bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on concentrated frequency-dependent parameter model for short overhead transmission lines based on first-order rational function fitting
Authors: Li Botong , Sun Mingyang , Wen Weijie , Ji Xiaotong , Xiao Fan
Published: August 2023

The impedance of power lines is influenced by geological conditions and skin effect, resulting in frequency-dependent characteristics. In this study, a centralized parameter frequency-dependent line model based on first-order rational function fitting is investigated for short overhead transmission lines. The proposed model incorporates a parallel branch consisting of resistance and inductance obtained through rational function fitting, which mimics the frequency-dependent behavior of the line. The coupling between multiple conductors is represented using controlled sources. Comparative analysis of fitting accuracy and computational efficiency across various orders of rational functions reveals that the first-order rational function fitting offers superior computational efficiency while maintaining high accuracy in the medium and low-frequency range. Simulation results demonstrate that the proposed model, when disregarding wave propagation effects, exhibits comparable accuracy to the distributed parameter line model while achieving higher computational efficiency. Moreover, in transient analysis predominantly influenced by power frequency, the proposed model outperforms the frequency-independent pi(π) line model in terms of accuracy.
Satellite-based estimation of soil organic carbon in Portuguese grasslands
Authors: Morais Tiago G. , Jongen Marjan , Tufik Camila , Rodrigues Nuno R. , Gama Ivo , Serrano João , Gonçalves Maria C. , Mano Raquel , Domingos Tiago , Teixeira Ricardo F. M.
Published: August 2023

Introduction:Soil organic carbon (SOC) sequestration is one of the main ecosystem services provided by well-managed grasslands. In the Mediterranean region, sown biodiverse pastures (SBP) rich in legumes are a nature-based, innovative, and economically competitive livestock production system. As a co-benefit of increased yield, they also contribute to carbon sequestration through SOC accumulation. However, SOC monitoring in SBP require time-consuming and costly field work.

Methods:In this study, we propose an expedited and cost-effective indirect method to estimate SOC content. In this study, we developed models for estimating SOC concentration by combining remote sensing (RS) and machine learning (ML) approaches. We used field-measured data collected from nine different farms during four production years (between 2017 and 2021). We utilized RS data from both Sentinel-1 and Sentinel-2, including reflectance bands and vegetation indices. We also used other covariates such as climatic, soil, and terrain variables, for a total of 49 inputs. To reduce multicollinearity problems between the different variables, we performed feature selection using the sequential feature selection approach. We then estimated SOC content using both the complete dataset and the selected features. Multiple ML methods were tested and compared, including multiple linear regression (MLR), random forests (RF), extreme gradient boosting (XGB), and artificial neural networks (ANN). We used a random cross-validation approach (with 10 folds). To find the hyperparameters that led to the best performance, we used a Bayesian optimization approach.

Results:Results showed that the XGB method led to higher estimation accuracy than the other methods, and the estimation performance was not significantly influenced by the feature selection approach. For XGB, the average root mean square error (RMSE), measured on the test set among all folds, was 2.78 g kg−1(r2equal to 0.68) without feature selection, and 2.77 g kg−1(r2equal to 0.68) with feature selection (average SOC content is 13 g kg−1). The models were applied to obtain SOC content maps for all farms.

Discussion:This work demonstrated that combining RS and ML can help obtain quick estimations of SOC content to assist with SBP management.
Cytosine base editors optimized for genome editing in potato protoplasts
Authors: Westberg Ida , Carlsen Frida Meijer , Johansen Ida Elisabeth , Petersen Bent Larsen
Published: August 2023

In this study, we generated and compared three cytidine base editors (CBEs) tailor-made for potato (Solanum tuberosum), which conferred up to 43% C-to-T conversion of all alleles in the protoplast pool. Earlier, gene-edited potato plants were successfully generated by polyethylene glycol-mediated CRISPR/Cas9 transformation of protoplasts followed by explant regeneration. In one study, a 3–4-fold increase in editing efficiency was obtained by replacing the standard Arabidopsis thaliana AtU6-1 promotor with endogenous potato StU6 promotors driving the expression of the gRNA. Here, we used this optimized construct (SpCas9/StU6-1::gRNA1, target gRNA sequence GGTC4C5TTGGAGC12AAAAC17TGG) for the generation of CBEs tailor-made for potato and tested for C-to-T base editing in the granule-bound starch synthase 1 gene in the cultivar Desiree. First, the Streptococcus pyogenes Cas9 was converted into a (D10A) nickase (nCas9). Next, one of three cytosine deaminases from human hAPOBEC3A (A3A), rat (evo_rAPOBEC1) (rA1), or sea lamprey (evo_PmCDA1) (CDA1) was C-terminally fused to nCas9 and a uracil-DNA glycosylase inhibitor, with each module interspaced with flexible linkers. The CBEs were overall highly efficient, with A3A having the best overall base editing activity, with an average 34.5%, 34.5%, and 27% C-to-T conversion at C4, C5, and C12, respectively, whereas CDA1 showed an average base editing activity of 34.5%, 34%, and 14.25% C-to-T conversion at C4, C5, and C12, respectively. rA1 exhibited an average base editing activity of 18.75% and 19% at C4 and C5 and was the only base editor to show no C-to-T conversion at C12.
Interactions between genes involved in physiological dysregulation and axon guidance: role in Alzheimer’s disease
Authors: Arbeev Konstantin G. , Ukraintseva Svetlana , Bagley Olivia , Duan Hongzhe , Wu Deqing , Akushevich Igor , Stallard Eric , Kulminski Alexander , Christensen Kaare , Feitosa Mary F. , O’Connell Jeffrey R. , Parker Daniel , Whitson Heather , Yashin Anatoliy I.
Published: August 2023

Dysregulation of physiological processes may contribute to Alzheimer’s disease (AD) development. We previously found that an increase in the level of physiological dysregulation (PD) in the aging body is associated with declining resilience and robustness to major diseases. Also, our genome-wide association study found that genes associated with the age-related increase in PD frequently represented pathways implicated in axon guidance and synaptic function, which in turn were linked to AD and related traits (e.g., amyloid, tau, neurodegeneration) in the literature. Here, we tested the hypothesis that genes involved in PD and axon guidance/synapse function may jointly influence onset of AD. We assessed the impact of interactions between SNPs in such genes on AD onset in the Long Life Family Study and sought to replicate the findings in the Health and Retirement Study. We found significant interactions between SNPs in the UNC5C and CNTN6, and PLXNA4 and EPHB2 genes that influenced AD onset in both datasets. Associations with individual SNPs were not statistically significant. Our findings, thus, support a major role of genetic interactions in the heterogeneity of AD and suggest the joint contribution of genes involved in PD and axon guidance/synapse function (essential for the maintenance of complex neural networks) to AD development.
Case report: A case report and literature review of complete trisomy 9
Authors: Xu Chenxia , Li Miaoyuan , Peng Jianming , Zhang Yanfang , Li Haijun , Zheng Guobing , Wang Degang
Published: August 2023

Complete trisomy 9 is a rare and lethal chromosomal anomaly characterized by multisystem dysmorphism and central nervous system (CNS) malformations. This study presents a case of complete trisomy 9 with an unusual phenotypic association and investigates the genetic pathways involved in this chromosomal abnormality. Trisomy 9 leads to a wide range of organ abnormalities, and this research contributes to a better understanding of the phenotype associated with this rare aneuploidy. The literature on the phenotypes of fetuses with various systems affected by complete trisomy 9 was reviewed and summarized. Correct diagnosis and appropriate counseling based on the characteristics of previous reports of fetuses with trisomy 9 is essential in maternity care and clinical management. To provide guidance and help for clinical diagnosis, this study aimed to explore the clinical and genetic characteristics of trisomy 9 syndrome to improve clinicians’ understanding of the disease.
Exploring novel genetic and hematological predictors of response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer
Authors: Marinkovic Mladen , Stojanovic-Rundic Suzana , Stanojevic Aleksandra , Ostojic Marija , Gavrilovic Dusica , Jankovic Radmila , Maksimovic Natasa , Stroggilos Rafael , Zoidakis Jerome , Castellví-Bel Sergi , Fijneman Remond J. A. , Cavic Milena
Published: August 2023

Introduction: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT). To select patients who would benefit the most from nCRT, there is a need for predictive biomarkers. The aim of this study was to evaluate the role of clinical, pathological, radiological, inflammation-related genetic, and hematological parameters in the prediction of post-nCRT response.

Materials and methods:In silico analysis of published transcriptomics datasets was conducted to identify candidate genes, whose expression will be measured using quantitative Real Time PCR (qRT-PCR) in pretreatment formaline-fixed paraffin-embedded (FFPE) samples. In this study, 75 patients with LARC were prospectively included between June 2020—January 2022. Patients were assessed for tumor response in week 8 post-nCRT with pelvic MRI scan and rigid proctoscopy. For patients with a clinical complete response (cCR) and initially distant located tumor no immediate surgery was suggested (“watch and wait” approach). The response after surgery was assessed using histopathological tumor regression grading (TRG) categories from postoperative specimens by Mandard. Responders (R) were defined as patients with cCR without operative treatment, and those with TRG 1 and TRG 2 postoperative categories. Non-responders (NR) were patients classified as TRG 3-5.

Results: Responders group comprised 35 patients (46.6%) and NR group 53.4% of patients. Analysis of published transcriptomics data identified genes that could predict response to treatment and their significance was assessed in our cohort by qRT-PCR. When comparison was made in the subgroup of patients who were operated (TRG1 vs. TRG4), the expression of IDO1 was significantly deregulated (p < 0.05). Among hematological parameters between R and NR a significant difference in the response was detected for neutrophil-to-monocyte ratio (NMR), initial basophil, eosinophil and monocyte counts (p < 0.01). According to MRI findings, non-responders more often presented with extramural vascular invasion (p < 0.05).

Conclusion: Based on logistic regression model, factors associated with favorable response to nCRT were tumor morphology and hematological parameters which can be easily and routinely derived from initial laboratory results (NMR, eosinophil, basophil and monocyte counts) in a minimally invasive manner. Using various metrics, an aggregated score of the initial eosinophil, basophil, and monocyte counts demonstrated the best predictive performance.
Changes in subcutaneous white adipose tissue cellular composition and molecular programs underlie glucose intolerance in persons with HIV
Authors: Bailin Samuel S. , Kropski Jonathan A. , Gangula Rama D. , Hannah LaToya , Simmons Joshua D. , Mashayekhi Mona , Ye Fei , Fan Run , Mallal Simon , Warren Christian M. , Kalams Spyros A. , Gabriel Curtis L. , Wanjalla Celestine N. , Koethe John R.
Published: August 2023

Introduction

Subcutaneous adipose tissue (SAT) is a critical regulator of systemic metabolic homeostasis. Persons with HIV (PWH) have an increased risk of metabolic diseases and significant alterations in the SAT immune environment compared with the general population.

Methods

We generated a comprehensive single-cell multi-omic SAT atlas to characterize cellular compositional and transcriptional changes in 59 PWH across a spectrum of metabolic health.

Results

Glucose intolerance was associated with increased lipid-associated macrophages, CD4+ and CD8+ T effector memory cells, and decreased perivascular macrophages. We observed a coordinated intercellular regulatory program which enriched for genes related to inflammation and lipid-processing across multiple cell types as glucose intolerance increased. Increased CD4+ effector memory tissue-resident cells most strongly associated with altered expression of adipocyte genes critical for lipid metabolism and cellular regulation. Intercellular communication analysis demonstrated enhanced pro-inflammatory and pro-fibrotic signaling between immune cells and stromal cells in PWH with glucose intolerance compared with non-diabetic PWH. Lastly, while cell type-specific gene expression among PWH with diabetes was globally similar to HIV-negative individuals with diabetes, we observed substantially divergent intercellular communication pathways.

Discussion

These findings suggest a central role of tissue-resident immune cells in regulating SAT inflammation among PWH with metabolic disease, and underscore unique mechanisms that may converge to promote metabolic disease.
Chemically augmented malaria sporozoites display an altered immunogenic profile
Authors: Duszenko Nikolas , van Schuijlenburg Roos , Chevalley-Maurel Severine , van Willigen Danny M. , de Bes-Roeleveld Laura , van der Wees Stefanie , Naar Chanel , Baalbergen Els , Heieis Graham , Bunschoten Anton , Velders Aldrik H. , Franke-Fayard Blandine , van Leeuwen Fijs W. B. , Roestenberg Meta
Published: August 2023

Despite promising results in malaria-naïve individuals, whole sporozoite (SPZ) vaccine efficacy in malaria-endemic settings has been suboptimal. Vaccine hypo-responsiveness due to previous malaria exposure has been posited as responsible, indicating the need for SPZ vaccines of increased immunogenicity. To this end, we here demonstrate a proof-of-concept for altering SPZ immunogenicity, where supramolecular chemistry enables chemical augmentation of the parasite surface with a TLR7 agonist-based adjuvant (SPZ-SAS(CL307)). In vitro, SPZ-SAS(CL307) remained well recognized by immune cells and induced a 35-fold increase in the production of pro-inflammatory IL-6 (p < 0.001). More promisingly, immunization of mice with SPZ-SAS(CL307) yielded improved SPZ-specific IFN-γ production in liver-derived NK cells (percentage IFN-γ+ cells 11.1 ± 1.8 vs. 9.4 ± 1.5%, p < 0.05), CD4+ T cells (4.7 ± 4.3 vs. 1.8 ± 0.7%, p < 0.05) and CD8+ T cells (3.6 ± 1.4 vs. 2.5 ± 0.9%, p < 0.05). These findings demonstrate the potential of using chemical augmentation strategies to enhance the immunogenicity of SPZ-based malaria vaccines.
MiRNA 106a-5p in cerebrospinal fluid as signature of early relapsing remitting multiple sclerosis: a cross sectional study
Authors: Zanghì Aurora , Manuti Virginia , Serviddio Gaetano , D’Amico Emanuele , Avolio Carlo
Published: August 2023

Background

Circulating microRNAs (MiRNAs) have been investigated for their role in fine-tuning the adaptive immune response to inflammatory factors and in Multiple Sclerosis (MS). They have been investigated as possible biomarkers for the diagnosis and prognosis of the disease.

Methods

A cross sectional study conducted at the MS centre of Foggia, Italy. We enrolled patients with (1) an age between 18 and 55 years, (2) a definitive diagnosis of relapsing remitting MS (RRMS) as per the revised McDonald criteria, and (3) naïve to any disease modifying therapy (DMTs), as well as (4) patients with other neurological disorders (OND). The aim of the study was to compare the levels of expression of miRNA 21-5p, miRNA 106a-5p, miRNA 146a-5p, and miRNA223-3p in cell-free cerebrospinal fluid (CSF) in RRMS patients and OND. Investigated MiRNAs were extracted, retrotranscribed, and then assessed by real-time polymerase chain reaction assay (q-PCR). A receiver-operator characteristic (ROC) curve was used to test MiRNAs as a biomarker for diagnosing MS. A linear regression analysis was done to find any association with disease characteristics at the time of diagnosis.

Results

A total cohort of 70 subjects (70% women) was analyzed. Out of them, 35 had a RRMS diagnosis. MiRNA 106a-5p (7.8 ± 3.8 vs 1.3 ± 0.9, p=0.03) had higher levels in RRMS patients when compared to OND. The ROC curve indicated that MiRNA 106a-5p could be considered as a disease biomarker with an area under the curve of 0.812 (p<.001; 95% CI 0.686-0.937). Linear regression analysis showed an association between the number of oligoclonal bands and MiRNA 106a-5p levels (B-coeff 2.6, p<.001; 95% CI 1.3-4.9).

Conclusion

We described miRNA 106a-5p as a possible signature in the CSF of RRMS patients in early phases of the disease. Further studies are needed to characterize its role in early MS as a disease biomarker.
Long non-coding RNA AC099850.4 correlates with advanced disease state and predicts worse prognosis in triple-negative breast cancer
Authors: Vishnubalaji Radhakrishnan , Alajez Nehad M.
Published: August 2023

Our understanding of the function of long non-coding RNAs (lncRNAs) in health and disease states has evolved over the past decades due to the many advances in genome research. In the current study, we characterized the lncRNA transcriptome enriched in triple-negative breast cancer (TNBC, n = 42) and estrogen receptor (ER+, n = 42) breast cancer compared to normal breast tissue (n = 56). Given the aggressive nature of TNBC, our data revealed selective enrichment of 57 lncRNAs in TNBC. Among those, AC099850.4 lncRNA was chosen for further investigation where it exhibited elevated expression, which was further confirmed in a second TNBC cohort (n = 360) where its expression correlated with a worse prognosis. Network analysis of AC099850.4high TNBC highlighted enrichment in functional categories indicative of cell cycle activation and mitosis. Ingenuity pathway analysis on the differentially expressed genes in AC099850.4high TNBC revealed the activation of the canonical kinetochore metaphase signaling pathway, pyridoxal 5'-phosphate salvage pathway, and salvage pathways of pyrimidine ribonucleotides. Additionally, upstream regulator analysis predicted the activation of several upstream regulator networks including CKAP2L, FOXM1, RABL6, PCLAF, and MITF, while upstream regulator networks of TP53, NUPR1, TRPS1, and CDKN1A were suppressed. Interestingly, elevated expression of AC099850.4 correlated with worse short-term relapse-free survival (log-rank p = 0.01). Taken together, our data are the first to reveal AC099850.4 as an unfavorable prognostic marker in TNBC, associated with more aggressive clinicopathological features, and suggest its potential utilization as a prognostic biomarker and therapeutic target in TNBC.
Identification of the shared mechanisms and common biomarkers between Sjögren’s syndrome and atherosclerosis using integrated bioinformatics analysis
Authors: Qi Xiaoyi , Huang Qianwen , Wang Shijia , Qiu Liangxian , Chen Xiongbiao , Ouyang Kunfu , Chen Yanjun
Published: August 2023

Background

Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by exocrine and extra-glandular symptoms. The literature indicates that SS is an independent risk factor for atherosclerosis (AS); however, its pathophysiological mechanism remains undetermined. This investigation aimed to elucidate the crosstalk genes and pathways influencing the pathophysiology of SS and AS via bioinformatic analysis of microarray data.

Methods

Microarray datasets of SS (GSE40611) and AS (GSE28829) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were acquired using R software’s “limma” packages, and the functions of common DEGs were determined using Gene Ontology and Kyoto Encyclopedia analyses. The protein–protein interaction (PPI) was established using the STRING database. The hub genes were assessed via cytoHubba plug-in and validated by external validation datasets (GSE84844 for SS; GSE43292 for AS). Gene set enrichment analysis (GSEA) and immune infiltration of hub genes were also conducted.

Results

Eight 8 hub genes were identified using the intersection of four topological algorithms in the PPI network. Four genes (CTSS, IRF8, CYBB, and PTPRC) were then verified as important cross-talk genes between AS and SS with an area under the curve (AUC) ≥0.7. Furthermore, the immune infiltration analysis revealed that lymphocytes and macrophages are essentially linked with the pathogenesis of AS and SS. Moreover, the shared genes were enriched in multiple metabolisms and autoimmune disease-related pathways, as evidenced by GSEA analyses.

Conclusion

This is the first study to explore the common mechanism between SS and AS. Four key genes, including CTSS, CYBB, IRF8, and PTPRC, were associated with the pathogenesis of SS and AS. These hub genes and their correlation with immune cells could be a potential diagnostic and therapeutic target.
Diagnostic role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in abdominal lymphadenopathy of unknown etiology
Authors: Wang Wenli , Han Chaoqun , Ling Xin , Guo Xianwen , Liu Jun , Lin Rong , Ding Zhen
Published: August 2023

Background

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an established method for the evaluation of abdominal organ lesions. However, there are few studies on EUS-FNA for abdominal lymph node (LN) lesions. The purpose of this study was to evaluate the diagnostic role of EUS-FNA in isolated abdominal lymphadenopathy (LAP).

Methods

A retrospective analysis was performed on patients with isolated abdominal LAP who underwent a EUS-FNA examination. The diagnosis was made based on cytology, histology, and immunohistochemical (IHC) studies. The area under curve (AUC) value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated.

Results

A total of 99 patients were included in this study. The final diagnoses were metastatic tumor (n = 32), lymphoma (n = 32), tuberculosis (n = 17), sarcoidosis (n = 5), castleman’s disease (n = 1), and reactive LAP (n = 12). The AUC value, sensitivity, specificity, PPV, NPV, and accuracy of EUS-FNA in the diagnosis of malignant LAP were 0.9531, 90.6, 100, 100, 85.4, and 93.9%, respectively. For the diagnosis of lymphoma, the accuracy of EUS-FNA combined with IHC staining was 94.9%. Retroperitoneal LN enlargement is more commonly associated with lymphoma, while hepatic hilar LN enlargement predominantly suggests benign conditions or metastatic tumors. Malignant lymph nodes are more likely to be regular border, circular/quasi-circular, and fusion. Lymphomas are more likely to present with fusion and heterogeneous echogenicity than metastatic tumors.

Conclusion

EUS-FNA is a safe and effective method to diagnose isolated abdominal LAP.
Evaluation of the effectiveness of a joint general practitioner-pharmacist intervention on the implementation of benzodiazepine deprescribing in older adults (BESTOPH-MG trial): protocol for a cluster-randomized controlled trial
Authors: Huon Jean-François , Nizet Pierre , Caillet Pascal , Lecompte Hélène , Victorri-Vigneau Caroline , Fournier Jean-Pascal ,   the BESTOPH-MG consortium
Published: August 2023

Background

Deprescribing benzodiazepines and related drugs (BZDR) is a challenge due to a lack of time on physicians’ part, a lack of involvement of other health professionals, and the need for adapted tools. This study is based on primary care collaboration, by evaluating the effectiveness of a joint intervention between general practitioners and community pharmacists on the implementation of BZDR deprescribing in older adults.

Methods

This is a cluster randomized controlled trial in which each cluster will be formed by a physician-pharmacist pair. Within a cluster allocated to the intervention, the pharmacist will be trained in motivational interviewing (MI), and will offer the patient 3 interviews after inclusion by the physician. They will base their intervention on validated deprescribing guidelines. The pharmacist will receive methodological support during the first interviews. Interprofessional collaboration will be encouraged by writing reports for the physician after each interview. The following implementation outcomes will be evaluated: acceptability/adoption, appropriateness, cost, and fidelity. They will be measured by means of sociological interviews, observations, logbooks, and cost-utility analysis. Focus groups with physicians and pharmacists will be carried out to identify levers and barriers experienced in this collaboration. Observations will be conducted with pharmacists to assess their approach of the MIs. Effectiveness outcomes will be based on medication (discontinuation or reduction of BZDR) and clinical outcomes (such as quality of life, insomnia or anxiety), assessed by health insurance databases and validated questionnaires.

Discussion

This study will determine whether collaboration in primary care between physicians and pharmacists, as well as training and coaching of pharmacists in motivational interviewing, allows the implementation of BZDR deprescribing in the older adults.

This study will provide an understanding of the processes used to implement deprescribing guidelines, and the contribution of collaborative practice in implementing BZDR discontinuation. The cluster methodology will allow to assess the experience of the relationship between the different primary care actors, and the related obstacles and levers.

The results obtained will make it possible to produce guidelines on the involvement of community pharmacists in the management of substance abuse in older adults, or even to legislate new missions or care pathways.

Clinical trial registration

ClinicalTrials.gov, identifier, NCT05765656.
The effect of vitamin C in adults with sepsis: a meta-analysis of randomized controlled trials
Authors: Luo Xing , Zhu Youfeng , Zhang Rui , Zhu JianQiu , Kuang Huanming , Shao Yuebin , Guo Xinmin , Ning Bo
Published: August 2023

Background

The effect of intravenous (IV) vitamin C in the treatment of sepsis remains controversial. We aimed to explore the clinical efficacy of vitamin C in the treatment of sepsis.

Methods

Electronic databases (PubMed, Embase, Web of Science, and Cochrane Library) were searched from inception through November 15th, 2022, for randomized controlled trials evaluating the effect of IV vitamin C treatment in patients with sepsis. The primary outcome was short-term mortality, secondary outcomes included duration of vasopressor use, length of intensive care unit (ICU) stay, and Sequential Organ Failure Assessment (SOFA) score after vitamin C treatment. Subgroup analyses were performed based on the dose and duration of IV vitamin C and region to determine whether vitamin C benefited patients with sepsis.

Results

A total of 10 studies including 1,426 patients fulfilled the predefined criteria and were analyzed. Overall, there were no significant differences between the vitamin C group and the control group regarding short-term mortality [odds ratio (OR), 0.61; 95% confidence interval (CI) 0.37–1.01; p = 0.05], ICU length of stay [mean difference (MD), −1.24; 95% CI -3.54 to 1.05, p = 0.29] and SOFA score (MD, −0.85, 95% CI -2.38 to 0.67, p = 0.27). However, vitamin C significantly reduced the duration of vasopressor use (MD, −14.36, 95% CI −26.11 to −2.61, p = 0.02). Furthermore, subgroup analysis found that in developing countries, vitamin C was associated with a significant reduction in short-term mortality (OR, 0.33; 95% CI 0.12–0.90; p = 0.03), duration of vasopressor use (MD, −24.37, 95% CI -33.72 to −15.02, p < 0.001) and SOFA score (MD, −2.55, 95% CI -4.81 to −0.28, p = 0.03).

Conclusion

In our study, vitamin C administration for sepsis patients was not associated with a significant reduction in short-term mortality, length of ICU stay or SOFA score. However, we observed that vitamin C could reduce the duration of vasopressor use. Furthermore, sepsis patients in developing countries may benefit more from vitamin C administration than those in developed countries.

Systematic review registration: Identifier CRD42022380958, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=380958.
Patterns of asexual reproduction of the soybean aphid, Aphis glycines (Matsumura), with and without the secondary symbionts Wolbachia and Arsenophonus, on susceptible and resistant soybean genotypes
Authors: Giordano Rosanna , Weber Everett P. , Mitacek Ryan , Flores Alejandra , Ledesma Alonso , De Arun K. , Herman Theresa K. , Soto-Adames Felipe N. , Nguyen Minh Q. , Hill Curtis B. , Hartman Glen L.
Published: August 2023

Plant breeding is used to develop crops with host resistance to aphids, however, virulent biotypes often develop that overcome host resistance genes. We tested whether the symbionts, Arsenophonus (A) and Wolbachia (W), affect virulence and fecundity in soybean aphid biotypes Bt1 and Bt3 cultured on whole plants and detached leaves of three resistant, Rag1, Rag2 and Rag1 + 2, and one susceptible, W82, soybean genotypes. Whole plants and individual aphid experiments of A. glycines with and without Arsenophonus and Wolbachia did not show differences in overall fecundity. Differences were observed in peak fecundity, first day of deposition, and day of maximum nymph deposition of individual aphids on detached leaves. Bt3 had higher fecundity than Bt1 on detached leaves of all plant genotypes regardless of bacterial profile. Symbionts did not affect peak fecundity of Bt1 but increased it in Bt3 (A+W+) and all Bt3 strains began to deposit nymphs earlier than the Bt1 (A+W−). Arsenophonus in Bt1 delayed the first day of nymph deposition in comparison to aposymbiotic Bt1 except when reared on Rag1 + 2. For the Bt1 and Bt3 strains, symbionts did not result in a significant difference in the day they deposited the maximum number of nymphs nor was there a difference in survival or variability in number of nymphs deposited. Variability of number of aphids deposited was higher in aphids feeding on resistant plant genotypes. The impact of Arsenophonus on soybean aphid patterns of fecundity was dependent on the aphid biotype and plant genotype. Wolbachia alone had no detectable impact but may have contributed to the increased fecundity of Bt3 (A+W+). An individual based model, using data from the detached leaves experiment and with intraspecific competition removed, found patterns similar to those observed in the greenhouse and growth chamber experiments including a significant interaction between soybean genotype and aphid strain. Combining individual data with the individual based model of population growth isolated the impact of fecundity and host resistance from intraspecific competition and host health. Changes to patterns of fecundity, influenced by the composition and concentration of symbionts, may contribute to competitive interactions among aphid genotypes and influence selection on virulent aphid populations.
Microbe-host interactions: structure and functions of Gram-negative bacterial membrane vesicles
Authors: Xiao Min , Li Guiding , Yang Hefeng
Published: August 2023

Bacteria-host interaction is a common, relevant, and intriguing biological phenomena. The host reacts actively or passively to the bacteria themselves, their products, debris, and so on, through various defense systems containing the immune system, the bacteria communicate with the local or distal tissues of the host via their own surface antigens, secreted products, nucleic acids, etc., resulting in relationships of attack and defense, adaptation, symbiosis, and even collaboration. The significance of bacterial membrane vesicles (MVs) as a powerful vehicle for the crosstalk mechanism between the two is growing. In the recent decade, the emergence of MVs in microbial interactions and a variety of bacterial infections, with multiple adhesions to host tissues, cell invasion and evasion of host defense mechanisms, have brought MVs to the forefront of bacterial pathogenesis research. Whereas MVs are a complex combination of molecules not yet fully understood, research into its effects, targeting and pathogenic components will advance its understanding and utilization. This review will summarize structural, extraction and penetration information on several classes of MVs and emphasize the role of MVs in transport and immune response activation. Finally, the potential of MVs as a therapeutic method will be highlighted, as will future research prospects.
Lipid degradation and photosynthetic traits after prolonged darkness in four Antarctic benthic diatoms, including the newly described species Planothidium wetzelii sp. nov.
Authors: Juchem Desirée P. , Schimani Katherina , Holzinger Andreas , Permann Charlotte , Abarca Nélida , Skibbe Oliver , Zimmermann Jonas , Graeve Martin , Karsten Ulf
Published: August 2023

In polar regions, the microphytobenthos has important ecological functions in shallow-water habitats, such as on top of coastal sediments. This community is dominated by benthic diatoms, which contribute significantly to primary production and biogeochemical cycling while also being an important component of polar food webs. Polar diatoms are able to cope with markedly changing light conditions and prolonged periods of darkness during the polar night in Antarctica. However, the underlying mechanisms are poorly understood. In this study, five strains of Antarctic benthic diatoms were isolated in the field, and the resulting unialgal cultures were identified as four distinct species, of which one is described as a new species, Planothidium wetzelii sp. nov. All four species were thoroughly examined using physiological, cell biological, and biochemical methods over a fully controlled dark period of 3 months. The results showed that the utilization of storage lipids is one of the key mechanisms in Antarctic benthic diatoms to survive the polar night, although different fatty acids were involved in the investigated taxa. In all tested species, the storage lipid content declined significantly, along with an ultrastructurally observable degradation of the chloroplasts. Surprisingly, photosynthetic performance did not change significantly despite chloroplasts decreasing in thylakoid membranes and an increased number of plastoglobules. Thus, a combination of biochemical and cell biological mechanisms allows Antarctic benthic diatoms to survive the polar night.
Nitrogen fertilization promoted microbial growth and N2O emissions by increasing the abundance of nirS and nosZ denitrifiers in semiarid maize field
Authors: Fudjoe Setor Kwami , Li Lingling , Anwar Sumera , Shi Shangli , Xie Junhong , Wang Linlin , Xie Lihua , Yongjie Zhou
Published: August 2023

Nitrous oxide (N2O) emissions are a major source of gaseous nitrogen loss, causing environmental pollution. The low organic content in the Loess Plateau region, coupled with the high fertilizer demand of maize, further exacerbates these N losses. N fertilizers play a primary role in N2O emissions by influencing soil denitrifying bacteria, however, the underlying microbial mechanisms that contribute to N2O emissions have not been fully explored. Therefore, the research aimed to gain insights into the intricate relationships between N fertilization, soil denitrification, N2O emissions, potential denitrification activity (PDA), and maize nitrogen use efficiency (NUE) in semi-arid regions. Four nitrogen (N) fertilizer rates, namely N0, N1, N2, and N3 (representing 0, 100, 200, and 300 kg ha−1 yr.−1, respectively) were applied to maize field. The cumulative N2O emissions were 32 and 33% higher under N2 and 37 and 39% higher under N3 in the 2020 and 2021, respectively, than the N0 treatment. N fertilization rates impacted the abundance, composition, and network of soil denitrifying communities (nirS and nosZ) in the bulk and rhizosphere soil. Additionally, within the nirS community, the genera Cupriavidus and Rhodanobacter were associated with N2O emissions. Conversely, in the nosZ denitrifier, the genera Azospirillum, Mesorhizobium, and Microvirga in the bulk and rhizosphere soil reduced N2O emissions. Further analysis using both random forest and structural equation model (SEM) revealed that specific soil properties (pH, NO3−-N, SOC, SWC, and DON), and the presence of nirS-harboring denitrification, were positively associated with PDA activities, respectively, and exhibited a significant association to N2O emissions and PDA activities but expressed a negative effect on maize NUE. However, nosZ-harboring denitrification showed an opposite trend, suggesting different effects on these variables. Our findings suggest that N fertilization promoted microbial growth and N2O emissions by increasing the abundance of nirS and nosZ denitrifiers and altering the composition of their communities. This study provides new insights into the relationships among soil microbiome, maize productivity, NUE, and soil N2O emissions in semi-arid regions.
A method for temporal-spatial multivariate genomic analysis of acute wound healing via tissue stratification: a porcine negative pressure therapy pilot study
Authors: Hodge Jacob G. , Gunewardena Sumedha , Korentager Richard A. , Zamierowski David S. , Robinson Jennifer L. , Mellott Adam J.
Published: August 2023

Introduction: Wound therapies are capable of modulating the complex molecular signaling profile of tissue regeneration. However traditional, bulk tissue analysis results in nonspecific expressional profiles and diluted signaling that lacks temporal-spatial information.

Methods: An acute incisional porcine wound model was developed in the context of negative pressure wound therapy (NPWT). Dressing materials were inserted into wounds with or without NPWT exposure and evaluated over 8-hours. Upon wound explantation, tissue was stratified and dissected into the epidermis, dermis, or subcutaneous layer, or left undissected as a bulk sample and all groups processed for RNAseq. RNAseq of stratified layers provided spatial localization of expressional changes within defined tissue regions, including angiogenesis, inflammation, and matrix remodeling.

Results: Different expressional profiles were observed between individual tissue layers relative to each other within a single wound group and between each individual layer relative to bulk analysis. Tissue stratification identified unique differentially expressed genes within specific layers of tissue that were hidden during bulk analysis, as well as amplification of weak signals and/or inversion of signaling between two layers of the same wound, suggesting that two layers of skin can cancel out signaling within bulk analytical approaches.

Discussion: The unique wound stratification and spatial RNAseq approach in this study provides a new methodology to observe expressional patterns more precisely within tissue that may have otherwise not been detectable. Together these experimental data offer novel insight into early expressional patterns and genomic profiles, within and between tissue layers, in wound healing pathways that could potentially help guide clinical decisions and improve wound outcomes.
The role of sperm-specific glyceraldehyde-3-phosphate dehydrogenase in the development of pathologies—from asthenozoospermia to carcinogenesis
Authors: Naletova Irina , Schmalhausen Elena , Tomasello Barbara , Pozdyshev Denis , Attanasio Francesco , Muronetz Vladimir
Published: August 2023

The review considers various aspects of the influence of the glycolytic enzyme, sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDS) on the energy metabolism of spermatozoa and on the occurrence of several pathologies both in spermatozoa and in other cells. GAPDS is a unique enzyme normally found only in mammalian spermatozoa. GAPDS provides movement of the sperm flagellum through the ATP formation in glycolytic reactions. Oxidation of cysteine residues in GAPDS results in inactivation of the enzyme and decreases sperm motility. In particular, reduced sperm motility in diabetes can be associated with GAPDS oxidation by superoxide anion produced during glycation reactions. Mutations in GAPDS gene lead in the loss of motility, and in some cases, disrupts the formation of the structural elements of the sperm flagellum, in which the enzyme incorporates during spermiogenesis. GAPDS activation can be used to increase the spermatozoa fertility, and inhibitors of this enzyme are being tried as contraceptives. A truncated GAPDS lacking the N-terminal fragment of 72 amino acids that attaches the enzyme to the sperm flagellum was found in melanoma cell lines and then in specimens of melanoma and other tumors. Simultaneous production of the somatic form of GAPDH and sperm-specific GAPDS in cancer cells leads to a reorganization of their energy metabolism, which is accompanied by a change in the efficiency of metastasis of certain forms of cancer. Issues related to the use of GAPDS for the diagnosis of cancer, as well as the possibility of regulating the activity of this enzyme to prevent metastasis, are discussed.
Clinical features of progressive supranuclear palsy
Authors: Wen Yafei , Yang Qijie , Jiao Bin , Zhang Weiwei , Lin Jingyi , Zhu Yuan , Xu Qian , Zhou Hui , Weng Ling , Liao Xinxin , Zhou Yafang , Wang Junling , Guo Jifeng , Yan Xinxiang , Jiang Hong , Tang Beisha , Shen Lu
Published: August 2023

Background

Progressive supranuclear palsy (PSP) is a clinically heterogenous atypical parkinsonian syndrome. Therefore, early recognition and correct diagnosis of PSP is challenging but essential. This study aims to characterize the clinical manifestations, magnetic resonance imaging (MRI), and longitudinal MRI changes of PSP in China.

Method

Clinical and MRI presentations were compared among 150 cases with PSP. Then the longitudinal MRI changes among 20 patients with PSP were further explored. Additionally, a series of midbrain-based MRI parameters was compared between PSP-P and PD.

Results

Throughout the course of the disease, there were differences in the symptoms of the fall and hand tremor between the PSP-RS and PSP-P. There were significant differences in the six midbrain-based MRI parameters between the PSP-RS and the PSP-P, including hummingbird sign, midbrain diameter, midbrain to pons ratio (MTPR), midbrain area, midbrain area to pons area ratio (Ma/Pa), and midbrain tegmental length (MBTegm). Longitudinal MRI studies revealed that the annual rel.ΔMTPR and rel.Δ (Ma/Pa) for PSP were 5.55 and 6.52%, respectively; additionally, PSP-RS presented a higher decline rate than PSP-P. Moreover, MTPR ≤0.56, midbrain diameter ≤ 0.92, midbrain area ≤ 1.00, and third ventricle width ≤ 0.75 could identify PSP-P from PD.

Conclusion

PSP-P differs from PSP-RS regarding clinical manifestations, MRI, and longitudinal MRI changes. MRI parameters could be potential imaging markers to identify PSP-P from PD.
The neurophysiological basis of stress and anxiety - comparing neuronal diversity in the bed nucleus of the stria terminalis (BNST) across species
Authors: van de Poll Yana , Cras Yasmin , Ellender Tommas J.
Published: August 2023

The bed nucleus of the stria terminalis (BNST), as part of the extended amygdala, has become a region of increasing interest regarding its role in numerous human stress-related psychiatric diseases, including post-traumatic stress disorder and generalized anxiety disorder amongst others. The BNST is a sexually dimorphic and highly complex structure as already evident by its anatomy consisting of 11 to 18 distinct sub-nuclei in rodents. Located in the ventral forebrain, the BNST is anatomically and functionally connected to many other limbic structures, including the amygdala, hypothalamic nuclei, basal ganglia, and hippocampus. Given this extensive connectivity, the BNST is thought to play a central and critical role in the integration of information on hedonic-valence, mood, arousal states, processing emotional information, and in general shape motivated and stress/anxiety-related behavior. Regarding its role in regulating stress and anxiety behavior the anterolateral group of the BNST (BNSTALG) has been extensively studied and contains a wide variety of neurons that differ in their electrophysiological properties, morphology, spatial organization, neuropeptidergic content and input and output synaptic organization which shape their activity and function. In addition to this great diversity, further species-specific differences are evident on multiple levels. For example, classic studies performed in adult rat brain identified three distinct neuron types (Type I-III) based on their electrophysiological properties and ion channel expression. Whilst similar neurons have been identified in other animal species, such as mice and non-human primates such as macaques, cross-species comparisons have revealed intriguing differences such as their comparative prevalence in the BNSTALG as well as their electrophysiological and morphological properties, amongst other differences. Given this tremendous complexity on multiple levels, the comprehensive elucidation of the BNSTALG circuitry and its role in regulating stress/anxiety-related behavior is a major challenge. In the present Review we bring together and highlight the key differences in BNSTALG structure, functional connectivity, the electrophysiological and morphological properties, and neuropeptidergic profiles of BNSTALG neurons between species with the aim to facilitate future studies of this important nucleus in relation to human disease.