bluuebunny/crossref_metadata_2025 huggingface dataset:
Osmanlı Matbuatına Göre Hasan Fehmi Cinayeti
Authors: GÜNEŞ Hüseyin
Published: July 2023

Osmanlı İmparatorluğu’nun çöküşten kurtarılması adına ilan edilen II. Meşrutiyet ilk etapta toplumun hemen hemen tüm kesimlerinde olumlu bir karşılık buldu. Fakat bu süreçte gelişen iç ve dış hadiseler beklentilerin aksine durumun daha da kötüleşmesine neden oldu. Yeni dönemin ana aktörü İttihat ve Terakki Cemiyeti ile muhalifleri arasında başlayan mücadele ortaya pek çok yeni sorun çıkardı. Toprak kayıpları, azınlıkların ayrılıkçı tutumları, muhalif gruplarla mücadele ve matbuatın sınırsız özgürlük ortamında geliştirdiği tavır bu dönemin dikkati çeken olaylarıdır.

Serbestî gazetesi başmuharriri ve muhalif bir gazeteci olan Hasan Fehmi Bey’in 6/7 Nisan 1909 gecesi Galata köprüsü üzerinde suikasta uğraması ve katilin yakalanamayışı cinayetin İttihat ve Terakki tarafından işlendiği iddiasını gündeme getirdi. Cemiyet muhalifleri, basın organları başta olmak üzere farklı platformlarda bu iddiayı genel kabul haline getirmeye çalıştılar. İttihat ve Terakki ise kendisini bu töhmetten kurtarmaya çalıştı.31 Mart Vakasının hemen öncesinde meydana gelen bu fail-i meçhul cinayet daha sonraki dönemlerde de tartışılmasına rağmen hiçbir zaman aydınlatılamadı. Fakat etkileri bakımından önemli bir hadise olarak tarihteki yerini aldı.
Mosquitos (Diptera: Culicidae) em área impactada para construção de barragem no estado do Paraná, Brasil
Authors: Martins da Silva Allan , De Almeida Thayany Magalhães
Published: July 2023

Um monitoramento de fauna de mosquitos, ocorrentes em área de impacto ambiental para construção de barragem, foi realizado no norte do estado do Paraná, entre agosto de 1993 e agosto de 1994. Os resultados indicaram que diversas espécies de importância epidemiológica atuam de forma oportunista, com risco a saúde dos colaboradores do empreendimento e de residentes de áreas próximas.
Glucose promoting the early embryonic development by increasing the lipid synthesis at 2-cell stage
Authors: Wang Mingwen , Xue Jinfeng , Li Chanyi , Qi Lingbin , Nie Lan , Xue Zhigang
Published: July 2023

The optimization of culture conditions is one of the main strategies to improve the embryo development competence in in vitro fertilization (IVF). Glucose is an important carbon source while also exists in the oviductal fluid in vivo, the effect of glucose in embryo development microenvironment is still unclear. Here we employed the LC-MS to detect and analyze the metabolites in the culture medium of different cleavage stages including 2-Cell, 4-Cell and 8-Cell mouse embryos, respectively. The effects of the external glucose were estimated by measuring the development rate at different glucose concentrations from 0 to 5 mmol/L, and the gene expression changes were detected to explore the potential mechanism after the addition of glucose in the media. Our results indicated the 2-Cell and 8-Cell stages had defined characteristic metabolites, while 4-Cell stage was the transition state. Global and contiguous metabolic characteristics showed the glycometabolism play a critical role at each early cleavage stages during the embryo development. The 8-Cell rates demonstrated the addition of glucose in culture media significantly improve the embryo competence, the highest rate was 87.33% using 3 mmol/L glucose in media, in contrast only 9.95% using the media without glucose. Meanwhile, the blocked embryos were mainly enriched at 2-Cell stage. Further transcriptome study found 3 mmol/L glucose in media remarkably upregulated the gene expression of lipid biosynthesis at 2-Cell stage, the increased lipid was confirmed by nile red staining. These data indicated the glucose may promote the development competence through increasing the lipid biosynthesis to overcoming the 2-Cell block. Our findings were helpful for the further optimization of IVF culture media, as well as the estimation of embryo quality using metabolites in the culture media.
Shortening identification times: comparative observational study of three early blood culture testing protocols
Authors: Chatelard Paul-Antoine , Rousseau Nathalie , Parmeland Laurence , Metral Pierre , Pariset Caroline , Vivier Emmanuel
Published: July 2023

Background

While early appropriate antibiotic therapy is a proven means of limiting the progression of infections, especially bacteremia, empirical antibiotic therapy in sepsis is ineffective up to 30%. The aim of this study was to compare early blood culture testing protocols in terms of their ability to shorten the delay between blood sampling and appropriate antibiotic therapy.

Methods

In this french observational study, we compared three blood culture testing protocols. Positive blood cultures were tested using either GenMark ePlex panels (multiplex PCR period), a combination of MRSA/SA PCR, β-Lacta and oxidase tests (multitest period), or conventional identification and susceptibility tests only (reference period). Conventional identification and susceptibility tests were performed in parallel for all samples, as the gold standard.

Results

Among the 270 patients with positive blood cultures included, early and conventional results were in good agreement, especially for the multitest period. The delay between a blood culture positivity and initial results was 3.8 (2.9–6.9) h in the multiplex PCR period, 2.6 (1.3–4.5) h in the multitest period and 3.7 (1.8–8.2) h in the reference period (p<0.01). Antibiotic therapy was initiated or adjusted in 68 patients based on early analysis results. The proportion of patients receiving appropriate antibiotic therapy within 48 h of blood sampling was higher in the multiplex PCR and multitest periods, (respectively 90% and 88%) than in the reference period (71%).

Conclusion

These results suggest rapid bacterial identification and antibiotic resistance tests are feasible, efficient and can expedite appropriate antibiotic therapy.
The effect of peak serum estradiol level during ovarian stimulation on cumulative live birth and obstetric outcomes in freeze-all cycles
Authors: Huang Jiaan , Lu Yao , He Yaqiong , Wang Yuan , Zhu Qinling , Qi Jia , Ding Ying , Zhao Hanting , Ding Ziyin , Sun Yun
Published: July 2023

Objective

To determine whether the peak serum estradiol (E2) level during ovarian stimulation affects the cumulative live birth rate (CLBR) and obstetric outcomes in freeze-all cycles.

Methods

This retrospective cohort study involved patients who underwent their first cycle of in vitro fertilization followed by a freeze-all strategy and frozen embryo transfer cycles between January 2014 and June 2019 at a tertiary care center. Patients were categorized into four groups according to quartiles of peak serum E2 levels during ovarian stimulation (Q1-Q4). The primary outcome was CLBR. Secondary outcomes included obstetric and neonatal outcomes of singleton and twin pregnancies. Poisson or logistic regression was applied to control for potential confounders for outcome measures, as appropriate. Generalized estimating equations were used to account for multiple cycles from the same patient for the outcome of CLBR.

Result(s)

A total of 11237 patients were included in the analysis. Cumulatively, live births occurred in 8410 women (74.8%). The live birth rate (LBR) and CLBR improved as quartiles of peak E2 levels increased (49.7%, 52.1%, 54.9%, and 56.4% for LBR; 65.1%, 74.3%, 78.4%, and 81.6% for CLBR, from the lowest to the highest quartile of estradiol levels, respectively, P<0.001). Such association remained significant for CLBR after accounting for potential confounders in multivariable regression models, whereas the relationship between LBR and peak E2 levels did not reach statistical significance. In addition, no significant differences were noticed in adverse obstetric and neonatal outcomes (gestational diabetes mellitus, pregnancy-induced hypertension, preeclampsia, placental disorders, preterm birth, low birthweight, and small for gestational age) amongst E2 quartiles for either singleton or twin live births, both before and after adjustment.

Conclusion

In freeze-all cycles, higher peak serum E2 levels during ovarian stimulation were associated with increased CLBR, without increasing the risks of adverse obstetric and neonatal outcomes.
GDF10 is related to obesity as an adipokine derived from subcutaneous adipose tissue
Authors: Song Mi Kyung , Kim Ji Eun , Kim Jung Tae , Kang Yea Eun , Han Sun Jong , Kim Seok Hwan , Kim Hyun Jin , Ku Bon Jeong , Lee Ju Hee
Published: July 2023

Introduction

Adipokines are proteins that are secreted by the adipose tissue. Although they are associated with obesity-related metabolic disorders, most studies have focused on adipokines expressed by visceral adipose tissue (VAT). This study aimed to identify the adipokine potentially derived from subcutaneous adipose tissue (SAT) and its clinical significance.

Methods

Samples of SAT and VAT were obtained from six adult male patients who underwent laparoscopic surgery for benign gall bladder disease. Differentially expressed genes were analyzed by subjecting the samples to RNA sequencing. The serum concentration of selected proteins according to body mass index (BMI) was analyzed in 58 individuals.

Results

GDF10 showed significantly higher expression in the SAT, as per RNA sequencing (fold change = 5.8, adjusted P value = 0.009). Genes related to insulin response, glucose homeostasis, lipid homeostasis, and fatty acid metabolism were suppressed when GDF10 expression was high in SAT, as per genotype-tissue expression data. The serum GDF10 concentration was higher in participants with BMI ≥ 25 kg/m2 (n = 35, 2674 ± 441 pg/mL) than in those with BMI < 25 kg/m2 (n = 23, 2339 ± 639 pg/mL; P = 0.022). There was a positive correlation between BMI and serum GDF10 concentration (r = 0.308, P = 0.019).

Conclusions

GDF10 expression was higher in SAT than in VAT. Serum GDF10 concentration was high in patients with obesity. Therefore, GDF10 could be a SAT-derived protein related to obesity.
UBR4 deficiency causes male sterility and testis abnormal in Drosophila
Authors: Xie Shi-Ming , Lai Jia-Xuan , Liu Chu-Qiao , Zhang Xi-Xing , Lin Yong-Miao , Lan Qi-Wen , Hong De-Yao , Chen Xiao-Chuan , Qiao Jing-Da , Mao Yu-Ling
Published: July 2023

Introduction

It has been established that UBR4 encodes E3 ubiquitin ligase, which determines the specificity of substrate binding during protein ubiquitination and has been associated with various functions of the nervous system but not the reproductive system. Herein, we explored the role of UBR4 on fertility with a Drosophila model.

Methods

Different Ubr4 knockdown flies were established using the UAS/GAL4 activating sequence system. Fertility, hatchability, and testis morphology were studied, and bioinformatics analyses were conducted. Our results indicated that UBR4 deficiency could induce male sterility and influent egg hatchability in Drosophila.

Results

We found that Ubr4 deficiency affected the testis during morphological analysis. Proteomics analysis indicated 188 upregulated proteins and 175 downregulated proteins in the testis of Ubr4 knockdown flies. Gene Ontology analysis revealed significant upregulation of CG11598 and Sfp65A, and downregulation of Pelota in Ubr4 knockdown flies. These proteins were involved in the biometabolic or reproductive process in Drosophila. These regulated proteins are important in testis generation and sperm storage promotion. Bioinformatics analysis verified that UBR4 was low expressed in cryptorchidism patients, which further supported the important role of UBR4 in male fertility.

Discussion

Overall, our findings suggest that UBR4 deficiency could promote male infertility and may be involved in the protein modification of UBR4 by upregulating Sfp65A and CG11598, whereas downregulating Pelota protein expression.
Comparisons of different approaches and incisions of thyroid surgery and selection strategy
Authors: Lu Qiyu , Zhu Xuemei , Wang Peisong , Xue Shuai , Chen Guang
Published: July 2023

To date, the traditional open thyroid surgery via a low collar incision remains the standard approach for patients undergoing thyroidectomy. However, this conventional approach will inevitably leave patients a neck scar and even cause a variety of complications such as paresthesia, hypesthesia, and other uncomfortable sensations. With the progress in surgical techniques, especially in endoscopic surgery, and the increasing desire for cosmetic and functional outcomes, various new approaches for thyroidectomy have been developed to avoid or decrease side effects. Some of these alternative approaches have obvious advantages compared with traditional surgery and have already been widely used in the treatment of thyroid disease, but each has its limitations. This review aims to evaluate and compare the different approaches to thyroidectomy to help surgeons make the proper treatment strategy for different individuals.
Mets-IR as a predictor of cardiovascular events in the middle-aged and elderly population and mediator role of blood lipids
Authors: Qian Taoming , Sheng Xiaomeng , Shen Pengyu , Fang Yuting , Deng Yao , Zou Guoliang
Published: July 2023

Background

Cardiovascular disease (CVD) is a global health concern, with a significant impact on morbidity and mortality rates. Using fasting glucose, fasting triglycerides, body mass index (BMI), and high-density lipoprotein cholesterol (HDL-C), the metabolic score of insulin resistance (Mets-IR), a novel index created by Mexican researchers to assess insulin sensitivity, is a more precise way to measure insulin sensitivity. This study aimes to explore the association between Mets-IR and CVD, as well as investigate the potential mediating role of of low-density lipoprotein cholesterol (LDL-C).

Methods

The study’s data came from the 2011 and 2018 China Health and Retirement Longitudinal Studies (CHARLS). We used three logistic regression models to account for the potential effects of ten factors on cardiovascular disease/stroke/heart disease. Moreover, We performed mediation analyses to evaluate the role of LDL-C in the association between Mets-IR and incident CVD.

Results

This study comprised 4,540 participants, of whom 494 (10.88%) were found to develop disease (CVD). Each interquartile range (IQR) increased in Mets-IR raised the risk of developing CVD by 38% (OR=1.38; 95% CI, 1.21-1.56) and there was a linear dose-response relationship between Mets-IR and the risk of new-onset cardiovascular disease, stroke, and heart disease (Poverall<0.05, Pnon-linear>0.05). Approximately 5% (indirect effect/total effect) of the significant association of Mets-IR with stroke was mediated by LDL-C, respectively. With the addition of Mets-IR to the base model, the continuous net reclassification improvement and integrated discrimination improvement for predicting cardiovascular disease increased by 0.175 (P <0.001) and 0.006 (P <0.001), respectively.

Conclusion

ets-IR is associated with an increased risk of cardiovascular disease/stroke/cardiac issues, with LDL-C mediating these relationships. Improving insulin sensitivity and lipid regulation may be essential and effective preventive measures for cardiovascular events.
Pesticide control, physical control, or biological control? How to manage forest pests and diseases more effectively
Authors: Bai Yuntao , Wang Lan , Yuan Xiaolong
Published: July 2023

The frequent occurrence of forest diseases and insect pests has a significant impact on the forest ecosystem. The government needs to take measures to protect the forest ecosystem. The common management modes for forest pests and diseases include pesticide control, physical control, and biological control. In the process of governance, governments need to consider not only cost-effectiveness but also the impact on the ecosystem. In this article, the differential game model under these three modes is constructed, and the equilibrium results are compared and analyzed. Finally, the research conclusion is drawn that under the biological control mode, the income generated by the unit control quantity is inversely proportional to the balanced control quantity. However, under pesticide control and physical control modes, the revenue generated by the unit control quantity is proportional to the balanced control quantity. At the same time, under the biological control mode, the unit governance cost is proportional to the balanced control quantity. Under the pesticide control and physical control modes, the unit control cost is inversely proportional to the balanced control quantity. Social forces tend to adopt pesticide control. The government prefers physical control.
Epigenetic associations with adolescent grey matter maturation and cognitive development
Authors: Jensen Dawn , Chen Jiayu , Turner Jessica A. , Stephen Julia M. , Wang Yu-Ping , Wilson Tony W. , Calhoun Vince D. , Liu Jingyu
Published: July 2023

Introduction: Adolescence, a critical phase of human neurodevelopment, is marked by a tremendous reorganization of the brain and accompanied by improved cognitive performance. This development is driven in part by gene expression, which in turn is partly regulated by DNA methylation (DNAm).

Methods: We collected brain imaging, cognitive assessments, and DNAm in a longitudinal cohort of approximately 200 typically developing participants, aged 9–14. This data, from three time points roughly 1 year apart, was used to explore the relationships between seven cytosine–phosphate–guanine (CpG) sites in genes highly expressed in brain tissues (GRIN2D, GABRB3, KCNC1, SLC12A9, CHD5, STXBP5, and NFASC), seven networks of grey matter (GM) volume change, and scores from seven cognitive tests.

Results: The demethylation of the CpGs as well as the rates of change in DNAm were significantly related to improvements in total, crystalized, and fluid cognition scores, executive function, episodic memory, and processing speed, as well as several networks of GM volume increases and decreases that highlight typical patterns of brain maturation.

Discussion: Our study provides a first look at the DNAm of genes involved in myelination, excitatory and inhibitory receptors, and connectivity, how they are related to the large-scale changes occurring in the brain structure as well as cognition during adolescence.
Identification of cuproptosis-related molecular subtypes and a novel predictive model of COVID-19 based on machine learning
Authors: Luo Hong , Yan Jisong , Zhang Dingyu , Zhou Xia
Published: July 2023

Background

To explicate the pathogenic mechanisms of cuproptosis, a newly observed copper induced cell death pattern, in Coronavirus disease 2019 (COVID-19).

Methods

Cuproptosis-related subtypes were distinguished in COVID-19 patients and associations between subtypes and immune microenvironment were probed. Three machine algorithms, including LASSO, random forest, and support vector machine, were employed to identify differentially expressed genes between subtypes, which were subsequently used for constructing cuproptosis-related risk score model in the GSE157103 cohort to predict the occurrence of COVID-19. The predictive values of the cuproptosis-related risk score were verified in the GSE163151 cohort, GSE152418 cohort and GSE171110 cohort. A nomogram was created to facilitate the clinical use of this risk score, and its validity was validated through a calibration plot. Finally, the model genes were validated using lung proteomics data from COVID-19 cases and single-cell data.

Results

Patients with COVID-19 had higher significantly cuproptosis level in blood leukocytes compared to patients without COVID-19. Two cuproptosis clusters were identified by unsupervised clustering approach and cuproptosis cluster A characterized by T cell receptor signaling pathway had a better prognosis than cuproptosis cluster B. We constructed a cuproptosis-related risk score, based on PDHA1, PDHB, MTF1 and CDKN2A, and a nomogram was created, which both showed excellent predictive values for COVID-19. And the results of proteomics showed that the expression levels of PDHA1 and PDHB were significantly increased in COVID-19 patient samples.

Conclusion

Our study constructed and validated an cuproptosis-associated risk model and the risk score can be used as a powerful biomarker for predicting the existence of SARS-CoV-2 infection.
Combined intranasal and intramuscular parainfluenza 5-, simian adenovirus ChAdOx1- and poxvirus MVA-vectored vaccines induce synergistically HIV-1-specific T cells in the mucosa
Authors: Beavis Ashley C. , Wee Edmund G. -T. , Akis Yildirim Belkis M. , Borthwick Nicola , He Biao , Hanke Tomáš
Published: July 2023

Introduction

The primary goal of this work is to broaden and enhance the options for induction of protective CD8+ T cells against HIV-1 and respiratory pathogens.

Methods

We explored the advantages of the parainfluenza virus 5 (PIV5) vector for delivery of pathogen-derived transgenes alone and in combination with the in-human potent regimen of simian adenovirus ChAdOx1 prime-poxvirus MVA boost delivering bi-valent mosaic of HIV-1 conserved regions designated HIVconsvX.

Results

We showed in BALB/c mice that the PIV5 vector expressing the HIVconsvX immunogens could be readily incorporated with the other two vaccine modalities into a single regimen and that for specific vector combinations, mucosal CD8+ T-cell induction was enhanced synergistically by a combination of the intranasal and intramuscular routes of administration.

Discussion

Encouraging safety and immunogenicity data from phase 1 human trials of ChAdOx1- and MVA-vectored vaccines for HIV-1, and PIV5-vectored vaccines for SARS-CoV-2 and respiratory syncytial virus pave the way for combining these vectors for HIV-1 and other indications in humans.
Gut microbiota: a newly identified environmental factor in systemic lupus erythematosus
Authors: Yao Kaijin , Xie Yina , Wang Jiali , Lin Yongda , Chen Xiutian , Zhou Tianbiao
Published: July 2023

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women of childbearing age and is characterized by the damage to multiple target organs. The pathogenesis of SLE is complex, and its etiology mainly involves genetic and environmental factors. At present, there is still a lack of effective means to cure SLE. In recent years, growing evidence has shown that gut microbiota, as an environmental factor, triggers autoimmunity through potential mechanisms including translocation and molecular mimicry, leads to immune dysregulation, and contributes to the development of SLE. Dietary intervention, drug therapy, probiotics supplement, fecal microbiome transplantation and other ways to modulate gut microbiota appear to be a potential treatment for SLE. In this review, the dysbiosis of gut microbiota in SLE, potential mechanisms linking gut microbiota and SLE, and immune dysregulation associated with gut microbiota in SLE are summarized.
Interleukin-17–targeted treatment in patients with spondyloarthritis and associated cardiometabolic risk profile
Authors: Queiro Rubén , Aurrecoechea Elena , Alonso Castro Sara , Villa Blanco Ignacio , Brandy-Garcia Anahy , Linge Raquel
Published: July 2023

Spondyloarthritis is a group of immune-mediated rheumatic disorders that significantly impact patients’ physical function and quality of life. Patients with spondyloarthritis experience a greater prevalence of cardiometabolic disorders, such as obesity, hypertension, dyslipidemia and diabetes mellitus, and these comorbidities are associated with increased spondyloarthritis disease activity and risk of cardiovascular events. This narrative review summarizes the evidence for a physiological link between inflammatory status and cardiometabolic comorbidities in spondyloarthritis, as well as the impact of interleukin (IL)-17 blockade versus other molecular mechanisms in patients with cardiometabolic conditions. The IL-23/IL-17 axis plays a pivotal role in the pathophysiology of spondyloarthritis by promoting inflammation and tissue remodeling at the affected joints and entheses. The importance of the IL-23/IL-17 signaling cascade in underlying sub-clinical inflammation in common cardiometabolic disorders suggests the existence of shared pathways between these processes and spondyloarthritis pathophysiology. Thus, a bidirectional relationship exists between the effects of biologic drugs and patients’ cardiometabolic profile, which must be considered during treatment decision making. Biologic therapy may induce changes in patients’ cardiometabolic status and cardiometabolic conditions may conversely impact the clinical response to biologic therapy. Available evidence regarding the impact of IL-17 blockade with secukinumab on cardiometabolic parameters suggests this drug does not interfere with traditional cardiovascular risk markers and could be associated with a decreased risk of cardiovascular events. Additionally, the efficacy and retention rates of secukinumab do not appear to be negatively affected by obesity, with some studies reporting a positive impact on clinical outcomes, contrary to that described with other approaches, such as tumor necrosis factor blockade. In this article, we also review evidence for this bidirectional association with other treatments for spondyloarthritis. Current evidence suggests that IL-17–targeted therapy with secukinumab is highly effective in spondyloarthritis patients with cardiometabolic comorbidities and may provide additional cardiometabolic benefits.
NF-kB’s contribution to B cell fate decisions
Authors: Guldenpfennig Caitlyn , Teixeiro Emma , Daniels Mark
Published: July 2023

NF-κB signaling is essential to an effective innate and adaptive immune response. Many immune-specific functional and developmental outcomes depend in large on NF-κB. The formidable task of sorting out the mechanisms behind the regulation and outcome of NF-κB signaling remains an important area of immunology research. Here we briefly discuss the role of NF-κB in regulating cell fate decisions at various times in the path of B cell development, activation, and the generation of long-term humoral immunity.
CRISPR-Cas– induced IRF3 and MAVS knockouts in a salmonid cell line disrupt PRR signaling and affect viral replication
Authors: van der Wal Yorick A. , Nordli Henriette , Akandwanaho Allan , Greiner-Tollersrud Linn , Kool Jaap , Jørgensen Jorunn B.
Published: July 2023

Background

Interferon (IFN) responses are critical in the resolution of viral infections and are actively targeted by many viruses. They also play a role in inducing protective responses after vaccination and have been successfully tested as vaccine adjuvants. IFN responses are well conserved and function very similar in teleosts and mammals. Like in mammals, IFN responses in piscine cells are initiated by intracellular detection of the viral infection by different pattern recognition receptors. Upon the recognition of viral components, IFN responses are rapidly induced to combat the infection. However, many viruses may still replicate and be able to inhibit or circumvent the IFN response by different means.

Methods

By employing CRISPR Cas9 technology, we have disrupted proteins that are central for IFN signaling in the salmonid cell line CHSE-214. We successfully generated KO clones for the mitochondrial antiviral signaling protein MAVS, the transcription factors IRF3 and IRF7-1, as well as a double KO for IRF7-1/3 using an optimized protocol for delivery of CRISPR-Cas ribonucleoproteins through nucleofection.

Results

We found that MAVS and IRF3 KOs inhibited IFN and IFN-stimulated gene induction after intracellular poly I:C stimulation as determined through gene expression and promoter activation assays. In contrast, the IRF7-1 KO had no clear effect. This shows that MAVS and IRF3 are essential for initiation of intracellular RNA-induced IFN responses in CHSE-214 cells. To elucidate viral interference with IFN induction pathways, the KOs were infected with Salmon alphavirus 3 (SAV3) and infectious pancreatic necrosis virus (IPNV). SAV3 infection in control and IRF7-1 KO cells yielded similar titers and no cytopathic effect, while IRF3 and MAVS KOs presented with severe cytopathic effect and increased titers 6 days after SAV 3 infection. In contrast, IPNV yields were reduced in IRF3 and MAVS KOs, suggesting a dependency on interactions between viral proteins and pattern recognition receptor signaling components during viral replication.

Conclusion

Aside from more insight in this signaling in salmonids, our results indicate a possible method to increase viral titers in salmonid cells.
Dietary high β-conglycinin reduces the growth through enhancing hepatic lipid peroxidation and impairing intestinal barrier function of orange-spotted grouper (Epinephelus coioides)
Authors: Yang Lulu , Zhao Xingqiao , Yin Yanxia , Wang Kun , Sun Yunzhang , Ye Jidan
Published: July 2023

β-conglycinin is one of the major soy antigen proteins in soybean meal (SBM) and exhibits growth inhibition and intestinal health damage in grouper, but the underlying mechanisms are still poorly understood. In this study, orange-spotted grouper (Epinephelus coioides) was used to investigate whether the poor growth performance induced by dietary β-conglycinin levels is associated with intestinal structural integrity disruption, the intestinal apoptosis and intestinal microbiota. The basal diet (FM diet) was formulated to contained 48% protein and 12% fat without SBM supplementation. Fish meal protein in the FM diet was replaced by SBM to prepare a high SBM diet (SBM diet). β-conglycinin at 3% and 7% were added into FM diets to prepare two diets (B-3 and B-7). Triplicate groups of fish (20 fish/tank) were fed one of the experimental diets twice daily in a feeding period of 8 weeks. Compared with FM diet, fish fed diets SBM and B-7 had decreased the growth rate, hepatosomatic index, whole-body lipid and ash contents, and increased whole-body moisture content. However, the maximum growth was observed for diet B-3 and was not different from that of FM diet. The liver total antioxidant capacity and glutathione peroxidase activity, the muscle layer thickness of middle and distal intestine, and the mucosal fold length of distal intestine were lower, while liver malondialdehyde content, intestinal diamine oxidase activity, d-lactic acid and endotoxin contents, and the number of intestinal apoptosis were higher in SBM and B-7 groups than that in FM and/or B-3 groups. SBM and B-7 diets down-regulated the intestinal expression of tight junction genes (occludin,claudin-3andZO-1), apoptosis genes (bcl-2andbcl-xL) and anti-inflammatory factor genes (IκBα,TGF-β1andIL-10), but up-regulated the intestinal expression of apoptosis genes (caspase-3,caspase-8andcaspase-9) and pro-inflammatory factor genes (NF-κB1,RelA,TAK1,IKK,MyD88,TNF-α,IL-1β, andIL-8) vs FM and/or B-3 diets. The richness and diversity indexes of OTUs, Chao1, ACE, Shannon and Simpson were not affected by dietary treatments. The relative abundances of intestinal bacteria (phylum Proteobacteria and genusVibrio) were generally higher, and relative abundance of phylum Tenericutes was lower in SBM and/or B-7 groups than that in B-3 group. The above results indicate that high dietary β-conglycinin level, rather than intermediate level could decrease liver antioxidant capacity, reshape the intestinal microbiota, and impair the intestinal normal morphology through disrupting the intestinal tight junction structure, increasing intestinal mucosal permeability, and promoting intestinal apoptosis, which in turn triggers intestinal inflammatory responses and the occurrence of enteritis, and ultimately leads to poor growth performance in fish.
Effects of neuraxial labor analgesia on intrapartum maternal fever in full-term pregnancy and its influence on birth outcomes
Authors: Zhang Zhen , Deng Chun-Mei , Ma Jia-Hui , Li Shu , Lei Bo , Ding Ting
Published: July 2023

Introduction

This study aimed to explore the relationship between neuraxial labor analgesia and intrapartum fever and to demonstrate the influence of maternal fever on perinatal outcomes within 6 weeks after birth.

Methods

This was a secondary analysis of a multicenter prospective cohort study that enrolled women with single- and full-term cephalic pregnancy in northern China. Intrapartum maternal fever was defined as the highest axillary temperature during labor ≥37.5°C. Data on baseline characteristics, maternal variables, and neonatal outcomes were all collected. The association between neuraxial labor analgesia and intrapartum maternal fever was analyzed with logistic regression models, and the cutoff point was identified by the receiver operating characteristic curve.

Results

Of 577 parturients, 74 (12.8%) developed intrapartum fever. Neuraxial analgesia was associated with an increased risk of maternal intrapartum fever with or without adjusting for confounding factors (adjusted OR = 2.68; 95% CI: 1.32–5.47; p = 0.007). Further analysis showed that neuraxial analgesia of <5 h did not increase the risk of intrapartum fever compared with no analgesia (OR = 1.52; 95% CI: 0.63–3.64; p = 0.35), and longer neuraxial labor analgesia time (over 5 h) significantly increased the risk of fever (OR = 3.38; 95% CI: 1.63–7.01; p = 0.001). Parturients with intrapartum fever suffered more maternal adverse outcomes compared with those without fever (p< 0.001). Neonates of women with intrapartum fever had slightly higher rates of composite adverse neonatal outcomes compared with those without fever; however, the difference was not statistically significant (p = 0.098).

Conclusion

In women with low-risk pregnancies, a longer time of neuraxial labor analgesia was associated with an increased risk of intrapartum maternal fever. Intrapartum fever was related to adverse maternal outcomes but did not significantly affect neonatal outcomes within 6 weeks after delivery.
A rapid and reliable method for the determination of Lactiplantibacillus plantarum during wine fermentation based on PMA-CELL-qPCR
Authors: Wang Jie , Wei Bo , Chen Zhuojun , Chen Yixin , Liu Songyu , Zhang Bolin , Zhu Baoqing , Ye Dongqing
Published: July 2023

Real-time monitoring of microbial dynamics during fermentation is essential for wine quality control. This study developed a method that combines the fluorescent dye propidium monoazide (PMA) with CELL-qPCR, which can distinguish between dead and live microbes for Lactiplantibacillus plantarum. This method could detect the quantity of microbes efficiently and rapidly without DNA extraction during wine fermentation. The results showed that (1) the PMA-CELL-qPCR enumeration method developed for L. plantarum was optimized for PMA treatment concentration, PMA detection sensitivity and multiple conditions of sample pretreatment in wine environment, and the optimized method can accurately quantify 104–108 CFU/mL of the target strain (L. plantarum) in multiple matrices; (2) when the concentration of dead bacteria in the system is 104 times higher than the concentration of live bacteria, there is an error of 0.5–1 lg CFU/mL in the detection results. The optimized sample pretreatment method in wine can effectively reduce the inhibitory components in the qPCR reaction system; (3) the optimized PMA-CELL-qPCR method was used to monitor the dynamic changes of L. plantarum during the fermentation of Cabernet Sauvignon wine, and the results were consistent with the plate counting method. In conclusion, the live bacteria quantification method developed in this study for PMA-CELL-qPCR in L. plantarum wines is accurate in quantification and simple in operation, and can be used as a means to accurately monitor microbial dynamics in wine and other fruit wines.
The PapB/FocB family protein TosR acts as a positive regulator of flagellar expression and is required for optimal virulence of uropathogenic Escherichia coli
Authors: Hirakawa Hidetada , Shimokawa Mizuki , Noguchi Koshi , Tago Minori , Matsuda Hiroshi , Takita Ayako , Suzue Kazutomo , Tajima Hirotaka , Kawagishi Ikuro , Tomita Haruyoshi
Published: July 2023

Uropathogenic Escherichia coli (UPEC) is a major causative agent of urinary tract infections. The bacteria internalize into the uroepithelial cells, where aggregate and form microcolonies. UPEC fimbriae and flagella are important for the formation of microcolonies in uroepithelial cells. PapB/FocB family proteins are small DNA-binding transcriptional regulators consisting of approximately 100 amino acids that have been reported to regulate the expression of various fimbriae, including P, F1C, and type 1 fimbriae, and adhesins. In this study, we show that TosR, a member of the PapB/FocB family is the activator of flagellar expression. The tosR mutant had similar expression levels of type 1, P and F1C fimbriae as the parent strain, but flagellar production was markedly lower than in the parent strain. Flagellin is a major component of flagella. The gene encoding flagellin, fliC, is transcriptionally activated by the sigma factor FliA. The fliA expression is induced by the flagellar master regulator FlhDC. The flhD and flhC genes form an operon. The promoter activity of fliC, fliA and flhD in the tosR mutant was significantly lower than in the parent strain. The purified recombinant TosR does not bind to fliC and fliA but to the upstream region of the flhD gene. TosR is known to bind to an AT-rich DNA sequence consisting of 29 nucleotides. The characteristic AT-rich sequence exists 550–578 bases upstream of the flhD gene. The DNA fragment lacking this sequence did not bind TosR. Furthermore, loss of the tosR gene reduced motility and the aggregation ability of UPEC in urothelial cells. These results indicate that TosR is a transcriptional activator that increases expression of the flhDC operon genes, contributing to flagellar expression and optimal virulence.
Effects of acupuncture on the brain in primary insomnia: a coordinate-based meta-analysis of fMRI studies
Authors: Zang Shuhan , Chen Ying , Chen Haonan , Shi Huawei , Zhou Li
Published: July 2023

Importance

Primary insomnia (PI) has a high global incidence, and effective treatments with fewer side effects are needed. Acupuncture, a treatment used in traditional Chinese medicine, has become increasingly established as a treatment method for PI and is recognized by many physicians and patients. Some evidence has suggested that acupuncture was associated with improvements in objective sleep parameters and might induce changes in some brain regions. Individual studies with limited sample size and low detection thresholds may lead to false positives, and no systematic review of the effects of acupuncture has been conducted in PI.

Objective

The aim of this systematic review and coordinate-based meta-analysis was to summarize the literature on fMRI evaluation of patients with PI treated with acupuncture.

Design

We performed a methodical and comprehensive search of multiple publication databases (from inception to December 2022): Web of Science, PubMed, ScienceDirect, Embase, Wan Fang, China National Knowledge Infrastructure, and Chinese Scientific Journal Database. Bias and quality of studies were evaluated by three researchers. Furthermore, a seed-based D-mapping meta-analysis with permutation of subject images (SDM-PSI) was applied to investigate the central mechanisms behind acupuncture treatment at PI. The International Prospective Registry of Systematic Reviews received the protocol for this study. (PROSPERO: CRD42023400086).

Results

The analysis included 305 patients with PI and 116 healthy controls from 11 studies. SDM-PSI analysis showed that patients with PI exhibited increased amplitudes of regional homogeneity and low-frequency fluctuations in the left superior frontal gyrus (1352 voxels, p = 0.0028), right angular gyrus (14 voxels, p = 0.0457), and cerebellum (12 voxels, p = 0.0446). Acupuncture improved the function of right superior frontal gyrus (1, 404 voxels, p = 0.0123), left inferior frontal gyrus (1068 voxels, p = 0.0088), left inferior temporal gyrus (903 voxels, p = 0.0074), left supramarginal gyrus (888 voxels, p = 0.0113), left precuneus (457 voxels, p = 0.0247), right precuneus (302 voxels, p = 0.0191), left supplementary motor area (82 voxels, p = 0.0354), and right parahippocampal gyrus (28 voxels, p = 0.0379). The brain regions affected by non-acupoint acupuncture were all located in the frontal lobe. The Cochrane risk-of bias tool and MINORS5 were used for quality assessment and the included articles had high performance bias and attrition bias.

Conclusion

This coordinate-based meta-analysis found that acupuncture in patients with PI had significant effects on the default mode network, particularly on the frontal lobe and precuneus, and that non-acupoint acupuncture may provide some benefit to frontal brain region function.

Systematic review registration

PROSPERO: CRD42023400086.
Cenobamate significantly improves seizure control in intellectually disabled patients with drug-resistant epilepsy and allows drug load reduction
Authors: Friedo Anna-Lena , Greshake Benedikt , Makridis Konstantin L. , Straub Hans-Beatus
Published: July 2023

Introduction

Epilepsy patients with intellectual disability often suffer from drug-resistant epilepsy (DRE), which severely affects patients’ quality of life. Cenobamate (CNB) is a recently approved novel and effective ASM that can achieve high rates of seizure freedom in previously drug-resistant patients.

Methods

We performed a retrospective data analysis of the first patients treated with CNB at a single center. Outcome and treatment response were assessed at two different time points, and ASM burden was calculated.

Results

A 12 patients (7 males and 5 females) began treatment at a median age of 43 years, six of whom had developmental and epileptic encephalopathies. Prior to treatment with CNB, patients had tried a median of 13 different ASM. At the start of CNB therapy, patients were taking a median of 3 ASM. Treatment outcomes were available for 11 patients. After the first follow-up period (median 9 months), 55% of patients showed a significant seizure reduction of more than 50%, with three patients showing a reduction of more than 75% (27%). One patient achieved complete seizure freedom, while one patient did not respond to treatment. These response rates were consistently maintained at second follow-up after a median of 22 months. Ten patients (83%) reported adverse events (AE), the most common of which were dizziness and fatigue. No cases of drug reactions with eosinophilia and systemic symptoms (DRESS) were observed. The majority of AEs were mild and resolved over time. In addition, most patients were able to reduce their concomitant ASM.

Discussion

Cenobamate has been shown to be an effective ASM in patients with DRE and in patients with intellectual disabilities. After more than 1 year of treatment with CNB, close monitoring and management of drug–drug interactions may reduce enzyme-inducing ASMs and lead to better long-term outcomes. With CNB treatment, many patients can achieve a reduced overall drug burden while maintaining a reduction in seizures.
Association between intracranial vessel calcifications, structural brain damage, and cognitive impairment after minor strokes: a prospective study
Authors: Seyman Estelle Emanuelle , Sadeh-Gonik Udi , Berman Phillip , Blum Itay , Shendler Genady , Nathan Bornstein , Rothschild Ofer , Molad Jeremy , Ben Assayag Einor , Hallevi Hen ,   the TABASCO prospective cohort study group
Published: July 2023

Background

Vascular calcifications are a hallmark of atherosclerosis, and in the coronary arteries are routinely used as a prognostic marker. Calcifications of intracranial vessels (ICC) are frequently observed on non-contrast CT (NCCT) and their effect on post-stroke cognitive impairment (PSCI) remains unclear. Our aim was to explore the association of ICC with prospective long-term cognitive function and advanced MRI-measures in a large prospective cohort of cognitively intact mild stroke survivors.

Methods

Data from the Tel-Aviv brain acute stroke cohort (TABASCO) study [ClinicalTrials.gov #NCT01926691] were analyzed. This prospective cohort study (n = 575) aimed to identify predictors of PSCI, in cognitively intact mild stroke survivors. A quantitative assessment of the intracranial calcium content – The ICC score (ICCS) was calculated semi-automatically on NCCT using a validated calcium quantification application. Participants underwent a 3 T-MRI and prospective comprehensive cognitive clinical and laboratory assessments at enrollment, 6, 12, and 24-months.

Results

Data were available for 531 participants (67.4 years, 59.5% males). The incidence of PSCI at two-years doubled in the high ICCS group (26% vs. 13.7%, p < 0.001). The high ICCS group had significantly greater small-vessel-disease (SVD) tissue changes and reduced microstructural-integrity assessed by Diffusion-Tensor-Imaging (DTI) maps (p < 0.05 for all). In multivariate analysis, a higher ICCS was independently associated with brain atrophy manifested by lower normalized white and gray matter, hippocampal and thalamic volumes (β = −0.178, β = −0.2, β = −0.137, β = −0.157; p < 0.05) and independently predicted PSCI (OR 1.83, 95%CI 1.01–3.35).

Conclusion

Our findings suggest that the ICCS, which is a simple and readily available imaging marker on NCCT, is associated with brain atrophy, microstructural damage, the extent of SVD, and may predict PSCI. This finding has implications for identifying individuals at risk for PSCI and implementing targeted interventions to mitigate this risk.
Case report: Creutzfeldt-Jakob disease: a case that initiated with the onset of obsessive-compulsive state
Authors: Li Baizhu , Wang Shan , Han Shiyu , Hu Ning , Shang Xiuli
Published: July 2023

Background

Obsessive-compulsive disorder (OCD) is a common reason for patients to seek symptomatic treatment in psychiatric departments, which makes it challenging to consider underlying organic nervous system diseases. However, Creutzfeldt-Jakob disease (CJD) can present with atypical symptoms, sometimes even as initial symptoms, leading to misdiagnosis or missed diagnosis. Lumbar puncture and brain DWI are important diagnostic methods for CJD, and the detection of 1,433 protein can be performed to confirm the diagnosis.

Case presentation

We present the case of a 63-year-old woman who was initially diagnosed with obsessive-compulsive disorder in 2022. Despite seven months of symptomatic treatment, her symptoms did not improve. She also developed symptoms of altered consciousness, such as upper limb tremors and mutism. Based on brain DWI and positive results from the detection of 1,433 protein, she was ultimately diagnosed with CJD.

Conclusion

Creutzfeldt-Jakob disease (CJD) can manifest initially as obsessive-compulsive disorder (OCD) with atypical symptoms, making it prone to misdiagnosis. Therefore, it is crucial to conduct further investigations, including lumbar puncture and imaging, to exclude organic nervous system diseases before initiating symptomatic treatment for psychiatric disorders. This approach can facilitate early diagnosis of CJD and other potential organic neurological diseases.