. These changes were related to bilinguals’ phonological processing.
Non-invasive Vagus Nerve Stimulation in Treatment of Disorders of Consciousness – Longitudinal Case Study
Authors: Osińska Albertyna , Rynkiewicz Andrzej , Binder Marek , Komendziński Tomasz , Borowicz Anna , Leszczyński Antoni
Published: May 2022

Neuromodulatory electroceuticals such as vagus nerve stimulation have been recently gaining traction as potential rehabilitation tools for disorders of consciousness (DoC). We present a longitudinal case study of non-invasive auricular vagus nerve stimulation (taVNS) in a patient diagnosed with chronic unresponsive wakefulness syndrome (previously known as vegetative state). Over a period of 6 months we applied taVNS daily and regularly evaluated the patient’s behavioral outcomes using Coma Recovery Scale – Revised. We also took electrophysiological measures: resting state electroencephalography (EEG), heart rate (HR) and heart rate variability (HRV). All these methods revealed signs of improvement in the patient’s condition. The total CRS-R scores fluctuated but rose from 4 and 6 at initial stages to the heights of 12 and 13 in the 3rd and 5th month, which would warrant a change in diagnosis to a Minimally Conscious State. Scores obtained in a 2 months follow-up period, though, suggest this may not have been a lasting improvement. Behavioral signs of recovery are triangulated by EEG frequency spectrum profiles with re-emergence of a second oscillatory peak in the alpha range, which has been shown to characterize aware people. However, sustained spontaneous theta oscillations did not predictably diminish, which most likely reflects structural brain damage. ECG measures revealed a steady decrease in pre-stimulation HR combined with an increase in HRV-HR. This suggests a gradual withdrawal of sympathetic and an increase in parasympathetic control of the heart, which the previous literature has also linked with DoC improvements. Together, this study suggests that taVNS stimulation holds promise as a DoC treatment.
Hippocampal Volume and Plasma Brain-Derived Neurotrophic Factor Levels in Patients With Depression and Healthy Controls
Authors: Fujii Rintaro , Watanabe Keita , Okamoto Naomichi , Natsuyama Tomoya , Tesen Hirofumi , Igata Ryohei , Konishi Yuki , Ikenouchi Atsuko , Kakeda Shingo , Yoshimura Reiji
Published: May 2022

The aim of the present study was to investigate associations between hippocampal subfield volumes and plasma levels of brain-derived neurotrophic factor (BDNF) in patients experiencing a first episode of major depression (MD) (n = 30) as compared to healthy controls (HC) (n = 49). Covariate-adjusted linear regression was performed to compare the MD and healthy groups, adjusting for age, sex, and total estimated intracranial volume. We demonstrated that there were no differences in total hippocampal volume between the MD and HC groups. However, the volumes of the hippocampus-amygdala-transition-area (HATA) on the left side of the brain as well as the parasubiculum, presubiculum, and fimbria on the right side were statistically significantly smaller in the MD group than in the HC group. Furthermore, the volume of the hippocampal fissure on the right side was statistically significantly smaller in the HC group than in the MD group. In the MD group, we found a positive linear correlation between hippocampal volume and plasma BDNF concentrations in the CA4 area on the left side (p = 0.043). In contrast, in the HC group, we found a negative linear correlation between parasubiculum volume on the right side and plasma BDNF concentrations (p = 0.04). These results suggest that some hippocampal subfields may already be atrophic at the start of MD. In addition, our findings suggest that the sensitivity of the right parasubiculum region to BDNF may differ between MD and HC groups. These findings guide future research directions and, if confirmed, may ultimately inform medical guidelines.
The Expression Profile, Clinical Application and Potential Tumor Suppressing Mechanism of hsa_circ_0001675 in Head and Neck Carcinoma
Authors: Cao Yujie , Ye Dong , Shen Zhisen , Li Zan , Li Qun , Rong Hao
Published: May 2022

Purpose

This study sought to identify circular RNAs (circRNA) that participate in the regulation of head and neck cancer (HNC), analyze their clinical application, and predict their molecular mechanism during HNC.

Materials and Methods

High-throughput sequencing was used to analyze circRNA expression in 18 matched HNC and adjacent normal tissues. Target circRNAs with significantly differential expression were obtained. In 103 HNC and adjacent normal tissues, real-time fluorescent quantitative PCR (qRT-PCR) was used to verify the differential expression of target circRNAs. This data was combined with clinicopathological information to analyze the diagnostic value of target circRNA. Bioinformatics was used to find target circRNAs that acted as competitive endogenous RNA (ceRNA) and construct a circRNA-miRNA-mRNA regulatory network. mRNA expression was verified by immunohistochemistry (IHC).

Results

A total of 714 differentially expressed circRNAs were detected in HNC, and the low expression of hsa_circ_0001675 was particularly significant (fold change [FC] = -4.85, P = 6.305E-05). hsa_circ_0001675 had significantly lower expression in HNC than in normal tissue (P < 0.01). Low hsa_circ_0001675 expression was positively associated with tumor invasion and clinical staging (P < 0.05), and its area under the ROC curve (AUC) was 0.7776. Low hsa_circ_0001675 expression also correlated with the overall survival (OS) rate and the progression-free survival (PFS) rate of HNC patients (P < 0.001). Bioinformatics was used to construct a ceRNA network of hsa_circ_0001675 with six differentially expressed miRNAs (hsa-miR-330-5p, hsa-miR-498, hsa-miR-532-3p, hsa-miR-577, hsa-miR-1248, and hsa-miR-1305) and 411 differentially expressed mRNAs and found that the neuroactive ligand-receptor interaction, and the cAMP and calcium signaling pathways were particularly enriched. Further bioinformatics and IHC analysis showed that miR577/TESC is the likely downstream signaling pathway for hsa_circ_0001675.

Conclusion

This study showed that hsa_circ_0001675 is downregulated in HNC and could be an effective biomarker for HNC diagnosis. In addition, hsa_circ_0001675 may have a potential ceRNA mechanism and suppress HNC disease progression through the hsa_circ_0001675-miRNA-mRNA axis.
Association Between DPP-4 Inhibitors and Events of Colorectal and Liver Cancers in Patients With Diabetes Receiving Second-Line Agents: A Nested Case-Control Study
Authors: Chou Chu-Lin , Juan Shu-Hui , Li Ching-Hao , Chen Hsi-Hsien , Kao Chih-Chin , Chen Li-Ying , Chien Li-Nien , Fang Te-Chao
Published: May 2022

Objective

Plasma dipeptidyl peptidase-4 (DPP4) levels were significantly lower in patients with colorectal and liver cancers, and animal studies also showed DPP4 inhibitors (DPP4is) have procarcinogenic effects in colorectal cancer. Until now, whether DPP4is therapy affects the progression of liver cancer and colorectal cancer in patients with T2DM has not been well investigated. We investigated the association between cumulative defined daily dose (cDDD) of DPP4is exposure and risks of liver and colorectal cancers in patients with type 2 diabetes.

Materials and Methods

We identified 268,520 patients with diabetes receiving DPP4is as second-line agents between March 1, 2009, and December 31, 2013, from Taiwan’s National Health Insurance Research Database, Taiwan Cancer Registry, and National Death Registry of Taiwan. The amount of DPP4is were divided into three groups (low, medium, and high) based on the interquartile range of the cDDD of the DPP4is.

Results

The data showed that the low cDDD of DPP-4is was associated with a reducing risk of colorectal cancer [adjusted odds ratio (OR), 0.49; 95% CI, 0.32–0.75; P=0.001]. However, the high cDDD of DPP-4is was associated with an increasing risk of colorectal cancer (adjusted OR, 1.86; 95% CI, 1.32–2.61; P<0.001). No association between DPP4is use and liver cancer risk was observed.

Conclusions

This nested case study revealed a J-shaped association between the cDDD of DPP-4is and colorectal cancer risk, but not liver cancer risk. Therefore, the effects of long-term DPP4is use on colorectal cancer risk warrant further study.
Would the Addition of Immunotherapy Impact the Prognosis of Patients With Malignant Pericardial Effusion?
Authors: Chiruvella Varsha , Ullah Asad , Elhelf Islam , Patel Nikhil , Karim Nagla Abdel
Published: May 2022

Pericardial effusion is a common finding in advanced-stage lung cancer. The presence of malignant cells or drainage of exudate effusion in the pericardial space may cause symptoms of dyspnea, pleuritic chest pain, and syncope. In addition to the difficulty physicians face in the detection and diagnosis of malignant pericardial effusion, treatment may be challenging considering the cancer prognosis and cardiovascular stability of the patient. Despite the availability of several treatment modalities for malignant pericardial effusion, including chemotherapy and surgery, patients with lung cancer historically present with poor prognoses. In addition to lung adenocarcinoma with malignant pericardial effusion, this case was complicated by COVID-19 and malignancy-associated obstructive pneumonia. We present a case of a 64-year-old woman with advanced non-small cell lung carcinoma (NSCLC) with malignant pericardial effusion who, despite testing positive for COVID-19 and having obstructive pneumonia, had favorable outcomes following systemic therapy with combined chemo-immunotherapy.
Chimeric Antigen Receptor Based Cellular Therapy for Treatment Of T-Cell Malignancies
Authors: Polgárová Kamila , Otáhal Pavel , Šálek Cyril , Pytlík Robert
Published: May 2022

T-cell malignancies can be divided into precursor (T-acute lymphoblastic leukemia/lymphoblastic lymphoma, T-ALL/LBL) and mature T-cell neoplasms, which are comprised of 28 different entities. Most of these malignancies are aggressive with rather poor prognosis. Prognosis of relapsed/refractory (R/R) disease is especially dismal, with an expected survival only several months after progression. Targeted therapies, such as antiCD30 immunotoxin brentuximab vedotin, antiCD38 antibody daratumumab, and anti-CCR4 antibody mogamulizumab are effective only in subsets of patients with T-cell neoplasms. T-cells equipped with chimeric antigen receptor (CAR-Ts) are routinely used for treatment of R/R B-cell malignancies, however, there are specific obstacles for their use in T-cell leukemias and lymphomas which are fratricide killing, risk of transfection of malignant cells, and T-cell aplasia. The solution for these problems relies on target antigen selection, CRISPR/Cas9 or TALEN gene editing, posttranslational regulation of CAR-T surface antigen expression, and safety switches. Structural chromosomal changes and global changes in gene expression were observed with gene-edited products. We identified 49 studies of CAR-based therapies registered on www.clinicaltrials.gov. Most of them target CD30 or CD7 antigen. Results are available only for a minority of these studies. In general, clinical responses are above 50% but reported follow-up is very short. Specific toxicities of CAR-based therapies, namely cytokine release syndrome (CRS), seem to be connected with the antigen of interest and source of cells for manufacturing. CRS is more frequent in antiCD7 CAR-T cells than in antiCD30 cells, but it is mild in most patients. More severe CRS was observed after gene-edited allogeneic CAR-T cells. Immune effector cell associated neurotoxicity (ICANS) was mild and infrequent. Graft-versus-host disease (GvHD) after allogeneic CAR-T cells from previous hematopoietic stem cell donor was also observed. Most frequent toxicities, similarly to antiCD19 CAR-T cells, are cytopenias. CAR-based cellular therapy seems feasible and effective for T-cell malignancies, however, the optimal design of CAR-based products is still unknown and long-term follow-up is needed for evaluation of their true potential.
Case Report: Implantation of Dedifferentiated to Poorly Differentiated Thyroid Carcinoma After Endoscopic Thyroid Surgery
Authors: Hu Jin , Xu Xia , Wang Shuntao , Dong Fang , Zhang Ximeng , Ming Jie , Huang Tao
Published: May 2022

Background

Endoscopic thyroidectomy is widely accepted for its advantages. However, implant metastasis remains a significant complication of endoscopic thyroidectomy.

Methods

This is the first report of breast implantation diagnosed with poorly differentiated thyroid carcinoma following endoscopic thyroidectomy.

Results

We present a case of a 35-year-old woman who was initially diagnosed with a 3.0 cm conventional papillary thyroid carcinoma after endoscopic thyroidectomy via total areola. Two years later, she was reported to have recurring poorly differentiated thyroid carcinoma in the right areola. Implantation after endoscopic thyroidectomy is rare, and even rarer is dedifferentiated papillary thyroid carcinoma around the implant site.

Conclusions

Stringently evaluated endoscopic surgery indications, appropriate preoperative evaluation, meticulous surgical technique, and adequate protective measures can significantly reduce the incidence of local implantation or recurrence.
Early Unplanned Reoperation After Glioma Craniotomy: Incidence, Predictor and Process Improvement
Authors: Zhang Yu , Ji Peigang , Wang Shoujie , Qin Huaizhou , Cai Qing
Published: May 2022

Objective

To evaluate the rate of, reasons for, and predictors of unplanned reoperation after craniotomy for glioma in a single-institution consecutive series.

Methods

Patients who underwent glioma resection at our hospital from 2015 to 2021 were included (n=1563). Multivariate logistic regression was used to examine the predictors of early unplanned cranial reoperation. The predictors that were screened included patient age, sex, tumor properties, blood loss, blood pressure and antiplatelets drugs usage.

Results

A total of 3.6% (56/1563) of the patients underwent an early unplanned reoperation after craniotomy for glioma. The reasons for early unplanned reoperation were brain edema (48.2%), cerebral infarction (33.9%) and hemorrhage (17.9%). The predictors of early unplanned reoperation were WHO grade III-IV, peritumoral edema ≥1 cm, subtotal resection, arterial/venous involvement and elevation in blood pressure ≥50 mmHg.

Conclusions

Glioma properties and blood pressure management are decisive predictors of early unplanned reoperation for glioma resection. The authors provide a nuanced discussion regarding early unplanned reoperations and perioperative process improvement as a quality indicator for glioma patient populations.