bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole-Genome Metagenomic Analysis of the Gut Microbiome in HIV-1-Infected Individuals on Antiretroviral Therapy
Authors: Bai Xiangning , Narayanan Aswathy , Nowak Piotr , Ray Shilpa , Neogi Ujjwal , Sönnerborg Anders
Published: June 2021

Gut microbiome plays a significant role in HIV-1 immunopathogenesis and HIV-1-associated complications. Previous studies have mostly been based on 16S rRNA gene sequencing, which is limited in taxonomic resolution at the genus level and inferred functionality. Herein, we performed a deep shotgun metagenomics study with the aim to obtain a more precise landscape of gut microbiome dysbiosis in HIV-1 infection. A reduced tendency of alpha diversity and significantly higher beta diversity were found in HIV-1-infected individuals on antiretroviral therapy (ART) compared to HIV-1-negative controls. Several species, such as Streptococcus anginosus, Actinomyces odontolyticus, and Rothia mucilaginosa, were significantly enriched in the HIV-1-ART group. Correlations were observed between the degree of immunodeficiency and gut microbiome in terms of microbiota composition and metabolic pathways. Furthermore, microbial shift in HIV-1-infected individuals was found to be associated with changes in microbial virulome and resistome. From the perspective of methodological evaluations, our study showed that different DNA extraction protocols significantly affect the genomic DNA quantity and quality. Moreover, whole metagenome sequencing depth affects critically the recovery of microbial genes, including virulome and resistome, while less than 5 million reads per sample is sufficient for taxonomy profiling in human fecal metagenomic samples. These findings advance our understanding of human gut microbiome and their potential associations with HIV-1 infection. The methodological assessment assists in future study design to accurately assess human gut microbiome.
Surfaceome and Exoproteome Dynamics in Dual-Species Pseudomonas aeruginosa and Staphylococcus aureus Biofilms
Authors: Reigada Inés , San-Martin-Galindo Paola , Gilbert-Girard Shella , Chiaro Jacopo , Cerullo Vincenzo , Savijoki Kirsi , Nyman Tuula A. , Fallarero Adyary , Miettinen Ilkka
Published: June 2021

Bacterial biofilms are an important underlying cause for chronic infections. By switching into the biofilm state, bacteria can evade host defenses and withstand antibiotic chemotherapy. Despite the fact that biofilms at clinical and environmental settings are mostly composed of multiple microbial species, biofilm research has largely been focused on single-species biofilms. In this study, we investigated the interaction between two clinically relevant bacterial pathogens (Staphylococcus aureusandPseudomonas aeruginosa) by label-free quantitative proteomics focusing on proteins associated with the bacterial cell surfaces (surfaceome) and proteins exported/released to the extracellular space (exoproteome). The changes observed in the surfaceome and exoproteome ofP. aeruginosapointed toward higher motility and lower pigment production when co-cultured withS. aureus. InS. aureus, lower abundances of proteins related to cell wall biosynthesis and cell division, suggesting increased persistence, were observed in the dual-species biofilm. Complementary phenotypic analyses confirmed the higher motility and the lower pigment production inP. aeruginosawhen co-cultured withS. aureus.Higher antimicrobial tolerance associated with the co-culture setting was additionally observed in both species. To the best of our knowledge, this study is among the first systematic explorations providing insights into the dynamics of both the surfaceome and exoproteome ofS. aureusandP. aeruginosadual-species biofilms.
Synergistic Activity of Colistin Combined With Auranofin Against Colistin-Resistant Gram-Negative Bacteria
Authors: Feng Xiaoxuan , Liu Shuai , Wang Yang , Zhang Yulin , Sun Lingxiao , Li Haibo , Wang Chunlei , Liu Yingmei , Cao Bin
Published: June 2021

Colistin-resistant (Col-R) bacteria are steadily increasing, and are extremely difficult to treat. New drugs or therapies are urgently needed to treat infections caused by these pathogens. Combination therapy with colistin and other old drugs, is an important way to restore the activity of colistin. This study aimed to investigate the activity of colistin in combination with the anti-rheumatic drug auranofin against Col-R Gram-negative bacteria. The results of checkerboard analysis demonstrated that auranofin synergized with colistin against Col-R Gram-negative bacteria. Time-kill assays showed significant synergistic antimicrobial activity of colistin combined with auranofin. Electron microscopy revealed that the combination resulted in more cellular structural alterations compared to each drug alone. Auranofin enhanced the therapeutic effectiveness of colistin in mouse peritoneal infection models. These results suggested that the combination of colistin and auranofin might be a potential alternative for the treatment of Col-R Gram-negative bacterial infections.
Characterization of Supragingival Plaque and Oral Swab Microbiomes in Children With Severe Early Childhood Caries
Authors: de Jesus Vivianne Cruz , Khan Mohd Wasif , Mittermuller Betty-Anne , Duan Kangmin , Hu Pingzhao , Schroth Robert J. , Chelikani Prashen
Published: June 2021

The human oral cavity harbors one of the most diverse microbial communities with different oral microenvironments allowing the colonization of unique microbial species. This study aimed to determine which of two commonly used sampling sites (dental plaque vs. oral swab) would provide a better prediction model for caries-free vs. severe early childhood caries (S-ECC) using next generation sequencing and machine learning (ML). In this cross-sectional study, a total of 80 children (40 S-ECC and 40 caries-free) < 72 months of age were recruited. Supragingival plaque and oral swab samples were used for the amplicon sequencing of the V4-16S rRNA and ITS1 rRNA genes. The results showed significant differences in alpha and beta diversity between dental plaque and oral swab bacterial and fungal microbiomes. Differential abundance analyses showed that, among others, the cariogenic species Streptococcus mutans was enriched in the dental plaque, compared to oral swabs, of children with S-ECC. The fungal species Candida dubliniensis and C. tropicalis were more abundant in the oral swab samples of children with S-ECC compared to caries-free controls. They were also among the top 20 most important features for the classification of S-ECC vs. caries-free in oral swabs and for the classification of dental plaque vs. oral swab in the S-ECC group. ML approaches revealed the possibility of classifying samples according to both caries status and sampling sites. The tested site of sample collection did not change the predictability of the disease. However, the species considered to be important for the classification of disease in each sampling site were slightly different. Being able to determine the origin of the samples could be very useful during the design of oral microbiome studies. This study provides important insights into the differences between the dental plaque and oral swab bacteriome and mycobiome of children with S-ECC and those caries-free.
The Feasibility of Using Virtual Reality and Eye Tracking in Research With Older Adults With and Without Alzheimer's Disease
Authors: Davis Rebecca
Published: June 2021

Aim: To examine the feasibility of using large scale spatial, self-mobile, virtual reality, and eye tracking in older adults with and without Alzheimer's disease (AD).

Methods: Older adults with early stage AD (n = 38) and a control group without AD (n = 50) were asked to find their way in a large, projected VR simulation of a retirement community repeatedly over 10 trials for each of 2 days, while wearing eye tracking glasses. Feasibility measures, including tolerance, side effects, and ability to complete the VR and eye tracking were collected. This study reports the analysis of the feasibility data for the VR and eye tracking and comparison of findings between the groups.

Results: Over 80% of the subjects were able to complete the VR portion of the study. Only four subjects, all in the AD group, could not use the joystick and were excluded. Withdrawal rate (18%) was similar between the groups [X2(2) = 2.82, N = 88, p = 0.245] with most withdrawals occurring after the fourth trial. Simulation sickness was not significantly different between the groups. Only 60% of the subjects had completed eye tracking videos; more subjects in the AD group had complete eye tracking videos than the control group; X2(1) = 7.411, N = 88, p = 0.006. Eye tracking incompletion was primarily due to inability to calibration issues.

Conclusion: Virtual reality testing and eye tracking can be used in older adults with and without AD in a large-scale way-finding task, but that there are some limitations.
Ultrarapid Inflammation of the Olfactory Bulb After Spinal Cord Injury: Protective Effects of the Granulocyte Colony-Stimulating Factor on Early Neurodegeneration in the Brain
Authors: Lin Muh-Shi , Chiu I-Hsiang , Lin Chai-Ching
Published: June 2021

The correlation among olfactory dysfunction, spinal cord injury (SCI), subjective cognitive decline, and neurodegenerative dementia has been established. Impaired olfaction is considered a marker for neurodegeneration. Hence, there is a need to examine if SCI leads to olfactory dysfunction. In this study, the brain tissue of mice with spinal cord hemisection injury was subjected to microarray analysis. The mRNA expression levels of olfactory receptors in the brain began to decline at 8 h post-SCI. SCI promoted neuroinflammation, downregulated the expression of olfactory receptors, decreased the number of neural stem cells (NSCs), and inhibited the production of neurotrophic factors in the olfactory bulbs at 8 h post-SCI. In particular, the SCI group had upregulated mRNA and protein expression levels of glial fibrillary acidic protein (GFAP; a marker of astrocyte reactivation) and pro-inflammatory mediators [IL-1β, IL-6, and Nestin (marker of NSCs)] in the olfactory bulb compared to levels in the sham control group. The mRNA expression levels of olfactory receptors (Olfr1494, Olfr1324, Olfr1241, and Olfr979) and neurotrophic factors [brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and nerve growth factor (NGF)] were downregulated in the olfactory bulb of the SCI group mice at 8 h post-SCI. The administration of granulocyte colony-stimulating factor (G-CSF) mitigated these SCI-induced pathological changes in the olfactory bulb at 8 h post-SCI. These results indicate that the olfactory bulb is vulnerable to environmental damage even if the lesion is located at sites distant from the brain, such as the spinal cord. Additionally, SCI initiated pathological processes, including inflammatory response, and impaired neurogenesis, at an early stage. The findings of this study will provide a basis for future studies on pathological mechanisms of early neurodegenerative diseases involving the olfactory bulb and enable early clinical drug intervention.
High-Resolution Insights Into the in vitro Developing Blood-Brain Barrier: Novel Morphological Features of Endothelial Nanotube Function
Authors: Mentor Shireen , Fisher David
Published: June 2021

High-resolution electron microscopy (HREM) imaging of the in vitro blood-brain barrier (BBB), is a promising modality for investigating the dynamic morphological interplay underpinning BBB development. The successful establishment of BBB integrity is grounded in the brain endothelial cells (BEC’s) ability to occlude its paracellular spaces of brain capillaries through the expression of the intercellular tight junction (TJ) proteins. The impermeability of these paracellular spaces are crucial in the regulation of transcellular transport systems to achieve homeostasis of the central nervous system. To-date research describing morphologically, the dynamics by which TJ interaction is orchestrated to successfully construct a specialized barrier remains undescribed. In this study, the application of HREM illuminates the novel, dynamic and highly restrictive BEC paracellular pathway which is founded based on lateral membrane alignment which is the functional imperative for the mechanical juxtapositioning of TJ zones that underpin molecular bonding and sealing of the paracellular space. For the first time, we report on the secretion of a basement membrane in vitro, which allow BECs to orientate themselves into distinct basolateral and apicolateral domains and establish a 3-dimensional BEC construct. We report for the first time, on the expression of nanovesicles bound to the plasma membrane surfaces of the BECs. These membrane-bound vesicles are reported to possess an array of DNA/RNA constituents and chemotaxic properties affecting the formation of nanotubes that span the paracellular space between BECs, facilitating BBB construction, alluding to a functional role in mediating cell-to-cell communication. This study suggests that novel, ultrathin nanotubular (NT) structures are involved in functional roles in bringing into alignment the paracellular space of BECs. Immortalized mouse BECs (b.End3, b.End5) and primary rat cardiac microvascular ECs were used to further validate the in vitro BBB model by profiling variances in peripheral EC monolayer development. These cardiac capillary ECs presented with an opposite topographical profile: large fenestra and intercellular spaces, devoid of morphological ultrastructures. This comparative study alludes to the role of NT facilitation in TJ-induced hemifusion of apicolateral BEC membranes, as a structural event forming the basis for establishing a polarized BBB.
Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?
Authors: Boscia Francesca , Elkjaer Maria Louise , Illes Zsolt , Kukley Maria
Published: June 2021

Despite significant advances in our understanding of the pathophysiology of multiple sclerosis (MS), knowledge about contribution of individual ion channels to axonal impairment and remyelination failure in progressive MS remains incomplete. Ion channel families play a fundamental role in maintaining white matter (WM) integrity and in regulating WM activities in axons, interstitial neurons, glia, and vascular cells. Recently, transcriptomic studies have considerably increased insight into the gene expression changes that occur in diverse WM lesions and the gene expression fingerprint of specific WM cells associated with secondary progressive MS. Here, we review the ion channel genes encoding K+, Ca2+, Na+, and Cl−channels; ryanodine receptors; TRP channels; and others that are significantly and uniquely dysregulated in active, chronic active, inactive, remyelinating WM lesions, and normal-appearing WM of secondary progressive MS brain, based on recently published bulk and single-nuclei RNA-sequencing datasets. We discuss the current state of knowledge about the corresponding ion channels and their implication in the MS brain or in experimental models of MS. This comprehensive review suggests that the intense upregulation of voltage-gated Na+channel genes in WM lesions with ongoing tissue damage may reflect the imbalance of Na+homeostasis that is observed in progressive MS brain, while the upregulation of a large number of voltage-gated K+channel genes may be linked to a protective response to limit neuronal excitability. In addition, the altered chloride homeostasis, revealed by the significant downregulation of voltage-gated Cl−channels in MS lesions, may contribute to an altered inhibitory neurotransmission and increased excitability.
Watching TV and Cognition: The SPAH 2-Year Cohort Study of Older Adults Living in Low-Income Communities
Authors: Fajersztajn Laís , Di Rienzo Vanessa , Nakamura Carina Akemi , Scazufca Marcia
Published: June 2021

Watching TV is a highly prevalent leisure activity among older adults and, in many cases, the only leisure option of those living in low-income communities. While engaging in leisure activities have proven to protect older adults from cognitive decline, the effects of watching TV on cognition of this population is controversial in the literature. This study investigated the impact of watching TV on global cognitive function, immediate memory, verbal fluency, risk of dementia of amnestic mild cognitive impairment (aMCI) in a cohort of older adults residents of socioeconomically deprived areas of São Paulo, Brazil. We used data from the São Paulo Aging & Health Study (SPAH). Participants aged 65 years or over, with no dementia diagnosis at baseline and who completed the 2-year follow-up assessment were included in this study (n = 1,243). Multivariable linear regression models were performed to assess the effect of watching TV on global cognitive function, immediate memory and verbal fluency. Multivariable logistic regression models were used to evaluate the risk of developing dementia and aMCI. Models were controlled by cognitive performance at baseline, sociodemographic characteristics and functional status. Cognitive performance at baseline and follow-up were similar. Thirty-one participants were diagnosed with dementia, and 23 with aMCI 24 months after inclusion in the study. Watching TV did not show any positive or negative effect on global cognitive function, immediate memory, verbal fluency, risk of dementia and risk of aMCI. It is good news that watching TV did not predict the decline in cognition in elders. However, it is essential to increase opportunities for other leisure activities for low-income and low-educated older adults if we do consider that leisure activities protect cognition decline in older adults. In the coming decades, developing countries will experience the highest burden of dementia and more than fun, public policies to promote leisure activities might be a strategy to alleviate this burden shortly.
A Rare Variant of ANK3 Is Associated With Intracranial Aneurysm
Authors: Liu Junyu , Liao Xin , Zhou Jilin , Li Bingyang , Xu Lu , Liu Songlin , Li Yifeng , Yuan Dun , Hu Chongyu , Jiang Weixi , Yan Junxia
Published: June 2021

Intracranial aneurysm (IA) is a cerebrovascular disorder in which abnormal dilation of a blood vessel results from weakening of the blood vessel wall. The aneurysm may rupture, leading to subarachnoid hemorrhage with severe outcomes. This study was conducted to identify the genetic factors involved in the etiology of IA. Whole-exome sequencing was performed in three IA-aggregate families to identify candidate variants. Further association studies of candidate variants were performed among sporadic cases and controls. Bioinformatic analysis was used to predict the functions of candidate genes and variants. Twenty variants were identified after whole-exome sequencing, among which eight were selected for replicative association studies. ANK3 c.4403G>A (p.R1468H) was significantly associated with IA (odds ratio 4.77; 95% confidence interval 1.94–11.67; p-value = 0.00019). Amino acid R1468 in ANK3 was predicted to be located in the spectrin-binding domain of ankyrin-G and may regulate the migration of vascular endothelial cells and affect cell–cell junctions. Therefore, the variation p.R1468H may cause weakening of the artery walls, thereby accelerating the formation of IA. Thus, ANK3 is a candidate gene highly related to IA.
Effects of Probiotic Bacteria Lactobacillaceae on the Gut Microbiota in Children With Celiac Disease Autoimmunity: A Placebo-Controlled and Randomized Clinical Trial
Authors: Oscarsson Elin , Håkansson Åsa , Andrén Aronsson Carin , Molin Göran , Agardh Daniel
Published: June 2021

Disturbances of the gut microbiota may influence the development of various autoimmune diseases. This study investigated the effects of supplementations with the probiotic bacteria, Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2, on the microbial community in children with celiac disease autoimmunity (CDA). The study included 78 genetically predisposed children for celiac disease with elevated levels of tissue transglutaminase autoantibodies (tTGA) signaling for ongoing CDA. Among those children, 38 received a placebo and 40 received the probiotic supplement daily for 6 months. Fecal and plasma samples were collected at baseline and after 3 and 6 months, respectively. The bacterial community was investigated with 16S rRNA gene sequencing and terminal restriction fragment length polymorphism (T-RFLP), and tTGA levels were measured in radiobinding assays. In children that received probiotic supplementation, the relative abundance of Lactobacillaceae increased over time, while it remained unchanged in the placebo group. There was no overall correlation between tTGA levels and bacterial genus except for a positive correlation between Dialister and IgG-tTG in the probiotic group. The abundance of specific bacterial amplicon sequence variant (ASV:s) changed during the study in both groups, indicating that specific bacterial strains might be affected by probiotic supplementation.
The Mediterranean and Nordic Diet: A Review of Differences and Similarities of Two Sustainable, Health-Promoting Dietary Patterns
Authors: Krznarić Željko , Karas Irena , Ljubas Kelečić Dina , Vranešić Bender Darija
Published: June 2021

The Mediterranean diet (MD) and the Nordic diet (ND) share more similarities than differences. Both diets are based on typical local and seasonal foods, share similar nutritional recommendations based on plant-based dietary principles, and are both now orienting toward environmental protection and sustainability. The main difference between the two diets is the primary fat source. Olive oil is the synonym for MD while the ND uses more rapeseed/canola oil. While longitudinal epidemiological studies support adherence to MD as a way to prevent chronic diseases, ND still needs more such studies because the current results are discrepant. Notably, studies that assessed the association between both diets and lower risks of chronic diseases, disability, and mortality from specific and all causes, implied that ND could also have an advantageous effect as MD. Hopefully, there will be more longitudinal and large prospective studies in the future that will provide more evidence-based recommendations.
Role of the Gut Microbiota in Regulating Non-alcoholic Fatty Liver Disease in Children and Adolescents
Authors: Tokuhara Daisuke
Published: June 2021

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in children and adolescents. Although obesity is the leading cause of NAFLD, the etiologies of NAFLD are multifactorial (e.g., high-fat diet, a lack of exercise, gender, maternal obesity, the antibiotic use), and each of these factors leads to dysbiosis of the gut microbiota community. The gut microbiota is a key player in the development and regulation of the gut mucosal immune system as well as the regulation of both NAFLD and obesity. Dysbiosis of the gut microbiota promotes the development of NAFLDviaalteration of gut-liver homeostasis, including disruption of the gut barrier, portal transport of bacterial endotoxin (lipopolysaccharide) to the liver, altered bile acid profiles, and decreased concentrations of short-chain fatty acids. In terms of prevention and treatment, conventional approaches (e.g., dietary and exercise interventions) against obesity and NAFLD have been confirmed to recover the dysbiosis and dysbiosis-mediated altered metabolism. In addition, increased understanding of the importance of gut microbiota-mediated homeostasis in the prevention of NAFLD suggests the potential effectiveness of gut microbiota-targeted preventive and therapeutic strategies (e.g., probiotics and fecal transplantation) against NAFLD in children and adolescents. This review comprehensively summarizes our current knowledge of the gut microbiota, focusing on its interaction with NAFLD and its potential therapeutic role in obese children and adolescents with this disorder.
A Comparative Analysis of Six Machine Learning Models Based on Ultrasound to Distinguish the Possibility of Central Cervical Lymph Node Metastasis in Patients With Papillary Thyroid Carcinoma
Authors: Zou Ying , Shi Yan , Liu Jihua , Cui Guanghe , Yang Zhi , Liu Meiling , Sun Fang
Published: June 2021

Current approaches to predict central cervical lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) have failed to identify patients who would benefit from preventive treatment. Machine learning has offered the opportunity to improve accuracy by comparing the different algorithms. We assessed which machine learning algorithm can best improve CLNM prediction. This retrospective study used routine ultrasound data of 1,364 PTC patients. Six machine learning algorithms were compared to predict the possibility of CLNM. Predictive accuracy was assessed by sensitivity, specificity, positive predictive value, negative predictive value, and the area under the curve (AUC). The patients were randomly split into the training (70%), validation (15%), and test (15%) data sets. Random forest (RF) led to the best diagnostic model in the test cohort (AUC 0.731 ± 0.036, 95% confidence interval: 0.664–0.791). The diagnostic performance of the RF algorithm was most dependent on the following five top-rank features: extrathyroidal extension (27.597), age (17.275), T stage (15.058), shape (13.474), and multifocality (12.929). In conclusion, this study demonstrated promise for integrating machine learning methods into clinical decision-making processes, though these would need to be tested prospectively.
Efficacy and Safety of Camrelizumab Monotherapy and Combination Therapy for Cancers: A Systematic Review and Meta-Analysis
Authors: Wang Jiting , Su Song , Li Jun , Li Yaling
Published: June 2021

Objective

This meta-analysis compared the safety and efficacy of camrelizumab monotherapy and combination therapy, aiming to provide a reference for the clinical combined use of camrelizumab in the treatment of cancers and also provide a reference for the development of subsequent indications of camrelizumab.

Methods

Meta-analysis was used to analyze the four eligible literatures. Primary endpoints of effectiveness index were objective response rate (ORR), progression-free survival (PFS), control rate (CR). Primary endpoint of safety index was rating of severity of adverse drug reactions (grades 1–5).

Results

The ORR, PFS, and CR values of combined treatment with camrelizumab was better than alone treatment, camrelizumab alone was better than chemotherapy (RR = 0.45; 95% CI, 0.30–0.67; P < 0.001; RR = 1.63; 95% CI, 1.25–2.13; P < 0.001; RR = 0.73; 95% CI, 0.52–1.02; P<0.001). When grade > 2, the incidence rate of combined treatment and chemotherapy are higher than monotherapy (RR = 0.66; 95% CI, 0.51–0.86; P<0.001). In any grade, the safety of camrelizumab combination therapy was better than that of monotherapy, the safety of chemotherapy was better than camrelizumab plus chemotherapy.

Conclusion

In terms of effectiveness, the combination of camrelizumab is better than monotherapy, and monotherapy is better than chemotherapy. In terms of safety, when the grade > 2, single use is better than combination therapy and chemotherapy. In any grade of adverse event, the safety of combined use of camrelizumab is better than that of single use, and the safety of chemotherapy is better than the combined use of camrelizumab plus chemotherapy.
Prognostic Impact of Memory CD8(+) T Cells on Immunotherapy in Human Cancers: A Systematic Review and Meta-Analysis
Authors: Jin Yao , Tan Aili , Feng Jia , Xu Zexi , Wang Peiwei , Ruan Peng , Luo Ruijun , Weng Yiming , Peng Min
Published: June 2021

Objective

The objective of this systematic review and meta-analysis was to determine the prognostic value of memory CD8(+) T cells in cancer patients with immunotherapy.

Methods

EMBASE, MEDLINE (PubMed), and Web of Science databases were searched to identify suitabile articles published before March 2021. Risk of bias on the study level was assessed using the Cochrane Bias Risk Assessment Tool. The hazard ratios (HRs) and 95% confidence intervals (CIs) of pooled progression-free survival (PFS) and overall survival (OS) were calculated using RevMan 5.4 to evaluate the prognostic impact of memory CD8(+) T cells.

Results

In total, nine studies were included in the final analysis. High levels of memory CD8(+) T cells were significantly closely correlated with better progression-free survival (PFS) and overall survival (OS) of cancer patients with immunotherapy (PFS, HR 0.64, 95% CI 0.53–0.78; OS, HR 0.37, 95% CI 0.21–0.65). Memory CD8(+) T cells still have significant prognostic value in cancer patients given immunotherapy alone after excluding of other interfering factors such as chemotherapy, radiotherapy, and targeted therapy (PFS, HR 0.65, 95% CI 0.48–0.89; OS, HR 0.23, 95% CI 0.13–0.42). However, high memory CD8(+) T cells levels did not correspond to a longer PFS or OS in cancer patients with non-immunotherapy (PFS, HR 1.05, 95% CI 0.63–1.73; OS, HR 1.29, 95% CI 0.48–3.48). Thus, memory CD8(+) T cells might be a promising predictor in cancer patients with immunotherapy.

Conclusions

The host’s overall immune status, and not only the tumor itself, should be considered to predict the efficacy of immunotherapy in cancer patients. This study is the first to show the significant prognostic value of memory CD8(+) T cells in immunotherapy of cancer patients through systematic review and meta-analysis. Thus, the detection of memory CD8(+) T cells has a considerable value in clinical practice in cancer patients with immunotherapy. Memory CD8(+) T cells may be promising immunotherapy targets.
Case Report: Acute Intracardiac Thrombosis in Children With Coronavirus Disease 2019 (COVID-19)
Authors: Bigdelian Hamid , Sedighi Mohsen , Sabri Mohammad Reza , Dehghan Bahar , Mahdavi Chehreh , Ahmadi Alireza , Ghaderian Mehdi , Rahimi Hamid , Sadeghizadeh Atefeh , Emadoleslami Monirsadat , Mostafavi Seyed Nasser , Saleh Rana , Javadi Niloofar , Derakhshan Maryam , Pourmoghaddas Zahra , Sarfarazi Moghadam Shima
Published: June 2021

We herein describe a case series of children with SARS-CoV-2 infection (COVID-19) complicated with acute intracardiac thrombosis. The diagnosis of COVID-19 was confirmed through the reverse transcription-polymerase chain reaction (RT-PCR). Transthoracic echocardiography of patients revealed large intracardiac mobile masses resected successfully via cardiac surgery. The underlying mechanisms of this thrombus in the COVID-19 infection may be attributed to the hypercoagulation and inflammatory state of the disease incurred by the SARS-CoV-2 virus.
Immature Platelet Counts and Thrombopoietin Plasma Concentrations in Thrombocytopenic and Non-thrombocytopenic Preterm Infants
Authors: Sallmon Hannes , Weimann Andreas , Bührer Christoph , Metze Boris , Dame Christof , Cremer Malte
Published: June 2021

Objective: Immature platelet counts (IPC) may prove useful in guiding platelet transfusion management in preterm neonates. However, the relationship between IPCs and thrombopoietin (Tpo) concentrations has not been evaluated in preterm neonates.

Methods: Prospective cohort study in thrombocytopenic (n = 31) and non-thrombocytopenic very low birth weight (VLBW) infants (n = 38), and healthy term neonates (controls; n = 41). Absolute platelet counts (APCs), IPCs, and Tpo concentrations were assessed by a fully-automated hematological analyzer (IPC, APC) and by ELISA (Tpo concentrations) in parallel on day 1 of life (d1), d3, and d7.

Results: In healthy term neonates, APCs remained stable between d1 and d3. In non-thrombocytopenic VLBW infants, APCs increased from d1 to d7, while in the thrombocytopenia group, APCs declined from d1 to d3, before they slightly increased again by d7. Median IPCs were similar in healthy term vs. non-thrombocytopenic VLBW infants and remained stable between d1 and d3 (p > 0.05). Notably, IPCs significantly increased between d3 and d7 in both non-thrombocytopenic and thrombocytopenic VLBW infants. However, in thrombocytopenic VLBW infants, IPC values were significantly lower at each time point as compared to non-thrombocytopenic VLBWs (p < 0.001). In each subgroup, Tpo concentrations increased from d1 to d3. The median Tpo concentrations were significantly higher in thrombocytopenic as compared to non-thrombocytopenic VLBW infants at d3 (p = 0.01) and d7 (p = 0.002).

Discussion: Term infants, thrombocytopenic, and non-thrombocytopenic preterm infants display similar developmental changes in indices of megakaryopoietic activity. In thrombocytopenic preterm infants, however, the responsive increases in Tpo and immature platelets appear to be developmentally limited.
Risk Factors and Outcomes of Pulmonary Hypertension in Infants With Bronchopulmonary Dysplasia: A Meta-Analysis
Authors: Chen Ying , Zhang Di , Li Ying , Yan Aixia , Wang Xiaoying , Hu Xiaoming , Shi Hangting , Du Yue , Zhang Wenhui
Published: June 2021

Background: Pulmonary hypertension is one of the most common co-morbidities in infants with bronchopulmonary dysplasia (BPD), but its risk factors are unclear. The onset of pulmonary hypertension in BPD has been associated with poor morbidity- and mortality-related outcomes in infants. Two review and meta-analysis studies have evaluated the risk factors and outcomes associated with pulmonary hypertension in infants with BPD. However, the limitations in those studies and the publication of recent cohort studies warrant our up-to-date study. We designed a systematic review and meta-analysis to evaluate the risk factors and outcomes of pulmonary hypertension in infants with BPD.

Objective: To systematically evaluate the risk factors and outcomes associated with pulmonary hypertension in infants with BPD.

Methods: We systematically searched the academic literature according to the PRISMA guidelines across five databases (Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE). We conducted random-effects meta-analyses to evaluate the pulmonary hypertension risk factors in infants with BPD. We also evaluated the overall morbidity- and mortality-related outcomes in infants with BPD and pulmonary hypertension.

Results: We found 15 eligible studies (from the initial 963 of the search result) representing data from 2,156 infants with BPD (mean age, 25.8 ± 0.71 weeks). The overall methodological quality of the included studies was high. Our meta-analysis in infants with severe BPD revealed increased risks of pulmonary hypertension [Odds ratio (OR) 11.2], sepsis (OR, 2.05), pre-eclampsia (OR, 1.62), and oligohydramnios (OR, 1.38) of being small for gestational age (3.31). Moreover, a comparative analysis found medium-to-large effects of pulmonary hypertension on the total duration of hospital stay (Hedge's g, 0.50), the total duration of oxygen received (g, 0.93), the cognitive score (g, −1.5), and the overall mortality (g, 0.83) in infants with BPD.

Conclusion: We identified several possible risk factors (i.e., severe BPD, sepsis, small for gestational age, pre-eclampsia) which promoted the onset of pulmonary hypertension in infants with BPD. Moreover, our review sheds light on the morbidity- and mortality-related outcomes associated with pulmonary hypertension in these infants. Our present findings are in line with the existing literature. The findings from this research will be useful in development of efficient risk-based screening system that determine the outcomes associated with pulmonary hypertension in infants with BPD.
Risk Factors for Tracheobronchomalacia in Preterm Infants With Bronchopulmonary Dysplasia
Authors: Su Ya-Ting , Chiu Chun-Che , Lai Shen-Hao , Hsia Shao-Hsuan , Lin Jainn-Jim , Chan Oi-Wa , Chiu Chih-Yung , Tseng Pei-Ling , Lee En-Pei
Published: June 2021

Aim:To identify the risk factors associated with the development of tracheobronchomalacia (TBM) in preterm infants with bronchopulmonary dysplasia (BPD).

Methods:This was a retrospective cohort study using chart reviews of preterm infants born at ≤ 36 week's gestation who underwent flexible fiberoptic bronchoscopy in a tertiary pediatric referral center between January 2015 and January 2020. Indications for the bronchoscopy examination included lobar atelectasis on plain chest film, persistent CO2retention, recurrent extubation failure, or abnormal breathing sounds such as wheeze or stridor. Optimal cutoff values for each risk factor were also determined.

Results:Fifty-eight preterm infants with BPD were enrolled, of whom 29 (50%) had TBM. There were no significant differences in gestational age and birth weight between those with and without TBM. Significantly more of the patients with TBM had severe BPD compared to those without TBM (68.9 vs. 20.6%,p< 0.001). Clinical parameters that were significantly different between the two groups were included in multivariate analysis. Among these factors, severe BPD was the most powerful risk factor for the development of TBM (odds ratio 5.57, 95% confidence interval 1.32–23.5,p= 0.019). The areas under the receiver operating characteristic curves for peak inspiratory pressure (PIP) and the duration of intubation were 0.788 and 0.75, respectively. The best predictive cutoff values of PIP and duration of intubation for TBM were 18.5 mmHg and 82 days, respectively.

Conclusion:Preterm infants with severe BPD are at high risk for the development of TBM, and the risk is even higher in those who receive a higher PIP or are intubated for longer. Bronchoscopy examinations should be considered for the early diagnosis and management of TBM in infants with these risk factors.
Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology
Authors: Yang Kailin , Zeng Liuting , Ge Anqi , Chen Yi , Wang Shanshan , Zhu Xiaofei , Ge Jinwen
Published: June 2021

Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound (HCC) has definite curative effect on cerebral ischemic diseases, such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its mechanism for treating cerebral ischemia is still not fully explained.

Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. The CIR genes were obtained from Genecards and OMIM and the protein-protein interaction (PPI) data of HCC’s targets and IS genes were obtained from String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Finally, a series of animal experiments were carried out to further explore the mechanism of HCC intervention in CIR.

Results: The prediction results of systematic pharmacology showed that HCC can regulate CIR-related targets (such as AKT1, MAPK1, CASP3, EGFR), biological processes (such as angiogenesis, neuronal axonal injury, blood coagulation, calcium homeostasis) and signaling pathways (such as HIF-1, VEGF, Ras, FoxO signaling). The experiments showed that HCC can improve the neurological deficit score, decrease the volume of cerebral infarction and up-regulate the expression of HIF-1α/VEGF and VEGFR protein and mRNA (p < 0.05).

Conclusion: HCC may play a therapeutic role by regulating CIR-related targets, biological processes and signaling pathways found on this study.
Non-Destructive Evaluation of Hidden Defects Beneath the Multilayer Organic Protective Coatings Based on Terahertz Technology
Authors: Tu Wanli , Zhong Shuncong , Luo Manting , Zhang Qiukun
Published: June 2021

An organic protective coating system plays an important role for the corrosion protection of offshore metallic structures. It is of practical importance to detect possible coating defects and evaluate coating performance for corrosion degradation monitoring. Reliable defect identification can provide timely and effective maintenance to avoid serious consequences. This work investigated various multilayer organic coating systems by terahertz pulse imaging technology and aimed to explore the inspection ability of terahertz non-destructive testing (THz NDT) of protective coatings. Several types of defective coating samples were measured. The comparison of measurements obtained for sites with and without defects was provided. The changes in the signals caused by the presence of defects were explained. Structural analysis, quantitative evaluation, and defect identification were carried out in detail. The results of measurements showed that corrosion defects, paint bulge defects, and paint detachment defects can be distinguished and identified in combination with the causes of defects. It can provide effective technical guidance for terahertz technology to be gradually extended to engineering applications.
The Vagus Nerve and Spleen: Influence on White Adipose Mass and Histology of Obese and Non-obese Rats
Authors: Kuchler Joice Cristina , Siqueira Bruna Schumaker , Ceglarek Vanessa Marieli , Chasko Fernanda Vigilato , Moura Isllany Carvalho , Sczepanhak Bruna Fatima , Vettorazzi Jean Franciesco , Balbo Sandra Lucinei , Grassiolli Sabrina
Published: June 2021

The vagus nerve (VN) and spleen represent a complex interface between neural and immunological functions, affecting both energy metabolism and white adipose tissue (WAT) content. Here, we evaluated whether vagal and splenic axis participates in WAT mass regulation in obese and non-obese male Wistar rats. High doses of monosodium glutamate (M; 4 g/Kg) were administered during the neonatal period to induce hypothalamic lesion and obesity (M-Obese rats). Non-obese or Control (CTL) rats received equimolar saline. At 60 days of life, M-Obese and CTL rats were randomly distributed into experimental subgroups according to the following surgical procedures: sham, subdiaphragmatic vagotomy (SV), splenectomy (SPL), and SV + SPL (n = 11 rats/group). At 150 days of life and after 12 h of fasting, rats were euthanized, blood was collected, and the plasma levels of glucose, triglycerides, cholesterol, insulin, and interleukin 10 (IL10) were analyzed. The visceral and subcutaneous WAT depots were excised, weighed, and histologically evaluated for number and size of adipocytes as well as IL10 protein expression. M-Obese rats showed higher adiposity, hyperinsulinemia, hypertriglyceridemia, and insulin resistance when compared with CTL groups (p < 0.05). In CTL and M-Obese rats, SV reduced body weight gain and triglycerides levels, diminishing adipocyte size without changes in IL10 expression in WAT (p< 0.05). The SV procedure resulted in high IL10 plasma levels in CTL rats, but not in the M-Obese group. The splenectomy prevented the SV anti-adiposity effects, as well as blocked the elevation of IL10 levels in plasma of CTL rats. In contrast, neither SV nor SPL surgeries modified the plasma levels of IL10 and IL10 protein expression in WAT from M-Obese rats. In conclusion, vagotomy promotes body weight and adiposity reduction, elevating IL10 plasma levels in non-obese animals, in a spleen-dependent manner. Under hypothalamic obesity conditions, VN ablation also reduces body weight gain and adiposity, improving insulin sensitivity without changes in IL10 protein expression in WAT or IL10 plasma levels, in a spleen-independent manner. Our findings indicate that the vagal-spleen axis influence the WAT mass in a health state, while this mechanism seems to be disturbed in hypothalamic obese animals.
Microbiota Modulates Cardiac Transcriptional Responses to Intermittent Hypoxia and Hypercapnia
Authors: Zhou Dan , Xue Jin , Miyamoto Yukiko , Poulsen Orit , Eckmann Lars , Haddad Gabriel G.
Published: June 2021

The microbiota plays a critical role in regulating organismal health and response to environmental stresses. Intermittent hypoxia and hypercapnia, a condition that represents the main hallmark of obstructive sleep apnea in humans, is known to induce significant alterations in the gut microbiome and metabolism, and promotes the progression of atherosclerosis in mouse models. To further understand the role of the microbiome in the cardiovascular response to intermittent hypoxia and hypercapnia, we developed a new rodent cage system that allows exposure of mice to controlled levels of O2 and CO2 under gnotobiotic conditions. Using this experimental setup, we determined the impact of the microbiome on the transcriptional response to intermittent hypoxia and hypercapnia in the left ventricle of the mouse heart. We identified significant changes in gene expression in both conventionally reared and germ-free mice. Following intermittent hypoxia and hypercapnia exposure, we detected 192 significant changes in conventionally reared mice (96 upregulated and 96 downregulated) and 161 significant changes (70 upregulated and 91 downregulated) in germ-free mice. Only 19 of these differentially expressed transcripts (∼10%) were common to conventionally reared and germ-free mice. Such distinct transcriptional responses imply that the host microbiota plays an important role in regulating the host transcriptional response to intermittent hypoxia and hypercapnia in the mouse heart.
Spinal Cord Stimulation Attenuates Mechanical Allodynia and Increases Central Resolvin D1 Levels in Rats With Spared Nerve Injury
Authors: Tao Xueshu , Luo Xin , Zhang Tianhe , Hershey Brad , Esteller Rosana , Ji Ru-Rong
Published: June 2021

Mounting evidence from animal models of inflammatory and neuropathic pain suggests that inflammation regulates the resolution of pain by producing specialized pro-resolving mediators (SPMs), such as resolvin D1 (RvD1). However, it remains unclear how SPMs are induced in the central nervous system and whether these mechanisms can be reconciled with outcomes of neuromodulation therapies for pain, such as spinal cord stimulation. Here, we show that in a male rat model of neuropathic pain produced by spared nerve injury (SNI), 1 kHz spinal cord stimulation (1 kHz SCS) alone was sufficient to reduce mechanical allodynia and increase RvD1 in the cerebrospinal fluid (CSF). SNI resulted in robust and persistent mechanical allodynia and cold allodynia. Spinal cord electrode implantation was conducted at the T11-T13 vertebral level 1 week after SNI. The spinal locations of the implanted electrodes were validated by X-Ray radiography. 1 kHz SCS was applied for 6 h at 0.1 ms pulse-width, and this stimulation alone was sufficient to effectively reduce nerve injury-induced mechanical allodynia during stimulation without affecting SNI-induced cold allodynia. SCS alone significantly reduced interleukin-1β levels in both serum and CSF samples. Strikingly, SCS significantly increased RvD1 levels in the CSF but not serum. Finally, intrathecal injection of RvD1 (100 and 500 ng, i.t.) 4 weeks after nerve injury reduced SNI-induced mechanical allodynia in a dose-dependent manner. Our findings suggest that 1 kHz SCS may alleviate neuropathic pain via reduction of IL-1β and via production and/or release of RvD1 to control SNI-induced neuroinflammation.