bluuebunny/crossref_metadata_2025 huggingface dataset:
Periconceptional diet quality is associated with gestational diabetes risk and glucose concentrations among nulliparous gravidas
Authors: Lindsay Karen L. , Milone Gina F. , Grobman William A. , Haas David M. , Mercer Brian M. , Simhan Hyagriv N. , Saade George R. , Silver Robert M. , Chung Judith H.
Published: September 2022

Background

Gestational diabetes mellitus (GDM) and elevated glucose concentrations below the threshold for GDM diagnosis have been associated with adverse pregnancy and offspring outcomes. Dietary interventions initiated during pregnancy have demonstrated inconsistent beneficial effects. Limited data exist regarding the effects of periconceptional diet on gestational glycemia.

Objective

To evaluate independent associations between periconceptional diet quality with GDM frequency and glucose concentrations from GDM screening and diagnostic tests among nulliparous gravidas.

Design

This is a secondary analysis of N=7997 participants from the NuMoM2b multicenter, prospective, observational cohort study of first pregnancies. The Alternative Healthy Eating Index (AHEI)-2010 was computed from food frequency questionnaires completed in early pregnancy (6-13 weeks), reporting usual dietary intake over the preceding 3 months. GDM screening was performed either by non-fasting 1-hour 50g glucose load (N=6845), followed by 3-hour 100g glucose tolerance test (GTT) for those with raised glucose concentrations (N=1116; at risk for GDM), or by a single 2-hour 75g GTT (N=569; all GDM risk levels). Logistic and linear regression were used to estimate the associations between the AHEI-2010 score with odds of GDM, having raised blood glucose on the 1-hour screening test, and continuous glucose concentrations on screening and diagnostic tests. All models were adjusted for a priori covariates: maternal age, race/ethnicity, early-pregnancy body mass index, smoking habits, rate of gestational weight gain, energy intake, nausea and vomiting in early pregnancy, study site.

Results

Poorer periconceptional diet quality was observed among participants who were younger, with higher BMI, lower income levels, and of non-Hispanic Black or Hispanic ethnicity. The GDM rate was 4%. Each 1-point increase in AHEI-2010 score was associated with a 1% decrease in the odds of being diagnosed with GDM (beta=-0.015, p=0.022, OR=0.986, 95% CI 0.973 to 0.998). Diet quality was inversely associated with each post glucose load concentration on the non-fasting screening test and the 2-hour and 3-hour GTT.

Conclusion

Poor periconceptional diet quality is independently associated with an increased risk of GDM and with minor elevations in serum glucose concentrations on GDM screening and diagnostic tests, in a diverse cohort of nulliparas. Periconception intervention studies targeting diet quality are warranted.
Relationship between indices of circulating blood cells and bone homeostasis in osteoporosis
Authors: Li Yuan , Hao Weimin , Guan Jianming , Li Bo , Meng Li , Sun Shuangjiao , Sheng Tianyuan , Dong Shuangxi , Zhou Qian , Liu Mingjie , Zhang Zhongkai , Shen Tao , Shen Yuemao , Zhao Baobing
Published: September 2022

Bone development have been shown to play an important role in regulating hematopoiesis as one major component of bone marrow microenvironment. Recent studies support the notion that there is an intricate relationship between hematopoiesis and bone homeostasis, however, little is known about the alterations in the hematopoietic lineages in pathologic conditions. Using various osteoporotic mouse models, we show here that bone microarchitecture abnormalities alter parameters of peripheral blood cells. The level of white blood cells is dynamics and negatively correlated with bone mineral density during the progression of osteoporosis. Furthermore, our clinical data confirm that osteoporosis is associated with abnormal circulating blood cell counts. These results demonstrated a causal link that osteoporosis is accompanied by the altered circulating blood cells, supporting the idea of a close interplay between hematopoiesis and bone homeostasis. Our study would propose that routine complete blood count might be applied as a potential diagnostic and putative marker for osteoporosis.
Feasibility analysis of incorporating infertility into medical insurance in China
Authors: Wang Lin , Zhu Ye , Wang Tong , Xu Xinrong , Tang Qiuqin , Li Jinhui , Wang Yanchen , Hu Weiyue , Wu Wei
Published: September 2022

In recent years, the incidence of infertility has been increasing gradually, while the natural rate of population growth is declining or even at zero growth. China is observed to enter a depth of aging society, leading to more severe infertility. Infertility patients face many predicaments, and many unreasonable behaviors existed in seeking medical diagnosis and treatment, of which the main influencing factor is economic condition. In China, Beijing has taken the lead in providing medical insurance for 16 assisted reproductive technology items. Assuming that all infertile couples with the option of assisted reproduction are treated, there would be a huge market gap. The reimbursement rate can be adjusted based on some factors within the affordable range of the medical insurance fund. Progress on infertility coverage in other countries was also reviewed. This paper cited the data of medical insurance funds in China in the recent 4 years as a reference. Based on the data, it is not currently able to cover all the costs of infertility diagnosis and treatment during the research period, but it is feasible to access selective reimbursement and subsidies for those in particular need as well as to develop some commercial insurances. There is a big gap in the application of assisted reproductive technology between China and developed countries. More comprehensive and constructive policies should be formulated countrywide to standardize the market. Assisted reproduction-related technologies and acceleration of the domestic medical apparatus and instrument replacement should be improved to reduce the cost.
Integration of non-energy among the end-use demands of bottom-up whole-energy system models
Authors: Rixhon Xavier , Tonelli Davide , Colla Martin , Verleysen Kevin , Limpens Gauthier , Jeanmart Hervé , Contino Francesco
Published: September 2022

The complexity of bottom-up energy system models has progressively grown to enhance the representativeness of the system under analysis. Among them, whole-energy system models aim at representing the energy resources, conversion technologies, and energy demands of regions (i.e., a country) in its entirety. Despite this effort leading to an increased number of conversion processes modeled, the typologies of the end-use demand have remained limited to three categories: electricity, heat, and transportation. A fourth category, herein addressed as the non-energy demand, has widely been neglected. Being associated with the production of chemicals (i.e., plastics and fertilizers), the non-energy demand represents 10% of the world’s total end-use demand. Its relevance becomes fundamental in analyses that define the optimal defossilization pathways of energy systems with high dependence on fossil resources. This contribution introduces a schematic representation of the conversion processes involved in the satisfaction of the non-energy demand. Through its implementation in a bottom-up whole-energy system model, it evaluates the impact of this additional end-use in the configuration of the optimal energy system. In this study, the Belgian energy system, characterized by a penetration of the chemical and the petrochemical industries up to 20% of its total end-use demand, is taken as a reference case. The transition to a defossilized energy system is enforced through a snapshot analysis with a progressively more restrictive emissions cap. The results emphasize the role of renewable carriers (i.e., methanol and ammonia) in the defossilization of the energy system, otherwise hindered when the non-energy demand is neglected. The 100% import of these carriers at the lowest emissions cap highlights the potential dependence of the country under analysis, with limited availability of renewable resources, from countries exporting renewable methanol and ammonia.
Modelling the significance of value-belief-norm theory in predicting workplace energy conservation behaviour
Authors: Al Mamun Abdullah , Hayat Naeem , Mohiuddin Muhammad , Salameh Anas A. , Ali Mohd Helmi , Zainol Noor Raihani
Published: September 2022

A country’s energy usage can depict the development of its economy. Excessive energy consumption generates carbon emissions that degrade the climate and present challenges for sustainable global development. China is achieving economic development with excessive energy consumption and excessive carbon emissions, damaging the climate. As more energy is consumed at workplaces than in households and other buildings, energy conservation behaviors at workplaces can help mitigate environmental issues. In this study, we explore energy conservation behaviors in the workplace using the value-belief-norm (VBN) theory that has been extended and tested with survey data collected from China. Online survey-based data were collected from a total of 1,061 respondents and analyzed with partial least square regression structural equation modelling (PLS-SEM). The results of our analysis indicate that biospheric values significantly predict pro-environment beliefs, awareness of consequences, and ascription of responsibility. Moreover, pro-environment beliefs positively affect awareness of consequences, and awareness of consequences positively affects the ascription of responsibility. Findings further revealed that pro-environment beliefs, awareness of consequences, an ascription of responsibility, and social norms positively affect personal norms. Furthermore, social and personal norms lead to intentions to engage in energy conservation behavior, which influences energy conservation behavior in the workplace. The current study contributes to our knowledge and understanding about workplace energy conservation behaviors by constructing biospheric values that lead to developing the necessary beliefs and norms to activate energy conservation behaviors. Policy and managerial implications are reported, which involve inculcating the necessary values and beliefs that generate norms that lead to pro-climate behavior.
Role of technological innovation, renewable and non-renewable energy, and economic growth on environmental quality. Evidence from African countries
Authors: Wen Yuzhao , Onwe Joshua Chukwuma , Haseeb Mohammad , Saini Seema , Matuka Adelajda , Sahoo Deeptimayi
Published: September 2022

This study examines the impact of renewable and non-renewable energy consumption on carbon emissions, considering the role of population density, urbanization, foreign direct investment, technological innovation, and trade openness for African countries from 1990 to 2019. We apply an advanced econometric methodology like the cross-sectional autoregressive distributed model (CS-ARDL) for long-run and short-run estimation, which allows for the cross-sectional dependencies and slope heterogeneity. Our finding shows that the non-renewable resources, population density, urbanization, and foreign direct investment contribute to the carbon emissions; in contrast, renewable resources and trade openness reduce the carbon emissions in African countries. Results also report a unidirectional causality from non-renewable energy consumption to carbon emissions, while there is evidence of a feedback hypothesis between renewable energy consumption and carbon emissions. This study provides several policy implications for sustainable development.
Solar irradiance prediction based on self-attention recursive model network
Authors: Kang Ting , Wang Huaizhi , Wu Ting , Peng Jianchun , Jiang Hui
Published: September 2022

In recent years, with the continued development and popularity of sustainable energy sources and the increasing utilization of solar energy, accurate solar radiation prediction has become important. In this paper, we propose a new model based on deep learning, Feature-enhanced Gated Recurrent Unit, hereafter referred to as FEGRU, for solar radiation prediction. This model takes the source data with one-dimensional convolution and self-attention to feature attention and processes the data features, and then GRU performs feature extraction on solar irradiance data. Finally, the data dimensionality is transformed by a fully connected layer. The main advantage of FEGRU is that it does not require auxiliary data, but only time series data of solar irradiance can be used for good solar irradiance prediction. Our experiments with solar irradiance samples in Lyon, France, show that our model has better prediction results than the baseline model.
Freeze-thaw cycles alter soil hydro-physical properties and dissolved organic carbon release from peat
Authors: Liu Haojie , Rezanezhad Fereidoun , Zak Dominik , Li Xiujun , Lennartz Bernd
Published: September 2022

The ongoing climate warming is likely to increase the frequency of freeze-thaw cycles (FTCs) in cold-temperate peatland regions. Despite the importance of soil hydro-physical properties in water and carbon cycling in peatlands, the impacts of FTCs on peat properties as well as carbon sequestration and release remain poorly understood. In this study, we collected undisturbed topsoil samples from two drained lowland fen peatlands to investigate the impact of FTCs on hydro-physical properties as well as dissolved organic carbon (DOC) fluxes from peat. The soil samples were subject to five freeze-thaw treatments, including a zero, one, three, five, ten cycles (FTC0, FTC1, FTC3, FTC5, and FTC10, respectively). Each FTC was composed of 24 h of freezing (−5°C) and 24 h of thawing (5°C) and the soil moisture content during the freeze-thaw experiment was adjusted to field capacity. The results showed that the FTCs substantially altered the saturated hydraulic conductivity (Ks) of peat. For peat samples with low initial Ks values (e.g., < 0.2 × 10−5 m s−1), Ks increased after FTCs. In contrast, the Ks of peat decreased after freeze-thaw, if the initial Ks was comparably high (e.g., > 0.8 × 10−5 m s−1). Overall, the average Ks values of peatlands decreased after FTCs. The reduction in Ks values can be explained by the changes in macroporosity. The DOC experiment results revealed that the FTCs could increase DOC concentrations in leachate, but the DOC fluxes decreased mainly because of a reduction in water flow rate as well as Ks. In conclusion, soil hydraulic properties of peat (e.g., Ks) are affected by freezing and thawing. The dynamics of soil hydraulic properties need to be explicitly addressed in the quantification and modelling of the water flux and DOC release from peatlands.
Comparative study of two methods for rare earth elements analysis in human urine samples using inductively coupled plasma-mass spectrometry
Authors: Brouziotis Antonios Apostolos , Giarra Antonella , Marano Alessandra , Di Nunzio Aldo , Lombardo Francesco , Guida Marco , Libralato Giovanni , Trifuoggi Marco
Published: September 2022

The application of rare earth elements (REEs) in several areas, including high-tech technology, agriculture, medicine, and fuels, has made them an essential component of our everyday life. This extensive use of REEs in several technologies is expected to potentially impact human health. Even if several studies investigated the levels of REEs in human matrices, until now no standard method has been established for analyzing these elements in human matrices. The sample analysis should be of high quality, and the methods should be validated properly to ensure the quality of the procedure and traceability of the analytical data. In this research, we compared the validation and effectiveness of two different methods of sample preparation for human urine samples: a simple dilution of the sample (DIL) was compared with microwave assisted-acid decomposition (MIN) for tracing REE levels in human urine samples. The analysis was carried out by inductively coupled plasma mass spectrometry (ICP-MS). The working conditions have been set in high-sensitivity mode. Accuracy of the proposed method was evaluated by spiking the sample matrix with known concentrations of analyte standards. Both methods showed adequate precision of repeatability and intra-laboratory reproducibility, with the DIL method showing better precision of both repeatability and reproducibility than the MIN method. The CVr% values of repeatability range from 1.5 to 12% for the DIL and from 8.4 to 16% for the MIN method. The CVr% values of reproducibility range from 6.2–23% for the DIL and from 8.6 to 24% for the MIN method. REE recoveries for both methods were very close to 100%. Both methods proved to be effective for the determination of REE levels in human urine matrices.
Seasonal co-pollution characteristics of parent-PAHs and alkylated-PAHs in karst mining area soil of Guizhou, Southwest China
Authors: An Xianjin , Li Wei , Lan Jiacheng , Di Xinyue , Adnan Muhammad
Published: September 2022

The research on polycyclic aromatic hydrocarbons (PAHs) in karst soil mainly focuses on 16 kinds of parent-PAHs (p- PAHs), and little attention is given to alkylated-PAHs (a-PAHs) with higher concentration and greater toxicity. Five surface soils of coal mining area and their surrounding areas in karst area were sampled as subject investigated, and the spatiotemporal pollution characteristics of p-PAHs and a-PAHs were analyzed to discuss the impact of karst soil properties and environmental conditions on the migration of a-PAHs. The research results showed that the pollution concentration of a-PAHs in the soil of the southwestern karst area, especially the coal mining area, was significantly higher compared to the 16 kinds of p-PAHs, and the average concentration of the p-PAHs was 177.29 ± 37.36 ng/g; the concentration of a-PAHs was 346.87 ± 104.91 ng/g; the concentration of PAHs presented a seasonal pattern of that in winter > spring > autumn > summer. At the same time, seasonal rainfall could affect and change the occurrence state of PAHs in karst soils, but the effect on p-PAHs was weaker than on a-PAHs. The concentration of PAHs in the coal mining area and forest soil were 651.68 ng/g and 755.38 ng/g, respectively, so they belonged to contaminated soil, while the concentrations of two cultivated soil and abandoned soil were 475.51 ng/g, 367.58 ng/g and 370.63 ng/g, respectively, belonging to weakly contaminated. Toxicity assessment showed that p-BaP with a maximum toxic equivalent of 62.35 ng/g, C1-BaP (42.09 ng/g), DaA (37.82 ng/g) and C1-3 BaA (25.91 ng/g) were toxic PAHs with higher risk. The results of the correlation study showed that soil organic carbon, soil clay and soil calcium content were the dominant factors affecting the spatiotemporal distribution of PAHs of soils in karst coal mining areas and their surrounding areas. The research can provide data guidance for the management, control and restoration of soil pollution in karst areas, and offer a reference for Guizhou province to implement the big-ecological strategy.
Identification, expression, and association analysis of calcineurin B-like protein–interacting protein kinase genes in peanut
Authors: Ren Weifang , Zhang Juncheng , He Jie , Fang Jiahai , Wan Liyun
Published: September 2022

Plants usually respond to the external environment by initiating a series of signal transduction processes mediated by protein kinases, especially calcineurin B-like protein–interacting protein kinases (CIPKs). In this study, 54 CIPKs were identified in the peanut genome, of which 26 were from cultivated species (named AhCIPKs) and 28 from two diploid progenitors (Arachis duranensis—AdCIPKs and Arachis ipaensis—AiCIPKs). Evolution analysis revealed that the 54 CIPKs were composed of two different evolutionary branches. The CIPK members were unevenly distributed at different chromosomes. Synteny analysis strongly indicated that whole-genome duplication (allopolyploidization) contributed to the expansion of CIPK. Comparative genomics analysis showed that there was only one common collinear CIPK pairs among peanut, Arabidopsis, rice, grape, and soybean. The prediction results of cis-acting elements showed that AhCIPKs, AdCIPKs, and AiCIPKs contained different proportions of transcription factor binding motifs involved in regulating plant growth, abiotic stress, plant hormones, and light response elements. Spatial expression profiles revealed that almost all AhCIPKs had tissue-specific expression patterns. Furthermore, association analysis identified one polymorphic site in AdCIPK12 (AhCIPK11), which was significantly associated with pod length, seed length, hundred seed weight, and shoot root ratio. Our results provide valuable information of CIPKs in peanut and facilitate better understanding of their biological functions.
Systematic selections and forensic application evaluations of 111 individual identification SNPs in the Chinese Inner Mongolia Manchu group
Authors: Zhao Congying , Xu Hui , Fang Yating , Zhao Ming , Lan Qiong , Chen Man , Mei Shuyan , Zhu Bofeng
Published: September 2022

Single nucleotide polymorphism (SNP) possesses a promising application in forensic individual identification due to its wide distribution in the human genome and the ability to carry out the genotyping of degraded biological samples by designing short amplicons. Some commonly used individual identification SNPs are less polymorphic in East Asian populations. In order to improve the individual identification efficiencies in East Asian populations, SNP genetic markers with relatively higher polymorphisms were selected from the 1,000 Genome Project phase III database in East Asian populations. A total of 111 individual identification SNPs (II-SNPs) with the observed heterozygosity values greater than 0.4 were screened in East Asian populations, and then, the forensic efficiencies of these selected SNPs were also evaluated in Chinese Inner Mongolia Manchu group. The observed heterozygosity and power of discrimination values at 111 II-SNPs in the Inner Mongolia Manchu group ranged from 0.4011 to 0.7005, and 0.5620 to 0.8025, respectively, and the average value of polymorphism information content was greater than 0.3978. The cumulative match probability and combined probability of exclusion values at II-SNPs were 7.447E-51 and 1-4.17E-12 in the Inner Mongolia Manchu group, respectively. The accumulative efficiency results indicated that the set of II-SNPs could be used as a potential tool for forensic individual identification and parentage testing in the Manchu group. The sequencing depths ranged from 781× to 12374×. And the mean allele count ratio and noise level were 0.8672 and 0.0041, respectively. The sequencing results indicated that the SNP genetic marker detection based on the massively parallel sequencing technology for SNP genetic markers had high sequencing performance and could meet the sequencing requirements of II-SNPs in the studied group.
The role of ACE1 I/D and ACE2 polymorphism in the outcome of Iranian COVID-19 patients: A case-control study
Authors: Faridzadeh Arezoo , Mahmoudi Mahmoud , Ghaffarpour Sara , Zamani Mohammad Saber , Hoseinzadeh Akram , Naghizadeh Mohammad Mehdi , Ghazanfari Tooba
Published: September 2022

Background: Since the beginning of the pandemic of coronavirus disease 2019 (COVID-19), many countries have experienced a considerable number of COVID-19 cases and deaths. The etiology of a broad spectrum of symptoms is still debated. Host genetic variants might also significantly influence the outcome of the disease. This study aimed to evaluate the association of angiotensin-converting enzyme (ACE1) gene Insertion/Deletion (I/D) polymorphism (rs1799752) and ACE2 gene rs1978124 single nucleotide polymorphism with the COVID-19 severity.

Methods: This study was conducted on 470 COVID-19 patients and a control group of 56 healthy individuals across several major cities in Iran. The blood sample and clinical data were collected from the participants, and their ACE1 I/D and ACE2 rs1978124 polymorphisms were determined using polymerase chain reaction and PCR-RFLP, respectively. Serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and ACE1 were measured in the blood samples.

Results: We found that the ACE1 DD genotype frequency was inversely correlated with the risk of intubation (p = 0.017) and mortality in COVID-19 patients (p = 0.049). Even after adjustment, logistic regression demonstrated that this significant inverse association remained constant for the above variables at odds ratios of (OR) = 0.35 and Odds Ratio = 0.49, respectively. Also, in the expired (p = 0.042) and intubated (p = 0.048) groups with II + ID genotypes, the mean level of CRP was significantly higher than in the DD genotype group. Furthermore, in both intubated and expired groups, the mean serum level of ACE1 was higher compared with non-intubated and survived groups with II or II + ID genotypes. The results also indicated that ACE2 rs1978124 TT + CT genotypes in females have a significant positive role in susceptibility to COVID-19; however, in females, the TT + CT genotypes had a protective effect (OR = 0.098) against the severity of COVID-19.

Conclusion: These findings suggest that ACE1 I/D and ACE2 rs1978124 polymorphism could potentially influence the outcome of COVID-19 in the Iranian population.
Non-canonical DNA structures: Diversity and disease association
Authors: Bansal Aparna , Kaushik Shikha , Kukreti Shrikant
Published: September 2022

A complete understanding of DNA double-helical structure discovered by James Watson and Francis Crick in 1953, unveil the importance and significance of DNA. For the last seven decades, this has been a leading light in the course of the development of modern biology and biomedical science. Apart from the predominant B-form, experimental shreds of evidence have revealed the existence of a sequence-dependent structural diversity, unusual non-canonical structures like hairpin, cruciform, Z-DNA, multistranded structures such as DNA triplex, G-quadruplex, i-motif forms, etc. The diversity in the DNA structure depends on various factors such as base sequence, ions, superhelical stress, and ligands. In response to these various factors, the polymorphism of DNA regulates various genes via different processes like replication, transcription, translation, and recombination. However, altered levels of gene expression are associated with many human genetic diseases including neurological disorders and cancer. These non-B-DNA structures are expected to play a key role in determining genetic stability, DNA damage and repair etc. The present review is a modest attempt to summarize the available literature, illustrating the occurrence of non-canonical structures at the molecular level in response to the environment and interaction with ligands and proteins. This would provide an insight to understand the biological functions of these unusual DNA structures and their recognition as potential therapeutic targets for diverse genetic diseases.
Case report: Rare among ultrarare—Clinical odyssey of a new patient with Ogden syndrome
Authors: Hofman Jagoda , Hutny Michal , Chwialkowska Karolina , Korotko Urszula , Loranc Karolina , Kruk Anna , Lechowicz Urszula , Rozy Adriana , Gajdanowicz Pawel , Kwasniewski Miroslaw , Krajewska-Walasek Malgorzata , Paprocka Justyna , Jezela-Stanek Aleksandra
Published: September 2022

Introduction: The definition of ultra-rare disease in terms of its prevalence varies between the sources, usually amounting to ca. 1 in 1.000.000 births. Nonetheless, there are even less frequent disorders, such as Ogden syndrome, which up to this day was diagnosed in less than 10 patients worldwide. They present typically with a variety of developmental defects, including postnatal growth retardation, psychomotor delay and hypotonia. This disorder is caused by the heterozygous mutations in NAA10 gene, which encodes N-alpha-acetyltransferase 10, involved in protein biosynthesis. Therefore, Ogden syndrome belongs to the broader group of genetic disorders, collectively described as NAA10-related syndrome.

Case report: We present a case of a Polish male infant, born in 39. GW with c-section due to the pathological cardiotocography signal. Hypotrophy (2400 g) and facial dysmorphism were noted in the physical examination. From the first minute, the child required mechanical ventilation - a nasal continuous positive airway pressure. For the first 27 days, the patient was treated in a neonatal intensive care unit, where a series of examinations were conducted. On their basis, the presence of the following defects was determined: muscular ventricular septal defects, patent foramen ovale, pectus excavatum, clubfoot and axial hypotonia. Child was then consequently referred to the genetic clinic for counselling. Results of the tests allowed the diagnosis of Ogden syndrome. In the following months the patient’s condition worsened due to the numerous pulmonary infections. Despite the advanced treatment including the variety of medications, the patient eventually died at the age of 10 months.

Conclusion: This case report presents a tenth patient diagnosed with Ogden syndrome reported worldwide. It expands the morphologic and clinical phenotype, emphasizing the possible severity of pneumonological disorders in these patients, which may pose a greater threat to a child’s life than more frequently described cardiovascular dysfunctions associated with this syndrome.
Safety monitoring in inactivated COVID-19 vaccines by clinical pharmacists from a single center in China
Authors: Hu Min , Guo Wei , Liu Li , Yang Yu , Xu Qiling , Cheng Fang , Zeng Fang , Zhang Yu
Published: September 2022

Given that vaccine-induced adverse effects were mostly based on previous laboratory research and clinical trials, real-world data on the safety of coronavirus disease 2019 (COVID-19) vaccination were lacking. This study reported the adverse events (AEs) among inactivated COVID-19 vaccine recipients. Data were collected from a total of 2,808 hospital employees and their family members in Wuhan, China, with all of them receiving the first dose of inactivated COVID-19 vaccines from two pharmaceutical companies. The first dose was given between 29th April and 13th May 2021. A total of 2,732 vaccinees received the second dose between 27th May and 8th July 2021. The whole process of receiving the vaccine was monitored by clinical pharmacists, and the information on AEs including demographics, occurrence, types, and severity was recorded through an online questionnaire and telephone follow-up. Most of the common AEs were mild and tolerable, and the overall incidence of AEs was lower than the data from the safety profile in clinical trials. Moreover, the incidence of AEs in the first dose (21.30%, 598) was higher than that in the second dose (16.07%, 439). Furthermore, the first injection had more severe AEs (4, 0.14%) than the second injection (2, 0.07%). The AEs involved the skin, muscle, respiratory tract, gastrointestinal tract, cardiovascular system, and other tissues and systems. The most common AE was pain at the injection site (first dose: 10.19%, second dose: 12.55%). All the vaccinees with AEs for both doses recovered fully in the end. It was noted that some AEs might cause blood coagulation disorder and bleeding risk. Therefore, ongoing monitoring of AEs after COVID-19 vaccination is essential in evaluating the benefits and risks of each vaccine.
The bidirectional biological interplay between microbiome and viruses in periodontitis and type-2 diabetes mellitus
Authors: Tang Boyu , Yan Caixia , Shen Xin , Li Yan
Published: September 2022

Periodontitis was an inflammatory disease associated with a dysbiosis of the oral flora characterized by a chronic sustained inflammation inducing the resorption of alveolar bone and leading to tooth loss. Type 2 diabetes mellitus (T2D) was a metabolic disease caused by impaired insulin action. The oral microbiome played a crucial role in modulating both the innate and adaptive immune system during the trigger and exacerbation of periodontitis and T2D. The bidirectional relationship of T2D and periodontitis had been the focus of intensive research, but those were not well explored. In this commentary, an in-depth analysis of the changes of microbiome and bacterial metabolites in periodontitis with or without diabetes was described. The promotion of periodontitis to T2D might involve inflammatory factors/receptors, oxidative stress, microRNA and so on. The effect of diabetes on periodontitis might involve adipose factor pathway, AGE/RAGE and RANK/RANKL pathway etc. Generally, periodontitis and diabetes are closely related to the microecological-epithelial interaction, soft tissue degradation, bone coupling disorder, immune regulation and gene transcription. The viruses, including HBV, HCV, HSV-1, Coronavirus, HCMV, EBV, HIV, phageome and so on, played an important role in the development of T2D and periodontitis. An in-depth understanding of the relationship between microbiome and host was of great significance to clarify the bidirectional mechanisms, suggesting that the periodontitis or T2D remission will have a positive impact on the other.
Clinical application of transcranial magnetic stimulation in multiple sclerosis
Authors: Zhou Xiaoliang , Li Kailin , Chen Si , Zhou Wenbin , Li Jing , Huang Qing , Xu Tingting , Gao Zhiyuan , Wang Dongyu , Zhao Shuo , Dong Hao
Published: September 2022

Multiple sclerosis (MS) is a common chronic, autoimmune-mediated inflammatory and neurodegenerative disease of the central nervous system. The treatment of MS has enormous progress with disease-modifying drugs, but the complexity of the disease course and the clinical symptoms of MS requires personalized treatment and disease management, including non-pharmacological treatment. Transcranial magnetic stimulation (TMS) is a painless and non-invasive brain stimulation technique, which has been widely used in neurological diseases. In this review, we mainly focus on the progress of physiological assessment and treatment of TMS in MS.
Exploration of shared TF-miRNA‒mRNA and mRNA-RBP-pseudogene networks in type 2 diabetes mellitus and breast cancer
Authors: Tong Wu , Wenze Gu , Libing Hong , Yuchen Cao , Hejia Zhao , Xi Guo , Xiongyi Yang , Guoguo Yi , Min Fu
Published: September 2022

Type 2 diabetes mellitus (T2DM) has been confirmed to be closely associated with breast cancer (BC). However, the shared mechanisms between these diseases remain unclear. By comparing different datasets, we identified shared differentially expressed (DE) RNAs in T2DM and BC, including 427 mRNAs and 6 miRNAs from the GEO(Gene Expression Omnibus) database. We used databases to predict interactions to construct two critical networks. The transcription factor (TF)-miRNA‒mRNA network contained 236 TFs, while the RNA binding protein (RBP)-pseudogene-mRNA network showed that the pseudogene S-phase kinase associated protein 1 pseudogene 1 (SKP1P1) might play a key role in regulating gene expression. The shared mRNAs between T2DM and BC were enriched in cytochrome (CYP) pathways, and further analysis of CPEB1 and COLEC12 expression in cell lines, single cells and other cancers showed that they were strongly correlated with the survival and prognosis of patients with BC. This result suggested that patients with T2DM presenting the downregulation of CPEB1 and COLEC12 might have a higher risk of developing BC. Overall, our work revealed that high expression of CYPs in patients with T2DM might be a susceptibility factor for BC and identified novel gene candidates and immune features that are promising targets for immunotherapy in patients with BC.
Extracellular vesicles from Listeria monocytogenes-infected dendritic cells alert the innate immune response
Authors: Izquierdo-Serrano Raúl , Fernández-Delgado Irene , Moreno-Gonzalo Olga , Martín-Gayo Enrique , Calzada-Fraile Diego , Ramírez-Huesca Marta , Jorge Inmaculada , Camafeita Emilio , Abián Joaquín , Vicente-Manzanares Miguel , Veiga Esteban , Vázquez Jesús , Sánchez-Madrid Francisco
Published: September 2022

Communication through cell-cell contacts and extracellular vesicles (EVs) enables immune cells to coordinate their responses against diverse types of pathogens. The function exerted by EVs in this context depends on the proteins and nucleic acids loaded into EVs, which elicit specific responses involved in the resolution of infection. Several mechanisms control protein and nucleic acid loading into EVs; in this regard, acetylation has been described as a mechanism of cellular retention during protein sorting to exosomes. HDAC6 is a deacetylase involved in the control of cytoskeleton trafficking, organelle polarity and cell migration, defense against Listeria monocytogenes (Lm) infection and other immune related functions. Here, we show that the protein content of dendritic cells (DCs) and their secreted EVs (DEVs) vary during Lm infection, is enriched in proteins related to antiviral functions compared to non-infected cells and depends on HDAC6 expression. Analyses of the post-translational modifications revealed an alteration of the acetylation and ubiquitination profiles upon Lm infection both in DC lysates and DEVs. Functionally, EVs derived from infected DCs upregulate anti-pathogenic genes (e.g. inflammatory cytokines) in recipient immature DCs, which translated into protection from subsequent infection with vaccinia virus. Interestingly, absence of Listeriolysin O in Lm prevents DEVs from inducing this anti-viral state. In summary, these data underscore a new mechanism of communication between bacteria-infected DC during infection as they alert neighboring, uninfected DCs to promote antiviral responses.
Immune features of the peritumoral stroma in pancreatic ductal adenocarcinoma
Authors: Ahmed Azaz , Klotz Rosa , Köhler Sophia , Giese Nathalia , Hackert Thilo , Springfeld Christoph , Jäger Dirk , Halama Niels
Published: September 2022

Background

The peritumoral stroma is a hallmark of pancreatic ductal adenocarcinoma (PDA) with implications for disease development, progression and therapy resistance. We systematically investigated immune features of the stroma in PDA patients to identify markers of clinical importance and potential therapeutic targets.

Methods

Tissue and blood samples of 51 PDA patients with clinical and follow-up information were included. Laser Capture Microdissection allowed us to analyze the stromal compartment in particular. Systematic immunohistochemistry, followed by software-based image analysis were conducted. Also, multiplex cytokine analyses (including 50 immune-related molecules) were performed. Functional analyses were performed using patient-derived 3D bioprints. Clinical information was used for survival analyses. Intercompartmental IL9 and IL18 gradients were assessed in matched samples of tumor epithelium, stroma, and serum of patients. Serum levels were compared to an age-matched healthy control group.

Results

Stromal IL9 and IL18 are significantly associated with patient survival. While IL9 is a prognostic favorable marker (p=0.041), IL18 associates with poor patient outcomes (p=0.030). IL9 correlates with an anti-tumoral cytokine network which connects regulation of T helper (Th) 9, Th1 and Th17 cells (all: p<0.05 and r>0.5). IL18 correlates with a Th1-type cytokine phenotype and stromal CXCL12 expression (all: p<0.05 and r>0.5). Further, IL18 associates with a higher level of exhausted T cells. Inhibition of IL18 results in diminished Th1- and Th2-type cytokines. Patients with high stromal IL9 expression have a tumor-to-stroma IL9 gradient directed towards the stroma (p=0.019). Low IL18 expression associates with a tumor-to-stroma IL18 gradient away from the stroma (p=0.007). PDA patients showed higher serum levels of IL9 than healthy controls while serum IL18 levels were significantly lower than in healthy individuals. The stromal immune cell composition is distinct from the tumor epithelium. Stromal density of FoxP3+ regulatory T cells showed a tendency towards improved patient survival (p=0.071).

Conclusion

An unexpected high expression of the cytokines IL9 and IL18 at different ends is of significance in the stroma of PDA and relates to opposing patient outcomes. Sub-compartmental cytokine analyses highlight the importance of a differentiated gradient assessment. The findings suggest stromal IL9 and/or IL18 as markers for patient stratification and as potential therapeutic targets. Future steps include investigating e. g. the role of local microbiota as both cytokines are also regulated by microbial compositions.
Severe aplastic anemia patients with infection who received an allogeneic hematopoietic stem cell transplantation had a better chance: Long-term outcomes of a multicenter study
Authors: Liu Limin , Miao Miao , He Hailong , Wang Shunqing , Zhang Yanming , Guo Ailian , Jiao Wenjing , Lei Meiqing , Cai Yifeng , Shangguan Xiaohui , Liu Zefa , Xu Jinge , Li Xiaoli , Zhang Liansheng , Wu Depei
Published: September 2022

Background and aims

How to select the treatment is a challenge for the management of acquired patients with infections. This study aimed at comparing the outcomes of SAA with infections who had an allogeneic hematopoietic stem cell transplantation (allo-HSCT)with that of patients who had an infection and received non-HSCT therapy.

Methods

We retrospectively compared the outcomes of patients with acquired SAA and infections who had an allo-HSCT (n = 141) with that of patients who had an infection and received non-HSCT therapy (n = 186) between July 2004 and January 2020.

Results

The treatment-related mortality (TRM) of grade 1-2 infections in the HSCT and non-HSCT groups was 24.99% and 13.68%, respectively (P = 0.206), while the TRM of grade 3-4 infections was lower in the HSCT group than that observed in the non-HSCT group (18.54% vs. 33.33%, P = 0.036). At 6 months post-treatment, 91.30% patients in the HSCT group and 8.78% patients in the non-HSCT group had achieved a normal blood profile (P < 0.0001). The time required to discontinue transfusions of red blood cells and platelets in the non-HSCT group was longer than in the HSCT group (P < 0.0001). Estimated overall survival (OS) at 6 years was similar in the two groups (75.5% ± 3.9% vs. 76.3% ± 3.1%, P = 0.996), while the estimated failure-free survival (FFS) at 6 years was 75.2% ± 3.8% in the HSCT group and 48.9% ± 3.7% in the non-HSCT group (P < 0.0001). Multivariate analysis showed that younger age, lower grade of infection (grade 1-2), and SAA (vs. very SAA) were favorable factors for OS (P < 0.05), and that the choice of HSCT and younger age were favorable factors for FFS (P < 0.0001).

Conclusion

These results suggest that allo-HSCT has a better chance of a successful outcome than non-HSCT in SAA patients with an infection.
Decoding human-macaque interspecies differences in Fc-effector functions: The structural basis for CD16-dependent effector function in Rhesus macaques
Authors: Tolbert William D. , Gohain Neelakshi , Kremer Paul G. , Hederman Andrew P. , Nguyen Dung N. , Van Verna , Sherburn Rebekah , Lewis George K. , Finzi Andrés , Pollara Justin , Ackerman Margaret E. , Barb Adam W. , Pazgier Marzena
Published: September 2022

Fc mediated effector functions of antibodies play important roles in immunotherapies and vaccine efficacy but assessing those functions in animal models can be challenging due to species differences. Rhesus macaques, Macaca mulatta (Mm) share approximately 93% sequence identity with humans but display important differences in their adaptive immune system that complicates their use in validating therapeutics and vaccines that rely on Fc effector functions. In contrast to humans, macaques only have one low affinity FcγRIII receptor, CD16, which shares a polymorphism at position 158 with human FcγRIIIa with Ile158 and Val158 variants. Here we describe structure-function relationships of the Ile/Val158 polymorphism in Mm FcγRIII. Our data indicate that the affinity of the allelic variants of Mm FcγRIII for the macaque IgG subclasses vary greatly with changes in glycan composition both on the Fc and the receptor. However, unlike the human Phe/Val158 polymorphism in FcγRIIIa, the higher affinity variant corresponds to the larger, more hydrophobic side chain, Ile, even though it is not directly involved in the binding interface. Instead, this side chain appears to modulate glycan-glycan interactions at the Fc/FcγRIII interface. Furthermore, changes in glycan composition on the receptor have a greater effect for the Val158 variant such that with oligomannose type glycans and with glycans only on Asn45 and Asn162, Val158 becomes the variant with higher affinity to Fc. These results have implications not only for the better interpretation of nonhuman primate studies but also for studies performed with human effector cells carrying different FcγRIIIa alleles.
Initial activation of STAT2 induced by IAV infection is critical for innate antiviral immunity
Authors: Li Xinxin , Liu Siya , Rai Kul Raj , Zhou Wenzhuo , Wang Song , Chi Xiaojuan , Guo Guijie , Chen Ji-Long , Liu Shasha
Published: September 2022

STAT2 is an important transcription factor activated by interferons (IFNs) upon viral infection and plays a key role in antiviral responses. Interestingly, here we found that phosphorylation of STAT2 could be induced by several viruses at early infection stage, including influenza A virus (IAV), and such initial activation of STAT2 was independent of type I IFNs and JAK kinases. Furthermore, it was observed that the early activation of STAT2 during viral infection was mainly regulated by the RIG-I/MAVS-dependent pathway. Disruption of STAT2 phosphorylation at Tyr690 restrained antiviral response, as silencing STAT2 or blocking STAT2 Y690 phosphorylation suppressed the expression of several interferon-stimulated genes (ISGs), thereby facilitating viral replication. In vitro experiments using overexpression system or kinase inhibitors showed that several kinases including MAPK12 and Syk were involved in regulation of the early phosphorylation of STAT2 triggered by IAV infection. Moreover, when MAPK12 kinase was inhibited, expression of several ISGs was clearly decreased in cells infected with IAV at the early infection stage. Accordingly, inhibition of MAPK12 accelerated the replication of influenza virus in host. These results provide a better understanding of how initial activation of STAT2 and the early antiviral responses are induced by the viral infection.
RAB20 deficiency promotes the development of silicosis via NLRP3 inflammasome
Authors: Peng Zhouyangfan , Duan Mingwu , Zhao Kai , Tang Yiting , Liang Fang
Published: September 2022

Silicosis is a worldwide serious occupational disease that is caused by inhalation of silica crystals. However, little is known about the pathogenesis mechanism of silicosis. We performed single-cell sequencing in bronchoalveolar lavage fluid (BALF) from mine workers with silicosis and their co-workers who did not develop silicosis, and found that the RAB20 deficiency in monocytes/macrophages was strongly linked to the development of silicosis. In the silicosis murine model, RAB20 knockout markedly enhanced the silica crystal-induced pulmonary interstitial fibrosis and respiratory dysfunction. Moreover, this process is strongly accompanied by IL-1β release and NLRP3 activation. In vitro, RAB20 knockout macrophages aggravated the crystalline silica-induced IL-1β release and NLRP3 inflammasome activation partly by increased ratio of crystalline silica/phagosomal areas/volumes to induce lysosomal injury. Thus, these findings provide novel molecular insights into the intricate mechanisms underlying lysosomal protein RAB20 that are necessary for environmental irritant-mediated innate immunity, and shed light on the future development of novel therapy target for the prevention of silicosis.