bluuebunny/crossref_metadata_2025 huggingface dataset:
Anatomic distribution of lower extremity deep venous thrombosis is associated with an increased risk of pulmonary embolism: A 10-year retrospective analysis
Authors: Zhang Jianjun , Chen Yan , Wang Zhicong , Chen Xi , Liu Yuehong , Liu Mozhen
Published: March 2023

Aims

To investigate the potential relationship between anatomic distribution of lower extremity deep venous thrombosis (LEDVT) and pulmonary embolism (PE).

Methods

A retrospective case-control study was performed in patients diagnosed with LEDVT, which were confirmed by bilateral lower extremity compression ultrasonography (CUS) examination. According to the ultrasound reports, thrombus sidedness was categorized as unilateral and bilateral lower extremity, thrombus location was classified into distal and proximal LEDVT. Anatomic distributions of LEDVT were further subdivided depending on the combination of thrombus sidedness and location. Patients with PE were identified using the International Classification of Diseases-10 (ICD-10) codes (I26.0 and I26.9), and divided into PE group and Non-PE group. Univariate and multivariate logistic regression analyses were used to assess the association between anatomic distribution of LEDVT and PE. Sensitivity analyses were also conducted.

Results

A total of 2,363 consecutive patients with LEDVT were included, of whom 66.10% and 33.90% were unilateral and bilateral LEDVT, as well as 71.39% and 28.61% were isolated distal and proximal LEDVT, respectively. After the diagnosis of LEDVT, 185 patients (7.83%) developed PE. The proportions of PE ranged between the lowest (4.07%) in unilateral-distal LEDVT and highest (14.55%) in bilateral-proximal LEDVT. Multivariate logistic regression analysis showed that bilateral LEDVT (odds ratios [OR] = 2.455, 95% confidence interval [CI]: 1.803–3.344, P < 0.001) and proximal LEDVT (OR = 1.530, 95% CI: 1.105–2.118, P = 0.010) were risk factors for developing PE. Moreover, unilateral-proximal (OR = 2.129, 95% CI: 1.365–3.320, P = 0.00), bilateral-distal (OR = 3.193, 95% CI: 2.146–4.752, P < 0.001) and bilateral-proximal LEDVT(OR = 3.425, 95% CI: 2.093–5.603, P < 0.001) were significantly associated with an increased risk of PE. Sensitivity analyses also confirmed the robustness of these associations.

Conclusion

Patients with unilateral-proximal, bilateral-distal or bilateral-proximal are more likely to suffer from PE than those with unilateral-distal LEDVT.
Research on weighting method of geological hazard susceptibility evaluation index based on apriori Algorithm
Authors: Chen Bin , Wei Na , Qu Tianqiang , Zhang Lianzhi , Li Yingyi , Long Xiao , Lin Youxi
Published: March 2023

Given the inconsistency between the information value and the weight value in the weighted information value model, a weight model based on the Apriori algorithm is established in this paper to analyze the correlation between the second-level intervals of disaster factors and the susceptibility of geological disasters. The objective weight of the second-level intervals of each index factor is calculated through the mining of association rules by the Apriori algorithm. The subjective uncertainty of the existing second-level factor weighting method is eliminated. Taking the geological disaster data of Xiangtan urban area as an example, 10 evaluation indexes were selected to establish the entropy weight method-information value (EWM-IV) model and the entropy weight method-Apriori algorithm-information value (EWM-Apriori-IV) model to evaluate the geological disaster susceptibility, and the disaster area ratio and the receiver operating characteristic curve (ROC) verification method were used to test and analyze the evaluation results. The results showed that compared with the EWM-IV model, the EWM-Apriori-IV model is used to evaluate the disaster area ratio of high-prone area increased by 58.3%, and the disaster area ratio of low-prone area decreased by 43.1%, the area under the curve (AUC) increased by 7.4%, and the evaluation accuracy was relatively improved compared with the former. This paper proves the rationality and practicability of the weighting method of the geological hazard susceptibility evaluation index based on the Apriori algorithm.
Field Test Research on the Downhole Multiphysics Micro-Measurer Based on the MEMS Microchip
Authors: Li Mu , Liu Wei , Zhang Hengrui , Tang Chunjing , Fu Jiasheng , Zhai Xiaoqiang , Wang Hao
Published: March 2023

Since pressure while drilling (PWD) has the disadvantages of single-point measurement and high cost of application, a micro-measurer based on MEMS (micro-electromechanical systems) sensor technology, which can measure downhole temperature, pressure, magnetic field, and dynamic signal, has been developed to achieve real-time, efficient, and accurate measurement of multiple parameters in the well. The kernel circuit system is the core of measurement and control, and the shell plays the role in protecting the kernel circuit. The shell of the micro-measurer is made of preferably selected materials with high-temperature and high-pressure resistance, corrosion resistance, small size, and low density, which can adapt to working in drilling fluid for a long time. The micro-measurer uses integrated interfaces on the shell to enable communication between the host computer and measuring machine. Based on the field test, both the functional integrity and data measurement accuracy of the micro-measurer are verified. Through analysis of the measured data, the profile of the downhole temperature field is constructed. The physical phenomena reflected by the measured magnetic field signal and dynamic signal are consistent with the actual working conditions observed in the test. Hence, as a new microchip measuring device, the micro-measurer can better serve the drilling engineering field and provide technical support for real-time measurement of downhole parameters in the future.
Rates of chronic absenteeism in Montessori and non-Montessori Title 1 schools
Authors: LeBoeuf Lee , Goldstein-Greenwood Jacob , Lillard Angeline S.
Published: March 2023

In this study, we asked whether Montessori schools, which tend to have high student engagement, are associated with lower average rates of chronic absenteeism and/or smaller racial disparities therein relative to non-Montessori schools. Using data from the Civil Rights Data Collection, we identified a sample of Title 1 Montessori and non-Montessori schools with propensity score matching, and we used multilevel modeling to compare racial disparities in chronic absenteeism rates across school types. There was no significant difference in the average overall rates of chronic absenteeism across school types; nor were there sizable or significant differences in average racial disparities in the rates of chronic absenteeism between Black and White or Hispanic and White students, though Montessori schools had slightly lower average rates for White students. We discuss how shortcomings in the way chronic absenteeism data are collected limit intervention work by preventing researchers from answering questions about why students are chronically absent.
Metabolomics analysis reveals serum biomarkers in patients with diabetic sarcopenia
Authors: Tan Yuwei , Liu Xiaosong , Yang Yinping , Li Baoying , Yu Fei , Zhao Wenqian , Fu Chunli , Yu Xin , Han Zhenxia , Cheng Mei
Published: March 2023

Introduction

Diabetic sarcopenia (DS) is characterized by muscle atrophy, slower nerve conduction, reduced maximum tension generated by skeletal muscle contraction, and slower contraction rate. Hence, DS can cause limb movement degeneration, slow movement, reduced balance, reduced metabolic rate, falls, fractures, etc. Moreover, the relevant early biological metabolites and their pathophysiological mechanism have yet to be characterized.

Method

The current cross-sectional study employed serum metabolomics analysis to screen potential noninvasive biomarkers in patients with diabetic sarcopenia. A total of 280 diabetic patients were enrolled in the study (n = 39 sarcopenia [DS], n = 241 without sarcopenia [DM]). Ten patients were randomly selected from both groups. Non-targeted metabolomic analysis was performed by ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.

Results

A total of 632 differential metabolites were identified, including 82 that were significantly differentially abundant (P < 0.05, VIP > 1, FC > 1.2 or FC < 0.8). Compared with the DM group, the contents of pentadecanoic acid, 5'-methylthioadenosine (5'-MTA), N,N-dimethylarginine (asymmetric dimethylarginine, ADMA), and glutamine in the DS group were significantly increased, while that of isoxanthohumol was decreased.

Discussion

Based on receiver operating characteristic curve analysis, pentadecanoic acid, 5'-MTA, ADMA, and glutamine may serve as potential biomarkers of DS. Moreover, ATP-binding cassette (ABC) transporters and the mammalian target of the rapamycin signaling pathway were found to potentially have important regulatory roles in the occurrence and development of DS (P < 0.05). Collectively, the differential metabolites identified in this study provide new insights into the underlying pathophysiology of DS and serve as a basis for therapeutic interventions.
Pure androgen-secreting adrenal tumor (PASAT): A rare case report of bilateral PASATs and a systematic review
Authors: Liao Zhangcheng , Gao Yuting , Zhao Yang , Wang Zhan , Wang Xu , Zhou Jiaquan , Zhang Yushi
Published: March 2023

Background

Adult pure androgen–secreting adrenal tumors (PASATs) are extremely rare, and their characteristics are largely unknown.

Methods

A rare case of adult bilateral PASATs was reported, and a systematic literature review of adult PASATs was conducted to summarize the characteristics of PASATs.

Results

In total, 48 studies, including 40 case reports and 8 articles, were identified in this review. Analysis based on data of 42 patients (including current case and 41 patients from 40 case reports) showed that average age was 40.48 ± 15.80 years (range of 18-76). The incidence of adult PASAT peaked at 21-30 years old, while that of malignant PASAT peaked at 41-50 years old. Most PASAT patients were female (40/42, 95.23%), and hirsutism was the most common symptom (37/39, 94.87%). Testosterone (T) was the most commonly elevated androgen (36/42, 85.71%), and 26 of 32 tested patients presented increased dehydroepiandrosterone sulfate (DS) levels. In malignancy cases, disease duration was significantly decreased (1.96 vs. 4.51 years, P=0.025), and tumor diameter was significantly increased (8.9 vs. 4.9 cm, p=0.011). Moreover, the androgen levels, namely, T/upper normal range limit (UNRL) (11.94 vs. 4.943, P=0.770) and DS/UNRL (16.5 vs. 5.28, P=0.625), were higher in patients with malignancy. In total, 5 out of 7 patients showed an increase in DS or T in the human chorionic gonadotropin (HCG) stimulation test. Overall, 41 out of 42 patients (including current case) underwent adrenal surgery, and recurrence, metastasis, or death was reported in 5 out of 11 malignant patients even with adjuvant or rescue mitotane chemotherapy.

Conclusion

Adult PASAT, which is predominant in women, is characterized by virilism and menstrual dysfunction, especially hirsutism. Elevated T and DS may contribute to the diagnosis of adult PASAT, and HCG stimulation test might also be of help in diagnosis. Patients with malignant PASAT have a shorter disease duration, larger tumor sizes and relatively higher androgen levels. Surgery is recommended for all local PASATs, and Malignancy of PASAT should be fully considered due to the high risk of malignancy, poor prognosis and limited effective approaches.
Differential voltage analysis for battery manufacturing process control
Authors: Weng Andrew , Siegel Jason B. , Stefanopoulou Anna
Published: March 2023

Voltage-based battery metrics are ubiquitous and essential in battery manufacturing diagnostics. They enable electrochemical “fingerprinting” of batteries at the end of the manufacturing line and are naturally scalable, since voltage data is already collected as part of the formation process which is the last step in battery manufacturing. Yet, despite their prevalence, interpretations of voltage-based metrics are often ambiguous and require expert judgment. In this work, we present a method for collecting and analyzing full cell near-equilibrium voltage curves for end-of-line manufacturing process control. The method builds on existing literature on differential voltage analysis (DVA or dV/dQ) by expanding the method formalism through the lens of reproducibility, interpretability, and automation. Our model revisions introduce several new derived metrics relevant to manufacturing process control, including lithium consumed during formation and the practical negative-to-positive ratio, which complement standard metrics such as positive and negative electrode capacities. To facilitate method reproducibility, we reformulate the model to account for the “inaccessible lithium problem” which quantifies the numerical differences between modeled versus true values for electrode capacities and stoichiometries. We finally outline key data collection considerations, including C-rate and charging direction for both full cell and half cell datasets, which may impact method reproducibility. This work highlights the opportunities for leveraging voltage-based electrochemical metrics for online battery manufacturing process control.
Immune transgene-dependent myocarditis in macaques after systemic administration of adeno-associated virus expressing human acid alpha-glucosidase
Authors: Hordeaux Juliette , Ramezani Ali , Tuske Steve , Mehta Nickita , Song Chunjuan , Lynch Anna , Lupino Katherine , Chichester Jessica A. , Buza Elizabeth L. , Dyer Cecilia , Yu Hongwei , Bell Peter , Weimer Jill M. , Do Hung , Wilson James M.
Published: March 2023

Immune responses to human non-self transgenes can present challenges in preclinical studies of adeno-associated virus (AAV) gene therapy candidates in nonhuman primates. Although anti-transgene immune responses are usually mild and non-adverse, they can confound pharmacological readouts and complicate translation of results between species. We developed a gene therapy candidate for Pompe disease consisting of AAVhu68, a clade F AAV closely related to AAV9, that expresses an engineered human acid-alpha glucosidase (hGAA) tagged with an insulin-like growth factor 2 variant (vIGF2) peptide for enhanced cell uptake. Rhesus macaques were administered an intravenous dose of 1x1013 genome copies (GC)/kg, 5x1013 GC/kg, or 1 x 1014 GC/kg of AAVhu68.vIGF2.hGAA. Some unusually severe adaptive immune responses to hGAA presented, albeit with a high degree of variability between animals. Anti-hGAA responses ranged from absent to severe cytotoxic T-cell-mediated myocarditis with elevated troponin I levels. Cardiac toxicity was not dose dependent and affected five out of eleven animals. Upon further investigation, we identified an association between toxicity and a major histocompatibility complex class I haplotype (Mamu-A002.01) in three of these animals. An immunodominant peptide located in the C-terminal region of hGAA was subsequently identified via enzyme-linked immunospot epitope mapping. Another notable observation in this preclinical safety study cohort pertained to the achievement of robust and safe gene transfer upon intravenous administration of 5x1013 GC/kg in one animal with a low pre-existing neutralizing anti-capsid antibodies titer (1:20). Collectively, these findings may have significant implications for gene therapy inclusion criteria.
Characterization of the inflammatory proteome of synovial fluid from patients with psoriatic arthritis: Potential treatment targets
Authors: Barbarroja Nuria , López-Montilla Maria Dolores , Cuesta-López Laura , Pérez-Sánchez Carlos , Ruiz-Ponce Miriam , López-Medina Clementina , Ladehesa-Pineda Maria Lourdes , López-Pedrera Chary , Escudero-Contreras Alejandro , Collantes-Estévez Eduardo , Arias-de la Rosa Iván
Published: March 2023

Objectives

1) To characterize the inflammatory proteome of synovial fluid (SF) from patients with Psoriatic Arthritis (PsA) using a high-quality throughput proteomic platform, and 2) to evaluate its potential to stratify patients according to clinical features.

Methods

Inflammatory proteome profile of SF from thirteen PsA patients with active knee arthritis were analyzed using proximity extension assay (PEA) technology (Olink Target 96 Inflammation panel). Four patients with OA were included as control group.

Results

Seventy-nine inflammation-related proteins were detected in SF from PsA patients (SF-PsA). Unsupervised analyzes of the molecular proteome profile in SF-PsA identified two specific phenotypes characterized by higher or lower levels of inflammation-related proteins. Clinically, SF-PsA with higher levels of inflammatory proteins also showed increased systemic inflammation and altered glucose and lipid metabolisms. Besides, SF from PsA patients showed 39 out of 79 proteins significantly altered compared to SF-OA specifically related to cell migration and inflammatory response. Among these, molecules such as TNFα, IL-17A, IL-6, IL-10, IL-8, ENRAGE, CCL20, TNFSF-14, OSM, IFNγ, MCP-3, CXCL-11, MCP4, CASP-8, CXCL-6, CD-6, ADA, CXCL-10, TNFβ and IL-7 showed the most significantly change.

Conclusion

This is the first study that characterizes the inflammatory landscape of synovial fluid of PsA patients by analyzing a panel of 92 inflammatory proteins using PEA technology. Novel SF proteins have been described as potential pathogenic molecules involved in the pathogenesis of PsA. Despite the flare, inflammatory proteome could distinguish two different phenotypes related to systemic inflammation and lipid and glucose alterations.
Maternal provisions in type 1 diabetes: Evidence for both protective & pathogenic potential
Authors: Strachan Erin , Clemente-Casares Xavier , Tsai Sue
Published: March 2023

Maternal influences on the immune health and development of an infant begin in utero and continue well into the postnatal period, shaping and educating the child’s maturing immune system. Two maternal provisions include early microbial colonizers to initiate microbiota establishment and the transfer of antibodies from mother to baby. Maternal antibodies are a result of a lifetime of antigenic experience, reflecting the infection history, health and environmental exposure of the mother. These same factors are strong influencers of the microbiota, inexorably linking the two. Together, these provisions help to educate the developing neonatal immune system and shape lymphocyte repertoires, establishing a role for external environmental influences even before birth. In the context of autoimmunity, the transfer of maternal autoantibodies has the potential to be harmful for the child, sometimes targeting tissues and cells with devastating consequences. Curiously, this does not seem to apply to maternal autoantibody transfer in type 1 diabetes (T1D). Moreover, despite the rising prevalence of the disease, little research has been conducted on the effects of maternal dysbiosis or antibody transfer from an affected mother to her offspring and thus their relevance to disease development in the offspring remains unclear. This review seeks to provide a thorough evaluation of the role of maternal microorganisms and antibodies within the context of T1D, exploring both their pathogenic and protective potential. Although a definitive understanding of their significance in infant T1D development remains elusive at present, we endeavor to present what has been learned with the goal of spurring further interest in this important and intriguing question.
An ELISA-based assay for determining haemagglutinin potency in egg, cell, or recombinant protein derived influenza vaccines
Authors: Bodle Jesse , Vandenberg Kirsten , Laurie Karen , Barr Ian G. , Zhang Ying , Rockman Steven
Published: March 2023

Background

The current compendial assay for haemagglutinin antigen potency in influenza vaccine is the single radial immunodiffusion (SRID) which is time consuming and can lead to delays in release of vaccine. We previously described an alternate capture and detection enzyme linked immunoassay (ELISA) that utilizes sub-type specific, sub-clade cross-reactive monoclonal antibodies (mAbs) that are haemagglutination inhibiting (HAI) and correlate with SRID. The aim of this study is to determine the applicability of ELISA across current platforms for quantitation of seasonal quadrivalent vaccine.

Methods

A single mAb capture and detection ELISA was employed to quantitate hemagglutinin (HA) derived from different vaccine platforms and host organisms and compared to SRID and a polyclonal antibody based ELISA.

Results

We selected mAbs that displayed appropriate characteristics for a stability indicating potency assay which reacted to avian, insect and mammalian derived HA. Qualification of the homologous mAb assay against egg and cell derived HA demonstrated performance similar to that of the SRID however, superiority in sensitivity and specificity against strains from both influenza B/Victoria and B/Yamagata lineages. Analysis of drifted strains across multiple seasons demonstrated continued utility of this approach, reducing the need to develop reagents each season. With modification of the assay, we were able to accurately measure HA from different platforms and process stages using a single calibrated reference standard. We demonstrated the accuracy of ELISA when testing vaccine formulations containing selected adjuvants at standard and higher concentrations. Accelerated stability analysis indicated a strong correlation in the rate of degradation between the homologous mAb ELISA and SRID but not with ELISA utilizing polyclonal antisera. Further, we demonstrated specificity was restricted to the trimeric and oligomeric forms of HA but not monomeric HA.

Conclusion

We believe this homologous mAb ELISA is a suitable replacement for the SRID compendial assay for HA antigen quantitation and stability assessment. Identification of suitable mAbs that are applicable across multiple vaccine platforms with extended sub-type reactivity across a number of influenza seasons, indicate that this assay has broad applicability, leading to earlier availability of seasonal and pandemic vaccines without frequent replacement of polyclonal antisera that is required with SRID.
Quantitative liver SPECT/CT is a novel tool to assess liver function, prognosis, and response to treatment in cirrhosis
Authors: Kaur Amritjyot , Verma Nipun , Singh Baljinder , Kumar Ajay , Kumari Sunita , De Arka , Sharma Ratti Ram , Singh Virendra
Published: March 2023

Background

Functional liver reserve is an important determinant of survival in cirrhosis. The traditional indocyanine green test (ICG) is cumbersome. Hence, we developed and validated a novel liver imaging, a hybrid of SPECT and CT (Q-SPECT/CT), for evaluating disease severity, outcomes, and response to treatment in decompensated cirrhosis (DC).

Methods

We recruited a cohort of DC patients at a tertiary institute between 2016–2019. First, we standardized the Q-SPECT/CT across a predefined range of volumes through phantom experiments. Then we performed clinical and laboratory evaluations, ICG test (retention at 15 min), and Q-SPECT/CT at baseline and 12 months of granulocyte colony-stimulating factor (G-CSF) and standard medical treatment (SMT).

Results

In 109 DC patients, 87.1% males, aged 51 ± 10 years, MELD: 14 (7–21), the percent quantitative liver uptake (%QLU) on Q-SPECT/CT exhibited a strong correlation with CTP (r = −0.728, p < 0.001), MELD (r = −0.743; p < 0.001) and ICG-R-15 (r = −0.720, p < 0.001) at baseline. %QLU had the maximum discrimination (AUC: 0.890–0.920), sensitivity (88.9–90.3%), specificity (81.2–90.7%), and accuracy (85.8–89.4%) than liver volumes on Q-SPECT/CT or ICG test for classifying patients in CTP/MELD based prognostic categories. A significant increase in %QLU (26.09 ± 10.06 to 31.2 ± 12.19, p = 0.001) and improvement in CTP/MELD correlated with better survival of G-CSF treated DC patients (p < 0.05). SMT did not show any improvement in Q-SPECT/CT or clinical severity scores (p > 0.05). %QLU > 25 (adj.H.R.: 0.234, p = 0.003) and G-CSF treatment (adj.H.R.: 0.414, p = 0.009) were independent predictors of better 12-months survival in DC.

Conclusion

Q-SPECT/CT (%QLU) is a novel non-invasive, diagnostic, prognostic, and theragnostic marker of liver reserve and its functions in cirrhosis patients.

Clinical trial registration

Clinicaltrials.gov, NCT02451033 and NCT03415698.
Seropositive for hepatitis B and C viruses is associated with the risk of decreased bone mineral density in adults: An analysis of studies from the NHANES database
Authors: Tao Jiasheng , Yan Zijian , Huang Wenmian , Feng Tao
Published: March 2023

Background

Some studies had reported that patients with viral hepatitis are at increased risk of reduced bone mineral density and even osteoporosis. However, the interaction between reduced bone mineral density (BMD) and viral hepatitis remains inconclusive. Therefore, our study collected hepatitis test results and bone mineral density from respondents in the NHANES database. The aim of this study was to investigate whether there is an association between hepatitis and a decrease in bone mineral density.

Methods

The respondents with both hepatitis- and BMD-related indicators from the NHANES database in the United States from 2005–2010, 2013–2014, to 2017–2020 were collected for this study. BMD were compared between respondents who were positive and negative for respondents related to hepatitis B and C. BMD was measured using dual-energy X-ray absorptiometry of the femur and lumbar spine. Finally, multiple regression analysis was performed between hepatitis B surface antigen (HBsAg) and hepatitis C RNA (HCV-RNA) and BMD in the respondents.

Results

A total of 15,642 respondents were included in the hepatitis B surface antigen-related survey. Of these, 1,217 respondents were positive for hepatitis B surface antigen. A total of 5111 hepatitis C RNA-related responders were included. Hepatitis C RNA-positive had 268 respondents. According to the results of the multiple regression analysis, the femoral BMD was significantly lower in HBsAg (+) respondents compared to HBsAg (–) respondents: −0.018 (−0.026, −0.009) (P < 0.01). Moreover, spinal BMD was significantly lower in HBsAg (+) respondents compared to HBsAg (–) respondents: −0.020 (−0.030, −0.010) (P < 0.01). According to the results of multiple regression analysis for hepatitis C RNA, HCV-RNA (+) respondents had significantly lower BMD compared to HCV-RNA (–) respondents: −0.043 (−0.059, −0.026) (P < 0.01).

Conclusion

During the analysis of respondents in the NHANES database in the United States, positive tests for hepatitis B surface antigen and hepatitis C RNA were found to be associated with a reduction in BMD. Positive serology for these hepatitis indicators may increase the risk of reduced BMD. Of course, this conclusion still needs to be further confirmed by more large clinical trials.
The forgotten key players in rheumatoid arthritis: IL-8 and IL-17 – Unmet needs and therapeutic perspectives
Authors: Gremese Elisa , Tolusso Barbara , Bruno Dario , Perniola Simone , Ferraccioli Gianfranco , Alivernini Stefano
Published: March 2023

Despite the relevant advances in our understanding of the pathogenetic mechanisms regulating inflammation in rheumatoid arthritis (RA) and the development of effective therapeutics, to date, there is still a proportion of patients with RA who do not respond to treatment and end up progressing toward the development of joint damage, extra-articular complications, and disability. This is mainly due to the inter-individual heterogeneity of the molecular and cellular taxonomy of the synovial membrane, which represents the target tissue of RA inflammation. Tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) are crucial key players in RA pathogenesis fueling the inflammatory cascade, as supported by experimental evidence derived from in vivo animal models and the effectiveness of biologic-Disease Modifying Anti-Rheumatic Drugs (b-DMARDs) in patients with RA. However, additional inflammatory soluble mediators such as IL-8 and IL-17 exert their pathogenetic actions promoting the detrimental activation of immune and stromal cells in RA synovial membrane, tendons, and extra-articular sites, as well as blood vessels and lungs, causing extra-articular complications, which might be excluded by the action of anti-TNFα and anti-IL6R targeted therapies. In this narrative review, we will discuss the role of IL-8 and IL-17 in promoting inflammation in multiple biological compartments (i.e., synovial membrane, blood vessels, and lung, respectively) in animal models of arthritis and patients with RA and how their selective targeting could improve the management of treatment resistance in patients.
Seasonal variation in the soil fungal community structure of Larix gmelinii forests in Northeast China
Authors: Zhao Wen , Wang Dan-Dan , Huang Kai-Chuan , Liu Shun , Reyila Mumin , Sun Yi-Fei , Li Jun-Ning , Cui Bao-Kai
Published: March 2023

Soil fungi play an indispensable role in forest ecosystems by participating in energy flow, material circulation, and assisting plant growth and development. Larix gmelinii is the dominant tree species in the greater Khingan Mountains, which is the only cold temperate coniferous forest in China. Understanding the variations in underground fungi will help us master the situation of L. gmelinii above ground. We collected soil samples from three seasons and analyzed the differences in soil fungal community structure using high-throughput sequencing technology to study the seasonal changes in soil fungal community structure in L. gmelinii forests. We found that the Shannon and Chao1 diversity in autumn was significantly lower than in spring and summer. The community composition and functional guild varied significantly between seasons. Furthermore, we showed that ectomycorrhizal fungi dominated the functional guilds. The relative abundance of ectomycorrhizal fungi increased dramatically from summer to autumn and was significantly negatively correlated with temperature and precipitation. Temperature and precipitation positively affect the alpha diversity of fungi significantly. In addition, pH was negatively correlated with the Chao1 diversity. Temperature and precipitation significantly affected several dominant genera and functional guilds. Among the soil physicochemical properties, several dominant genera were affected by pH, and the remaining individual genera and functional guilds were significantly correlated with total nitrogen, available phosphorus, soil organic carbon, or cation exchange capacity. For the composition of total fungal community, temperature and precipitation, as well as soil physicochemical properties except AP, significantly drove the variation in community composition.
Bacterial DNA methyltransferase: A key to the epigenetic world with lessons learned from proteobacteria
Authors: Gao Qun , Lu Shuwei , Wang Yuwei , He Longgui , Wang Mingshu , Jia Renyong , Chen Shun , Zhu Dekang , Liu Mafeng , Zhao Xinxin , Yang Qiao , Wu Ying , Zhang Shaqiu , Huang Juan , Mao Sai , Ou Xumin , Sun Di , Tian Bin , Cheng Anchun
Published: March 2023

Epigenetics modulates expression levels of various important genes in both prokaryotes and eukaryotes. These epigenetic traits are heritable without any change in genetic DNA sequences. DNA methylation is a universal mechanism of epigenetic regulation in all kingdoms of life. In bacteria, DNA methylation is the main form of epigenetic regulation and plays important roles in affecting clinically relevant phenotypes, such as virulence, host colonization, sporulation, biofilm formation et al. In this review, we survey bacterial epigenomic studies and focus on the recent developments in the structure, function, and mechanism of several highly conserved bacterial DNA methylases. These methyltransferases are relatively common in bacteria and participate in the regulation of gene expression and chromosomal DNA replication and repair control. Recent advances in sequencing techniques capable of detecting methylation signals have enabled the characterization of genome-wide epigenetic regulation. With their involvement in critical cellular processes, these highly conserved DNA methyltransferases may emerge as promising targets for developing novel epigenetic inhibitors for biomedical applications.
Microbial biotransformation to obtain stilbene methylglucoside with GPR119 agonistic activity
Authors: Peng Yu , Huan Yi , Chen Jing-Jing , Chen Tian-Jiao , Lei Lei , Yang Jin-Ling , Shen Zhu-Fang , Gong Ting , Zhu Ping
Published: March 2023

Introduction

Limitation of pharmaceutical application of resveratrol (RSV) and piceatannol (PIC) continue to exist, there is a need to obtain the superior analogs of two stilbenes with promoted activity, stability, and bioavailability. Microbial transformation has been suggested as a common and efficient strategy to solve the above problems.

Methods

In this study, Beauveria bassiana was selected to transform RSV and PIC. LC-MS and NMR spectroscopies were used to analyze the transformed products and identify their structures. The biological activities of these metabolites were evaluated in vitro with GPR119 agonist and insulin secretion assays. Single factor tests were employed to optimize the biotransformation condition.

Results

Three new methylglucosylated derivatives of PIC (1–3) and two known RSV methylglucosides (4 and 5) were isolated and characterized from the fermentation broth. Among them, 1 not only showed moderate GPR119 agonistic activity with 65.9%, but also promoted insulin secretion level significantly (12.94 ng/mg protein/hour) at 1 μM. After optimization of fermentation conditions, the yield of 1 reached 45.53%, which was increased by 4.2-fold compared with the control.

Discussion

Our work presents that 3-O-MG PIC (1), obtained by microbial transformation, is an effective and safer ligand targeting GPR119, which lays a foundation for the anti-diabetic drug design in the future.
Emergence and genomic analysis of a novel sublineage of bovine ephemeral fever virus in Southwest China
Authors: Chen Jing , Liu Mengru , Li Yixuan , Yang Liu , Tang Yunhan , Dan Ruitong , Xie Muhan , Fang Rendong , Li Nengzhang , Ye Chao , Peng Yuanyi
Published: March 2023

Introduction

Bovine ephemeral fever virus (BEFV), belonging to the genus Ephemerovirus under the family Rhabdoviridae, is the etiological cause for the bovine ephemeral fever (BEF) in cattle and water buffalo.

Methods

In this study, we report recent BEF outbreaks in Southwest China and sequence the complete genome sequence of one BEFV isolate BEFV/CQ1/2022.

Results and Discussion

Comparative genomic analyses between BEFV/CQ1/2022 and isolates available in GenBank revealed remarkable inter-isolate divergence. Meanwhile, the sequence divergence was related to the evolutionary relationships and geographical distribution of the isolates. Phylogenetic analysis indicated that the global BEFV isolates can be divided into 4 distinct lineages. The East Asia lineage was the most diverse and could be subdivided into 4 sublineages. Notably, BEFV/CQ1/2022 and other 10 recent isolates from Mainland China were found to be clustered in sublineage 2. Additionally, recombination analysis provided evidence of BEFV recombination among East Asian isolates for the first time. Taken together, a novel sublineage of the East Asian BEFV emerged in Southwest China, and large divergence and potential recombination among BEFV strains were investigated in this study, which may improve understanding of BEFV epidemiology and evolution.
Case report: Stem cell-based suicide gene therapy mediated by the herpes simplex virus thymidine kinase gene reduces tumor progression in multifocal glioblastoma
Authors: Oraee-Yazdani Saeed , Akhlaghpasand Mohammadhosein , Rostami Fatemeh , Golmohammadi Maryam , Tavanaei Roozbeh , Shokri Gelareh , Hafizi Maryam , Oraee-Yazdani Maryam , Zali Ali-Reza , Soleimani Masoud
Published: March 2023

Introduction

The prognosis for glioblastoma multiforme (GBM), a malignant brain tumor, is poor despite recent advancements in treatments. Suicide gene therapy is a therapeutic strategy for cancer that requires a gene to encode a prodrug-activating enzyme which is then transduced into a vector, such as mesenchymal stem cells (MSCs). The vector is then injected into the tumor tissue and exerts its antitumor effects.

Case presentation

A 37-year-old man presented to our department with two evident foci of glioblastoma multiforme at the left frontal and left parietal lobes. The patient received an injection of bone marrow-derived MSCs delivering the herpes simplex virus thymidine kinase (HSV-tk) gene to the frontal focus of the tumor, followed by ganciclovir administration as a prodrug for 14 days. For follow-up, the patient was periodically assessed using magnetic resonance imaging (MRI). The growth and recurrence patterns of the foci were assessed. After the injection on 09 February 2019, the patient's follow-up appointment on 19 December 2019 MRI revealed a recurrence of parietal focus. However, the frontal focus had a slight and unremarkable enhancement. On the last follow-up (18 March 2020), the left frontal focus had no prominent recurrence; however, the size of the left parietal focus increased and extended to the contralateral hemisphere through the corpus callosum. Eventually, the patient passed away on 16 July 2020 (progression-free survival (PFS) = 293 days, overall survival (OS) = 513 days).

Conclusion

The gliomatous focus (frontal) treated with bone marrow-derived MSCs carrying the HSV-TK gene had a different pattern of growth and recurrence compared with the non-treated one (parietal).

Trial registration

IRCT20200502047277N2. Registered 10 May 2020—Retrospectively registered, https://eng.irct.ir/trial/48110.
Alteration of neurofilament heavy chain and its phosphoforms reveals early subcellular damage beyond the optic nerve head in glaucoma
Authors: Zhou Lan , Lin Dongyue , Xu Guihua , Wang Xiaoyi , Chen Zilin , Wang Dingding , Fan Huiya
Published: March 2023

Background

Retinal ganglion cells (RGCs) axon loss at the site of optic nerve head (ONH) is long believed as the common pathology in glaucoma since different types of glaucoma possessing different characteristic of intraocular pressure, and this damage was only detected at the later stage.

Methods

To address these disputes and detect early initiating events underlying RGCs, we firstly detected somatic or axonal change and compared their difference in acute and chronic phase of primary angle-closed glaucoma (PACG) patient using optical coherence tomography (OCT), then an axonal-enriched cytoskeletal protein neurofilament heavy chain and its phosphoforms (NF-H, pNF-H) were utilized to reveal spatio-temporal undetectable damage insulted by acute and chronic ocular hypertension (AOH, COH) in two well characterized glaucoma mice models.

Results

In clinic, we detected nonhomogeneous changes such as ONH and soma of RGCs presenting edema in acute phase but atrophy in chronic one by OCT. In AOH animal models, an increase expression of NF-H especially its phosphorylation modification was observed as early as 4 h before RGCs loss, which presented as somatic accumulation in the peripheral retina and at the sites of ONH. In contrast, in microbeads induced COH model, NF-H and pNF-H reduced significantly, these changes firstly occurred as NF-H or pNF-H disconnection at ONH and optic nerve after 2 weeks when the intraocular pressure reaching the peak; Meanwhile, we detected aqueous humor pNF-H elevation after AOH and slight reduction in the COH.

Conclusion

Together, our data supports that early alteration of NF-H and its phosphoforms would reveal undetectable subcellular damage consisting of peripheral somatic neurofilament compaction, impaired axonal transport and distal axonal disorganization of cytoskeleton beyond the ONH, and identifies two distinct axonal degeneration which were Wallerian combination with retrograde degeneration in acute PACG and retrograde degeneration in the chronic one.
Angiotensin-converting enzyme gene insertion/deletion polymorphism and risk of ischemic stroke complication among patients with hypertension in the Ethiopian population
Authors: Melake Addisu , Berhane Nega
Published: March 2023

Background

Ischemic stroke is a complicated, multifaceted condition brought on by a confluence of vascular, environmental, and genetic variables. The burden of ischemic stroke is currently rising in terms of death, morbidity, and disability worldwide. Genetic variables also play significant roles in the pathophysiology of hypertension and ischemic stroke in addition to the greatest effects of demographic, clinical, and behavioral risk factors. The key functional variation of the ACE gene that has drawn the most interest is the ACE I/D variant. Even though the ACE gene I/D polymorphism has been widely studied, the findings of investigations on the involvement of this polymorphism in ischemic stroke were contradictory and provide conflicting data. The goal of this study was to look into the effect of the ACE gene I/D polymorphism on the risk of ischemic stroke in patients with hypertension.

Methods

A hospital-based case–control study was carried out in 36 cases of patients with hypertensive IS and 36 age- and sex-matched healthy controls. Clinical and biochemical parameters were measured to assess the associated risk factors. The DNA was isolated from blood samples, and the ACE I/D genotypes were identified using polymerase chain reaction and analyzed by agarose gel electrophoresis.

Results

The ACE-DD genotype (OR = 3.71, 95% CI = 1.02–13.5; P < 0.05) and D allele (OR = 2.07, 95% CI = 1.06–4.03; P < 0.05) were significantly more common in patients than in controls, indicating that it is a risk factor for the development of ischemic stroke in hypertensive individuals.

Conclusion

There is a significant correlation between the ACE gene I/D polymorphism and the development of ischemic stroke in patients with a history of hypertension in the Ethiopian population.
MCP extensors respond faster than flexors in individuals with severe-to-moderate stroke-caused impairment: Evidence of uncoupled neural pathways
Authors: Kim Dongwon , Baghi Raziyeh , Koh Kyung , Zhang Li-Qun
Published: March 2023

Damage in the corticospinal system following stroke produces imbalance between flexors and extensors in the upper extremity, eventually leading to flexion-favored postures. The substitution of alternative tracts for the damaged corticospinal tract is known to excessively activate flexors of the fingers while the fingers are voluntarily being extended. Here, we questioned whether the cortical source or/and neural pathways of the flexors and extensors of the fingers are coupled and what factor of impairment influences finger movement. In this study, a total of seven male participants with severe-to-moderate impairment by a hemiplegic stroke conducted flexion and extension at the metacarpophalangeal (MCP) joints in response to auditory tones. We measured activation and de-activation delays of the flexor and extensor of the MCP joints on the paretic side, and force generation. All participants generated greater torque in the direction of flexion (p = 0.017). Regarding co-contraction, coupled activation of the extensor is also made during flexion in the similar way to coupled activation of the flexor made during extension. As opposite to our expectation, we observed that during extension, the extensor showed marginally significantly faster activation (p = 0.66) while it showed faster de-activation (p = 0.038), in comparison to activation and de-activation of the flexor during flexion. But movement smoothness was not affected by those factors. Our results imply that the cortical source and neural pathway for the extensors of the MCP joints are not coupled with those for the flexors of the MCP joints.
Circadian disruption of memory consolidation in Drosophila
Authors: Yin Jerry C. P. , Cui Ethan , Hardin Paul E. , Zhou Hong
Published: March 2023

The role of the circadian system in memory formation is an important question in neurobiology. Despite this hypothesis being intuitively appealing, the existing data is confusing. Recent work in Drosophila has helped to clarify certain aspects of the problem, but the emerging sense is that the likely mechanisms are more complex than originally conceptualized. In this report, we identify a post-training window of time (during consolidation) when the circadian clock and its components are involved in memory formation. In the broader context, our data suggest that circadian biology might have multiple roles during memory formation. Testing for its roles at multiple timepoints, and in different cells, will be necessary to resolve some of the conflicting data.
Efficacy and safety of COVID-19 vaccines for patients with spinal tumors receiving denosumab treatment: An initial real−clinical experience study
Authors: Wang Pengru , Li Bo , Zhou Shangbin , Xin Yingye , Zhu Zhipeng , Duan Shujie , Bai Danyang , Yuan Hao , Xu Wei , Xiao Jianru
Published: March 2023

Background

Even if COVID-19 vaccine has gradually been adopted in the world, information of side effects and crosstalk in patients with spinal tumors is absent due to the exclusion from clinical research. In this research, we aimed to investigate the efficacy and safety for the patients with spinal tumors treated by denosumab.

Methods

In this retrospective research, 400 patients under treatment of denosumab against spinal tumors in real-clinical experience were grouped into two cohorts according to the treatment of COVID-19 vaccine. And linked hospital data, serum samples and unsolicited related adverse events had been collected from January 22nd 2021 to June 1st 2021 respectively.

Results

233 patients of all participants who received regular treatment of denosumab were vaccinated by mRNA or inactivated vaccine. Patients of metastatic disease and primary osseous spinal tumor showed similar distribution in both two groups. Over the study period, within 176 patients tested the status of serologic response of vaccine, 88(81.48%) and 41(87.23%) individuals injected one or two inactivated vaccines had effective antibody against SARS-CoV-2 infections. As 21 patients (85.71%) treated by mRNA vaccine did. Considering of the safety of vaccine, most common systemic adverse events were nausea or vomiting (45 events vs 23events). Interestingly, fewer participants in the vaccine group were statistically recorded in local adverse events than in the placebo group (16 events vs 33 events).

Conclusions

Our initial real-clinical experience suggests that COVID-19 vaccines are likely safe and effective in in patients with spinal tumors receiving denosumab treatment.