bluuebunny/crossref_metadata_2025 huggingface dataset:
Common Dietary Modifications in Preclinical Models to Study Skeletal Health
Authors: Rendina-Ruedy Elizabeth , Smith Brenda J.
Published: July 2022

Bone is a highly dynamic tissue that undergoes continuous remodeling by bone resorbing osteoclasts and bone forming osteoblasts, a process regulated in large part by osteocytes. Dysregulation of these coupled catabolic and anabolic processes as in the case of menopause, type 2 diabetes mellitus, anorexia nervosa, and chronic kidney disease is known to increase fracture risk. Recent advances in the field of bone cell metabolism and bioenergetics have revealed that maintenance of the skeleton places a high energy demand on these cells involved in bone remodeling. These new insights highlight the reason that bone tissue is the beneficiary of a substantial proportion of cardiac output and post-prandial chylomicron remnants and requires a rich supply of nutrients. Studies designed for the specific purpose of investigating the impact of dietary modifications on bone homeostasis or that alter diet composition and food intake to produce the model can be found throughout the literature; however, confounding dietary factors are often overlooked in some of the preclinical models. This review will examine some of the common pre-clinical models used to study skeletal biology and its pathologies and the subsequent impact of various dietary factors on these model systems. Furthermore, the review will include how inadvertent effects of some of these dietary components can influence bone cell function and study outcomes.
Association Between Diabetic Retinopathy and Insomnia Risk: A Nationwide Population-Based Study
Authors: Um Yoo Hyun , Kim Tae-Won , Jeong Jong-Hyun , Hong Seung-Chul , Seo Ho-Jun , Han Kyung-Do
Published: July 2022

Background

Previous studies have suggested a close link between sleep disturbances and diabetic retinopathy (DR). However, to date, no confirmatory findings have been reported. We aimed to explore the risk of insomnia in DR by considering demographic factors and diabetes mellitus (DM)-related variables.

Methods

A nationwide population-based cohort of 2,206,619 patients with type 2 diabetes from the Korean National Insurance Service Database was followed up for insomnia incidence. DR, non-proliferative DR (NPDR), and proliferative DR (PDR) were defined according to ICD-10 codes. The interactive effects of sex, age, and DM-related variables were analyzed to evaluate their impact on insomnia risk in DR.

Results

Compared with the non-DR group, insomnia risk was increased in the DR [(adjusted hazard ratio (aHR): 1.125, 95% confidence interval (CI):1.108-1.142), NPDR (aHR:1.117, 95% CI:1.099-1.134), and PDR (aHR:1.205, 95% CI: 1.156-1.256), even after controlling for comorbidities, lifestyle factors, and DM-related variables. The men and youngest age groups (<40 years) were most vulnerable to insomnia risk. Sex, age, DM duration, and chronic kidney disease (CKD) status exerted interactive effects with DR status in increasing the insomnia risk. In the PDR group, sex, age, DM duration, insulin therapy status, and CKD status exerted interactive effects that increased the risk of insomnia.

Conclusion

Insomnia risk is significantly higher in patients with DR, and clinical attention is warranted.
Endoscopic Management of Weight Recurrence Following Bariatric Surgery
Authors: Abboud Donna Maria , Yao Rebecca , Rapaka Babusai , Ghazi Rabih , Ghanem Omar M. , Abu Dayyeh Barham K.
Published: July 2022

Metabolic and bariatric surgery is the most effective therapy for weight loss and improving obesity-related comorbidities, comprising the Roux-en-Y gastric bypass (RYGB), gastric banding, sleeve gastrectomy (SG), and biliopancreatic diversion with duodenal switch. While the effectiveness of weight loss surgery is well-rooted in existing literature, weight recurrence (WR) following bariatric surgery is a concern. Endoscopic bariatric therapy presents an anatomy-preserving and minimally invasive option for managing WR in select cases. In this review article, we will highlight the endoscopic management techniques for WR for the most commonly performed bariatric surgeries in the United States –RYGB and SG. For each endoscopic technique, we will review weight loss outcomes in the short and mid-terms and discuss safety and known adverse events. While there are multiple endoscopic options to help address anatomical issues, patients should be managed in a multidisciplinary approach to address anatomical, nutritional, psychological, and social factors contributing to WR.
Metal Mobilization From CO2 Storage Cap-Rocks: Experimental Reactions With Pure CO2 or CO2 SO2 NO
Authors: Pearce J. K. , Dawson G. W. , Southam G. , Paterson D. , Kirste D. , Golding S. D.
Published: July 2022

CO2 geological storage will be needed as part of the transition to lower greenhouse gas emissions. During CO2 storage, the mobilization of metals from minerals to formation water via CO2 water rock reactions may be a concern for water quality. The sources, behavior, and fate of metals, however, are not well understood. Metals in minerals of calcite cemented sandstone, feldspar-rich sandstone, and ironstone seal drill cores from a target storage site were characterized. The cores were reacted with low-salinity water and pure supercritical CO2 or impure CO2 with SO2 and nitric oxide (NO), under reservoir conditions. Calcite cemented core underwent calcite dissolution with chlorite, plagioclase, and sulfide alteration. The highest concentrations of calcium and manganese were released in the reaction of calcite cemented sandstone seal, with the lowest mobilized arsenic concentration. Pure CO2 reaction of the feldspar-rich sandstone seal resulted in calcite dissolution, with plagioclase, chlorite, kaolinite, illite, and sulfides corroded. Impure CO2 reaction of the feldspar-rich sandstone led to additional corrosion of apatite, pyrite, and sphalerite cements. Generally, dissolved iron, lead, zinc, and arsenic were released and then re-precipitated in oxide minerals or adsorbed. Calcium, manganese, and strontium were released primarily from calcite cement dissolution. Plagioclase corrosion was a second source of dissolved strontium, and chlorite dissolution a second source of manganese. Although sulfides contained higher concentrations of metals, the higher reactivity of carbonates meant that the latter were the main sources contributing to dissolved metal concentrations. The mineral content of the seal cores, and the injected gas mixture, had an impact on the type and concentration of metals released. The ubiquitous presence of carbonate minerals means that this study is applicable to understanding the potential risk factors for water quality changes, and the mobilization and fate of environmentally regulated metals, in both CO2 storage complexes and overlying drinking water aquifers worldwide.
Probabilistic Optimal Power Flow-Based Spectral Clustering Method Considering Variable Renewable Energy Sources
Authors: Kim Juhwan , Lee Jaehyeong , Kang Sungwoo , Hwang Sungchul , Yoon Minhan , Jang Gilsoo
Published: July 2022

Power system clustering is an effective method for realizing voltage control and preventing failure propagation. Various approaches are used for power system clustering. Graph-theory-based spectral clustering methods are widely used because they follow a simple approach with a short calculation time. However, spectral clustering methods can only be applied in system environments for which the power generation amount and load are known. Moreover, it is often impossible to sufficiently reflect the influence of volatile power sources (e.g., renewable energy sources) in the clustering. To this end, this study proposes a probabilistic spectral clustering algorithm applicable to a power system, including a photovoltaic (PV) model (for volatile energy sources) and a classification method (for neutral buses). The algorithm applies a clustering method that reflects the random outputs of PV sources, and the neutral buses can be reclassified via clustering to obtain optimal clustering results. The algorithm is verified through an IEEE 118-bus test system, including PV sources.
Reliability Assessment of the Integrated Energy System Considering Gas–Thermal Inertia
Authors: Zhu Yaopei , Sun Weijia , Miao Cairan , Wang Qi , Tang Yi , Huang Yunkai
Published: July 2022

The electrical–thermal coupling integrated energy system (IES) has multi-timescale characteristics, and the gas–thermal slow dynamic characteristics of the IES contain rich flexibilities. The state of the gas–thermal system changes relatively with a time delay when the external conditions change, which can provide power support for the system over a certain timescale. Based on the gas–thermal inertia power support capability, a reliability assessment method of the IES considering gas–thermal inertia is proposed. According to research, the reliability assessment of the IES based on gas–thermal inertia can reduce the size and frequency of load shedding, alleviate the system operation risk caused by heavy load, reduce the system operation cost, and improve the system long-term operation reliability and economy. The greater the importance assessment index of energy conversion equipment, the greater its impact on system reliability, which is the weak node that should be focused on and protected.
Research on Efficient Channel Decoding Algorithm for Memory Channel and Short Packet Transmission in Smart Grid
Authors: Qin Mingwei , Gao Yongxiang , Hou Baolin , Wang Huan , Zhou Wenmao , Yao Yuancheng
Published: July 2022

Many smart factories use the smart grid for power system automation, and its wireless control technology requires low-time-delay and high-reliability communication. Guessing random additive noise decoding algorithm has outstanding short packet error correction performance. In the decoding process, the order of noise parameter combination affects the decoding delay. Aiming at the communication problem of the smart grid in the process of factory power supply and distribution, this study analyzes the characteristics of the original noise parameter ranking algorithm. When the steady-state flip probability is large, more search times are required to obtain the correct combination of noise parameters, which means that greater delay is required for decoding in the time-varying channel. To solve the aforementioned problems, this study optimizes the noise parameter ranking before the noise error mode arrangement and proposes a noise parameter ranking algorithm for predicting the symbol string. First, the channel perception is completed by edge computing. Then, the algorithm uses the obtained soft information to rank the channel noise parameters. Simulation results show that the proposed algorithm has better search performance than the original sorting algorithm, especially when the channel parameter b is greater than 0.5. Finally, by comparing the BM Decoding Algorithm of BCH with different noise parameter ranking algorithms of decoding, the results show that the noise parameter ranking algorithm proposed in this study has better decoding performance in the environmental channel of the smart factory, so as to improve the reliability of the smart grid in the process of factory power supply and distribution.
Research on Decarbonization Pathway of China’s Coal-Fired Power Industry From the Perspective of Conflict Mediation
Authors: Fang Yinhai , Xu Haiyan
Published: July 2022

The transition to a low-carbon energy system is imminent under the constraints of carbon-peaking and carbon-neutral targets. Undoubtedly, coal-related carbon emissions over the past decades have had profound negative impacts on human life and the global climate. However, the main position of coal in the energy system determines that pure coal reduction strategy will inevitably lead to a systemic energy crisis. To this end, we explore the conflict formation mechanism among coal enterprises, downstream coal-fired power plants, and government in the process of strategic energy decarbonization transformation from the perspective of industrial chain, and analyze the feasible conflict states and their NASH, GMR, SMR, and SEQ equilibrium characteristics by constructing a ternary GMCR model. It is found that there are two feasible conflict states s10 and s12 that simultaneously satisfy the conditions of the above four types of equilibria. In this context, the evolution paths of s10 and s12 are further analyzed and conflict mediation strategies are proposed accordingly. Meanwhile, the decarbonization transition of the energy system needs to consider both the stage characteristics and regional differences of energy reform, as well as the important role of green low-carbon technological innovation as a grip for the decarbonization transition of energy.
DNA Barcoding Technology Used to Successfully Sub-Classify a Museum Whale Specimen as Balaenoptera edeni edeni
Authors: Ren Xiaoying , Ma Xiaolin , Allen Edward , Fang Yuan , Wen Shaoqing
Published: July 2022

DNA barcoding technology is becoming an increasingly powerful tool in resolving issues of detailed species identification based on morphology, as commonly employed by museums. In the present study, we aimed to identify a stranded Bryde’s whale on Hainan Island, China by extracting DNA from a vertebra pre-treated by physical and/or chemical processes. Based on morphological characteristics, this Bryde’s whale was initially determined as Balaenoptera edeni. Then, DNA was efficiently extracted using ancient DNA techniques. The mitochondrial gene (COI) phylogenetic analysis further revealed that this museum whale specimen belonged to the sub-species B. e. edeni. This study provides a testable and rapid method for museum species verification, by using ancient DNA extraction methods to compensate the disadvantage of traditional DNA extraction methods that are difficult to extract valid DNA.
Cognitive-Behavioral Divergence Is Greater Across Alternative Male Reproductive Phenotypes Than Between the Sexes in a Wild Wrasse
Authors: Cummings Molly E. , Marsh-Rollo Susan E. , Alonzo Suzanne H.
Published: July 2022

Sexual selection is a powerful diversifier of phenotype, behavior and cognition. Here we compare cognitive-behavioral traits across four reproductive phenotypes (females and three alternative males) of wild-caught ocellated wrasse (Symphodus ocellatus). Both sex and alternative male phenotypes are environmentally determined with sex determination occuring within the first year, and males transition between alternative phenotypes across 2 years (sneaker to satellite or satellite to nesting). We captured 151 ocellated wrasse and tested them on different behavior and cognition assays (scototaxis, shoaling, and two detour-reaching tasks). We found greater divergence across alternative male reproductive phenotypes than differences between the sexes in behavior, problem-solving, and relationships between these traits. Nesting males were significantly less bold than others, while sneaker males were faster problem-solvers and the only phenotype to display a cognitive-behavioral syndrome (significant correlation between boldness and problem-solving speed). Combining these results with prior measurements of sex steroid and stress hormone across males, suggests that nesting and sneaker males represent different coping styles. Our data suggests that transitioning between alternative male phenotypes requires more than changes in physiology (size and ornamentation) and mating tactic (sneaking vs. cooperation), but also involves significant shifts in cognitive-behavioral and coping style plasticity.
Examination of the Cell Cycle Dependence of Cytosine and Adenine Base Editors
Authors: Burnett Cameron A. , Wong Ashley T. , Vasquez Carlos A. , McHugh Colleen A. , Yeo Gene W. , Komor Alexis C.
Published: July 2022

Base editors (BEs) are genome editing agents that install point mutations with high efficiency and specificity. Due to their reliance on uracil and inosine DNA damage intermediates (rather than double-strand DNA breaks, or DSBs), it has been hypothesized that BEs rely on more ubiquitous DNA repair pathways than DSB-reliant genome editing methods, which require processes that are only active during certain phases of the cell cycle. We report here the first systematic study of the cell cycle-dependence of base editing using cell synchronization experiments. We find that nickase-derived BEs (which introduce DNA backbone nicks opposite the uracil or inosine base) function independently of the cell cycle, while non-nicking BEs are highly dependent on S-phase (DNA synthesis phase). We found that synchronization in G1 (growth phase) during the process of cytosine base editing causes significant increases in C•G to A•T “byproduct” introduction rates, which can be leveraged to discover new strategies for precise C•G to A•T base editing. We observe that endogenous expression levels of DNA damage repair pathways are sufficient to process base editing intermediates into desired editing outcomes, and the process of base editing does not significantly perturb transcription levels. Overall, our study provides mechanistic data demonstrating the robustness of nickase-derived BEs for performing genome editing across the cell cycle.
A Genetic Polymorphism in the WDR72 Gene is Associated With Calcium Nephrolithiasis in the Chinese Han Population
Authors: Wang Lujia , Zhou Zijian , Yang Yuanyuan , Gao Peng , Lin Xiaoling , Wu Zhong
Published: July 2022

A previous genome-wide association study (GWAS) reported several novel loci for nephrolithiasis in British and Japanese population, some of which were predicted to influence CaSR signaling. In this study, we aimed to evaluate the association of these loci with calcium nephrolithiasis in Chinese Han population. We performed a case-control association analysis involving 691 patients with calcium nephrolithiasis and 1008 control subjects. We were able to genotype a total of 17 single-nucleotide polymorphisms (SNPs), which were previously reported to be significantly associated with nephrolithiasis in GWAS. rs578595 at WDR72 was significantly associated with calcium nephrolithiasis in Chinese Han population (p < 0.001, OR = 0.617). Moreover, rs12654812 at SLC34A1 (p = 0.0427, OR = 1.170), rs12539707 at HIBADH (p = 0.0179, OR = 0.734), rs1037271 at DGKH (p = 0.0096, OR = 0.828) and rs12626330 at CLDN14 (p = 0.0080, OR = 1.213) indicated suggestive associations with calcium nephrolithiasis. Our results elucidated the significance of genetic variation at WDR72, DGKH, CLDN14, SLC34A1, and HIBADH in Chinese patients with nephrolithiasis. Since polymorphisms of WDR72, DGKH, and CLDN14 are predicted to influence in CaSR signaling, our results emphasized the role of abnormal calcium homeostasis in calcium nephrolithiasis.
Identification of the KCNQ1OT1/ miR-378a-3p/ RBMS1 Axis as a Novel Prognostic Biomarker Associated With Immune Cell Infiltration in Gastric Cancer
Authors: Yue Ting , Li Jingjing , Liang Manguang , Yang Jiaman , Ou Zhiwen , Wang Shuchen , Ma Wuhua , Fan Dehui
Published: July 2022

Background: Gastric cancer (GC) is the second leading cause of cancer-related mortality and the fifth most common cancer worldwide. However, the underlying mechanisms of competitive endogenous RNAs (ceRNAs) in GC are unclear. This study aimed to construct a ceRNA regulation network in correlation with prognosis and explore a prognostic model associated with GC.

Methods: In this study, 1,040 cases of GC were obtained from TCGA and GEO datasets. To identify potential prognostic signature associated with GC, Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression were employed. The prognostic value of the signature was validated in the GEO84437 training set, GEO84437 test set, GEO15459 set, and TCGA-STAD. Based on the public databases, TargetScan and starBase, an mRNA-miRNA-lncRNA regulatory network was constructed, and hub genes were identified using the CytoHubba plugin. Furthermore, the clinical outcomes, immune cell infiltration, genetic variants, methylation, and somatic copy number alteration (sCNA) associated with the ceRNA network were derived using bioinformatics methods.

Results: A total of 234 prognostic genes were identified. GO and GSEA revealed that the biological pathways and modules related to immune response and fibroblasts were considerably enriched in GC. A nomogram was generated to provide accurate prognostic outcomes and individualized risk estimates, which were validated in the training, test dataset, and two independent validation datasets. Thereafter, an mRNA-miRNA-lncRNA regulatory network containing 4 mRNAs, 22 miRNAs, 201 lncRNAs was constructed. The KCNQ1OT1/hsa-miR-378a-3p/RBMS1 ceRNA network associated with the prognosis was obtained by hub gene analysis and correlation analysis. Importantly, we found that the KCNQ1OT1/miR-378a-3p/RBMS1 axis may play a vital role in the diagnosis and prognosis of GC patients based on Cox regression analyses. Furthermore, our findings demonstrated that mutations and sCNA of the KCNQ1OT1/miR-378a-3p/RBMS1 axis were associated with increased immune infiltration, while the abnormal upregulation of the axis was primarily a result of hypomethylation.

Conclusion: Our findings suggest that the KCNQ1OT1/miR-378a-3p/RBMS1 axis may be a potential prognostic biomarker and therapeutic target for GC. Moreover, such findings provide insights into the molecular mechanisms of GC pathogenesis.
Relevance of RNA N6-Methyladenosine Regulators for Pulmonary Fibrosis: Implications for Chronic Hypersensitivity Pneumonitis and Idiopathic Pulmonary Fibrosis
Authors: Zhou Yiyi , Fang Chen , Sun Qinying , Dong Yuchao
Published: July 2022

N6-methyladenosine (m6A) modification plays a pivotal role in post-transcriptionally regulating gene expression and biological functions. Nonetheless, the roles of m6A modification in the regulation of chronic hypersensitivity pneumonitis (CHP) and idiopathic pulmonary fibrosis (IPF) remain unclear. Twenty-two significant m6A regulators were selected from differential gene analysis between the control and treatment groups from the GSE150910 dataset. Five candidate m6A regulators (insulin-like growth factor binding protein 2, insulin-like growth factor binding protein 3, YTH domain-containing protein 1, zinc finger CCCH domain-containing protein 13, and methyltransferase-like 3) were screened by the application of a random forest model and nomogram model to predict risks of pulmonary fibrosis. The consensus clustering method was applied to divide the treatment samples into two groups with different m6A patterns (clusters A and B) based on the 22 m6A regulators. Our study performed principal component analysis to obtain the m6A-related score of the 288 samples to quantify the two m6A patterns. The study reveals that cluster A was linked to T helper cell (Th) 2-type cytokines, while the immune infiltration of Th1 cytokines was higher in cluster B. Our results suggest that m6A cluster A is likely related to pulmonary fibrosis, indicating m6A regulators play notable roles in the occurrence of pulmonary fibrosis. The m6A patterns could be considered as biomarkers to identify CHP and IPF, which will be helpful to develop immunotherapy strategies for pulmonary fibrosis in the future.
Knowledge and Expectations of Perinatal Care Among Pregnant Women During the COVID-19 Pandemic
Authors: Lim Caleb Chun Wei , Goh Marlene Samantha Sze Minn , Chua Ka-Hee , Seet Meei Jiun , Tay Siew Guek , Mathur Manisha , Kong Juin Yee , Yeo Kee Thai
Published: July 2022

Introduction

This study aimed to investigate the knowledge and expectations of pregnant women on perinatal care during the coronavirus disease 2019 (COVID-19) pandemic.

Methods

A cross-sectional survey was conducted among pregnant women ≥21 years, without a history of confirmed COVID-19, attending antenatal clinics between August and September 2020 via a secure online platform. The survey consisted of 10 questions which evaluated the knowledge and expectations on perinatal and neonatal care during the current pandemic.

Results

A total of 313 pregnant women completed the survey. The mean age of the participants was 30 years (SD 4; range 22–43 years). The median gestational age was 25 weeks (range 4–40 weeks). The participants were predominantly multiparous (54%) and almost all (98%) had completed secondary level education. Majority of participants were aware of the spread of COVID-19 by respiratory secretions and contact (90%), and the importance of prevention strategies (94%). Up to 72% agreed or strongly agreed that in-utero transmission of SARS-CoV-2 was possible. Most were unsure of the optimal mode of delivery (77%) and only 22% believed that breastfeeding was safe in a pregnant woman with active COVID-19. Although 46% were concerned about increased transmission risk with antenatal clinic visits, only 37% were agreeable to teleconferencing of clinic appointments. Maternal age >35 years was significantly associated with agreement with separation of mother-infant after birth [AOR 1.89 (95% CI 1.05, 3.39)], restrictions of visitors during the postnatal period [1.92 (1.05, 3.49)] and having their confinement practices were affected [2.3 (1.26, 4.17)]. Pregnant women who were multiparous disagreed that breastfeeding was safe in women with active COVID-19 [0.42 (0.23, 0.75)].

Conclusions

There was significant uncertainty about the optimal delivery method and safety of breastfeeding with COVID-19 among expectant mothers, along with variable agreement with alterations to routine perinatal care.
Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo
Authors: Wang Xue , Wang Rui , Bu Dingfang , Wang Leyi , Zhang Yuexin , Chang Yuan , Zhang Chenyang , Chen Xixue , Zhu Xuejun , Liu Zhi , Wang Mingyue
Published: July 2022

Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease associated with underlying neoplasms and characterized by antibodies against desmoglein 3 (Dsg 3) and plakins. Autoantibodies against desmoglein 3 in sera of patients with PNP have been proven to cause acantholysis in vivo in neonatal mice. As a member of the plakin family, autoantibodies against desmoplakin were detected frequently by immunoprecipitation in the sera of PNP. The recombinant C-terminus of desmoplakin was expressed and purified to adsorb the specific autoantibodies against the C-terminus of desmoplakin. In vitro dispase-dependent keratinocyte dissociation assay and in vivo IgG passive transfer into neonatal mice assay were performed, followed by the electronic microscopy examination and TUNEL assay. We found that anti-C terminus of desmoplakin autoantibodies caused blisters and acantholysis in mice skin at a dose-dependent manner. Moreover, dissociated fragments were observed after incubation with the purified IgG against desmoplakin, compared with normal human IgG (P-value =0.0207). The electronic microscopy examination showed the disconnection of keratin intermediate filaments from desmosomes. Lastly, apoptosis of keratinocytes in the TUNEL assay was all detected in the skins of neonatal mice after injection of the anti-C terminus of desmoplakin autoantibodies. Taken together, the study suggests that autoantibodies against the C-terminus of desmoplakin might be pathogenic in PNP.
Infiltration Patterns of Cervical Epithelial Microenvironment Cells During Carcinogenesis
Authors: Zhang Jianwei , Meng Silu , Zhang Xiuqing , Shao Kang , Lin Cong
Published: July 2022

Background

Local cellular microenvironment plays a crucial role in the HPV-induced cervical malignant transformation. Characterization of the dynamic infiltration changes of microenvironment cells during cervical carcinogenesis would contribute to a better understanding of involved mechanisms.

Methods

Three public gene expression datasets of cervical squamous epithelium samples were collected and combined. We applied seven up-to-date computational methods for infiltrating estimation and compared their results (CD4+ and CD8+ T cells) to the known fraction. After benchmarking the applied methods, the cell filtration patterns were determined and clustered through fuzzy c-means algorithm.

Results

Most methods displayed better performance in predicting the abundance of CD4+ T cell than that of CD8+ T cell. The infiltration patterns of 33 microenvironment cell types (including 31 immune cells and 2 non-immune cells) were determined, and five immune cell clusters with distinct features were then derived. Meanwhile, opposite changes in abundance were observed between the activated and resting state of some immune cells from the progression perspective.

Conclusions

Based on characteristics and evaluation performance of different methods, as well as previous findings, for the first time we provide a comprehensive overview of the infiltration patterns of microenvironment cells throughout cervical cancer progression.
Levamisole Suppresses CD4+ T-Cell Proliferation and Antigen-Presenting Cell Activation in Aplastic Anemia by Regulating the JAK/STAT and TLR Signaling Pathways
Authors: Wang Jiali , Liu Jia , Wang Mingyang , Zhao Fei , Ge Meili , Liu Li , Jiang Erlie , Feng Sizhou , Han Mingzhe , Pei Xiaolei , Zheng Yizhou
Published: July 2022

Aplastic anemia (AA) is a life-threatening disease primarily caused by a metabolic disorder and an altered immune response in the bone marrow (BM) microenvironment, where cytotoxic immune cells attack resident cells and lead to hematopoietic failure. We previously reported an efficient strategy by applying cyclosporin (CSA) combined with levamisole (CSA+LMS-based regimen) in the treatment of AA, but the immunoregulatory mechanism of LMS was still unclear. Here, the therapeutic effects of LMS were examined in vivo using the BM failure murine model. Meanwhile, the proportion and related function of T cells were measured by flow cytometry in vivo and in vitro. The involved signaling pathways were screened by RNA-seq and virtual binding analysis, which were further verified by interference experiments using the specific antagonists on the targeting cells by RT-PCR in vitro. In this study, the CSA+LMS-based regimen showed a superior immune-suppressive response and higher recession rate than standard CSA therapy in the clinical retrospective study. LMS improved pancytopenia and extended the survival in an immune-mediated BM failure murine model by suppressing effector T cells and promoting regulatory T-cell expansion, which were also confirmed by in vitro experiments. By screening of binding targets, we found that JAK1/2 and TLR7 showed the highest docking score as LMS targeting molecules. In terms of the underlying molecular mechanisms, LMS could inhibit JAK/STAT and TLR7 signaling activity and downstream involved molecules. In summary, LMS treatment could inhibit T-cell activation and downregulate related molecules by the JAK/STAT and TLR signaling pathways, supporting the valuable clinical utility of LMS in the treatment of AA.
Investigating the Mechanism of Germinal Center Shutdown
Authors: Arulraj Theinmozhi , Binder Sebastian C. , Meyer-Hermann Michael
Published: July 2022

Germinal centers (GCs) are transient structures where affinity maturation of B cells gives rise to high affinity plasma and memory cells. The mechanism of GC shutdown is unclear, despite being an important phenomenon maintaining immune homeostasis. In this study, we used a mathematical model to identify mechanisms that can independently promote contraction of GCs leading to shutdown. We show that GC shutdown can be promoted by antigen consumption by B cells, antigen masking by soluble antibodies, alterations in follicular dendritic cell (FDC) network area, modulation of immune complex cycling rate constants, alterations in T follicular helper signaling, increased terminal differentiation and reduced B cell division capacity. Proposed mechanisms promoted GC contraction by ultimately decreasing the number of B cell divisions and recycling cells. Based on the in-silico predictions, we suggest a combination of experiments that can be potentially employed by future studies to unravel the mechanistic basis of GC shutdown such as measurements of the density of pMHC presentation of B cells, FDC network size per B cell, fraction of cells expressing differentiation markers. We also show that the identified mechanisms differentially affect the efficiency of GC reaction estimated based on the quantity and quality of resulting antibodies.
SARS-CoV2 Infection During Pregnancy Causes Persistent Immune Abnormalities in Women Without Affecting the Newborns
Authors: Vazquez-Alejo Elena , Tarancon-Diez Laura , Carrasco Itzíar , Vigil-Vázquez Sara , Muñoz-Chapuli Mar , Rincón-López Elena , Saavedra-Lozano Jesús , Santos-Sebastián Mar , Aguilera-Alonso David , Hernanz-Lobo Alicia , Santiago-García Begoña , de León-Luis Juan Antonio , Muñoz Patricia , Sánchez-Luna Manuel , Navarro María Luisa , Muñoz-Fernández Mª Ángeles
Published: July 2022

SARS-CoV2 infection in pregnancy and exposed newborns is poorly known. We performed a longitudinal analysis of immune system and determined soluble cytokine levels in pregnant women infected with SARS-CoV2 and in their newborns. Women with confirmed SARS-CoV2 infection and their exposed uninfected newborns were recruited from Hospital General Universitario Gregorio Marañón. Peripheral blood mononuclear cells (PBMCs), cord cells and plasma were collected at birth and 6 months later. Immunophenotyping of natural killer (NK), monocytes and CD4/CD8 T-cells were studied in cryopreserved PBMCs and cord cells by multiparametric flow cytometry. Up to 4 soluble pro/anti-inflammatory cytokines were assessed in plasma/cord plasma by ELISA assay. SARS-CoV2-infected mothers and their newborns were compared to matched healthy non-SARS-CoV2-infected mothers and their newborns. The TNFα and IL-10 levels of infected mothers were higher at baseline than those of healthy controls. Infected mothers showed increased NK cells activation and reduced expression of maturation markers that reverted after 6 months. They also had high levels of Central Memory and low Effector Memory CD4-T cell subsets. Additionally, the increased CD4- and CD8-T cell activation (CD154 and CD38) and exhaustion (TIM3/TIGIT) levels at baseline compared to controls remained elevated after 6 months. Regarding Treg cells, the levels were lower at infected mothers at baseline but reverted after 6 months. No newborn was infected at birth. The lower levels of monocytes, NK and CD4-T cells observed at SARS-CoV2-exposed newborns compared to unexposed controls significantly increased 6 months later. In conclusion, SARS-CoV2 infection during pregnancy shows differences in immunological components that could lead newborns to future clinical implications after birth. However, SARS-CoV2 exposed 6-months-old newborns showed no immune misbalance, whereas the infected mothers maintain increased activation and exhaustion levels in T-cells after 6 months.
Attribution of Plastic Sources Using Bayesian Inference: Application to River-Sourced Floating Plastic in the South Atlantic Ocean
Authors: Pierard Claudio M. , Bassotto Deborah , Meirer Florian , van Sebille Erik
Published: July 2022

Most marine plastic pollution originates on land. However, once plastic is at sea, it is difficult to determine its origin. Here we present a Bayesian inference framework to compute the probability that a piece of plastic found at sea came from a particular source. This framework combines information about plastic emitted by rivers with a Lagrangian simulation, and yields maps indicating the probability that a particle sampled somewhere in the ocean originates from a particular river source. We showcase the framework for floating river-sourced plastic released into the South Atlantic Ocean. We computed the probability as a function of the particle age at three locations, showing how probabilities vary according to the location and age. We computed the source probability of beached particles, showing that plastic found at a given latitude is most likely to come from the closest river source. This framework lays the basis for source attribution of marine plastic.
Graphene Oxide-Hybridized Waterborne Epoxy Coating for Simultaneous Anticorrosive and Antibiofilm Functions
Authors: Zhou Ying , Wang Haoran , Zhang Cheng , Zhou Qixin , Rodrigues Debora F.
Published: July 2022

Multifunctional coatings with simultaneous antibacterial and anticorrosive properties are essential for marine environments, oil and gas industry, medical settings, and domestic/public appliances to preserve integrity and functionality of pipes, instruments, and surfaces. In this work, we developed a simple and effective method to prepare graphene oxide (GO)-hybridized waterborne epoxy (GOWE) coating to simultaneously improve anticorrosive and antibacterial properties. The effects of different GO filler ratios (0.05, 0.1, and 0.5, 1 wt%) on the electrochemical and antibacterial behaviors of the waterborne epoxy coating were investigated over short- and long-term periods. The electrochemical behavior was analyzed with salt solution for 64 days. The antibacterial effect of GOWE coating was evaluated with Shewanella oneidensis (MR-1), which is a microorganism that can be involved in corrosion. Our results revealed that concentrations as low as 0.1 wt% of the GO was effective performance than the waterborne epoxy coating without graphene oxide. This result is due to the high hydrophilicity of the graphene oxide fillers, which allowed great dispersion in the waterborne epoxy coating matrix. Furthermore, this study used a corrosion relevant bacterium as a model organism, that is, Shewanella oneidensis (MR-1), which is more relevant for real-word applications. This as-prepared GO-hybridized waterborne polymeric hybrid film provides new insight into the application of 2D nanomaterial polymer composites for simultaneous anticorrosive and antibacterial applications.
One Year Overview and Follow-Up in a Post-COVID Consultation of Critically Ill Patients
Authors: González Jessica , Zuil María , Benítez Iván D. , de Gonzalo-Calvo David , Aguilar María , Santisteve Sally , Vaca Rafaela , Minguez Olga , Seck Faty , Torres Gerard , de Batlle Jordi , Gómez Silvia , Barril Silvia , Moncusí-Moix Anna , Monge Aida , Gort-Paniello Clara , Ferrer Ricard , Ceccato Adrián , Fernández Laia , Motos Ana , Riera Jordi , Menéndez Rosario , Garcia-Gasulla Darío , Peñuelas Oscar , Labarca Gonzalo , Caballero Jesús , Barberà Carme , Torres Antoni , Barbé Ferran
Published: July 2022

The long-term clinical management and evolution of a cohort of critical COVID-19 survivors have not been described in detail. We report a prospective observational study of COVID-19 patients admitted to the ICU between March and August 2020. The follow-up in a post-COVID consultation comprised symptoms, pulmonary function tests, the 6-minute walking test (6MWT), and chest computed tomography (CT). Additionally, questionnaires to evaluate the prevalence of post-COVID-19 syndrome were administered at 1 year. A total of 181 patients were admitted to the ICU during the study period. They were middle-aged (median [IQR] of 61 [52;67]) and male (66.9%), with a median ICU stay of 9 (5–24.2) days. 20% died in the hospital, and 39 were not able to be included. A cohort of 105 patients initiated the follow-up. At 1 year, 32.2% persisted with respiratory alterations and needed to continue the follow-up. Ten percent still had moderate/severe lung diffusion (DLCO) involvement (<60%), and 53.7% had a fibrotic pattern on CT. Moreover, patients had a mean (SD) number of symptoms of 5.7 ± 4.6, and 61.3% met the criteria for post-COVID syndrome at 1 year. During the follow-up, 46 patients were discharged, and 16 were transferred to other consultations. Other conditions, such as emphysema (21.6%), COPD (8.2%), severe neurocognitive disorders (4.1%), and lung cancer (1%) were identified. A high use of health care resources is observed in the first year. In conclusion, one-third of critically ill COVID-19 patients need to continue follow-up beyond 1 year, due to abnormalities on DLCO, chest CT, or persistent symptoms.
The Digital Twin in Medicine: A Key to the Future of Healthcare?
Authors: Sun Tianze , He Xiwang , Song Xueguan , Shu Liming , Li Zhonghai
Published: July 2022

There is a growing need for precise diagnosis and personalized treatment of disease in recent years. Providing treatment tailored to each patient and maximizing efficacy and efficiency are broad goals of the healthcare system. As an engineering concept that connects the physical entity and digital space, the digital twin (DT) entered our lives at the beginning of Industry 4.0. It is evaluated as a revolution in many industrial fields and has shown the potential to be widely used in the field of medicine. This technology can offer innovative solutions for precise diagnosis and personalized treatment processes. Although there are difficulties in data collection, data fusion, and accurate simulation at this stage, we speculated that the DT may have an increasing use in the future and will become a new platform for personal health management and healthcare services. We introduced the DT technology and discussed the advantages and limitations of its applications in the medical field. This article aims to provide a perspective that combining Big Data, the Internet of Things (IoT), and artificial intelligence (AI) technology; the DT will help establish high-resolution models of patients to achieve precise diagnosis and personalized treatment.
Gender-Diverse Inclusion in Immunological Research: Benefits to Science and Health
Authors: Peckham Hannah , Webb Kate , Rosser Elizabeth C. , Butler Gary , Ciurtin Coziana
Published: July 2022

The differences between male and female immune systems are an under-researched field, ripe for discovery. This is evidenced by the stark sex biases seen in autoimmunity and infectious disease. Both the sex hormones (oestrogen and testosterone), as well as the sex chromosomes have been demonstrated to impact immune responses, in multiple ways. Historical shortcomings in reporting basic and clinical scientific findings in a sex-disaggregated manner have led not only to limited discovery of disease aetiology, but to potential inaccuracies in the estimation of the effects of diseases or interventions on females and gender-diverse groups. Here we propose not only that research subjects should include bothcis-gender men andcis-gender women, but also transgender and gender-diverse people alongside them. The known interaction between the hormonal milieu and the sex chromosomes is inseparable incis-gender human research, without the confounders of puberty and age. By inclusion of those pursuing hormonal affirmation of their gender identity- the individual and interactive investigation of hormones and chromosomes is permitted. Not only does this allow for a fine-tuned dissection of these individual effects, but it allows for discovery that is both pertinent and relevant to a far wider portion of the population. There is an unmet need for detailed treatment follow-up of the transgender community- little is known of the potential benefits and risks of hormonal supplementation on the immune system, nor indeed on many other health and disease outcomes. Our research team has pioneered the inclusion of gender-diverse persons in our basic research in adolescent autoimmune rheumatic diseases. We review here the many avenues that remain unexplored, and suggest ways in which other groups and teams can broaden their horizons and invest in a future for medicine that is both fruitful and inclusive.
Speculation on the pathophysiology of musculoskeletal injury with COVID-19 infection
Authors: Veronesi Francesca , Contartese Deyanira , Martini Lucia , Visani Andrea , Fini Milena
Published: July 2022

Coronavirus disease 2019 (COVID-19) primarily affects the respiratory tract, but also many other organs and tissues, leading to different pathological pictures, such as those of the musculoskeletal tissues. The present study should be considered as a speculation on the relationship between COVID-19 infection and some frequent musculoskeletal pathologies, in particular sarcopenia, bone loss/osteoporosis (OP) and fracture risk and osteoarthritis (OA), to hypothesize how the virus acts on these pathologies and consequently on the tissue regeneration/healing potential. The study focuses in particular on the modalities of interaction of COVID-19 with Angiotensin-Converting Enzyme 2 (ACE2) and on the “cytokine storm.” Knowing the effects of COVID-19 on musculoskeletal tissues could be important also to understand if tissue regenerative/reparative capacity is compromised, especially in elderly and frail patients. We speculate that ACE2 and serine proteases together with an intense inflammation, immobilization and malnutrition could be the responsible for muscle weakness, altered bone remodeling, increase in bone fracture risk and inflammatory joint pathologies. Future preclinical and clinical studies may focus on the regenerative/reparative properties of the musculoskeletal tissues after COVID-19 infection, toward a personalized treatment usually based on scaffolds, cells, and growth factors.
Extracorporeal Membrane Oxygenation Supported Transbronchial Cryobiopsy in the Diagnosis of Severe Organizing Pneumonia: A Case Report
Authors: Zhang Xiaoyan , Wang Yuqiong , Feng Yingying , Zhao Ling , Zhang Yunxia , Yang Hanbo , Xing Bin , Guo Wenlin , Sun Ting , Zhan Qingyuan , Tian Ye
Published: July 2022

This case report describes a 58-year-old, never-smoking housewife with chief complaints of progressively worsening cough, dyspnea, and intermittent fever, who was initially misdiagnosed with community-acquired pneumonia (CAP). However, her pulse oximetry oxygen saturation continued to decline, and eventually, she underwent an endotracheal intubation. Fortunately, transbronchial cryobiopsy (TBCB) assisted by extracorporeal membrane oxygenation (ECMO) was performed in the most critical situation, and it revealed an organizing pneumonia (OP) pattern. OP describes a histological pattern of acute or subacute pulmonary damage, which may be idiopathic or associated with a known or unknown underlying disease. A definitive diagnosis of OP usually obtained from pathology, and surgical lung biopsy with large lung tissue is recommended. However, since the surgical lung biopsy was not convenient for this patient after mechanical ventilation, bedside TBCB supported by ECMO was selected. To our knowledge, we are the first to report the pathological diagnosis of ECMO assisted TBCB in acute respiratory failure. When oxygenation cannot be maintained after endotracheal intubation and surgical lung biopsy is not feasible, ECMO-supported TBCB may be a good choice to obtain lung tissue for histopathological diagnosis in patients with acute lung injury of unknown etiology.