bluuebunny/crossref_metadata_2025 huggingface dataset:
Case report: Clinical features of COVID-19 vaccine-induced exacerbation of psoriasis–A case series and mini review
Authors: Ständer Sascha , Zirpel Henner , Bujoreanu Florin , Tatu Alin Laurentiu , Ludwig Ralf J. , Thaçi Diamant
Published: September 2022

Recently, COVID-19 vaccination-induced exacerbation or new-onset of psoriasis have been reported. Underlying immune pathogenesis is unclear and different mechanisms are assumed. Further, clinical- and vaccine-related features and characteristics are partly inconsistent and remain to be elucidated. To add to the understanding of COVID-19 vaccination-triggered psoriasis, we report five cases with exacerbation or new-onset of psoriasis. In our cohort, one patient experienced the new onset of psoriasis, while four had an exacerbation following COVID-19 vaccination. In most patients, exacerbation or new onset occurred after the 2nd or 3rd vaccination. The mean latency from the day of vaccination was 7.2 (1.8) days (SD). The clinical impact with a mean PASI increase following COVID-19 vaccination of 7.2 (5.6) was considered relevant. In most cases, psoriatic lesions almost cleared after applying topical steroids in addition to current treatment, while one patient with psoriatic arthritis required systemic treatment. New onset and exacerbation of psoriasis have also been noted following COVID-19 infections. Hence, the underlying inflammatory response is most likely the culprit agent triggering psoriasis. This underscores that the benefits of COVID-19 vaccination far outweigh the risks, as also in patients with psoriasis.
Positive feedback between peanut and arbuscular mycorrhizal fungi with the application of hairy vetch in Ultisol
Authors: Xiang Xingjia , Zhang Jinyi , Li Guilong , Leng Ke , Sun Luyuan , Qin Wenjing , Peng Chunrui , Xu Changxu , Liu Jia , Jiang Yuji
Published: September 2022

Multiple agricultural practices are being applied to increase crop yield in order to overcome the food shortage. Green manure has emerged as an appropriate practice to improve soil fertility and crop yield. However, the potential functions of arbuscular mycorrhizal fungi (AMF) in the below-ground ecosystems following the application of green manure in Ultisols remain largely unexplored. In this study, qPCR and high-throughput sequencing were used to investigate the response of AMF abundance and communities in different treatment groups, i.e., control (without fertilization), mineral fertilization (NPK), mineral fertilization with returning peanut straw (NPKS), and with green manure (hairy vetch; NPKG). The NPKG treatment significantly increased soil fertility compared to other treatment groups. Compared with control, the NPK, NPKS, and NPKG treatments increased peanut yield by 12.3, 13.1, and 25.4%, respectively. NPKS and NPKG treatments significantly altered the AMF community composition decreased the AMF diversity and increased AMF abundance compared to the control. The AMF network of the NPKG treatment group showed the highest complexity and stability compared to other treatment groups. The structural equation modeling revealed that the application of hairy vetch improved soil nutrients and peanut yield by increasing the soil AMF abundance and network stability. Overall, the results suggested that the application of hairy vetch might trigger positive feedback between the peanut and AMF community, contributing to fertility and yield improvement in the dryland of Ultisol.
Controllable preparation of chitosan oligosaccharides via a recombinant chitosanase from marine Streptomyces lydicus S1 and its potential application on preservation of pre-packaged tofu
Authors: Chen Hao , Lin Bilian , Zhang Rui , Gong Zhouliang , Wen Ming , Su Weiming , Zhou Jinsong , Zhao Liangzhong , Wang Jianrong
Published: September 2022

Chitosan oligosaccharides (COSs) are widely applied in many areas due to its various biological activities. Controllable preparation of COSs with desired degree of polymerization (DP) via suitable chitosanase is of great value. Herein, a novel glycoside hydrolase (GH) family 46 chitosanase (SlCsn46) from marine Streptomyces lydicus S1 was prepared, characterized and used to controllably produce COSs with different DP. The specific activity of purified recombinant SlCsn46 was 1,008.5 U/mg. The optimal temperature and pH of purified SlCsn46 were 50°C and 6.0, respectively. Metal ions Mn2+ could improve the stability of SlCsn46. Additionally, SlCsn46 can efficiently hydrolyze 2% and 4% colloidal chitosan to prepare COSs with DP 2–4, 2–5, and 2–6 by adjusting the amount of SlCsn46 added. Moreover, COSs with DP 2–4, 2–5, and 2–6 exhibited potential application value for prolonging the shelf-life of pre-packaged Tofu. The water-holding capacity (WHC), sensorial properties, total viable count (TVC), pH and total volatile base nitrogen (TVB-N) of pre-packed tofu incorporated with 4 mg/mL COSs with DP 2–4, 2–5, and 2–6 were better than those of the control during 15 days of storage at 10°C. Thus, the controllable hydrolysis strategy provides an effective method to prepare COSs with desired DP and its potential application on preservation of pre-packed tofu.
Polyketides isolated from an endophyte Penicillium oxalicum 2021CDF-3 inhibit pancreatic tumor growth
Authors: Weng Wenya , Li Ruidian , Zhang Yanxia , Pan Xiaofu , Jiang Shicui , Sun Chuchu , Zhang Chi , Lu Xuemian
Published: September 2022

Fungal secondary metabolites are inherently considered valuable resources for new drugs discovery. To search for novel fungal secondary metabolites with lead compounds potential, a fungal strain Penicillium oxalicum 2021CDF-3, an endophyte of the marine red algae Rhodomela confervoides, was chemically studied. Cultivation of this fungus on solid rice medium yielded 10 structurally diverse metabolites (1–10), including two new polyketides, namely oxalichroman A (1) and oxalihexane A (2). Their structures were determined by detailed analysis of NMR and HRESIMS spectroscopic data. Oxalihexane A (2) was elucidated as a novel polyketide formed by a cyclohexane and cyclohexanone moiety via an ether bond. The stereochemistry of 2 was successfully assigned by NMR and ECD calculations. In the cytotoxic assay, the new compound 2 showed remarkable inhibitory effect on the human pancreatic cancer PATU8988T cell line. Further pharmacological study demonstrated that the expression level of Cyclin D1 was down-regulated by the treatment with 2, which suggested that cell cyclin abnormity was involved in pancreatic tumor cell apoptosis. Moreover, the activation of Wnt5a/Cyclin D1 signaling pathway might be involved in the mechanism of panreatic tumor cell apoptosis induced by 2.
Integrated analysis of the salivary microbiome and metabolome in chronic and aggressive periodontitis: A pilot study
Authors: Wei Yiping , Shi Meng , Nie Yong , Wang Cui , Sun Fei , Jiang Wenting , Hu Wenjie , Wu Xiaolei
Published: September 2022

This pilot study was designed to identify the salivary microbial community and metabolic characteristics in patients with generalized periodontitis. A total of 36 saliva samples were collected from 13 patients with aggressive periodontitis (AgP), 13 patients with chronic periodontitis (ChP), and 10 subjects with periodontal health (PH). The microbiome was evaluated using 16S rRNA gene high-throughput sequencing, and the metabolome was accessed using gas chromatography-mass spectrometry. The correlation between microbiomes and metabolomics was analyzed by Spearman’s correlation method. Our results revealed that the salivary microbial community and metabolite composition differed significantly between patients with periodontitis and healthy controls. Striking differences were found in the composition of salivary metabolites between AgP and ChP. The genera Treponema, Peptococcus, Catonella, Desulfobulbus, Peptostreptococcaceae_[XI] ([G-2], [G-3] [G-4], [G-6], and [G-9]), Bacteroidetes_[G-5], TM7_[G-5], Dialister, Eikenella, Fretibacterium, and Filifactor were present in higher levels in patients with periodontitis than in the healthy participants. The biochemical pathways that were significantly different between ChP and AgP included pyrimidine metabolism; alanine, aspartate, and glutamate metabolism; beta-alanine metabolism; citrate cycle; and arginine and proline metabolism. The differential metabolites between ChP and AgP groups, such as urea, beta-alanine, 3-aminoisobutyric acid, and thymine, showed the most significant correlations with the genera. These differential microorganisms and metabolites may be used as potential biomarkers to monitor the occurrence and development of periodontitis through the utilization of non-invasive and convenient saliva samples. This study reveals the integration of salivary microbial data and metabolomic data, which provides a foundation to further explore the potential mechanism of periodontitis.
Comparison of gut microflora of donkeys in high and low altitude areas
Authors: Guo Rong , Zhang Shuer , Chen Jianxing , Shen Wei , Zhang Guoliang , Wang Junjie , Zhang Fali , Pan Qingjie , Xie Taifeng , Ai Deqiang , Dong Jianbao , Suo Jiajia , Sun Yujiang , Liu Shuqin
Published: September 2022

Donkeys’ gut microbe is critical for their health and adaptation to the environment. Little research has been conducted on the donkey gut microbiome compared with other domestic animals. The Tibetan Plateau is an extreme environment. In this study, 6 Qinghai donkeys (QH) from the Tibetan Plateau and 6 Dezhou donkeys (DZ) were investigated, and the contents of 4 parts—stomach, small intestine, cecum, and rectum—were collected. 16S rRNA sequencing and metagenomic sequencing were used to analyze the composition and diversity of gut microbial communities in donkeys. The results showed that the flora diversity and richness of the hindgut were significantly higher than those of the foregut (p < 0.01), with no sex differences, and the community structure and composition of the same or adjacent regions (stomach, small intestine, cecum, and rectum) were similar. Besides, the flora diversity and richness of QH on the Tibetan Plateau were significantly higher than those of DZ (p < 0.05). The major pathways associated with QH were signal transduction mechanisms and carbohydrate transport and metabolism, and Bacteroidales were the major contributors to these functions. Our study provides novel insights into the contribution of microbiomes to the adaptive evolution of donkeys.
Soil-atmosphere fluxes of CO2, CH4, and N2O across an experimentally-grown, successional gradient of biocrust community types
Authors: Richardson Andrew D. , Kong Gary V. , Taylor Katrina M. , Le Moine James M. , Bowker Matthew A. , Barber Jarrett J. , Basler David , Carbone Mariah S. , Hayer Michaela , Koch George W. , Salvatore Mark R. , Sonnemaker A. Wesley , Trilling David E.
Published: September 2022

Biological soil crusts (biocrusts) are critical components of dryland and other ecosystems worldwide, and are increasingly recognized as novel model ecosystems from which more general principles of ecology can be elucidated. Biocrusts are often diverse communities, comprised of both eukaryotic and prokaryotic organisms with a range of metabolic lifestyles that enable the fixation of atmospheric carbon and nitrogen. However, how the function of these biocrust communities varies with succession is incompletely characterized, especially in comparison to more familiar terrestrial ecosystem types such as forests. We conducted a greenhouse experiment to investigate how community composition and soil-atmosphere trace gas fluxes of CO2, CH4, and N2O varied from early-successional light cyanobacterial biocrusts to mid-successional dark cyanobacteria biocrusts and late-successional moss-lichen biocrusts and as biocrusts of each successional stage matured. Cover type richness increased as biocrusts developed, and richness was generally highest in the late-successional moss-lichen biocrusts. Microbial community composition varied in relation to successional stage, but microbial diversity did not differ significantly among stages. Net photosynthetic uptake of CO2 by each biocrust type also increased as biocrusts developed but tended to be moderately greater (by up to ≈25%) for the mid-successional dark cyanobacteria biocrusts than the light cyanobacterial biocrusts or the moss-lichen biocrusts. Rates of soil C accumulation were highest for the dark cyanobacteria biocrusts and light cyanobacteria biocrusts, and lowest for the moss-lichen biocrusts and bare soil controls. Biocrust CH4 and N2O fluxes were not consistently distinguishable from the same fluxes measured from bare soil controls; the measured rates were also substantially lower than have been reported in previous biocrust studies. Our experiment, which uniquely used greenhouse-grown biocrusts to manipulate community composition and accelerate biocrust development, shows how biocrust function varies along a dynamic gradient of biocrust successional stages.
Conquering the host: Bordetella spp. and Pseudomonas aeruginosa molecular regulators in lung infection
Authors: Holban Alina M. , Gregoire Courtney M. , Gestal Monica C.
Published: September 2022

When bacteria sense cues from the host environment, stress responses are activated. Two component systems, sigma factors, small RNAs, ppGpp stringent response, and chaperones start coordinate the expression of virulence factors or immunomodulators to allow bacteria to respond. Although, some of these are well studied, such as the two-component systems, the contribution of other regulators, such as sigma factors or ppGpp, is increasingly gaining attention. Pseudomonas aeruginosa is the gold standard pathogen for studying the molecular mechanisms to sense and respond to environmental cues. Bordetella spp., on the other hand, is a microbial model for studying host-pathogen interactions at the molecular level. These two pathogens have the ability to colonize the lungs of patients with chronic diseases, suggesting that they have the potential to share a niche and interact. However, the molecular networks that facilitate adaptation of Bordetella spp. to cues are unclear. Here, we offer a side-by-side comparison of what is known about these diverse molecular mechanisms that bacteria utilize to counteract host immune responses, while highlighting the relatively unexplored interactions between them.
Residues from black soldier fly (Hermetia illucens) larvae rearing influence the plant-associated soil microbiome in the short term
Authors: Fuhrmann Adrian , Wilde Benjamin , Conz Rafaela Feola , Kantengwa Speciose , Konlambigue Matieyedou , Masengesho Barthazar , Kintche Kokou , Kassa Kinfe , Musazura William , Späth Leonhard , Gold Moritz , Mathys Alexander , Six Johan , Hartmann Martin
Published: September 2022

The larvae of the black soldier fly (BSFL, Hermetia illucens) efficiently close resource cycles. Next to the nutrient-rich insect biomass used as animal feed, the residues from the process are promising plant fertilizers. Besides a high nutrient content, the residues contain a diverse microbial community and application to soil can potentially promote soil fertility and agricultural production through the introduction of beneficial microbes. This research assessed the application of the residues on plant-associated bacterial and fungal communities in the rhizosphere of a grass-clover mix in a 42-day greenhouse pot study. Potted soil was amended with BSFL residues (BR+) or conventional compost (CC+) produced by Rwandan waste management companies in parallel to residues and compost sterilized (BR-, CC-) by high-energy electron beam (HEEB) as abiotic controls. The fertilizers were applied at a rate of 150  kg N  ha−1. Soil bacterial and fungal communities in both fertilizer and soil were assessed by high-throughput sequencing of ribosomal markers at different times after fertilizer application. Additionally, indicators for soil fertility such as basal respiration, plant yield and soil physicochemical properties were analyzed. Results showed that the application of BSFL residues influenced the soil microbial communities, and especially fungi, stronger than CC fertilizers. These effects on the microbial community structure could partly be attributed to a potential introduction of microbes to the soil by BSFL residues (e.g., members of genus Bacillus) since untreated and sterilized BSFL residues promoted different microbial communities. With respect to the abiotic effects, we emphasize a potential driving role of particular classes of organic matter like fiber and chitin. Indeed, especially taxa associated with decomposition of organic matter (e.g., members of the fungal genus Mortierella) were promoted by the application of BSFL residues. Soil fertility with respect to plant yield (+17% increase compared to unamended control) and basal respiration (+16% increase compared to unamended control) tended to be improved with the addition of BSFL residues. Findings underline the versatile opportunities for soil fertility arising from the application of BSFL residues in plant production and point to further research on quantification of the described effects.
The IRE1α pathway in glomerular diseases: The unfolded protein response and beyond
Authors: Navarro-Betancourt José R. , Cybulsky Andrey V.
Published: September 2022

Endoplasmic reticulum (ER) function is vital for protein homeostasis (“proteostasis”). Protein misfolding in the ER of podocytes (glomerular visceral epithelial cells) is an important contributor to the pathogenesis of human glomerular diseases. ER protein misfolding causes ER stress and activates a compensatory signaling network called the unfolded protein response (UPR). Disruption of the UPR, in particular deletion of the UPR transducer, inositol-requiring enzyme 1α (IRE1α) in mouse podocytes leads to podocyte injury and albuminuria in aging, and exacerbates injury in glomerulonephritis. The UPR may interact in a coordinated manner with autophagy to relieve protein misfolding and its consequences. Recent studies have identified novel downstream targets of IRE1α, which provide new mechanistic insights into proteostatic pathways. Novel pathways of IRE1α signaling involve reticulophagy, mitochondria, metabolism, vesicular trafficking, microRNAs, and others. Mechanism-based therapies for glomerulopathies are limited, and development of non-invasive ER stress biomarkers, as well as targeting ER stress with pharmacological compounds may represent a therapeutic opportunity for preventing or attenuating progression of chronic kidney disease.
Recent findings on the role of wild-type and mutant p53 in cancer development and therapy
Authors: Babamohamadi Mehregan , Babaei Esmaeil , Ahmed Salih Burhan , Babamohammadi Mahshid , Jalal Azeez Hewa , Othman Goran
Published: September 2022

The p53 protein is a tumor suppressor encoded by the TP53 gene and consists of 393 amino acids with four main functional domains. This protein responds to various cellular stresses to regulate the expression of target genes, thereby causing DNA repair, cell cycle arrest, apoptosis, metabolic changes, and aging. Mutations in the TP53 gene and the functions of the wild-type p53 protein (wtp53) have been linked to various human cancers. Eight TP53 gene mutations are located in codons, constituting 28% of all p53 mutations. The p53 can be used as a biomarker for tumor progression and an excellent target for designing cancer treatment strategies. In wild-type p53-carrying cancers, abnormal signaling of the p53 pathway usually occurs due to other unusual settings, such as high MDM2 expression. These differences between cancer cell p53 and normal cells have made p53 one of the most important targets for cancer treatment. In this review, we have dealt with various issues, such as the relative contribution of wild-type p53 loss of function, including transactivation-dependent and transactivation-independent activities in oncogenic processes and their role in cancer development. We also discuss the role of p53 in the process of ferroptosis and its targeting in cancer treatment. Finally, we focus on p53-related drug delivery systems and investigate the challenges and solutions.
Accounting for retest effects in cognitive testing with the Bayesian double exponential model via intensive measurement burst designs
Authors: Oravecz Zita , Harrington Karra D. , Hakun Jonathan G. , Katz Mindy J. , Wang Cuiling , Zhaoyang Ruixue , Sliwinski Martin J.
Published: September 2022

Monitoring early changes in cognitive performance is useful for studying cognitive aging as well as for detecting early markers of neurodegenerative diseases. Repeated evaluation of cognition via a measurement burst design can accomplish this goal. In such design participants complete brief evaluations of cognition, multiple times per day for several days, and ideally, repeat the process once or twice a year. However, long-term cognitive change in such repeated assessments can be masked by short-term within-person variability and retest learning (practice) effects. In this paper, we show how a Bayesian double exponential model can account for retest gains across measurement bursts, as well as warm-up effects within a burst, while quantifying change across bursts in peak performance. We also highlight how this approach allows for the inclusion of person-level predictors and draw intuitive inferences on cognitive change with Bayesian posterior probabilities. We use older adults’ performance on cognitive tasks of processing speed and spatial working memory to demonstrate how individual differences in peak performance and change can be related to predictors of aging such as biological age and mild cognitive impairment status.
Caloric and video head impulse test dissociated results in dizzy patients
Authors: Waissbluth Sofia , Sepúlveda Valeria , Leung Jai-Sen , Oyarzún Javier
Published: September 2022

Introduction

We are now able to detect abnormalities for any semicircular canal with the use of the video head impulse test (vHIT). Prior to the vHIT, the gold standard for unilateral canal paresis of the lateral canal was considered the caloric test. Clinical cases where the caloric test and vHIT are discordant are not uncommon.

Methods

Retrospective study. All consecutive cases of dizziness seen from 11/2020 to 12/2021 for which the patient underwent both caloric and vHIT tests performed within 10 days, were reviewed. Patients with discordant results were included. We evaluated the caloric response, vHIT gains for all canals and saccades, with and without gain abnormalities.

Results

We included 74 cases of dizziness with dissociated results. The most common finding was a normal caloric response with abnormal vHIT results (60.8%); the main abnormal finding on vHIT was the presence of saccades. In this group, 37.7% of patients had normal gains and refixation saccades. In addition, the most found low gain was for the posterior canal. The main diagnosis in this group was vestibular migraine. For the group with unilateral caloric paresis and normal vHIT gain in the lateral canal, the main diagnosis was Ménière's disease.

Discussion

The most common disorders with discordant results were Ménière's disease and vestibular migraine. The caloric test and vHIT are complementary and combining both tests provide greater clinical information. Further research is needed to understand refixation saccades with normal gains.
Microstructural changes of the vestibulocochlear nerve in patients with Ménière's disease using diffusion tensor imaging
Authors: Yuan Xiaojia , Li Xiaozhen , Xu Yu , Zhong Liqun , Yan Zhanfeng , Chen Zhengguang
Published: September 2022

Objective

To evaluate the microstructural changes of the vestibulocochlear nerve in patients with Ménière's disease.

Methods

A total of 26 subjects, 13 patients with MD and 13 healthy controls, underwent diffusion tensor imaging (DTI) on a 3T scanner. The independent sample t-test was used to compare the differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) between the two groups. A Pearson correlation was used between DTI and the dizziness handicap inventory (DHI) scores.

Results

There was a significant decrease in FA and an increase in ADC of the vestibulocochlear nerve in MD patients compared with healthy controls (P = 0.04, P = 0.001). FA had negative correlations with the DHI score (r = −0.62, P = 0.02) and DHI-functional score (r = −0.64, P = 0.02).

Conclusion

These results are the first evidence of possible changes in the microstructure of the vestibulocochlear nerves in patients with MD. DTI is a potential technique for evaluating the vestibulocochlear nerve in patients with MD.
Novel therapeutic modulators of astrocytes for hydrocephalus
Authors: Yang Yijian , Wang Chuansen , Chen Rui , Wang Yuchang , Tan Changwu , Liu Jingping , Zhang Qinghua , Xiao Gelei
Published: September 2022

Hydrocephalus is mainly characterized by excessive production or impaired absorption of cerebrospinal fluid that causes ventricular dilation and intracranial hypertension. Astrocytes are the key response cells to inflammation in the central nervous system. In hydrocephalus, astrocytes are activated and show dual characteristics depending on the period of development of the disease. They can suppress the disease in the early stage and may aggravate it in the late stage. More evidence suggests that therapeutics targeting astrocytes may be promising for hydrocephalus. In this review, based on previous studies, we summarize different forms of hydrocephalus-induced astrocyte reactivity and the corresponding function of these responses in hydrocephalus. We also discuss the therapeutic effects of astrocyte regulation on hydrocephalus in experimental studies.
Reaching and maintaining higher dietary diversity is associated with decreased risk of all-cause mortality: A longitudinal study from the China Health and Nutrition Survey
Authors: Qu Xiaochen , Na Xiaona , Yang Jiaqi , Yu Haoran , Chen Aiwen , Zhao Ai
Published: September 2022

It is generally believed that higher dietary diversity is associated with better health status. The dietary diversity of individuals may change with age; however, evidence on the trajectory of change in the long-term and whether it is related to all-cause mortality is still scant. In this study, we used data from the China Health and Nutrition Survey (CHNS) collected in five follow-ups between 2004 and 2015 to explore the association between changes in dietary diversity scores (DDS) and all-cause mortality, as well as the dynamic change in DDS with age. In total, 6,737 subjects (aged between 30 and 60 at enrollment) were included in the analysis. Latent Class Trajectory Modeling (LCTM) was used to explore the different trajectories of DDS changes among participants. Four classes were identified: class 1 with the lowest average DDS (3.0) that showed a gradual decline during the follow-ups; class 2 with relatively low DDS (4.0) that experienced slight growth; class 3 with medium DDS (5.2) that also demonstrated similar growth rate to class 2; and class 4 with the highest DDS (6.7) maintained at a high level. Cox proportional hazards regression models were applied to investigate the association between the DDS trajectories and the risk of death. Only class 4, which was characterized by the highest and stable DDS, had significant reduced risk of all-cause mortality of 71.0% (hazard ratio [HR]: 0.29; 95% confidence interval [CI]: 0.10–0.83), 68% (HR: 0.32; 95% CI: 0.11–0.89), and 66.0% (HR: 0.34; 95% CI: 0.12–0.94), compared to classes 1, 2, and 3, respectively, while the first three classes showed no significant inter-class differences. When considering the average DDS during the study period, each point of increase in DDS corresponded to a 22% reduced risk of mortality (HR: 0.78; 95% CI: 0.69–0.89). In summary, reaching and maintaining a higher DDS was associated with a decreased risk of all-cause mortality. Therefore, promoting diversified eating and increasing the accessibility of varieties of foods should be paid more attention from policymakers and be more emphasized in dietary guidelines.
Carotenoids in orange carrots mitigate non-alcoholic fatty liver disease progression
Authors: Balbuena Emilio , Cheng Junrui , Eroglu Abdulkerim
Published: September 2022

Background

Carotenoids are abundant in colored fruits and vegetables. Non-alcoholic fatty liver disease (NAFLD) is a global burden and risk factor for end-stage hepatic diseases. This study aims to compare the anti-NAFLD efficacy between carotenoid-rich and carotenoid-deficient vegetables.

Materials and methods

Male C57BL/6J mice were randomized to one of four experimental diets for 15 weeks (n = 12 animals/group): Low-fat diet (LFD, 10% calories from fat), high-fat diet (HFD, 60% calories from fat), HFD with 20% white carrot powders (HFD + WC), or with 20% orange carrot powders (HFD + OC).

Results

We observed that carotenoids in the orange carrots reduced HFD-induced weight gain, better than white carrots. Histological and triglyceride (TG) analyses revealed significantly decreased HFD-induced hepatic lipid deposition and TG content in the HFD + WC group, which was further reduced in the HFD + OC group. Western blot analysis demonstrated inconsistent changes of fatty acid synthesis-related proteins but significantly improved ACOX-1 and CPT-II, indicating that orange carrot carotenoids had the potential to inhibit NAFLD by improving β-oxidation. Further investigation showed significantly higher mRNA and protein levels of PPARα and its transcription factor activity.

Conclusion

Carotenoid-rich foods may display more potent efficacy in mitigating NAFLD than those with low carotenoid levels.
A risk-based approach to measuring population micronutrient status from blood biomarker concentrations
Authors: Ghosh Santu , Kurpad Anura V. , Sachdev Harshpal S. , Thomas Tinku
Published: September 2022

Background

Nutrient biomarkers and their definitive cut-offs are used to classify individuals as nutrient-deficient or sufficient. This determinism does not consider any uncertainty, and a probability approach, using biomarker distributions, is then preferable to define the risk of nutrition deficiency when in populations.

Method

Healthy 1–19-year-old children and adolescents were selected from the Comprehensive National Nutrition Survey (CNNS), to obtain probability distributions of their retinol, zinc and vitamin B12, along with erythrocyte folate. Model-based estimates of location, scale and shape parameters of these distributions were obtained across ages. Subsequently, in the entire sample of 1–19 year old children of CNNS, the population risk of deficiency (PRD) which is average risk of deficiency in individuals in the population was computed, which is “of concern” when >50%. When individual risk of deficiency is >97.5% it is called “severe risk of deficiency” (SRD).

Results

In the entire CNNS sample, the PRD of concern was low for serum retinol (3.6–8.2%), zinc (0–5.5%), and SRD of vitamin B12 and erythrocyte folate were 2.3–7.2% and 4.2–9.7%, respectively, across age and sex groups.

Conclusion

This proposed method assesses the adequacy of nutrient exposures without relying on pre-defined deterministic biomarker cut-offs to define micronutrient deficiency and avoids errors in exposure assessment.
Serum creatinine to cystatin C ratio and clinical outcomes in adults with non-dialysis chronic kidney disease
Authors: Hyun Young Youl , Lee Kyu-Beck , Kim Hyoungnae , Kim Yaeni , Chung Wookyung , Park Hayne Cho , Han Seung Hyeok , Oh Yun Kyu , Park Sue Kyung , Oh Kook-Hwan
Published: September 2022

Background

Studies have suggested that the serum creatinine/cystatin C (Cr/CysC) ratio is a surrogate marker for muscle wasting is associated with adverse outcomes in several disease conditions. To clarify the utility of the Cr/CysC ratio as a prognostic marker in chronic kidney disease (CKD) we evaluated the association between the Cr/CysC ratio clinical outcomes in patients with non-dialysis CKD.

Methods

This prospective observational cohort study included 1,966 participants of the KoreaN cohort study Outcomes in patients With CKD (KNOW-CKD). We evaluated associated factors with the serum Cr/CysC ratio and association between the serum Cr/CysC ratio and composite outcomes of all-cause death and cardiovascular events (CVEs).

Results

The mean age was 54 ± 12 (SD) years and 61% were men. The mean serum Cr/CysC ratio was 10.97 ± 1.94 in men and 9.10 ± 1.77 in women. The Cr/CysC ratio correlated positively with urinary creatinine excretion, a marker of muscle mass. In the fully adjusted Cox proportional hazard model, the Cr/CysC ratio was associated with the occurrence of adverse outcomes through a median follow-up of 5.9 years [hazard ratio (HR) = 0.92, 95% confidence interval (CI) = 0.85–0.99 for the composite outcomes, HR = 0.87, 95% CI, 0.78 − 0.97 for all-cause death, and HR = 0.93; 95% CI, 0.84–1.04 for CVEs]. In subgroup analyses, there were interactions of the Cr/CysC ratio with age and sex for risk of the clinical outcomes, but not eGFR group.

Conclusion

A higher Cr/CysC ratio is associated with a lower risk of the composite outcomes, especially all-cause mortality, even after adjusting for eGFR. These suggest that the Cr/CysC ratio is a useful prognostic marker in CKD.
Association between dairy consumption and the risk of diabetes: A prospective cohort study from the China Health and Nutrition Survey
Authors: Yang Yucheng , Na Xiaona , Xi Yuandi , Xi Menglu , Yang Haibing , Li Zhihui , Zhao Ai
Published: September 2022

Diet is closely related to the risk of diabetes; yet the relationship between dairy consumption and the risk of diabetes is unclear with conflicting evidence from previous studies. This study used data from the Chinese Health and Nutrition Survey to investigate the association between dairy consumption and diabetes. A total of 15,512 adults were included; dairy consumption at each survey was assessed by the 3-day 24-h recall and weighed food record methods, and diabetes occurrence was derived from self-reported information. The association between dairy consumption and diabetes was explored using Cox regression and further stratified with BMI and energy intake. Results indicated that 12,368 (79.7%) participants had no dairy consumption, while 2,179 (14.0%) and 947 (6.1%) consumed dairy at 0.1–100 and >100 g/day, respectively. After adjusting for potential confounders, dairy consumption of 0.1–100 g/day was associated with lower risk of diabetes in all participants (HR 0.53, 95% CI:0.38 −0.74; P < 0.001) and males (HR 0.50, 95% CI: 0.31–0.80; P = 0.004). According to the restricted cubic splines (RCS), the protective effect on diabetes was significant in the total population with dairy consumption ranging from 25 to 65 g/day (HR <1, P = 0.025). In the stratified analysis, consuming 30–80 g/day was associated with reduced diabetes risk among the ≤ 2,000 kcal/day energy intake group (HR <1, P = 0.023). In conclusion, dairy consumption was inversely associated with a reduced diabetes risk in Chinese population. Further studies are required to examine the optimal level of dairy consumption for preventing diabetes in the Chinese population.
Association between dietary inflammatory index and oral cancer risk: A systematic review and dose–response meta-analysis
Authors: Luo Zhicheng , Zhu Xidi , Hu Yingyun , Yan Shipeng , Chen Lizhang
Published: September 2022

Background

Dietary inflammatory index (DII) has been suggested to be associated with oral cancer risk. However, a quantitative comprehensive assessment of the dose–response relationship has not been reported. We performed a meta-analysis to clarify the risk of oral cancer with DII.

Methods

We searched PubMed, Embase, Cochrane Library, and Web of Science databases for relevant articles published up to 1 March 2022. Fixed- or random-effects models were utilized to estimate the pooled odds ratio (OR) of oral cancer with DII, as appropriate. Restricted cubic splines were used to model the dose–response relationship.

Results

We included five case–control studies involving 1,278 cases and 5,137 controls in the meta-analysis. Risk of oral cancer was increased by 135% with the highest versus lowest DII level [OR: 2.35, 95% confidence interval (CI): 1.88–2.94], and 79% with higher versus lower DII level (OR: 1.79, 95% CI: 1.49–2.15). We found no evidence of a nonlinear dose–response association of DII with oral cancer (pnon-linearity = 0.752), and the risk was increased by 17% (OR: 1.17, 95% CI: 1.05–1.30) with 1 unit increment in DII score.

Conclusion

This meta-analysis suggested that a higher DII score was associated with increased risk of oral cancer. Therefore, reducing pro-inflammatory components and promoting anti-inflammatory components of diet may be effective in the prevention of oral cancer.
Occult neck metastases risk factors and the role of elective neck dissection in cT3-4N0 adenoid cystic carcinoma of the parotid gland
Authors: Yuan Junhui , Meng Fan , Xu Chunmiao , Li Wenlu , Wu Shuang , Li Hailiang
Published: September 2022

Objectives

To determine the predictor for occult neck metastases and the role of elective neck dissection (END) in cT3-4N0 parotid adenoid cystic carcinoma (ACC).

Methods

Patients with surgically treated parotid ACC were retrospectively enrolled. Predictors of occult neck metastases and the effect of END on disease specific survival (DSS), overall survival (OS), locoregional control survival (LRC), and distant metastasis free survival (DMS) were analyzed.

Results

Occult neck metastases occurred in 35 (19.7%) of the 178 patients undergoing an END. The tumor stage [p=0.011, 4.215 (1.387–10.435)] and intra-parotid lymph node metastasis [p=0.032, 3.671 (1.693–8.775)] were related to the possibility of occult neck metastases independently. The END group had better 10-year LRC than the observation group (56% vs. 43%, p=0.002) and also better 10-year DMS than the observation group (43% vs. 32%, p<0.001). The two groups had similar 10-year DSS (40% vs. 33%, p=0.230) and OS (31% vs. 23%, p=0.094) rates. Furthermore, the Cox model confirmed that END was independently associated with better LRC rate [p=0.022, 2.576 (1.338–6.476)] and better DMS [p=0.011, 2.343 (1.274–7.462)].

Conclusions

Occult neck metastases in cT3-4N0 parotid ACC was not common. A T4 tumor with intra-parotid lymph node metastasis had the highest possibility of occult neck metastases. END had no effect on DSS or OS but significantly decreased the risk of locoregional recurrence and distant metastasis.
Surgical techniques and function outcome for cingulate gyrus glioma, how we do it
Authors: Gong Fangyuan , Jin Lei , Song Qiuwei , Yang Zhong , Chen Hong , Wu Jinsong
Published: September 2022

Objective

Cingulate cortex and cingulum both play crucial roles in limbic system. The aim of study is to observe and analyze surgical outcomes of cingulate gyrus glioma through extents of resection (EORs), overall survival (OS), and postsurgical neurological outcome.

Method

The authors retrospectively studied 95 consecutive adult cases of primary cingulate gliomas that all underwent craniotomies and tumor resection. The patients were classified into unitary sub-region based on the four-division model. The information of clinical symptoms, pathology, EOR, postoperative neurological outcome and survival were analyzed through group comparison.

Result

Low-grade gliomas (LGGs) were more prevalent (69.47%) for cingulate gyrus. Diffuse astrocytoma (40.00%) was most common histopathological diagnosis in total. Regarding sub-regions tumor involved in, midcingulate cortex (MCC) glioma was most prevalent (54.74%) followed by anterior cingulate cortex (ACC) glioma. Among all patients, 83 patients (87.37%) received EOR ≥ 90%. In LGG group, 58 patients (87.88%) received EOR ≥ 90%. The achievement of EOR significantly correlated with survival (P = 0.006). MCC cases were significantly associated with short-term morbidity in either language or motor function (P = 0.02). Majority of ACC cases (80.65%) escaped from any short-term deficits and nearly 90% free for permanent morbidity. Tumors in the dominant hemisphere were significantly associated with language dysfunction or cognition dysfunction, either short-term (P=0.0006) or long-term morbidity (P=0.0111). Age was the only postoperative susceptible predictor for all types of transient (P=0.021) and permanent (P=0.02) neurological deficit.

Conclusion

Regarding cingulate gyrus glioma, the management of surgical plans could be carried out into four sub-region level. In spite of short-term neurological dysfunction caused by surgical procedure, majority of transient dysfunction could be relieved or recovered in long-term. The necessary effort to prolong overall survival is still to achieve advisable EOR.
Interleukin-1 receptor associated kinase 1 (IRAK1) is epigenetically activated in luminal epithelial cells in prostate cancer
Authors: Schagdarsurengin Undraga , Breiding Vanessa , Loose Maria , Wagenlehner Florian , Dansranjav Temuujin
Published: September 2022

The use of immune adjuvants such as toll-like receptor (TLR) agonists reflects a novel strategy in prostate cancer (PCa) therapy. However, interleukin-1 receptor associated kinase 1 (IRAK1), a central effector of TLR signaling, has been shown to be responsible for resistance to radiation-induced tumor cell death. In order to better understand the function and epigenetic regulation of IRAK1 in PCa, we performedin vitrocell culture experiments together with integrative bioinformatic studies using the latest single-cell RNA-sequencing data of human PCa and normal prostate (NOR), and data from The Cancer Genome Atlas. We focused on key effectors of TLR signaling, the Myddosome-complex components IRAK1, IRAK4 and MYD88 (myeloid differentiation primary response 88), and TRAF6 (tumor-necrosis-factor receptor associated factor 6). In PCa,IRAK1-mRNA was specifically enriched in luminal epithelial cells, representing 57% of all cells, whereasIRAK4andMYD88were predominantly expressed in leukocytes, andTRAF6, in endothelial cells. Compared to NOR, onlyIRAK1was significantly overexpressed in PCa (Benjamini-Hochberg adjusted p<2x10-8), whereas the expression ofIRAK4,MYD88, andTRAF6was unchanged in PCa, andIRAK1-expression was inversely correlated with a specific differentially methylated region (IRAK1-DMR) within a predicted promoter region enriched for H3K27ac (Spearman correlation r<-0.36; Fisher’s test, p<10-10). Transcription factors with high binding affinities inIRAK1-DMR were significantly enriched for canonical pathways associated with viral infection and carcinogenic transformation in the Kyoto Encyclopedia of Gene and Genomes analysis. DU145 cells, exhibiting hypermethylatedIRAK1-DMR and lowIRAK1-expression, reacted with 4-fold increasedIRAK1-expression upon combined treatment with 5-aza-2-deoxycytidine and trichostatin A, and were unresponsive to infection with the uropathogenicEscherichia colistrain UTI89. In contrast, PC3 and LNCaP cells, exhibiting hypomethylatedIRAK1-DMR and high endogenousIRAK1-mRNA levels, responded with strong activation ofIRAK1-expression to UTI89 infection. In summary, exclusive overexpression ofIRAK1was observed in luminal epithelial cells in PCa, suggesting it has a role in addition to Myddosome-dependent TLR signaling. Our data show that the endogenous epigenetic status of PCa cells withinIRAK1-DMR is decisive forIRAK1expression and should be considered as a predictive marker when selective IRAK1-targeting therapies are considered.
Establishment and validation of a clinicopathological prognosis model of gastroenteropancreatic neuroendocrine carcinomas
Authors: Chen Jing , Liu Yibing , Xu Ke , Ren Fei , Li Bowen , Sun Hong
Published: September 2022

Background

Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are a rare, highly malignant subset of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, how to predict the prognosis of GEP-NECs by clinical features is still under study. This study aims to establish and validate a nomogram model of overall survival (OS) in patients with GEP-NECs for predicting their prognosis.

Methods

We selected patients diagnosed with GEP-NECs from the Surveillance, Epidemiology, and End Results (SEER) database and two Chinese hospitals. After randomization, we divided the data in the SEER database into the train cohort and the test cohort at a ratio of 7:3 and used the Chinese cohort as the validation cohort. The Cox univariate and multivariate analyses were performed to incorporate statistically significant variables into the nomogram model. We then established a nomogram and validated it by concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, the area under the curve (AUC), and the decision curve analysis (DCA) curve.

Results

We calculated the nomogram C-index as 0.797 with a 95% confidence interval (95% CI) of 0.783–0.815 in the train cohort, 0.816 (95% CI: 0.794–0.833) in the test cohort and 0.801 (95% CI: 0.784–0.827) in the validation cohort. Then, we plotted the calibration curves and ROC curves, and AUCs were obtained to verify the specificity and sensitivity of the model, with 1-, 3- and 5-year AUCs of 0.776, 0.768, and 0.770, respectively, in the train cohort; 0.794, 0.808, and 0.799 in the test cohort; 0.922, 0.925, and 0.947 in the validation cohort. The calibration curve and DCA curves also indicated that this nomogram model had good clinical benefits.

Conclusions

We established the OS nomogram model of GEP-NEC patients, including variables of age, race, sex, tumor site, tumor grade, and TNM stage. This model has good fitting, high sensitivity and specificity, and good clinical benefits.
Population pharmacokinetic model of vancomycin in postoperative neurosurgical patients
Authors: Wei Shifeng , Zhang Dongjie , Zhao Zhigang , Mei Shenghui
Published: September 2022

Objective: Vancomycin is commonly used in postoperative neurosurgical patients for empirical anti-infective treatment due to the low success rate of bacterial culture in cerebrospinal fluid (about 20%) and the high mortality of intracranial infection. At conventional doses, the rate of target achievement for vancomycin trough concentration is low and the pharmacokinetics of vancomycin varies greatly in these patients, which often leads to treatment failure. The objective of this study was to establish a population pharmacokinetic (PPK) model of vancomycin in postoperative neurosurgical patients for precision medicine.

Method: A total of 895 vancomycin plasma concentrations from 560 patients (497 postoperative neurosurgical patients) were retrospectively collected. The model was analyzed by nonlinear mixed effects modeling method. One-compartment model and mixed residual model was employed. The influence of covariates on model parameters was tested by forward addition and backward elimination. Goodness-of-fit, bootstrap and visual predictive check were used for model evaluation. Monte Carlo simulations were employed for dosing strategies with AUC24 targets 400–600.

Result: Estimated glomerular filtration rate (eGFR), body weight (BW) and mannitol had significant influence on vancomycin clearance (CL). eGFR(mL/min)=144×(Scr/a)b×0.993age, for female, a = 0.7, Scr ≤ 0.7 mg/dl, b = −0.329, Scr > 0.7 mg/dl, b = −1.209; for male, a = 0.9, Scr ≤ 0.9 mg/dl, b = −0.411, Scr > 0.9 mg/dl, b = −1.210. Vancomycin clearance was accelerated when co-medicated with mannitol and increased with eGFR and BW. In the final model, the population typical value is 7.98 L/h for CL and 60.2 L for apparent distribution volume, CL (L/h)=7.98×(eGFR/115.2)0.8×(BW/70)0.3×eA, where A = 0.13 when co-medicated with mannitol, otherwise A = 0. The model is stable and effective, with good predictability.

Conclusion: In postoperative neurosurgical patients, a higher dose of vancomycin may be required due to the augmented renal function and the commonly used mannitol, especially in those with high body weight. Our vancomycin PPK model could be used for individualized treatment in postoperative neurosurgical patients.