bluuebunny/crossref_metadata_2025 huggingface dataset:
Scrutinizing GW-Based Methods Using the Hubbard Dimer
Authors: Di Sabatino S. , Loos P.-F. , Romaniello P.
Published: October 2021

Using the simple (symmetric) Hubbard dimer, we analyze some important features of the GW approximation. We show that the problem of the existence of multiple quasiparticle solutions in the (perturbative) one-shot GW method and its partially self-consistent version is solved by full self-consistency. We also analyze the neutral excitation spectrum using the Bethe-Salpeter equation (BSE) formalism within the standard GW approximation and find, in particular, that 1) some neutral excitation energies become complex when the electron-electron interaction U increases, which can be traced back to the approximate nature of the GW quasiparticle energies; 2) the BSE formalism yields accurate correlation energies over a wide range of U when the trace (or plasmon) formula is employed; 3) the trace formula is sensitive to the occurrence of complex excitation energies (especially singlet), while the expression obtained from the adiabatic-connection fluctuation-dissipation theorem (ACFDT) is more stable (yet less accurate); 4) the trace formula has the correct behavior for weak (i.e., small U) interaction, unlike the ACFDT expression.
Water Dynamics in a Peptide-appended Pillar[5]arene Artificial Channel in Lipid and Biomimetic Membranes
Authors: Barden Daniel Ryan , Vashisth Harish
Published: October 2021

Peptide-appended Pillar[5]arene (PAP) is an artificial water channel that can be incorporated into lipid and polymeric membranes to achieve high permeability and enhanced selectivity for angstrom-scale separations [Shen et al. Nat. Commun.9:2294 (2018)]. In comparison to commonly studied rigid carbon nanotubes, PAP channels are conformationally flexible, yet these channels allow a high water permeability [Y. Liu and H. Vashisth Phys. Chem. Chem. Phys.21:22711 (2019)]. Using molecular dynamics (MD) simulations, we study water dynamics in PAP channels embedded in biological (lipid) and biomimetic (block-copolymer) membranes to probe the effect of the membrane environment on water transport characteristics of PAP channels. We have resolved the free energy surface and local minima for water diffusion within the channel in each type of membrane. We find that water follows single file transport with low free-energy barriers in regions surroundings the central ring of the PAP channel and the single file diffusivity of water correlates with the number of hydrogen bonding sites within the channel, as is known for other sub-nm pore-size synthetic and biological water channels [Horner et al. Sci. Adv.1:e1400083 (2015)].
Chromium-Salophen as a Soluble or Silica-Supported Co-Catalyst for the Fixation of CO2 Onto Styrene Oxide at Low Temperatures
Authors: Balas Matthieu , K/Bidi Ludivine , Launay Franck , Villanneau Richard
Published: October 2021

Addition of a soluble or a supported CrIII-salophen complex as a co-catalyst greatly enhances the catalytic activity of Bu4NBr for the formation of styrene carbonate from styrene epoxide and CO2. Their combination with a very low co-catalyst:Bu4NBr:styrene oxide molar ratio = 1:2:112 (corresponding to 0.9 mol% of CrIII co-catalyst) led to an almost complete conversion of styrene oxide after 7 h at 80°C under an initial pressure of CO2 of 11 bar and to a selectivity in styrene carbonate of 100%. The covalent heterogenization of the complex was achieved through the formation of an amide bond with a functionalized {NH2}-SBA-15 silica support. In both conditions, the use of these CrIII catalysts allowed excellent conversion of styrene already at 50°C (69 and 47% after 24 h, respectively, in homogeneous and heterogeneous conditions). Comparison with our previous work using other metal cations from the transition metals particularly highlights the preponderant effect of the nature of the metal cation as a co-catalyst in this reaction, that may be linked to its calculated binding energy to the epoxides. Both co-catalysts were successfully reused four times without any appreciable loss of performance.
Developing an Evidence-Based Coexistence Strategy to Promote Human and Wildlife Health in a Biodiverse Agroforest Landscape
Authors: Bersacola Elena , Parathian Hannah , Frazão-Moreira Amélia , Jaló Maimuna , Sanhá Américo , Regalla Aissa , Saíd Abílio Rachid , Quecuta Queba , Camará Samba Tenem , Quade Sara Marunur Faria Fernandes , Jaquite Sidi Mohamed , Lopes Aristoteles Gomes , Patrono Livia V. , Ramon Marina , Bessa Joana , Godley Brendan J. , Bonneaud Camille , Leendertz Fabian H. , Hockings Kimberley J.
Published: October 2021

Agroforest mosaics represent one of the most extensive human-impacted terrestrial systems worldwide and play an increasingly critical role in wildlife conservation. In such dynamic shared landscapes, coexistence can be compromised if people view wildlife as a source of infectious disease. A cross-disciplinary One Health knowledge base can help to identify evolving proponents and threats to sustainable coexistence and establish long-term project goals. Building on an existing knowledge base of human–wildlife interactions at Cantanhez National Park (NP), Guinea-Bissau, we developed a causal pathway Theory-of-Change approach in response to a newly identified disease threat of leprosy in the Critically Endangered western chimpanzee (Pan troglodytes verus). The goals of our project are to improve knowledge and surveillance of leprosy in humans and wildlife and increase capacity to manage human–wildlife interactions. We describe the core project activities that aim to (1) quantify space use by chimpanzees across Cantanhez NP and determine the distribution of leprosy in chimpanzees; (2) understand the health system and local perceptions of disease; and (3) identify fine-scale risk sites through participatory mapping of resources shared by humans and chimpanzees across target villages. We discuss the development of a biodiversity and health monitoring programme, an evidence-based One Health campaign, and a One Health environmental management plan that incorporates the sharing of space and resources, and the disease implications of human–non-human great ape interactions. We demonstrate the importance of multi-stakeholder engagement, and the development of strategy that fully considers interactions between people, wildlife, and the environment.
Plasma Trimethylamine-N-Oxide Is an Independent Predictor of Long-Term Cardiovascular Mortality in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome
Authors: Eyileten Ceren , Jarosz-Popek Joanna , Jakubik Daniel , Gasecka Aleksandra , Wolska Marta , Ufnal Marcin , Postula Marek , Toma Aurel , Lang Irene M. , Siller-Matula Jolanta M.
Published: October 2021

To investigate the association of liver metabolite trimethylamine N-oxide (TMAO) with cardiovascular disease (CV)-related and all-cause mortality in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention. Our prospective observational study enrolled 292 patients with ACS. Plasma concentrations of TMAO were measured during the hospitalization for ACS. Observation period lasted seven yr in median. Adjusted Cox-regression analysis was used for prediction of mortality. ROC curve analysis revealed that increasing concentrations of TMAO levels assessed at the time point of ACS significantly predicted the risk of CV mortality (c-index=0.78, p < 0.001). The cut-off value of >4 μmol/L, labeled as high TMAO level (23% of study population), provided the greatest sum of sensitivity (85%) and specificity (80%) for the prediction of CV mortality and was associated with a positive predictive value of 16% and a negative predictive value of 99%. A multivariate Cox regression model revealed that high TMAO level was a strong and independent predictor of CV death (HR = 11.62, 95% CI: 2.26–59.67; p = 0.003). High TMAO levels as compared with low TMAO levels were associated with the highest risk of CV death in a subpopulation of patients with diabetes mellitus (27.3 vs. 2.6%; p = 0.004). Although increasing TMAO levels were also significantly associated with all-cause mortality, their estimates for diagnostic accuracy were low. High TMAO level is a strong and independent predictor of long-term CV mortality among patients presenting with ACS.
Cost-Effectiveness Evaluation of Add-on Empagliflozin in Patients With Heart Failure and a Reduced Ejection Fraction From the Healthcare System's Perspective in the Asia-Pacific Region
Authors: Liao Chia-Te , Yang Chun-Ting , Kuo Fang-Hsiu , Lee Mei-Chuan , Chang Wei-Ting , Tang Hsin-Ju , Hua Yi-Ming , Chang Hung-Yu , Chen Zhih-Cherng , Strong Carol , Ou Huang-Tz , Toh Han Siong
Published: October 2021

Background:EMPEROR-Reduced trial provides promising evidence on the efficacy of empagliflozin adding to the standard treatment in patients with heart failure and reduced ejection fraction (HFrEF). This study aimed to investigate the cost-effectiveness of add-on empagliflozin vs. standard therapy alone in HFrEF from the perspective of the Asia-Pacific healthcare systems.

Methods:A Markov model was constructed to simulate HFrEF patients and to project the lifetime direct medical costs and quality-adjusted life years (QALY) of both therapies. Transitional probabilities were derived from the EMPEROR-Reduced trial. Country-specific costs and utilities were extracted from published resources. Incremental cost-effectiveness ratio (ICER) against willingness to pay (WTP) threshold was used to examine the cost-effectiveness. A series of sensitivity analyses was performed to ensure the robustness of the results.

Results:The ICERs of add-on empagliflozin vs. standard therapy alone in HFrEF were US$20,508, US$24,046, US$8,846, US$53,791, US$21,543, and US$20,982 per QALY gained in Taiwan, Japan, South Korea, Singapore, Thailand, and Australia, respectively. Across these countries, the probabilities of being cost-effective for using add-on empagliflozin under the WTP threshold of 3-times country-specific gross domestic product per capita were 93.7% in Taiwan, 95.6% in Japan, 96.3% in South Korea, 94.2% Singapore, 51.9% in Thailand, and 95.9% in Australia. The probabilities were reduced when shortening the time horizon, assuming the same cardiovascular mortality for both treatments, and setting lower WTP thresholds.

Conclusion:Adding empagliflozin to HFrEF treatment is expected to be a cost-effective option among the Asia-Pacific countries. The cost-effectiveness is influenced by the WTP thresholds of different countries.
Radiomics-Based Classification of Left Ventricular Non-compaction, Hypertrophic Cardiomyopathy, and Dilated Cardiomyopathy in Cardiovascular Magnetic Resonance
Authors: Izquierdo Cristian , Casas Guillem , Martin-Isla Carlos , Campello Victor M. , Guala Andrea , Gkontra Polyxeni , Rodríguez-Palomares Jose F. , Lekadir Karim
Published: October 2021

Left Ventricular (LV) Non-compaction (LVNC), Hypertrophic Cardiomyopathy (HCM), and Dilated Cardiomyopathy (DCM) share morphological and functional traits that increase the diagnosis complexity. Additional clinical information, besides imaging data such as cardiovascular magnetic resonance (CMR), is usually required to reach a definitive diagnosis, including electrocardiography (ECG), family history, and genetics. Alternatively, indices of hypertrabeculation have been introduced, but they require tedious and time-consuming delineations of the trabeculae on the CMR images. In this paper, we propose a radiomics approach to automatically encode differences in the underlying shape, gray-scale and textural information in the myocardium and its trabeculae, which may enhance the capacity to differentiate between these overlapping conditions. A total of 118 subjects, including 35 patients with LVNC, 25 with HCM, 37 with DCM, as well as 21 healthy volunteers (NOR), underwent CMR imaging. A comprehensive radiomics characterization was applied to LV short-axis images to quantify shape, first-order, co-occurrence matrix, run-length matrix, and local binary patterns. Conventional CMR indices (LV volumes, mass, wall thickness, LV ejection fraction—LVEF—), as well as hypertrabeculation indices by Petersen and Jacquier, were also analyzed. State-of-the-art Machine Learning (ML) models (one-vs.-rest Support Vector Machine—SVM—, Logistic Regression—LR—, and Random Forest Classifier—RF—) were used for one-vs.-rest classification tasks. The use of radiomics models for the automated diagnosis of LVNC, HCM, and DCM resulted in excellent one-vs.-rest ROC-AUC values of 0.95 while generating these results without the need for the delineation of the trabeculae. First-order and texture features resulted to be among the most discriminative features in the obtained radiomics signatures, indicating their added value for quantifying relevant tissue patterns in cardiomyopathy differential diagnosis.
Clinical Application of Dynamic Contrast Enhanced Perfusion Imaging by Cardiovascular Magnetic Resonance
Authors: Franks Russell , Plein Sven , Chiribiri Amedeo
Published: October 2021

Functionally significant coronary artery disease impairs myocardial blood flow and can be detected non-invasively by myocardial perfusion imaging. While multiple myocardial perfusion imaging modalities exist, the high spatial and temporal resolution of cardiovascular magnetic resonance (CMR), combined with its freedom from ionising radiation make it an attractive option. Dynamic contrast enhanced CMR perfusion imaging has become a well-validated non-invasive tool for the assessment and risk stratification of patients with coronary artery disease and is recommended by international guidelines. This article presents an overview of CMR perfusion imaging and its clinical application, with a focus on chronic coronary syndromes, highlighting its strengths and challenges, and discusses recent advances, including the emerging role of quantitative perfusion analysis.
Digitization and Analysis of Capnography Using Image Processing Technique
Authors: Vijayam Bhuwaneswaran , Supriyanto Eko , Malarvili M. B.
Published: October 2021

The study of carbon dioxide expiration is called capnometry. The graphical representation of capnometry is called capnography. There is a growing interest in the usage of capnography as the usage has expanded toward the study of metabolism, circulation, lung perfusion and diffusion, quality of spontaneous respiration, and patency of airways outside of its typical usage in the anesthetic and emergency medicine field. The parameters of the capnograph could be classified as carbon dioxide (CO2) concentration and time points and coordinates, slopes angle, volumetric studies, and functional transformation of wave data. Up to date, there is no gold standard device for the calculation of the capnographic parameters. Capnography digitization using the image processing technique could serve as an option. From the algorithm we developed, eight identical breath waves were tested by four investigators. The values of the parameters chosen showed no significant difference between investigators. Although there were no significant differences between any of the parameters tested, there were a few related parameters that were not calculable. Further testing after refinement of the algorithm could be done. As more capnographic parameters are being derived and rediscovered by clinicians and researchers alike for both lung and non-lung-related diseases, there is a dire need for data analysis and interpretation. Although the proposed algorithm still needs minor refinements and further large-scale testing, we proposed that the digitization of the capnograph via image processing technique could serve as an intellectual option as it is fast, convenient, easy to use, and efficient.
Pathogenesis of Enamel-Renal Syndrome Associated Gingival Fibromatosis: A Proteomic Approach
Authors: Simancas Escorcia Victor , Guillou Clément , Abbad Lilia , Derrien Louise , Rodrigues Rezende Costa Claudio , Cannaya Vidjea , Benassarou Mourad , Chatziantoniou Christos , Berdal Ariane , Acevedo Ana Carolina , Cases Olivier , Cosette Pascal , Kozyraki Renata
Published: October 2021

The enamel renal syndrome (ERS) is a rare disorder featured by amelogenesis imperfecta, gingival fibromatosis and nephrocalcinosis. ERS is caused by bi-allelic mutations in the secretory pathway pseudokinase FAM20A. How mutations in FAM20A may modify the gingival connective tissue homeostasis and cause fibromatosis is currently unknown. We here analyzed conditioned media of gingival fibroblasts (GFs) obtained from four unrelated ERS patients carrying distinct mutations and control subjects. Secretomic analysis identified 109 dysregulated proteins whose abundance had increased (69 proteins) or decreased (40 proteins) at least 1.5-fold compared to control GFs. Proteins over-represented were mainly involved in extracellular matrix organization, collagen fibril assembly, and biomineralization whereas those under-represented were extracellular matrix-associated proteins. More specifically, transforming growth factor-beta 2, a member of the TGFβ family involved in both mineralization and fibrosis was strongly increased in samples from GFs of ERS patients and so were various known targets of the TGFβ signaling pathway including Collagens, Matrix metallopeptidase 2 and Fibronectin. For the over-expressed proteins quantitative RT-PCR analysis showed increased transcript levels, suggesting increased synthesis and this was further confirmed at the tissue level. Additional immunohistochemical and western blot analyses showed activation and nuclear localization of the classical TGFβ effector phospho-Smad3 in both ERS gingival tissue and ERS GFs. Exposure of the mutant cells to TGFB1 further upregulated the expression of TGFβ targets suggesting that this pathway could be a central player in the pathogenesis of the ERS gingival fibromatosis.

In conclusion our data strongly suggest that TGFβ -induced modifications of the extracellular matrix contribute to the pathogenesis of ERS. To our knowledge this is the first proteomic-based analysis of FAM20A-associated modifications.
Non-Invasive Detection of Fetal Vascular Endothelial Function in Gestational Diabetes Mellitus
Authors: Chen Yunyu , Huang Danping , Liu Jinrong , Zeng Fangling , Tang Guoyi , Lei Wenjia , Wang Haiyu , Jiang Yanmin , Shentu Weihui , Wang Hongying
Published: October 2021

Objectives

Endothelial dysfunction in the fetuses of women with gestational diabetes mellitus (GDM) is associated with their subsequent cardiovascular events. Prenatal assessment of endothelial function in fetuses exposed to intrauterine hyperglycemic environment remains challenging. The aim of this study was to assess the fetal vascular endothelial function in GDM patients using color M-mode derived aortic propagation velocity (APV) and evaluate the correlation of APV with endothelial function biomarkers.

Methods

This observational cross-sectional study included 31 gestational diabetic mothers and 30 healthy pregnant mothers from August 2019 to January 2020. Clinical data were compared between the groups. Fetal APV was measured using color M-mode echocardiography at late gestation. Concentrations of endothelial biomarkers including von Willebrand Factor (vWF), vascular endothelial-cadherin and endothelin-1 in umbilical cord serum were assessed. Measurements between diabetic group and controls were compared.

Results

vWF was the only endothelial functional marker that differed between the two groups. Fetuses in the GDM group had significantly lower APV levels and higher vWF levels compared with the healthy controls (P < 0.05). There was a moderate but significant correlation between APV and vWF (r =−0.58, P < 0.001). There were no associations between APV and ventricular wall thickness or umbilical artery pulsatility index.

Conclusions

Color M-mode propagation velocity of aorta is a non-invasive, practical method that correlates well with GDM and fetal endothelial function. This novel metric could contribute to recognizing early vascular functional alterations and hence represents a potential strategy for early risk factor surveillance and risk modification.
Study on the Impact of Energy Poverty on Energy Efficiency of Construction Industry: Mediating Role of Energy Consumption Structure
Authors: Zhang Jianhua , Liu Yushan , Zhang Weihua , Lin Xiangyi
Published: October 2021

In the process of continuously advancing urbanization, the energy efficiency of the construction industry, as a pillar industry of the national economy, has attracted much attention. The imbalance of regional economic development, the difference of regional resource endowment, and the incomplete energy infrastructure in some areas lead to the prominent problem of energy poverty in China. Based on the panel data of 30 provinces and cities from 2008 to 2017, this paper calculates the energy poverty index and the energy efficiency of the construction industry. Using OLS, Tobit, Probit, and other estimation methods, this paper analyzes the internal relationship between energy poverty and the energy efficiency of the construction industry, the mediating role of energy consumption structure, and the moderating effect of technological level and marketization degree. The results show the following: There is a negative correlation between energy poverty and the energy efficiency of the construction industry (Husnain, ENERG POLICY, 2021, 157). The energy consumption structure plays a partial mediating role in the impact of energy poverty on the energy efficiency of the construction industry (Li, CHEM ENG J, 2021, 408). It means that energy poverty inhibits the optimization of the energy consumption structure, and through this process, it also inhibits the improvement of the energy efficiency of the construction industry. The technological level and the degree of marketization play a moderating role in the main effect, which can weaken and strengthen the negative impact of energy poverty on the energy efficiency of the construction industry (Gajdzik, ENERGIES, 2021, 14).
Optimization Design and Analysis of Single-Stage Mixed Refrigerant Liquefaction Process
Authors: Wu Xiao , Wang Zhaoting , Dai Xiaodong , Ge Quan , Liu Fei
Published: October 2021

Small-scale natural gas liquefaction processes have several clear advantages, particularly in the exploitation of ‘unconventional’ natural gas (NG) from sources such as difficult-to-access and offshore gas fields. Moreover, conventional liquefaction processes have a number of disadvantages such as high energy consumption, large cooling loads required in the refrigeration cycle, and non-uniform matching of cold and hot flows in liquified natural gas (LNG) heat exchanger (HE). The main objective of this study was to optimize the most commonly used mixed refrigerant process. The liquefaction performance of the optimized process was analyzed and the influence of gas parameters on the power consumption, exergy loss, freezing mixture circulation, and cooling water load were investigated. The results show that compressor power consumption can be reduced by 29.8%, the cooling water load can be reduced by 21.3%, and the system exergy efficiency can be increased by 41% with the optimized process. Furthermore, throttling and compression of the freezing mixture were increased during the refrigeration stage. It can be concluded that reducing the feed gas temperature and increasing the feed gas pressure can reduce the total power consumption, exergy loss, freezing mixture circulation, and cooling water load, which can significantly improve liquefaction performance.
RNA Biological Characteristics at the Peak of Cell Death in Different Hereditary Retinal Degeneration Mutants
Authors: Wei Chunling , Li Yan , Feng Xiaoxiao , Hu Zhulin , Paquet-Durand François , Jiao Kangwei
Published: October 2021

Purpose: The present work investigated changes in the gene expression, molecular mechanisms, and pathogenesis of inherited retinal degeneration (RD) in three different disease models, to identify predictive biomarkers for their varied phenotypes and to provide a better scientific basis for their diagnosis, treatment, and prevention.

Methods: Differentially expressed genes (DEGs) between retinal tissue from RD mouse models obtained during the photoreceptor cell death peak period (Pde6brd1 at post-natal (PN) day 13, Pde6brd10 at PN23, Prphrd2 at PN29) and retinal tissue from C3H wild-type mice were identified using Illumina high-throughput RNA-sequencing. Co-expression gene modules were identified using a combination of GO and KEGG enrichment analyses and gene co-expression network analysis. CircRNA-miRNA-mRNA network interactions were studied by genome-wide circRNA screening.

Results:Pde6brd1, Pde6brd10, and Prphrd2 mice had 1,926, 3,096, and 375 DEGs, respectively. Genes related to ion channels, stress, inflammatory processes, tumor necrosis factor (TNF) production, and microglial cell activation were up-regulated, while genes related to endoplasmic reticulum regulation, metabolism, and homeostasis were down-regulated. Differential expression of transcription factors and non-coding RNAs generally implicated in other human diseases was detected (e.g., glaucoma, diabetic retinopathy, and inherited retinal degeneration). CircRNA-miRNA-mRNA network analysis indicated that these factors may be involved in photoreceptor cell death. Moreover, excessive cGMP accumulation causes photoreceptor cell death, and cGMP-related genes were generally affected by different pathogenic gene mutations.

Conclusion: We screened genes and pathways related to photoreceptor cell death. Additionally, up-stream regulatory factors, such as transcription factors and non-coding RNA and their interaction networks were analyzed. Furthermore, RNAs involved in RD were functionally annotated. Overall, this study lays a foundation for future studies on photoreceptor cell death mechanisms.
Dysphoric Milk Ejection Reflex: The Psychoneurobiology of the Breastfeeding Experience
Authors: Deif Reem , Burch Emily Michelle , Azar Jihan , Yonis Nouran , Abou Gabal Macy , El Kramani Nabila , DakhlAllah Duaa
Published: October 2021

Breastfeeding, given its biochemical and physiological basis, is known for its many benefits for both the lactating mother and the infant. Among the many challenges new breastfeeding mothers experience is the feeling of aversion in response to their newborn's suckling which has been termed dysphoric milk-ejection reflex (D-MER). Characterized by intense feelings of dysphoria which may eventually interfere with the mother's ability to breastfeed regularly, evidence suggests both the neurobiological and psychological basis of D-MER in an attempt to explain its complexity. Biologically, breastfeeding is expressed by the intracerebral release of oxytocin, an increased expression of oxytocin receptors in specific brain regions, increased mesocorticolimbic reward region activation, the secretion of prolactin and possibly the inhibition of dopamine. Hence, different theories explain D-MER in terms of disrupted neurotransmitter and hormonal activity. Breastfeeding has also proven to influence mood and stress reactivity in nursing mothers with a potential link with postpartum depression. Psychological theories attempt to explain D-MER from a sociopsychosexual lense shedding light on the significance of mother-infant attachment, the sexualization of the female body and the motherhood experience as a developmental stage in a woman's lifespan. The aim of this review is to provide a literature update of D-MER incorporating both neurobiological and psychological theories calling for raising awareness about the complexity of breastfeeding and for the need for mother-centered interventions for the management of D-MER and other postpartum-specific conditions.
Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response
Authors: Aevermann Brian D. , Shannon Casey P. , Novotny Mark , Ben-Othman Rym , Cai Bing , Zhang Yun , Ye Jamie C. , Kobor Michael S. , Gladish Nicole , Lee Amy Huei-Yi , Blimkie Travis M. , Hancock Robert E. , Llibre Alba , Duffy Darragh , Koff Wayne C. , Sadarangani Manish , Tebbutt Scott J. , Kollmann Tobias R. , Scheuermann Richard H.
Published: October 2021

Vaccination to prevent infectious disease is one of the most successful public health interventions ever developed. And yet, variability in individual vaccine effectiveness suggests that a better mechanistic understanding of vaccine-induced immune responses could improve vaccine design and efficacy. We have previously shown that protective antibody levels could be elicited in a subset of recipients with only a single dose of the hepatitis B virus (HBV) vaccine and that a wide range of antibody levels were elicited after three doses. The immune mechanisms responsible for this vaccine response variability is unclear. Using single cell RNA sequencing of sorted innate immune cell subsets, we identified two distinct myeloid dendritic cell subsets (NDRG1-expressing mDC2 and CDKN1C-expressing mDC4), the ratio of which at baseline (pre-vaccination) correlated with the immune response to a single dose of HBV vaccine. Our results suggest that the participants in our vaccine study were in one of two different dendritic cell dispositional states at baseline – an NDRG2-mDC2 state in which the vaccine elicited an antibody response after a single immunization or a CDKN1C-mDC4 state in which the vaccine required two or three doses for induction of antibody responses. To explore this correlation further, genes expressed in these mDC subsets were used for feature selection prior to the construction of predictive models using supervised canonical correlation machine learning. The resulting models showed an improved correlation with serum antibody titers in response to full vaccination. Taken together, these results suggest that the propensity of circulating dendritic cells toward either activation or suppression, their “dispositional endotype” at pre-vaccination baseline, could dictate response to vaccination.
Comprehensive of N1-Methyladenosine Modifications Patterns and Immunological Characteristics in Ovarian Cancer
Authors: Liu Jinhui , Chen Can , Wang Yichun , Qian Cheng , Wei Junting , Xing Yan , Bai Jianling
Published: October 2021

Background

recently, many researches have concentrated on the relevance between N1-methyladenosine (m1A) methylation modifications and tumor progression and prognosis. However, it remains unknown whether m1A modification has an effect in the prognosis of ovarian cancer (OC) and its immune infiltration.

Methods

Based on 10 m1A modulators, we comprehensively assessed m1A modification patterns in 474 OC patients and linked them to TME immune infiltration characteristics. m1Ascore computed with principal component analysis algorithm was applied to quantify m1A modification pattern in OC patients. m1A regulators protein and mRNA expression were respectively obtained by HPA website and RT-PCR in clinical OC and normal samples.

Results

We finally identified three different m1A modification patterns. The immune infiltration features of these m1A modification patterns correspond to three tumor immune phenotypes, including immune-desert, immune-inflamed and immune-excluded phenotypes. The results demonstrate individual tumor m1A modification patterns can predict patient survival, stage and grade. The m1Ascore was calculated to quantify individual OC patient’s m1A modification pattern. A high m1Ascore is usually accompanied by a better survival advantage and a lower mutational load. Research on m1Ascore in the treatment of OC patients showed that patients with high m1Ascore showed marked therapeutic benefits and clinical outcomes in terms of chemotherapy and immunotherapy. Lastly, we obtained four small molecule drugs that may potentially ameliorate prognosis.

Conclusion

This research demonstrates that m1A methylation modification makes an essential function in the prognosis of OC and in shaping the immune microenvironment. Comprehensive evaluation of m1A modifications improves our knowledge of immune infiltration profile and provides a more efficient individualized immunotherapy strategy for OC patients.
Clinical Features and Risk Factors for Active Tuberculosis in Takayasu Arteritis: A Single-Center Case-Control Study
Authors: Zhou Jiawei , Ji Ruoyu , Zhu Rui , Zhou Jingya , Li Jing , Tian Xinping , Chen Yuexin , Zheng Yuehong
Published: October 2021

Backgrounds

Takayasu arteritis (TAK) is a chronic, granulomatous vasculitis correlated with tuberculosis (TB). The two diseases share similar pathological characteristics and clinical manifestations which increase the difficulty to diagnose. Active tuberculosis (ATB) has implications for treatment strategies in TAK patients. Therefore, the investigation of clinical features and potential risk factors of ATB in TAK patients is vital.

Methods

The study reviewed hospitalized patients diagnosed with TAK in our hospital from 2008, to 2021. TAK patients with ATB were enrolled as the case group. The control group was randomly selected in a 3:1 ratio. The clinical characteristics of TAK patients with and without ATB were compared. Multivariate logistic regression analysis was performed to determine risk factors for ATB in TAK patients.

Results

We reviewed 1,789 patients and ultimately identified 30 (1.7%) ATB cases. TAK patients with ATB were more prone to develop symptoms including fever (p=0.001), fatigue (p=0.003), cough (p=0.037), expectoration (p<0.001), weight loss (p=0.003), and night sweating (p<0.001). Increased level of hypersensitive C reactive protein (hsCRP, p=0.001), decreased level of albumin (p=0.031), and higher positive rate of T-SPOT.TB test (p<0.001) were observed in the case group. Multivariate logistic regression analysis revealed that hsCRP >8 mg/L (OR 9.108; 95% CI, 1.096–75.711; p=0.041) and positive T-SPOT.TB result (OR 68.669; 95% CI, 7.291–646.738; p<0.001) were risk factors for ATB in TAK patients. The proportion of patients undergoing subsequent surgery for Takayasu arteritis was lower in patients with ATB (p<0.001).

Conclusion

Our study suggested that the diagnosis of ATB should be considered when TAK patients experienced symptoms including fever, fatigue, weight loss, etc. hsCRP >8 mg/L and positive T-SPOT.TB result were identified as independent risk factors for ATB in TAK patients.
Is Immune Therapy Plus Chemotherapy More Effective Than Immune Therapy Alone for Unresectable Recurrent Nasopharyngeal Carcinoma?
Authors: Zhou Xin , Niu XiaoShuang , Liu PeiYao , Ou Dan , Zhu Yi , Wang XiaoShen
Published: October 2021

Objective

To evaluate whether the combination of immune checkpoint inhibitor (ICI) with chemotherapy is more effective than ICI alone in the treatment of recurrent, locoregionally advanced, unresectable nasopharyngeal carcinoma (RAU-NPC), which has progressed after second line chemotherapy.

Methods and materials

Patients with RAU-NPC that progressed after second chemotherapy were prescribed ICI once every 3 weeks, either alone or combined with chemotherapy at the discretion of treating physicians, until confirmed disease progression, unacceptable toxicity, or voluntary withdrawal. The primary endpoint was the objective response rate (ORR). The secondary endpoints included safety, duration of response (DOR), and progression-free survival (PFS).

Results

From June 2016 to July 2021, 28 patients were enrolled in this study.21 patients received ICI plus chemotherapy, and 7 patients received ICI alone. Altogether, there were 7 (25%) complete response (CR) and 12 (42.8%) partial response (PR), respectively. Stable disease (SD) and progressive disease (PD) were defined in 4 (14.3%) and 5 (17.8%) cases, respectively. The ORR was 19 out of 28 (67.8%). The disease control rate (DCR) was 23 out of 28 (82.1%).Two patients (28.6%) in the ICI alone group and five (23.8%) in the combination group achieved CR (P=0.801). 2 patient (28.6%) in the ICI alone group and 10 (47.6%) in the combination group achieved PR (P=0.378). With a median follow-up of 16 months (2-61 months), five patients terminated ICI due to disease progression, one patient was lost to follow-up, and the remaining 22 patients continued with ICI. Neither the median PFS nor the median DOR was reached. All observed adverse events were defined as ≤ Grade 2.

Conclusion

ICI alone or combined with chemotherapy demonstrated promising antitumor activity in RAU-NPC patients that progressed after second line chemotherapy, with a low toxicity profile. Compared with ICI alone, chemotherapy plus ICI did not improve CR or PR in our study.
Mechanisms of Immune Checkpoint Inhibitor-Mediated Colitis
Authors: Westdorp Harm , Sweep Mark W. D. , Gorris Mark A. J. , Hoentjen Frank , Boers-Sonderen Marye J. , Post Rachel S. van der , Heuvel Michel M. van den , Piet Berber , Boleij Annemarie , Bloemendal Haiko J. , de Vries I. Jolanda M.
Published: October 2021

Immune checkpoint inhibitors (ICIs) have provided tremendous clinical benefit in several cancer types. However, systemic activation of the immune system also leads to several immune-related adverse events. Of these, ICI-mediated colitis (IMC) occurs frequently and is the one with the highest absolute fatality. To improve current treatment strategies, it is important to understand the cellular mechanisms that induce this form of colitis. In this review, we discuss important pathways that are altered in IMC in mouse models and in human colon biopsy samples. This reveals a complex interplay between several types of immune cells and the gut microbiome. In addition to a mechanistic understanding, patients at risk should be identifiable before ICI therapy. Here we propose to focus on T-cell subsets that interact with bacteria after inducing epithelial damage. Especially, intestinal resident immune cells are of interest. This may lead to a better understanding of IMC and provides opportunities for prevention and management.
Carbon Transfer Processes of Food Web and Trophic Pathways in a Tropical Eutrophic Seagrass Meadow
Authors: Cui Lijun , Jiang Zhijian , Huang Xiaoping , Wu Yunchao , Liu Songlin , Chen Qiming , Li Jinlong , He Jialu
Published: October 2021

Seagrass meadows provide important habitats and rich organic carbon sources for consumers at different trophic levels but are threatened by accelerating eutrophication in coastal waters. Nevertheless, at present, carbon transfer processes throughout the food web and trophic pathways in eutrophic seagrass meadows are still poorly known. To resolve this issue, carbon sources of different trophic communities in a eutrophic tropical seagrass meadow [Xincun (XC) bay, South China Sea] under eutrophication were examined in summer and winter using dual stable isotopes. The δ13C value of omnivores and carnivores overlapped more with that of herbivores and planktivores/filter feeders, which mainly overlapped with that of epiphytes in summer and macroalgae in winter. Meanwhile, epiphytes and macroalgae exhibited high biomass and corresponding highest contribution to herbivores, omnivores, and carnivores in summer and winter, respectively. These results suggest that the grazing food chain was the main trophic pathway in this eutrophic seagrass meadow, and that the transfer of carbon flow in the grazing food chain was mainly dominated by the proliferating epiphytes or macroalgae carbon. In contrast, the contribution of seagrass to detritivores in both seasons was higher than that of other food sources. Our findings suggest that in eutrophic tropical seagrass meadows, the proliferation of epiphytes or macroalgae induced by high nutrient loading, as well as their seasonal changes, has a greater impact on the transfer of carbon in the grazing food chain than that in the detritus food chain, and the seagrass fueled the food web mainly through the detritus food chain.
Effect of Surface Biphilicity on FC-72 Flow Boiling in a Rectangular Minichannel
Authors: Aboubakri Akam , Ahmadi Vahid Ebrahimpour , Celik Suleyman , Sadaghiani Abdolali K. , Sefiane Khellil , Kosar Ali
Published: October 2021

Flow boiling is one of the most effective mechanisms in heat transfer thanks to the latent heat of vaporization. Surface modifications such as mixed-wettability have a considerable effect on the boiling heat transfer performance in terms of enhancement in boiling heat transfer as well as critical heat flux. This study introduces a new method of fabrication of biphilic surfaces, where C4F8 (Octafluorocyclobutane) islands are surrounded by silicon. Two different biphilic surfaces were fabricated and compared with the entirely uniform hydrophobic surface taken as a reference,. Each of the biphilic surfaces has three different sections, namely inlet, middle and outlet regions. The first region is mainly hydrophobic (inlet), while the third region is mainly hydrophilic (outlet). The heat transfer coefficients were obtained at different heat fluxes. Compared to the entirely uniform hydrophobic surface, the results show that biphilic surfaces enhance the boiling heat transfer performance by up to 50%. The visualization results revealed that the biphilic surfaces lead to more nucleation sites in the bubbly flow regime and break up the elongated bubbles in the slug flow regime.
Comparison of Hysterosalpingography With Laparoscopy in the Diagnosis of Tubal Factor of Female Infertility
Authors: Tan Jifan , Deng Min , Xia Meng , Lai Muhua , Pan Wenwei , Li Yubin
Published: October 2021

Background:Laparoscopy is considered to be the gold standard in the evaluation of causes leading to infertility. Hysterosalpingography (HSG) permits indirect visualization of the cervical canal, uterine cavity, and tube patency, which is helpful for evaluating the causes of infertility.

Objective:This study aimed to detect tubal abnormalities in infertile women by HSG or laparoscopy and determine the value of HSG in diagnosing fallopian tube status.

Methods:The study group consisted of 1,276 patients. HSG was performed as a preliminary test for the evaluation of fallopian tube status. Women were subjected to laparoscopic examination on evidence of HSG abnormalities.

Results:The negative predictive value of HSG for detecting patency or occlusion for the right/left tube was 92.08 and 95.44%, respectively. The kappa values for the consistent diagnosis in the right/left tube were 0.470 and 0.574, respectively. In cases of low patency of the right/left tube, there was a greater than a 40% chance for the tube to be patent, and the remaining high probability was pelvic adhesion. The positive predictive value of HSG for detecting patency or occlusion for both tubes was 87.2%. The kappa value was 0.898 [95% CI (0.838, 0.937),p< 0.001], which meant that the diagnostic accuracy of HSG for both tube patency/occlusion was explicit. The kappa value for the diagnosis of hydrosalpinx (especially for bilateral tube hydrosalpinx) was 0.838 [95% CI (0.754, 0.922),p< 0.001], and the diagnostic accuracy for HSG was 79.8, 67.9, and 72.4%, respectively.

Conclusion:The current study concluded that HSG is a good diagnostic modality to detect tube abnormalities in infertile patients. HSG and laparoscopy are complementary to each other and whenever the patient is undertaken for diagnosis of infertility. Cost-effective HSG had good predictive value in identifying tubal factor infertility.
Glomerular Kidney Diseases in the Single-Cell Era
Authors: Latt Khun Zaw , Heymann Jurgen , Yoshida Teruhiko , Kopp Jeffrey B.
Published: October 2021

Recent advances in single-cell technology have enabled investigation of genomic profiles and molecular crosstalk among individual cells obtained from tissues and biofluids at unprecedented resolution. Glomerular diseases, either primary or secondary to systemic diseases, often manifest elements of inflammation and of innate and adaptive immune responses. Application of single-cell methods have revealed cellular signatures of inflammation, cellular injury, and fibrosis. From these signatures, potential therapeutic targets can be inferred and in theory, this approach might facilitate identification of precision therapeutics for these diseases. Single-cell analyses of urine samples and skin lesions from patients with lupus nephritis and of urine samples from patients with diabetic nephropathy and focal segmental glomerulosclerosis have presented potential novel approaches for the diagnosis and monitoring of disease activity. These single-cell approaches, in contrast to kidney biopsy, are non-invasive and could be repeated multiple times as needed.
Characterization of the Oral Microbiome Among Children With Type 1 Diabetes Compared With Healthy Children
Authors: Moskovitz Moti , Nassar Mira , Moriel Nadav , Cher Avital , Faibis Sarit , Ram Diana , Zangen David , Yassour Moran , Steinberg Doron
Published: October 2021

Aim: Current microbiome profiling of type 1 diabetes mellitus (T1D) patients is mostly limited to gut microbiome. We characterized the oral microbiome associated with T1D in children after the onset of the disease and explored its relationship with oral physiological factors and dental status.

Methods: This cohort study comprised 37 children aged 5–15 years with T1D and 29 healthy children matched in age and gender. Unstimulated whole saliva was collected from diabetic and non-diabetic children, in the morning after brushing their teeth and a fasting period of at least 1 h before sampling. 16S rRNA gene-based analysis was performed by Powersoil Pro kit by Qiagen and Phusion High-Fidelity PCR Master Mix. Oral physiological and dental parameters studied included decayed, missing, and filled teeth index, salivary flow rate, and salivary pH, glucose, calcium, phosphate, and urea levels.

Results: Of the identified 105 different genera and 211 different species, the most abundant genera were Streptococcus, Prevotella, Veillonella, Haemophilus, and Neisseria. Streptococcus was more abundant in T1D children. The diabetes group had 22 taxa at the genus level and 33 taxa at the species level that were not present in the control group and the control group exhibited 6 taxa at the genus level and 9 taxa at the species level that did not exist in the diabetes group. In addition, Catonella, Fusobacterium, and Mogibacterium differed between healthy and T1D subjects. Eight species and eight subspecies were significantly more abundant among healthy children than in T1D children. Porphyromonas and Mogibacterium genera were significantly correlated with salivary parameters. We found similarities between taxa revealed in the present study and those found in gut microbiome in type 1 diabetes mellitus according to gutMDisorder database.

Conclusions: Salivary microbiome analysis revealed unique microbial taxa that differed between T1D children and healthy subjects. Several genera found in the saliva of T1D children were associated with gut microbiome in T1D individuals.
Transcriptomic and Genetic Profiling of HIV-Associated Neurocognitive Disorders
Authors: Ojeda-Juárez Daniel , Kaul Marcus
Published: October 2021

Early in the HIV pandemic, it became evident that people living with HIV (PLWH) develop a wide range of neurological and neurocognitive complications. Even after the introduction of combination antiretroviral therapy (cART), which dramatically improved survival of PLWH, the overall number of people living with some form of HIV-associated neurocognitive disorders (HAND) seemed to remain unchanged, although the incidence of dementia declined and questions about the incidence and diagnosis of the mildest form of HAND arose. To better understand this complex disease, several transcriptomic analyses have been conducted in autopsy samples, as well as in non-human primates and small animal rodent models. However, genetic studies in the HIV field have mostly focused on the genetic makeup of the immune system. Much less is known about the genetic underpinnings of HAND. Here, we provide a summary of reported transcriptomic and epigenetic changes in HAND, as well as some of the potential genetic underpinnings that have been linked to HAND, and discuss future directions with hurdles to overcome and angles that remain to be explored.