bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of Pine Disease Susceptibility Under Experimental Climate Change
Authors: Ghosh Soumya K. , Slot Jason C. , Visser Erik A. , Naidoo Sanushka , Sovic Michael G. , Conrad Anna O. , Kyre Bethany , Vijayakumar Vinod , Bonello Pierluigi
Published: June 2022

Climate change (CC) conditions projected for many temperate areas of the world, expressed by way of excessive temperatures and low water availability, will impact forest health directly by means of abiotic stress but also by predisposing trees to pathogenic attack. However, we do not yet know how such environmental conditions alter the physiology and metabolism of trees to render them more susceptible to pathogens. To explore these mechanisms, we conditioned 3-year-old Austrian pine saplings to a simulated CC environment (combined drought and elevated temperatures), followed by pathogenic inoculation with two sister fungal species characterized by contrasting aggressiveness, Diplodia sapinea (aggressive) and D. scrobiculata (less aggressive). Lesion lengths resulting from infection were measured after 3 weeks to determine phenotypes, while dual transcriptomics analysis was conducted on tissues collected from the margins of developing lesions on separate branches 72 h post inoculation. As expected, climate change conditions enhanced host susceptibility to the less aggressive pathogen, D. scrobiculata, to a level that was not statistically different from the more aggressive D. sapinea. Under controlled climate conditions, D. sapinea induced suppression of critical pathways associated with host nitrogen and carbon metabolism, while enhancing its own carbon assimilation. This was accompanied by suppression of host defense-associated pathways. In contrast, D. scrobiculata infection induced host nitrogen and fatty acid metabolism as well as host defense response. The CC treatment, on the other hand, was associated with suppression of critical host carbon and nitrogen metabolic pathways, alongside defense associated pathways, in response to either pathogen. We propose a new working model integrating concurrent host and pathogen responses, connecting the weakened host phenotype under CC treatment with specific metabolic compartments. Our results contribute to a richer understanding of the mechanisms underlying the oft-observed increased susceptibility to fungal infection in trees under conditions of low water availability and open new areas of investigation to further integrate our knowledge in this critical aspect of tree physiology and ecology.
Tumor Suppressor 4.1N/EPB41L1 is Epigenetic Silenced by Promoter Methylation and MiR-454-3p in NSCLC
Authors: Yang Qin , Zhu Lin , Ye Mao , Zhang Bin , Zhan Peihe , Li Hui , Zou Wen , Liu Jing
Published: June 2022

Non–small-cell lung cancer (NSCLC) is divided into three major histological types, namely, lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and large-cell lung carcinoma (LCLC). We previously identified that 4.1N/EPB41L1 acts as a tumor suppressor and is reduced in NSCLC patients. In the current study, we explored the underlying epigenetic mechanisms of 4.1N/EPB41L1 reduction in NSCLC. The 4.1N/EPB41L1 gene promoter region was highly methylated in LUAD and LUSC patients. LUAD patients with higher methylation level in the 4.1N/EPB41L1 gene promoter (TSS1500, cg13399773 or TSS200, cg20993403) had a shorter overall survival time (Log-rank p = 0.02 HR = 1.509 or Log-rank p = 0.016 HR = 1.509), whereas LUSC patients with higher methylation level in the 4.1N/EPB41L1 gene promoter (TSS1500 cg13399773, TSS1500 cg07030373 or TSS200 cg20993403) had a longer overall survival time (Log-rank p = 0.045 HR = 0.5709, Log-rank p = 0.018 HR = 0.68 or Log-rank p = 0.014 HR = 0.639, respectively). High methylation of the 4.1N/EPB41L1 gene promoter appeared to be a relatively early event in LUAD and LUSC. DNA methyltransferase inhibitor 5-Aza-2′-deoxycytidine restored the 4.1N/EPB41L1 expression at both the mRNA and protein levels. MiR-454-3p was abnormally highly expressed in NSCLC and directly targeted 4.1N/EPB41L1 mRNA. MiR-454-3p expression was significantly correlated with 4.1N/EPB41L1 expression in NSCLC patients (r = −0.63, p < 0.0001). Therefore, we concluded that promoter hypermethylation of the 4.1N/EPB41L1 gene and abnormally high expressed miR-454-3p work at different regulation levels but in concert to restrict 4.1N/EPB41L1 expression in NSCLC. Taken together, this work contributes to elucidate the underlying epigenetic disruptions of 4.1N/EPB41L1 deficiency in NSCLC.
Association of Vitamin D Anabolism-Related Gene Polymorphisms and Susceptibility to Uterine Leiomyomas
Authors: Xie Shangdan , Jiang Mengying , Liu Hejing , Xue Fang , Chen Xin , Zhu Xueqiong
Published: June 2022

Background: Uterine leiomyomas (ULs) is the most common gynecological benign tumor in women. Our previous study showed that the phenomenon of vitamin D deficiency existed in patients with ULs. However, the association of vitamin D anabolism-related gene polymorphisms and susceptibility to ULs was unclear.

Methods: Vitamin D anabolism-related gene polymorphisms in 110 patients with ULs and 110 healthy controls were detected by sequencing and the differences of the 92 SNPs were analyzed in the two groups via chi-square test. To verify the association between the significantly different SNPs and the risk of ULs, the SNPs were genotyped in another 340 patients and 340 healthy controls. Additionally, an unconditional logistic regression model was conducted to calculate the odds ratio (OR) of ULs occurrence and the 95% confidence interval (CI), adjusting for age and BMI.

Findings: In sequencing samples, there were differences in DHCR7 rs1044482 C > T (p = 0.008) and NADSYN1 rs2276360 G > C (p = 0.025) between patients with ULs and healthy controls. DHCR7 rs1044482 was related to the susceptibility to ULs in validation samples (heterogeneous: adjusted OR = 1.967, p = 0.002; homogenous: adjusted OR = 2.494, p = 0.002; additive: adjusted OR = 1.485, p < 0.041; and dominant: adjusted OR = 2.084, p < 0.001). Stratified analysis further showed that the DHCR7 rs1044482 polymorphisms were associated with ULs risks in women over 40 and with 18.5–25.0 BMI. In contrast to the wild-type CG haplotype vectors, individuals with TC haplotypes had a higher risk of developing ULs.

Interpretation: The vitamin D anabolism-related gene DHCR7 rs1044482 C > T polymorphism was a risk factor of ULs, especially in patients over 40 with 18.5–25.0 BMI, while the relationship between NADSYN1 rs2276360 and ULs risk was not clear.
A Necroptosis-Related lncRNA Signature Predicts Prognosis and Indicates the Immune Microenvironment in Soft Tissue Sarcomas
Authors: Liu Binfeng , Liu Zhongyue , Feng Chengyao , Tu Chao
Published: June 2022

Background: The necroptosis and long noncoding RNA (lncRNA) are critical in the occurrence and development of malignancy, while the association between the necroptosis-related lncRNAs (NRlncRNAs) and soft tissue sarcoma (STS) remains controversial. Therefore, the present study aims to construct a novel signature based on NRlncRNAs to predict the prognosis of STS patients and investigate its possible role.

Methods: The transcriptome data and clinical characteristics were extracted from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression database (GTEx). A novel NRlncRNA signature was established and verified by the COX regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Subsequently, the K-M survival analysis, ROC, univariate, multivariate Cox regression analysis, and nomogram were used to evaluate the predictive value of the signature. Also, a variety of bioinformatic analysis algorithms explored the differences between the potential mechanism, tumor immune status, and drug sensitivity in the two-risk group. Finally, the RT-qPCR was performed to evaluate the expression of signature NRlncRNAs.

Results: A novel signature consisting of seven NRlncRNAs was successfully established and verified with stable prediction performance and general applicability for STS. Next, the GSEA showed that the patients in the high-risk group were mainly enriched with tumor-related pathways, while the low-risk patients were significantly involved in immune-related pathways. In parallel, we found that the STS patients in the low-risk group had a better immune status than that in the high-risk group. Additionally, there were significant differences in the sensitivity to anti-tumor agents between the two groups. Finally, the RT-qPCR results indicated that these signature NRlncRNAs were abnormally expressed in STS.

Conclusion: To the best of our knowledge, it is the first study to construct an NRlncRNA signature for STS. More importantly, the novel signature displays stable value and translational potential for predicting prognosis, tumor immunogenicity, and therapeutic response in STS.
Genome-Wide Identification and Expression Analysis Elucidates the Potential Role of PFK Gene Family in Drought Stress Tolerance and Sugar Metabolism in Cotton
Authors: Mehari Teame Gereziher , Xu Yanchao , Umer Muhammad Jawad , Hui Fang , Cai Xiaoyan , Zhou Zhongli , Hou Yuqing , Wang Kai , Wang Baohua , Liu Fang
Published: June 2022

Drought has been identified as a major threat for global crop production worldwide. Phosphofructokinase (PFK) is vital for sugar metabolism. During phosphorylation, plants have two enzymes: ATP-dependent phosphofructokinase (PFK) and pyrophosphate-dependent fructose-6-phosphate phosphotransferase (PFP). Genome-wide identification led to the identification of 80 PFK genes, 26 genes in G. hirsutum and G. barbadense, and 14 genes in G. arboreum and G. raimondii. Phylogenetic, gene structure, and motif analyses showed that PFK genes were grouped into two main categories, namely, PFK and PFP, with 18 and 8 genes in the allotetraploid species and 10 PFK and 4 PFP genes in the diploid species, respectively. Using the RNA-seq expressions of 26 genes from GhPFK, a co-expression network analysis was performed to identify the hub genes. GhPFK04, GhPFK05, GhPFK09, GhPFK11, GhPFK13, GhPFK14, and GhPFK17 in leaves and GhPFK02, GhPFK09, GhPFK11, GhPFK15, GhPFK16, and GhPFK17 in root tissues were found as hub genes. RT-qPCR analysis validated the expressions of identified hub genes. Interestingly, GhPFK11 and GhPFK17 were identified as common hub genes, and these might be the true candidate genes involved in the drought stress tolerance. In the KEGG enrichment analysis, amino acids such as L-valine, L-histidine, L-glutamine, L-serine, L-homoserine, L-methionine, L-cysteine, and gluconic acid were significantly upregulated, whereas sugars, mainly fructose-1-phosphate, D-mannitol, D-sorbitol, dulcitol, and lactose, were significantly downregulated during drought stress. Genome-wide analysis paves the way for a deeper understanding of the PFK genes and establishes the groundwork for future research into PFK’s role in enhancing drought stress tolerance and sugar metabolism in cotton.
MRSA Infection in the Thigh Muscle Leads to Systemic Disease, Strong Inflammation, and Loss of Human Monocytes in Humanized Mice
Authors: Hung Sophia , Dreher Liane , Diessner Joachim , Schwarz Stefan , Ohlsen Knut , Hertlein Tobias
Published: June 2022

MRSA (Methicillin-resistant Staphylococcus aureus) is the second-leading cause of deaths by antibiotic-resistant bacteria globally, with more than 100,000 attributable deaths annually. Despite the high urgency to develop a vaccine to control this pathogen, all clinical trials with pre-clinically effective candidates failed so far. The recent development of “humanized” mice might help to edge the pre-clinical evaluation closer to the clinical situation and thus close this gap. We infected humanized NSG mice (huNSG: (NOD)-scid IL2Rγnull mice engrafted with human CD34+ hematopoietic stem cells) locally with S. aureus USA300 LAC* lux into the thigh muscle in order to investigate the human immune response to acute and chronic infection. These mice proved not only to be more susceptible to MRSA infection than wild-type or “murinized” mice, but displayed furthermore inferior survival and signs of systemic infection in an otherwise localized infection model. The rate of humanization correlated directly with the severity of disease and survival of the mice. Human and murine cytokine levels in blood and at the primary site of infection were strongly elevated in huNSG mice compared to all control groups. And importantly, differences in human and murine immune cell lineages surfaced during the infection, with human monocyte and B cell numbers in blood and bone marrow being significantly reduced at the later time point of infection. Murine monocytes in contrast behaved conversely by increasing cell numbers. This study demonstrates significant differences in the in vivo behavior of human and murine cells towards S. aureus infection, which might help to sharpen the translational potential of pre-clinical models for future therapeutic approaches.
The Translational Potential of Microglia and Monocyte-Derived Macrophages in Ischemic Stroke
Authors: Wicks Elizabeth E. , Ran Kathleen R. , Kim Jennifer E. , Xu Risheng , Lee Ryan P. , Jackson Christopher M.
Published: June 2022

The immune response to ischemic stroke is an area of study that is at the forefront of stroke research and presents promising new avenues for treatment development. Upon cerebral vessel occlusion, the innate immune system is activated by danger-associated molecular signals from stressed and dying neurons. Microglia, an immune cell population within the central nervous system which phagocytose cell debris and modulate the immune response via cytokine signaling, are the first cell population to become activated. Soon after, monocytes arrive from the peripheral immune system, differentiate into macrophages, and further aid in the immune response. Upon activation, both microglia and monocyte-derived macrophages are capable of polarizing into phenotypes which can either promote or attenuate the inflammatory response. Phenotypes which promote the inflammatory response are hypothesized to increase neuronal damage and impair recovery of neuronal function during the later phases of ischemic stroke. Therefore, modulating neuroimmune cells to adopt an anti-inflammatory response post ischemic stroke is an area of current research interest and potential treatment development. In this review, we outline the biology of microglia and monocyte-derived macrophages, further explain their roles in the acute, subacute, and chronic stages of ischemic stroke, and highlight current treatment development efforts which target these cells in the context of ischemic stroke.
Post-Translational Modifications of Proteins in Cytosolic Nucleic Acid Sensing Signaling Pathways
Authors: Deng Yu , Wang Ying , Li Lupeng , Miao Edward A. , Liu Pengda
Published: June 2022

The innate immune response is the first-line host defense against pathogens. Cytosolic nucleic acids, including both DNA and RNA, represent a special type of danger signal to initiate an innate immune response. Activation of cytosolic nucleic acid sensors is tightly controlled in order to achieve the high sensitivity needed to combat infection while simultaneously preventing false activation that leads to pathologic inflammatory diseases. In this review, we focus on post-translational modifications of key cytosolic nucleic acid sensors that can reversibly or irreversibly control these sensor functions. We will describe phosphorylation, ubiquitination, SUMOylation, neddylation, acetylation, methylation, succinylation, glutamylation, amidation, palmitoylation, and oxidation modifications events (including modified residues, modifying enzymes, and modification function). Together, these post-translational regulatory modifications on key cytosolic DNA/RNA sensing pathway members reveal a complicated yet elegantly controlled multilayer regulator network to govern innate immune activation.
Loss of Gut Barrier Integrity In Lupus
Authors: Ma Longhuan , Morel Laurence
Published: June 2022

Systemic Lupus Erythematosus is a complex autoimmune disease and its etiology remains unknown. Increased gut permeability has been reported in lupus patients, yet whether it promotes or results from lupus progression is unclear. Recent studies indicate that an impaired intestinal barrier allows the translocation of bacteria and bacterial components into systemic organs, increasing immune cell activation and autoantibody generation. Indeed, induced gut leakage in a mouse model of lupus enhanced disease characteristics, including the production of anti-dsDNA antibody, serum IL-6 as well as cell apoptosis. Gut microbiota dysbiosis has been suggested to be one of the factors that decreases gut barrier integrity by outgrowing harmful bacteria and their products, or by perturbation of gut immune homeostasis, which in turn affects gut barrier integrity. The restoration of microbial balance eliminates gut leakage in mice, further confirming the role of microbiota in maintaining gut barrier integrity. In this review, we discuss recent advances on the association between microbiota dysbiosis and leaky gut, as well as their influences on the progression of lupus. The modifications on host microbiota and gut integrity may offer insights into the development of new lupus treatment.
A Novel PD-L1-Containing MSLN Targeting Vaccine for Lung Cancer Immunotherapy
Authors: Zeng Wuyi , Pan Jiayi , Fang Zixuan , Jia Jiangtao , Zhang Rong , He Menghua , Zhong Hanyu , He Jiashan , Yang Xinyu , Shi Yi , Zhong Bei , Zeng Jun , Fu Bishi , Huang Maoping , Liu Hui
Published: June 2022

Therapeutic tumor vaccines have become an important breakthrough in the treatment of various solid tumors including lung cancer. Dendritic cells (DCs)-based tumor vaccines targeting tumor-associated antigens (TAAs) play a key role in immunotherapy and immunoprevention. However, the weak immunogenicity of TAAs and low immune response rates are a major challenge faced in the application of therapeutic tumor vaccines. Here, we tested whether targeting an attractive target Mesothelin (MSLN) and PD-L1 immune checkpoint molecule to DCs in vivo would elicit therapeutic antitumor cytotoxic T lymphocyte (CTL) response. We generated specific MSLN fragment combined with PD-L1 and GM-CSF peptide immunogen (MSLN-PDL1-GMCSF) based on the novel anti-PD-L1 vaccination strategy we recently developed for the cancer treatment and prevention. We found that DCs loaded with MSLN-PDL1-GMCSF vaccine elicited much stronger endogenous anti-PD-L1 antibody and T cell responses in immunized mice and that antigen specific CTLs had cytolytic activities against tumor cells expressing both MSLN and PD-L1. We demonstrated that vaccination with MSLN-PDL1-GMCSF potently inhibited the tumor growth of MSLN+ and PD-L1+ lung cancer cells, exhibiting a significant therapeutic anti-tumor potential. Furthermore, PD-1 blockade further improved the synergistic antitumor therapeutic efficacy of MSLN-PDL1-GMCSF vaccine in immunized mice. In summary, our data demonstrated for the first time that this PD-L1-containing MSLN therapeutic vaccine can induce persistent anti-PD-L1 antibody and CTL responses, providing an effective immunotherapeutic strategy for lung cancer immunotherapy by combining MSLN-PDL1-GMCSF vaccine and PD-1 blockade.
Blood-Cell-Based Inflammatory Markers as a Useful Tool for Early Diagnosis in Colorectal Cancer
Authors: Hernandez-Ainsa Maria , Velamazan Raul , Lanas Angel , Carrera-Lasfuentes Patricia , Piazuelo Elena
Published: June 2022

Background

Systemic inflammation seems to be involved in the pathogenetic pathways of colorectal cancer (CRC). Analytical markers that reflect the inflammatory status, such as neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) or systemic immune-inflammation index (SII), have been proposed as tools for the prognosis of CRC. Nevertheless, their use for diagnosis has been scarcely investigated.

Aims

To analyze the ability of these markers and of a new marker combining SII and hemoglobin concentration, named NP/LHb = [neutrophils x platelets]/[lymphocytes x hemoglobin], as tools for CRC diagnosis. Furthermore, we studied their association with CRC-related variables.

Methods

Case-control study including 214 CRC patients and 214 controls without CRC, matched by age (±5 years) and sex. We collected demographic, CRC-related and laboratory variables to calculate NLR, PLR, SII, and NP/LHb. In the case group, the laboratory variables were collected at two different period times, 6 months (IQR 4–8) before the CRC diagnosis and at the time of the diagnosis. ROC analysis was performed to evaluate the discriminatory accuracy of each index and we calculated Se, Sp, PPV, NPV, and OR to identify the diagnostic performance of each positive marker.

Results

NP/LHb showed high Sp (92.06%) and PPV (87.50%) to diagnose patients with CRC. This index exhibited an OR of 14.52 (8.26–25.52) and the best area under the curve (AUC: 0.78) for a positive CRC diagnosis. We found significant differences in all indices according to the presence of CRC, observing the highest values in CRC patients at time of diagnosis, in comparison with the analysis performed in the previous months to diagnosis or with control patients. There were significant differences in all ratios according to TNM stages (p < 0.05). PLR, SII and NP/LHb (but not NLR) showed significant differences according to tumor location (p < 0.05). Right-sided colon cancers presented the highest values, in comparison with left-sided and rectal cancers.

Conclusions

Systemic inflammatory cell ratios (especially NP/LHb) change over time with the development of CRC, so they could be useful in its early diagnosis. We suggest that they could be routinely measured in patients with suspicion of CRC, to identify those ones with a higher risk of cancer, considering the high positive predictive value they have shown in our study.
Giant Cell Arteritis Presenting With Ocular Symptoms: Clinical Characteristics and Multimodal Imaging in a Chinese Case Series
Authors: Chen Qian , Chen Weimin , Feng Chaoyi , Gong Deshan , Zhang Jiong , Bi Yingwen , Sun Ping , Sun Xinghuai , Tian Guohong
Published: June 2022

Purpose

To evaluate demographic and clinical characteristics of a Chinese population with giant cell arteritis using multimodal imaging focusing on ophthalmic examinations.

Design

Retrospective observational case series.

Materials and Methods

In the neuro-ophthalmology division of the Eye, Ear, Nose, and Throat Hospital, Shanghai, we evaluated the demographic and clinical characteristics of patients diagnosed with giant cell arteritis between January 2016 and June 2021. Results of routine ophthalmic examinations including fundus examination, optical coherence tomography, color duplex ultrasonography of ocular and superficial temporal arteries, orbital magnetic resonance imaging, and superficial temporal artery biopsy were evaluated.

Results

A total of 15 patients (22 eyes; ten male and five female) were evaluated with a mean age of 77.0 ± 8.5 years. Among them, seven had bilateral involvement that occurred simultaneously or sequentially. Twelve patients presented with arteritic anterior ischemic optic neuropathy, two with arteritic anterior ischemic optic neuropathy combined with cilioretinal artery occlusion, and one with cotton-wool spots. In acute stages of optic neuropathy and retinopathy, optical coherence tomography revealed optic disc edema, thickening of the inner retinal nerve fiber layer and ganglion cell layer, and loss of layer structure. In late stages, optical coherence tomography revealed diffuse atrophy of the inner retina. The “halo” sign was observed in 12 patients in the superficial temporal artery ultrasound, and seven out of eight patients who underwent biopsy demonstrated classic giant cell arteritis pathological changes. Most patients having poor visual acuity but ability to perceive light; 10/22 eyes had permanent vision loss.

Conclusion

Although rare in Asians, giant cell arteritis may be underdiagnosed among elderly Chinese patients presenting with anterior ischemic optic neuropathy. Non-invasive superficial temporal artery ultrasound detecting inflammatory thickening of the intima as the “halo” sign combined with routine elevated erythrocyte sedimentation rate and C-reactive protein may be helpful in diagnosing patients with a high probability of having giant cell arteritis.
Gut Microbiota Shifting in Irritable Bowel Syndrome: The Mysterious Role of Blastocystis sp.
Authors: Olyaiee Alireza , Sadeghi Amir , Yadegar Abbas , Mirsamadi Elnaz Sadat , Mirjalali Hamed
Published: June 2022

Irritable bowel syndrome (IBS) is a chronic disorder, which its causative agent is not completely clear; however, the interaction between microorganisms and gastrointestinal (GI) epithelial cells plays a critical role in the development of IBS and presenting symptoms. During recent decades, many studies have highlighted the high prevalence of Blastocystis sp. in patients with IBS and suggested a probable role for this protist in this disease. Recent studies have documented changes in the gut microbiota composition in patients with IBS regarding the presence of Blastocystis sp., but it is not clear that either disturbance of the gut during GI disorders is a favorable condition for Blastocystis sp. colonization or the presence of this protist may lead to alteration in the gut microbiota in IBS patients. In this review, we comprehensively gather and discuss scientific findings covering the role of Blastocystis sp. in IBS via gut microbiota shifting.
Predicting Preeclampsia Pregnancy Termination Time Using sFlt-1
Authors: Tanaka Hiroaki , Tanaka Kayo , Takakura Sho , Enomoto Naosuke , Ikeda Tomoaki
Published: June 2022

Background

The aim of this study was to determine the usefulness of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in predicting the time for pregnancy termination in pregnant women with known preeclampsia (PE) onset.

Methods

Forty-four pregnant women diagnosed with PE (22 weeks 0 days to 33 weeks 6 days gestation) were included in this study. The levels of sFlt-1 and PlGF, and the sFlt-1/PlGF ratio were compared between the women that delivered in <24 h (T group) and those that delivered in more than 24 h (P group), and between women that delivered in <1 week (T group) and those that delivered in more than 1 week (P group). Cutoff values were calculated for the three markers that were the most significantly correlated with predicting pregnancy termination at <24 h and <1 week.

Results

Among sFlt-1, PlGF, and sFlt-1/PlGF, sFlt-1 was the most significantly associated with the timing of pregnancy termination. sFlt-1 cutoff values of 8682.1 pg/ml (AUC 0.71; 95%Cl, 0.5191–0.9052) and 7,394.5 pg/ml (AUC 0.78; 0.78, 95%Cl, 0.6394–0.9206) for delivery in <24 h and delivery within 1 week, respectively, were important predictive values. The positive predictive value for delivery within 24 h was 43.9%, with a sensitivity of 72.3% and specificity of 69.0%, when sFlt−1 was <8,682 pg/ml. A sFlt-1 level of 7,394 pg/ml or greater would result in delivery within 1 week, with a positive predictive value of 67.2%; the sensitivity was 79.0% and specificity was 72.0%.

Conclusion

This study showed that sFlt-1 may be effective in predicting the timing of pregnancy termination. However, the number of cases was small and, thus, the results were not definitive. This finding should be researched further in order to predict the optimal timing of pregnancy termination in PE to reduce severe maternal complications.
Relationship Between Invasive Fungal Infection and Hypostatic Pneumonia: A Prospective Cohort Study
Authors: Liu Lin , Liu Chang , Cai Jianrong , Chen Jiayun , Chen Jie , Fu Yuanyuan , Yi Kexin , Wang Hui , Li Xue
Published: June 2022

Background

The short-term mortality of hypostatic pneumonia (HP) is very high, and the treatment outcome is poor. The clinical diagnosis and treatment are primarily focused on bacterial and viral infection, ignoring the role of fungal infection at present. This study aims to validate the relationship between Invasive Fungal Infections (IFI) and HP.

Methods

In the cross-sectional study, a total of 11,371 participants have been enrolled. In the prospective cohort study, 4,441 individuals have been included at baseline and followed up from 2015 to 2019 with a total person years of 8,484.65. The standard procedures were used to assess questionnaire investigations, laboratory testing, and anthropometric indicators. For data analysis, logistic regression, restricted cubic spline, log-rank regression, Cox regression, and linear mixed effects model were applied to assess the relationship between IFI and HP risk longitudinally.

Results

In the cross-sectional study, elevated β-D-Glucan (BDG) concentrations are associated with a higher risk of HP prevalence in the total population, men, and women (ORT3 vs.T1 [95% CIs]: 2.12 [1.55, 2.91]; 2.01 [1.35, 2.99]; 2.34 [1.39, 3.94]), which were verified by a dose–effect relationship in the restricted cubic spline model. In the cohort study, Cox and Log-rank regression showed that the elevated BDG concentrations are associated with a significantly higher risk of HP incidence than participants with lower BDG concentrations (HRT3 vs.T1 [95% CIs]: 2.72 [1.36, 5.43], pLog–rank = 0.0086). During 5 years, the globulin (GLB) and C-reactive protein (CRP) were always on the top in the highest category of BDG concentrations. Between low and high BDG concentration, the total trend of GLB concentration was falling and the total trend of CRP concentration was rising with the increase of years (all the p-values < 0.0001).

Conclusion

In this study, IFI is associated with a higher risk of HP, with time sequence and related mechanisms requiring further investigation in the future.
The State of Microbiology Diagnostic of Prosthetic Joint Infection in Europe: An In-Depth Survey Among Clinical Microbiologists
Authors: Yusuf Erlangga , Roschka Charlotte , Esteban Jaime , Raglio Annibale , Tisler Anna , Willems Philippe , Kramer Tobias Siegfried
Published: June 2022

Background

This study aims to give an overview on how microbiology diagnosis tests of Prosthetic joint infections (PJI) is performed in Europe, and to explore whether any factor influences the decision on implementing a test.

Methods

An extensive online survey of clinical microbiologists from seven European countries (Belgium, Estonia, Germany, Italy, Netherlands, Switzerland, and Spain). Following items were assessed: (i). general information on the laboratory, (ii) preference of the laboratory and clinical microbiologists regarding samples, (iii) transportation and (iv) processing of explanted foreign bodies and tissues and synovial fluid, (v) culture media and culture duration, (vi) reporting (identification and susceptibility testing), and (vii) use of molecular microbiology techniques.

Results

Invited were 163 clinical microbiologists. The response rate from each country was above 50% (range 51–78%), except for Germany (36%). Frequent PJI diagnostics were the use of tissue pre-processing (58.1%), culturing synovial fluid in blood culture bottles (45.5%), use of sonication for processing explanted prosthesis (56.8%), reporting the presence of synovial leukocyte counts (67%), use of blood aerobic and anaerobic agar (97.7%), and enrichment media thioglycolate (69.3%). The most common incubation time of the culture media is 7–14 days (34.1–70.5%). The clinicians were called to report the culture results (80.7%), and to give antibiotic recommendation (67%).

Conclusion

There are common practices in processing PJI samples and reporting results, which is promising for harmonization of PJI diagnostic in the future. However, variation in diagnostic tests should also be considered in interpreting and comparing clinical microbiology results.
Influenza A, Influenza B, and SARS-CoV-2 Similarities and Differences – A Focus on Diagnosis
Authors: Havasi Andrei , Visan Simona , Cainap Calin , Cainap Simona Sorana , Mihaila Alin Adrian , Pop Laura-Ancuta
Published: June 2022

In late December 2019, the first cases of viral pneumonia caused by an unidentified pathogen were reported in China. Two years later, SARS-CoV-2 was responsible for almost 450 million cases, claiming more than 6 million lives. The COVID-19 pandemic strained the limits of healthcare systems all across the world. Identifying viral RNA through real-time reverse transcription-polymerase chain reaction remains the gold standard in diagnosing SARS-CoV-2 infection. However, equipment cost, availability, and the need for trained personnel limited testing capacity. Through an unprecedented research effort, new diagnostic techniques such as rapid diagnostic testing, isothermal amplification techniques, and next-generation sequencing were developed, enabling accurate and accessible diagnosis. Influenza viruses are responsible for seasonal outbreaks infecting up to a quarter of the human population worldwide. Influenza and SARS-CoV-2 present with flu-like symptoms, making the differential diagnosis challenging solely on clinical presentation. Healthcare systems are likely to be faced with overlapping SARS-CoV-2 and Influenza outbreaks. This review aims to present the similarities and differences of both infections while focusing on the diagnosis. We discuss the clinical presentation of Influenza and SARS-CoV-2 and techniques available for diagnosis. Furthermore, we summarize available data regarding the multiplex diagnostic assay of both viral infections.
Sporomusa ovata as Catalyst for Bioelectrochemical Carbon Dioxide Reduction: A Review Across Disciplines From Microbiology to Process Engineering
Authors: Madjarov Joana , Soares Ricardo , Paquete Catarina M. , Louro Ricardo O.
Published: June 2022

Sporomusa ovata is a bacterium that can accept electrons from cathodes to drive microbial electrosynthesis (MES) of acetate from carbon dioxide. It is the biocatalyst with the highest acetate production rate described. Here we review the research on S. ovata across different disciplines, including microbiology, biochemistry, engineering, and materials science, to summarize and assess the state-of-the-art. The improvement of the biocatalytic capacity of S. ovata in the last 10 years, using different optimization strategies is described and discussed. In addition, we propose possible electron uptake routes derived from genetic and experimental data described in the literature and point out the possibilities to understand and improve the performance of S. ovata through genetic engineering. Finally, we identify current knowledge gaps guiding further research efforts to explore this promising organism for the MES field.
Evaluation of Antiradical and Antioxidant Activities of Lipopeptides Produced by Bacillus subtilis Strains
Authors: Dussert Elodie , Tourret Mélissa , Dupuis Chloé , Noblecourt Alexandre , Behra-Miellet Josette , Flahaut Christophe , Ravallec Rozenn , Coutte François
Published: June 2022

This study investigated the antiradical and antioxidant potential of the three families of lipopeptides (i.e., surfactin, mycosubtilin, and plipastatin/fengycin) produced by Bacillus subtilis strains. The antiradical/antioxidant activities of highly purified lipopeptides were studied in acellular models using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide anion (O2.-), hydrogen peroxide, (H2O2) and hydroxyl radical (HO.). At a lipopeptide concentration of 500 mg.L−1, the maximum inhibition of DPPH reached 22.88% (obtained for plipastatin). Moreover, the scavenging effects of O2.-, H2O2, and HO. at the highest concentration tested (250 mg.L−1) were found to be 6, 21, and 3% for surfactin, 19, 9, and 15% for mycosubtilin, 21, 18, and 59% for plipastatin, 21, 31, and 61% for the mixture of surfactin/plipastatin, and 13, 16, and 15% for the mixture of surfactin/mycosubtilin, respectively. These results showed that plipastatin was the best candidate due to its antioxidant activities.
PCBP-1 Regulates the Transcription and Alternative Splicing of Inflammation and Ubiquitination-Related Genes in PC12 Cell
Authors: Yusufujiang Aishanjiang , Zeng Shan , Yang Chen , Jing Sha , Yang Lijuan , Li Hongyan
Published: June 2022

PCBP-1, a multifunctional RNA binding protein, is expressed in various human cell/tissue types and involved in post-transcriptional gene regulation. PCBP-1 has important roles in cellular Iron homeostasis, mitochondrial stability, and other cellular activities involved in the pathophysiological process of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD). However, it remains enigmatic whether PCPB-1 is associated with the pathogenesis of PD. In this study, we cloned and constitutively overexpressed PCBP-1 in rat PC12 cells (PC12 cell is the common cell line studying neurodegenerative disease include PD). RNA-seq was performed to analyze PCBP-1-regulated differentially expressed genes (DEGs) and alternative splicing events (ASEs) between control and PCBP1-overexpressed cells. GO and KEGG pathway analyses were performed to identify functional DEGs and alternatively spliced genes. Consequently, we validated PCBP-1-regulated genes using RT-qPCR. Finally, we downloaded CLIP-seq data from GEO (GSE84700) to analyze the mechanisms of PCBP-1’s regulation of gene expression and ASEs by revealing the binding profile of PCBP-1 on its target pre-mRNAs. Overexpression of PCBP-1 partially regulated the ASE and expression of genes enriched in neuroinflammation and protein ubiquitination, which were also associated with PD pathogenesis. Moreover, RT-qPCR assay verified the PCBP-1-modulated expression of neuroinflammatory genes, like LCN-2, and alternative splicing (AS) of ubiquitination-related gene WWP-2. Finally, CLIP-seq data analysis indicated that the first UC motif was the critical site for PCBP-1 binding to its targets. In this study, we provided evidence that PCBP-1 could regulate the expression of LCN-2 gene expression associated with neuroinflammation and AS of WWP-2 in relation to protein ubiquitination. These findings thus provided novel insights into the potential application of PCBP-1 as the disease pathophysiological or therapeutic target for neurodegenerative disease.
Depressive Symptoms Have Distinct Relationships With Neuroimaging Biomarkers Across the Alzheimer’s Clinical Continuum
Authors: Moulinet Inès , Touron Edelweiss , Mézenge Florence , Dautricourt Sophie , De La Sayette Vincent , Vivien Denis , Marchant Natalie L. , Poisnel Géraldine , Chételat Gaël
Published: June 2022

Background

Depressive and anxiety symptoms are frequent in Alzheimer’s disease and associated with increased risk of developing Alzheimer’s disease in older adults. We sought to examine their relationships to Alzheimer’s disease biomarkers across the preclinical and clinical stages of the disease.

Method

Fifty-six healthy controls, 35 patients with subjective cognitive decline and 56 amyloid-positive cognitively impaired patients on the Alzheimer’s continuum completed depression and anxiety questionnaires, neuropsychological tests and neuroimaging assessments. We performed multiple regressions in each group separately to assess within group associations of depressive and anxiety symptoms with either cognition (global cognition and episodic memory) or neuroimaging data (gray matter volume, glucose metabolism and amyloid load).

Results

Depressive symptoms, but not anxiety, were higher in patients with subjective cognitive decline and cognitively impaired patients on the Alzheimer’s continuum compared to healthy controls. Greater depressive symptoms were associated with higher amyloid load in subjective cognitive decline patients, while they were related to higher cognition and glucose metabolism, and to better awareness of cognitive difficulties, in cognitively impaired patients on the Alzheimer’s continuum. In contrast, anxiety symptoms were not associated with brain integrity in any group.

Conclusion

These data show that more depressive symptoms are associated with greater Alzheimer’s disease biomarkers in subjective cognitive decline patients, while they reflect better cognitive deficit awareness in cognitively impaired patients on the Alzheimer’s continuum. Our findings highlight the relevance of assessing and treating depressive symptoms in the preclinical stages of Alzheimer’s disease.
Identifying Depression in Parkinson's Disease by Using Combined Diffusion Tensor Imaging and Support Vector Machine
Authors: Yang Yunjun , Yang Yuelong , Pan Aizhen , Xu Zhifeng , Wang Lijuan , Zhang Yuhu , Nie Kun , Huang Biao
Published: June 2022

Objective

To investigate white matter microstructural alterations in Parkinson's disease (PD) patients with depression using the whole-brain diffusion tensor imaging (DTI) method and to explore the DTI–based machine learning model in identifying depressed PD (dPD).

Methods

The DTI data were collected from 37 patients with dPD and 35 patients with non-depressed PD (ndPD), and 25 healthy control (HC) subjects were collected as the reference. An atlas-based analysis method was used to compare fractional anisotropy (FA) and mean diffusivity (MD) among the three groups. A support vector machine (SVM) was trained to examine the probability of discriminating between dPD and ndPD.

Results

As compared with ndPD, dPD group exhibited significantly decreased FA in the bilateral corticospinal tract, right cingulum (cingulate gyrus), left cingulum hippocampus, bilateral inferior longitudinal fasciculus, and bilateral superior longitudinal fasciculus, and increased MD in the right cingulum (cingulate gyrus) and left superior longitudinal fasciculus-temporal part. For discriminating between dPD and ndPD, the SVM model with DTI features exhibited an accuracy of 0.70 in the training set [area under the receiver operating characteristic curve (ROC) was 0.78] and an accuracy of 0.73 in the test set (area under the ROC was 0.71).

Conclusion

Depression in PD is associated with white matter microstructural alterations. The SVM machine learning model based on DTI parameters could be valuable for the individualized diagnosis of dPD.
Excitatory Repetitive Transcranial Magnetic Stimulation Over the Ipsilesional Hemisphere for Upper Limb Motor Function After Stroke: A Systematic Review and Meta-Analysis
Authors: Tang Zhiqing , Han Kaiyue , Wang Rongrong , Zhang Yue , Zhang Hao
Published: June 2022

Background

Repetitive transcranial magnetic stimulation (rTMS) is a promising therapy to promote recovery of the upper limb after stroke. According to the regulation of cortical excitability, rTMS can be divided into excitatory rTMS and inhibitory rTMS, and excitatory rTMS includes high-frequency rTMS (HF-rTMS) or intermittent theta-burst stimulation (iTBS). We aimed to evaluate the effects of excitatory rTMS over the ipsilesional hemisphere on upper limb motor recovery after stroke.

Methods

Databases of PubMed, Embase, ISI Web of Science, and the Cochrane Library were searched for randomized controlled trials published before 31 December 2021. RCTs on the effects of HF-rTMS or iTBS on upper limb function in patients diagnosed with stroke were included. Two researchers independently screened the literature, extracted the data, and assessed quality. The meta-analysis was performed by using Review Manager Version 5.4 software.

Results

Fifteen studies with 449 participants were included in this meta-analysis. This meta-analysis found that excitatory rTMS had significant efficacy on upper limb motor function (MD = 5.88, 95% CI, 3.32–8.43,P< 0.001), hand strength (SMD = 0.53, 95% CI, 0.04–1.01,P= 0.03), and hand dexterity (SMD = 0.76, 95% CI, 0.39–1.14,P< 0.001). Subgroup analyses based on different types of rTMS showed that both iTBS and HF-rTMS significantly promoted upper limb motor function (iTBS,P< 0.001; HF-rTMS,P< 0.001) and hand dexterity (iTBS,P= 0.01; HF-rTMS,P< 0.001) but not hand strength (iTBS,P= 0.07; HF-rTMS,P= 0.12). Further subgroup analysis based on the duration of illness demonstrated that applying excitatory rTMS during the first 3 months (<1 month,P= 0.01; 1–3 months,P= 0.001) after stroke brought significant improvement in upper limb motor function but not in the patients with a duration longer than 3 months (P= 0.06). We found that HF-rTMS significantly enhanced the motor evoked potential (MEP) amplitude of affected hemisphere (SMD = 0.82, 95% CI, 0.32–1.33,P= 0.001).

Conclusion

Our study demonstrated that excitatory rTMS over the ipsilesional hemisphere could significantly improve upper limb motor function, hand strength, and hand dexterity in patients diagnosed with stroke. Both iTBS and HF-rTMS which could significantly promote upper limb motor function and hand dexterity, and excitatory rTMS were beneficial to upper limb motor function recovery only when applied in the first 3 months after stroke. HF-rTMS could significantly enhance the MEP amplitude of the affected hemisphere. High-quality and large-scale randomized controlled trials in the future are required to confirm our conclusions.

Clinical Trial Registration

www.crd.york.ac.uk/prospero/, identifier: CRD42022312288.
Role of Ca2+/Calmodulin-Dependent Protein Kinase Type II in Mediating Function and Dysfunction at Glutamatergic Synapses
Authors: Mohanan Archana G. , Gunasekaran Sowmya , Jacob Reena Sarah , Omkumar R. V.
Published: June 2022

Glutamatergic synapses harbor abundant amounts of the multifunctional Ca2+/calmodulin-dependent protein kinase type II (CaMKII). Both in the postsynaptic density as well as in the cytosolic compartment of postsynaptic terminals, CaMKII plays major roles. In addition to its Ca2+-stimulated kinase activity, it can also bind to a variety of membrane proteins at the synapse and thus exert spatially restricted activity. The abundance of CaMKII in glutamatergic synapse is akin to scaffolding proteins although its prominent function still appears to be that of a kinase. The multimeric structure of CaMKII also confers several functional capabilities on the enzyme. The versatility of the enzyme has prompted hypotheses proposing several roles for the enzyme such as Ca2+ signal transduction, memory molecule function and scaffolding. The article will review the multiple roles played by CaMKII in glutamatergic synapses and how they are affected in disease conditions.
Hearing Loss in Offspring Exposed to Antiretrovirals During Pregnancy and Breastfeeding
Authors: DeBacker J. Riley , Langenek Breanna , Bielefeld Eric C.
Published: June 2022

Over 27 million people worldwide currently receive daily antiretroviral therapy for the management of HIV/AIDS. In order to prevent the continued spread of HIV, the World Health Organization (WHO) recommends the use of highly active antiretroviral therapy by pregnant and nursing women. There is currently little research into the auditory effects of this therapy on children exposed during pregnancy and breastfeeding, and research to date on the direct effects of antiretroviral exposure on the auditory system is inconclusive. The current study examined the effects of WHO-recommended first-line antiretrovirals in a well-controlled animal model to evaluate the potential for auditory damage and dysfunction following these exposures. Female breeding mice were each exposed to one of four antiretroviral cocktails or a vehicle control once daily during pregnancy and breastfeeding. Offspring of these mice had their auditory status evaluated after weaning using auditory brainstem responses and distortion-product otoacoustic emissions (DPOAEs). Auditory brainstem response thresholds following antiretroviral exposure during gestation and breastfeeding showed elevated thresholds and increased wave latencies in offspring of exposed mice when compared to unexposed controls, but no corresponding decrease in DPOAE amplitude. These differences in threshold were small and so may explain the lack of identified hearing loss in antiretroviral-exposed children during hearing screenings at birth. Minimal degrees of hearing impairment in children have been correlated with decreased academic performance and impaired auditory processing, and so these findings, if also seen in human children, suggest significant implications for children exposed to antiretrovirals during development despite passing hearing screenings at birth.