bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct Roles of Adenosine Deaminase Isoenzymes ADA1 and ADA2: A Pan-Cancer Analysis
Authors: Gao Zhao-wei , Yang Lan , Liu Chong , Wang Xi , Guo Wen-tao , Zhang Hui-zhong , Dong Ke
Published: May 2022

Objective

Adenosine deaminase (ADA) plays an important role in immune response, which includes two isoenzymes: ADA1 and ADA2. This study aims to explore the roles of ADA1 and ADA2 in cancers.

Methods

Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis (GEPIA2) databases were used to analyze the mRNA expression of ADA1 and ADA2 in human normal cells and tumor tissues. The enzyme assay was used to detect the ADA1 and ADA2 activities in serum from cancer patients. The Kaplan–Meier (KM) plotter was used to analyze the prognostic value of ADA1 and ADA2. TIMER2.0 was used to explore how ADA1 and ADA2 correlate with immune infiltration and immune checkpoints. cBioPortal database was used to investigate the mutations of ADA1 and ADA2. LinkedOmics was used to screen the ADA1 and ADA2 expression-related genes.

Results

ADA1 was significantly increased in several tumor tissues, including cholangiocarcinoma (CHOL), lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), ovarian serous cystadenocarcinoma (OV), pancreatic adenocarcinoma (PAAD), thymoma (THYM), and uterine carcinosarcoma (UCS). ADA2 expression was significantly increased in esophageal carcinoma (ESCA), glioblastoma multiforme (GBM), acute myeloid leukemia (LAML), OV, PAAD, skin cutaneous melanoma (SKCM), and stomach adenocarcinoma (STAD). There were no significant changes in serum ADA1 activities in most cancers, while serum ADA2 activities were increased in most cancers. For prognosis, high ADA1 expression was associated with the poor survival in several cancers, including esophageal squamous cell carcinoma (ESCC), HNSC, KIRC, kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), and uterine corpus endometrial carcinoma (UCEC). However, high ADA2 expression showed a favorable prognosis in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), HNSC, KIRC, KIRP, LUAD, OV, PAAD, sarcoma, and THYM. ADA1 showed a moderate positive correlation with multiple infiltrating immune cells in most cancers. ADA2 was positively correlated with B cells, CD8 T cells, monocytes/macrophages, and dendritic cells (DCs) and was strongly negatively correlated with myeloid-derived suppressor cells. Function analysis showed that ADA1 expression-related genes were mainly enriched in cell division biological progression. However, ADA2-related genes were mainly associated with immune response.

Conclusion

As isoenzymes, ADA1 and ADA2 showed opposite prognostic values and different correlative patterns with immune infiltrating. These data demonstrated the distinct roles of ADA1 and ADA2 in cancer. ADA2 might act as a protective factor in cancer.
Nitric Oxide-Induced Calcineurin A Mediates Antimicrobial Peptide Production Through the IMD Pathway
Authors: Chen Kangkang , Wang Xinyan , Wei Xiangyi , Chen Jiaqian , Wei Youheng , Jiang Haobo , Lu Zhiqiang , Feng Congjing
Published: May 2022

Nitric oxide (NO) at a high concentration is an effector to kill pathogens during insect immune responses, it also functions as a second messenger at a low concentration to regulate antimicrobial peptide (AMP) production in insects. Drosophila calcineurin subunit CanA1 is a ubiquitous serine/threonine protein phosphatase involved in NO-induced AMP production. However, it is unclear how NO regulates AMP expression. In this study, we used a lepidopteran pest Ostrinia furnacalis and Drosophila S2 cells to investigate how NO signaling affects the AMP production. Bacterial infections upregulated the transcription of nitric oxide synthase 1/2 (NOS1/2), CanA and AMP genes and increased NO concentration in larval hemolymph. Inhibition of NOS or CanA activity reduced the survival of bacteria-infected O. furnacalis. NO donor increased NO level in plasma and upregulated the production of CanA and certain AMPs. In S2 cells, killed Escherichia coli induced NOS transcription and boosted NO production, whereas knockdown of NOS blocked the NO level increase caused by E. coli. As in O. furnacalis larvae, supplementation of the NO donor increased NO level in the culture medium and AMP expression in S2 cells. Suppression of the key pathway genes showed that the IMD (but not Toll) pathway was involved in the upregulation of CecropinA1, Defensin, Diptericin, and Drosomycin by killed E. coli. Knockdown of NOS also reduced the expression of CanA1 and AMPs induced by E. coli, indicative of a role of NO in the AMP expression. Furthermore, CanA1 RNA interference and inhibition of its phosphatase activity significantly reduced NO-induced AMP expression, and knockdown of IMD suppressed NO-induced AMP expression. Together, these results suggest that NO-induced AMP production is mediated by CanA1 via the IMD pathway.
Colony-Level Viral Load Influences Collective Foraging in Honey Bees
Authors: Penn Hannah J. , Simone-Finstrom Michael D. , de Guzman Lilia I. , Tokarz Philip G. , Dickens Rachel
Published: May 2022

Nutrition is an important component of social insect colony health especially in the face of stressors such as parasitism and viral infections. Honey bees are known to preferentially select nectar and pollen based on macronutrient and phytochemical contents and in response to pathogen loads. However, given that honey bees live in colonies, collective foraging decisions may be impacted directly by forager infection status but also by colony health. This field experiment was conducted to determine if honey bee viral infections are correlated with pollen and nectar foraging and if these associations are impacted more by colony or forager infection. By comparing regressions with and without forager and colony variables and through structural equation models, we were able to determine the relative contributions of colony and forager virus loads on forager decisions. We found that foragers had higher numbers and levels of BQCV and CBPV but lower levels of DWV viruses than their respective colonies. Overall, individuals appeared to forage based a combination of their own and colony health but with greater weight given to colony metrics. Colony parasitism by Varroa mites, positively correlated with both forager and colony DWV-B levels, was negatively associated with nectar weight. Further, colony DWV-B levels were negatively associated with individually foraged pollen protein: lipid ratios but positively correlated with nectar weight and sugar content. This study shows that both colony and forager health can simultaneously mediate individual foraging decisions and that the importance of viral infections and parasite levels varies with foraging metrics. Overall, this work highlights the continued need to explore the interactions of disease, nutrition, and genetics in social interactions and structures.
Chromosome-Level Genome Assembly of Acanthogobius ommaturus Provides Insights Into Evolution and Lipid Metabolism
Authors: Pan Yu , Sun Zhicheng , Gao Tianxiang , Zhao Linlin , Song Na
Published: May 2022

Acanthogobius ommaturus is a large, fast-growing annual fish widely distributed in coastal and estuarine areas. The adults will die after breeding, and its life cycle is only 1 year. The first chromosome-level genome assembly of A. ommaturus was obtained by PacBio and Hi-C sequencing in this study. The final genome assembly after Hi-C correction was 921.49 Mb, with contig N50 and scaffold N50 values of 15.70 Mb and 40.99 Mb, respectively. The assembled sequences were anchored to 22 chromosomes by using Hi-C data. A total of 18,752 protein-coding genes were predicted, 97.90% of which were successfully annotated. Benchmarking Universal Single-Copy Orthologs (BUSCO) assessment results for genome and gene annotations were 93.6% and 84.6%, respectively. A. ommaturus is phylogenetically closely related to Periophthalmodon magnuspinnatus and Boleophthalmus pectinirostris, diverging approximately 31.9 MYA with the two goby species. The A. ommaturus genome displayed 597 expanded and 3,094 contracted gene families compared with the common ancestor. A total of 1,155 positive selected genes (PSGs) (p < 0.05) were identified. Based on comparative genomic analyses, we obtained several expanded genes such as acsbg2, lrp1, lrp6, and znf638 involved in lipid metabolism. A total of twenty candidate genes were identified under positive selection, which associated with lifespan including ercc6, igf1, polg, and tert. Interspecific collinearity analysis showed a high genomic synteny between A. ommaturus and P. magnuspinnatus. The effective population size of A. ommaturus decreased drastically during 200–100 Ka because of Guxiang ice age and then increased gradually following warm periods. This study provides pivotal genetic resources for in-depth biological and evolutionary studies, and underlies the molecular basis for lipid metabolism.
Numerical Simulation and Experimental Studies on Stationary Shoulder Friction Stir Welding of Aluminum Alloy T-Joint
Authors: Wang Chungui , Deng Jun , Dong Chunlin , Zhao Yunqiang
Published: May 2022

The application of the corner stationary shoulder friction stir welding (CSSFSW) on T-shaped structures is exceptional, and adequate research is still required for the related theory. In this paper, taking 5,083 aluminum alloy as the workpiece, based on the Arbitrary Lagrangian Eulerian (ALE) method, a three-dimensional thermomechanical coupled model of the CSSFSW process was established. The temperature field and material flow were simulated and analyzed during the welding process. The friction heat formed an elliptical temperature gradient range, and expanded with the progress of the welding. The highest temperature of up to 575°C was recorded on the advanced side, which is higher than that on the retreating side (about 532°C). The forward and backward material flow directions were found to be opposite to each other. In the traverse direction, the material on both sides flowed upward along the pin and downward under the action of the stationary shoulder at the top. The difference between the simulated and the measured temperature lies within 7%, and the material flow also has good agreement with the experimental results.
Fecal Microbiota and Human Intestinal Fluid Transplantation: Methodologies and Outlook
Authors: Chen Ye , Zhiliang Lin , Jiaqu Cui , Xiaoqiong Lv , Shaoyi Zhang , Chunlian Ma , Yinmei Yan , Bo Yang , Di Zhao , Hongliang Tian , Ning Li , Qiyi Chen , Huanlong Qin
Published: May 2022

Fecal microbiota transplantation (FMT) is a therapy that involves the transplantation of healthy human fecal microorganisms into the gut of patients to rebuild or consolidate the intestinal microecology. It has been utilized in many diseases. However, FMT had a limited effect on patients with small intestinal diseases because of the unique ecological characteristics of the microorganisms. Thus, we proposed a new microecology transplantation therapy called human intestinal fluid transplantation (HIFT). Human intestinal fluid can be collected through a nasojejunal tube and be made into capsules using the freeze-dried powder method. In addition, strict standards for donor screening and management have been established. We are currently developing a high-standard HIFT preparation system and conducting high-quality clinical studies to validate the safety and efficacy of HIFT combined with FMT.
Case Report: Diagnosis of Acute Q Fever With Aseptic Meningitis in a Patient by Using Metagenomic Next-Generation Sequencing
Authors: Gu Meifeng , Mo Xiaoqin , Tang Zhenchu , Tang Jianguang , Wang Wei
Published: May 2022

Query fever (Q fever) is a widespread zoonotic disease caused by the bacterium of Coxiella burnetii (C. burnetii). Its neurological complications are rarely reported. But they may lead to severe consequences. It needs a rapid and accurate detective method to diagnose acute Q fever with neurological presentations in non-epidemic areas urgently. Here, we report an acute Q fever case with aseptic meningitis. The male patient, without any contact history in the epidemic area or with animals, was indicated to exhibit fever and headache symptoms. The cultures of blood, stool, urine, and sputum were all negative. But C. burnetii was repeatedly detected in blood by metagenomic next-generation sequencing (mNGS). He received Doxycycline therapy and quickly returned to normal. Therefore, for the diagnosis and identification of Q fever in non-reporting regions, mNGS has comparative advantages. Secondly, aseptic meningitis may be a direct infection of C. burnetii to central nervous system (CNS) or inflammatory reactions to systemic infection, we recommend detecting mNGS both in blood and cerebrospinal fluid (CSF).
Clinical Characteristics and Mortality of Non-tuberculous Mycobacterial Infection in Immunocompromised vs. Immunocompetent Hosts
Authors: Chai Jingjing , Han Xu , Mei Qimin , Liu Tao , Walline Joseph Harold , Xu Jia , Liu Yecheng , Zhu Huadong
Published: May 2022

Immunosuppression and host vulnerability play a key role in non-tuberculous mycobacteria (NTM) pathogenesis. The objective of this study was to compare the clinical characteristics and mortality of NTM infections in immunocompromised and immunocompetent patients. We used a retrospective dataset obtained from our large, tertiary, urban, teaching hospital which is the medical records of hospitalized patients with NTM infections between January 1, 2013 to December 31, 2020. The information including clinical manifestations, imaging, and NTM etiological data were obtained from the hospital's clinical data system. A total of 480 patients with NTM infections completed species identification. 118 hospitalized NTM patients who met ATS/IDSA NTM diagnostic criteria and had complete medical records were included in the study. The average age was 49.4 years, 57 (48.3%) were female, and 64 (54.2%) were immunosuppressed hosts. In our study, the most common species in order of frequency were: M. intracellulare, M. abscessus, M. avium, and M. kansasii among NTM patients. The most common comorbidity was history of previous tuberculosis (30.5%). Besides malignancy, the most common immunodeficiencies were adult-onset immunodeficiency induced by anti-interferon-gamma autoantibody, SLE, and vasculitis. The immunocompromised patients with NTM had more clinical symptoms, comorbidities and lower lymphocyte counts compared to immunocompetent patients. The mortality we observed in immunocompromised patients of NTM disease was significantly higher than that of immunocompetent patients (HR 3.537, 95% CI 1.526–8.362). Immunosuppressed NTM patients with lower B and CD4+ T lymphocyte counts may more frequently present with disseminated NTM infections, clinical exacerbations, and higher mortality than immunocompetent patients.
Heme Biosynthesis Factors and 5-ALA Induced Fluorescence: Analysis of mRNA and Protein Expression in Fluorescing and Non-fluorescing Gliomas
Authors: Mischkulnig Mario , Roetzer-Pejrimovsky Thomas , Lötsch-Gojo Daniela , Kastner Nina , Bruckner Katharina , Prihoda Romana , Lang Alexandra , Martinez-Moreno Mauricio , Furtner Julia , Berghoff Anna , Woehrer Adelheid , Berger Walter , Widhalm Georg , Kiesel Barbara
Published: May 2022

Objective

The intraoperative visualization of adult-type diffuse gliomas with 5-aminolevulinic acid (5-ALA) induced fluorescence is widely used in the neurosurgical field. While visible 5-ALA induced fluorescence is found in the majority of high-grade gliomas, most low-grade gliomas lack visible fluorescence during surgery. Recently, the heme biosynthesis pathway was identified as crucial influencing factor for presence of visible fluorescence since it metabolizes 5-ALA to fluorescing Protoporphyrin IX (PpIX). However, the exact alterations within the heme biosynthesis pathway resulting in visible 5-ALA induced fluorescence in gliomas are still unclear. The aim of the present study was thus to compare the mRNA and protein expression of promising intramitochondrial heme biosynthesis enzymes/transporters in glioma tissue samples of different fluorescence behavior.

Methods

A total of 19 strongly fluorescing and 21 non-fluorescing tissue samples from neurosurgical adult-type diffuse gliomas (WHO grades II-IV) were included in the current analysis. In these samples, we investigated the mRNA expression by quantitative real time PCR and protein expression using immunohistochemistry of the intramitochondrial heme biosynthesis enzymes Coproporphyrinogen Oxidase (CPOX), Protoporphyrinogen Oxidase (PPOX), Ferrochelatase (FECH), and the transporter ATP-binding Cassette Subfamily B Member 2 (ABCG2).

Results

Regarding mRNA expression analysis, we found a significantly decreased ABCG2 expression in fluorescing specimens compared to non-fluorescing samples (p = 0.001), whereas no difference in CPOX, PPOX and FECH was present. With respect to protein expression, significantly higher levels of CPOX (p = 0.005), PPOX (p < 0.01) and FECH (p = 0.003) were detected in fluorescing samples. Similar to mRNA expression analysis, the protein expression of ABCG2 (p = 0.001) was significantly lower in fluorescing samples.

Conclusion

Distinct alterations of the analyzed heme biosynthesis factors were found primarily on protein level. Our data indicate that heme biosynthesis pathway activity in general is enhanced in fluorescing gliomas with upregulation of PpIX generating enzymes and decreased ABCG2 mediated PpIX efflux outweighing the also increased further metabolization of PpIX to heme. Intramitochondrial heme biosynthesis factors thus constitute promising pharmacological targets to optimize intraoperative 5-ALA fluorescence visualization of usually non-fluorescing tumors such as low-grade gliomas.
Risk Factors Analysis and Prediction Model Establishment of Intestinal Metaplasia or Dysplasia in Patients With Chronic Atrophic Gastritis: A Multi-Center Retrospective Study
Authors: Pei Bei , Wen Ziang , Yang Qi , Wang Jieyu , Cao Qinglin , Dai Longfei , Li Xuejun
Published: May 2022

Objective

To investigate the risk factors and construct a prediction model of chronic atrophic gastritis (CAG) patients with intestinal metaplasia or dysplasia.

Method

The clinical data of 450 patients with CAG who were diagnosed and treated in the Department of Gastroenterology of the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine from June 2016 to February 2022 were collected. Single and multiple factors logistic regression analysis were used to explore the risk factors of intestinal metaplasia or dysplasia in patients of training cohort. Then, we constructed a model to predict the onset of intestinal metaplasia or dysplasia based on the data of training cohort, following which we tested the model in an external validation cohort of 193 patients from a local university teaching hospital. The ROC curve, calibration curve, and decision curve analysis were used to evaluate the accuracy of the prediction model.

Result

Helicobacter pylori(H. pylori, HP) infection, pepsinogen I, gastrin-17, and the number of lesions were found to be independent rick factors of the model. The liner prediction model showed excellent predictive value in both training cohort and validation cohort.

Conclusion

HP infection, pepsinogen I, gastrin-17, and the number of lesions are independent risk factors for intestinal metaplasia or dysplasia in patients with CAG. The prediction model constructed based on these factors has a high accuracy and excellent calibration, which can provide a great basis for condition assessment and individualized treatment of the patients.
A Comparative Analysis of Microbe-Based Technologies Developed at ICAR-NBAIM Against Erysiphe necator Causing Powdery Mildew Disease in Grapes (Vitis vinifera L.)
Authors: Malviya Deepti , Thosar Ratna , Kokare Namrata , Pawar Shital , Singh Udai B. , Saha Sujoy , Rai Jai P. , Singh Harsh V. , Somkuwar R. G. , Saxena Anil K.
Published: May 2022

Globally, Erysiphe necator causing powdery mildew disease in grapevines (Vitis vinifera L.) is the second most important endemic disease, causing huge economic losses every year. At present, the management of powdery mildew in grapes is largely dependent upon the use of chemical fungicides. Grapes are being considered as one of the high pesticide-demanding crops. Looking at the residual impact of toxic chemical pesticides on the environment, animal, and human health, microbe-based strategies for control of powdery mildew is an emerging technique. It offers an environment-friendly, residue-free, and effective yet safer approach to control powdery mildew disease in grapes. The mode of action is relatively diverse as well as specific to different pathosystems. Hence, the aim of this study was to evaluate the microbe-based technologies, i.e., Eco-pesticide®, Bio-Pulse®, and Bio-Care 24® developed at the Plant-Microbe Interaction and Rhizosphere Biology Lab, ICAR-NBAIM, Kushmaur, against grape powdery mildew and to integrate these technologies with a safer fungicide (sulfur) to achieve better disease control under organic systems of viticulture. The experiments were conducted at four different locations, namely, the vineyards of ICAR-NRCG, Rajya Draksha Bagayatdar Sangh (MRDBS), and two farmers' fields at Narayangaon and Junnar in the Pune district of Maharashtra. A significantly lower percent disease index (PDI) was recorded on the leaves of grape plants treated with Eco-Pesticide®/sulfur (22.37) followed by Bio-Pulse®/sulfur (22.62) and Bio-Care 24®/sulfur (24.62) at NRCG. A similar trend was observed with the lowest PDI on bunches of Eco-pesticide®/sulfur-treated plants (24.71) followed by Bio-Pulse®/sulfur (24.94) and Bio-Care®/sulfur (26.77). The application of microbial inoculants singly or in combination with sulfur has a significant positive impact on the qualitative parameters such as pH, total soluble solids (TSS), acidity, berry diameter, and berry length of the grapes at different locations. Among all the treatments, the Bio-Pulse®/sulfur treatment showed the highest yield per vine (15.02 kg), which was on par with the treatment Eco-Pesticide®/sulfur (14.94). When compared with the yield obtained from the untreated control, 2.5 to 3 times more yield was recorded in the plants treated with either of the biopesticides used in combination with sulfur. Even in the case of individual inoculation, the yield per vine was approximately two times higher than the untreated control and water-treated plants across the test locations. Results suggested that microbial technologies not only protect grapevines from powdery mildew but also enhance the quality parameters with increased yield across the test locations.
Influence of Human–Computer Interaction-Based Intelligent Dancing Robot and Psychological Construct on Choreography
Authors: Yang Liu
Published: May 2022

To study the influence of Artificial Intelligence (AI) on dancing robots in choreography, this paper introduces the biped-humanoid robot-imagined choreography model alongside the Psychological Space Construction (Psychological Construct) and Human–Computer Interaction (HCI). The proposed model is based on deep learning and imitating human thinking and is capable of imagining new dance elements. Finally, simulation experiments are designed to verify the model's effectiveness. Dance professionals are invited to evaluate the robot-imagined dance posture. The results show that the proposed model can vividly imitate human dancers and imagine and create new dance movements. The average basic feature retention and innovation scores of 30 new dance elements imagined on the L1 (head) are 7.29 and 7.64, respectively. By comparison, similar scores on 30 new elements in L2 (upper-body) are 7.73 and 7.40, respectively. Therefore, the proposed intelligent robot-imagined choreography model can help the dancing robot choreograph more finely and improve the choreography efficiency. The research results have significant practical value for dance teaching.
Brain-Derived Neurotrophic Factor Is an Important Therapeutic Factor in Mesenchymal Stem Cell Secretions for Treatment of Traumatic Peripheral Pelvic Injuries
Authors: Yuan Xiaoyi , Balog Brian M. , Lin Dan Li , Hanzlicek Brett , Kuang Mei , Yan Hao , Majerus Steve J. A. , Damaser Margot S.
Published: May 2022

Traumatic neuromuscular injury to the pudendal nerve and urethra during childbirth does not regenerate well and contributes to stress urinary incontinence in women. Mesenchymal stem cells (MSCs) can improve neuroregeneration via their secretions, or secretome, which includes brain-derived neurotrophic factor (BDNF). In this study, we investigated whether BDNF is a key factor in the secretome of MSCs for the facilitation of functional recovery following a dual simulated childbirth injury. BDNF knockdown (KD) MSCs were created using an anti-BDNF shRNA lentivirus vector. A scrambled sequence was used as a transduction control (scrambled). Cells were cultured for 24 h before media was concentrated 50x to create concentrated conditioned media (CCM) containing MSC secretome. CCM of unmanipulated MSCs was screened for high BDNF expression (high BDNF CCM). Concentrated control media (CM) was created by concentrating media not conditioned by cells. Female Sprague-Dawley rats underwent bilateral pudendal nerve crush and vaginal distension (Injury) or sham injury. One hour and 1 week after injury, sham injured rats received CM, and injured rats received CM, high BDNF CCM, KD CCM, or scrambled CCM (300 μl intraperitoneally). Three weeks after injury, rats underwent leak point pressure (LPP) and pudendal nerve sensory branch potential (PNSBP) recordings. The urethra and pudendal nerve were harvested for anatomical assessment. ANOVA followed by the Student-Newman-Keuls test determined significant differences between groups (p < 0.05). BDNF KD CCM had significantly decreased BDNF concentration compared to scrambled CCM, while the concentration in high BDNF CCM was significantly increased. LPP was significantly decreased in CM and KD CCM treated animals compared to sham injury, but not with scrambled or high BDNF CCM. PNSBP firing rate showed a significant decrease with CM treatment compared to sham injury. Neuromuscular junctions in the urethral sphincter in KD CCM, scrambled CCM, and high BDNF CCM were healthier than CM treated rats. While anatomical and nerve function tests demonstrate regeneration of the pudendal nerve with any CCM treatment, LPP results suggest it takes longer to recover continence with reduced BDNF in CCM. BDNF in MSC CCM is an important factor for the acceleration of recovery from a dual nerve and muscle injury.
Mathematical Models of Parathyroid Gland Biology: Complexity and Clinical Use
Authors: Schappacher-Tilp Gudrun , Kotanko Peter , Pirklbauer Markus
Published: May 2022

Altered parathyroid gland biology is a major driver of chronic kidney disease-mineral bone disorder (CKD-MBD) in patients with chronic kidney disease. CKD-MBD is associated with a high risk of vascular calcification and cardiovascular events. A hallmark of CKD-MBD is secondary hyperparathyroidism with increased parathyroid hormone (PTH) synthesis and release and reduced expression of calcium-sensing receptors on the surface of parathyroid cells and eventually hyperplasia of parathyroid gland cells. The KDIGO guidelines strongly recommend the control of PTH in hemodialysis patients. Due to the complexity of parathyroid gland biology, mathematical models have been employed to study the interaction of PTH regulators and PTH plasma concentrations. Here, we present an overview of various model approaches and discuss the impact of different model structures and complexities on the clinical use of these models.
Comparison of Pipeline Embolization Device and Traditional Endovascular Therapeutic Approaches in Distal Cerebral Circulation Aneurysms Using Propensity Score Matching Analysis
Authors: Ma Chao , Zhu Haoyu , Liang Shikai , Liang Fei , Sun Jidian , Zhang Yupeng , Jiang Chuhan
Published: May 2022

Background

Coiling and stent-assisted coiling remain the first-line treatments for distal cerebral circulation aneurysms (DCCAs). The off-label use of the pipeline embolization device (PED) for these aneurysms has been explored recently but remains controversial.

Objective

To compare traditional endovascular therapeutic approaches (coiling and stent-assisted coiling) and PED for DCCAs in a multicenter cohort of patients.

Methods

A multicenter, retrospective cohort comparison study was conducted that included consecutive patients with unruptured DCCAs treated with either traditional endovascular therapeutic approaches or PED placement at three centers between 2016 and 2020. Propensity score matching analysis was applied to adjust for baseline risk factors between the PED and TET groups. Matching was based on age, sex, aneurysm size, location, morphology, adjunctive coiling, treatment history, and preoperative mRS score.

Results

In total, 209 patients with DCCAs treated with PED or traditional endovascular therapeutic approaches were identified. Thirty-seven patients underwent PED treatment, and 172 patients underwent traditional endovascular therapeutic approaches. After propensity score matching, 37 aneurysm pairs were matched, and the baseline characteristics of the patients were balanced between the groups. The complete occlusion rate between PED and traditional endovascular therapeutic approach in both matched cohorts (91.7 vs. 92.3%, p > 0.78) was similar. The rate of periprocedural treatment-related complications in both the PED and traditional endovascular therapeutic groups was 13.5%. Univariate analysis identified average parent vessel diameter as the only predictor of complete occlusion (p = 0.038).

Conclusions

PED is a viable option for treating DCCAs by providing occlusion and complication rates similar to those of traditional endovascular therapeutic approaches. A rigid patient selection procedure and proper planning should be undertaken to reduce treatment-related complications.
Effects of Functional Acupuncture on Upper Limb Spasticity After Ischemic Stroke: A Protocol for a Randomized Controlled Parallel Clinical Trial
Authors: Mei Jinjin , Xue Yang , Li Jingwen , Zhang Lihong , Zhang Jianyun , Wang Yiying , Su Kaiqi , Gao Jing , Guo Jian , Li Ruiqing
Published: May 2022

Background

Upper limb spasticity (ULS) is a common complication after stroke, which seriously affects the quality of life and rehabilitation of patients. There are different treatment methods for post-stroke spasticity (PSS). Our group found that functional acupuncture (FA) can effectively improve forearm spasticity and hand dysfunction after stroke, but the efficacy of ULS needs to be further verified. Therefore, this subject has mainly used clinical randomized controlled trials to evaluate the clinical efficacy of FA in the treatment of ULS after ischemic stroke.

Method

This is a parallel design and randomized controlled trial. We selected 108 patients who met the predefined criteria and randomized them into two groups, the experimental group and the control group. The experimental group receives FA and routine rehabilitation treatment. The control group received traditional acupuncture (TA) and routine rehabilitation treatment. All patients received 20 courses of treatment for 4 weeks, and the modified Ashworth score (MAS), clinical neurological deficit score (CSS), Fugl-Meyer upper extremity function assessment (FMA-UE), and the Modified Barthel Index (MBI) scores were evaluated before and after treatment.

Discussion

This trial is mainly to study the clinical efficacy of FA in the treatment of ULS after ischemic stroke. It will not only provide a new idea for the clinical treatment of upper limb post-stroke spasticity (ULPSS) but also will provide effective experimental support and a theoretical basis for the clinic.

Trial registration

China Clinical Trials Registry No. ChiCTR2100050440. Registered on 27 August 27 2021.
Sex-Specific Transcriptomic Signatures in Brain Regions Critical for Neuropathic Pain-Induced Depression
Authors: Dai Weiping , Huang Shuying , Luo Yuan , Cheng Xin , Xia Pei , Yang Mengqian , Zhao Panwu , Zhang Yingying , Lin Wei-Jye , Ye Xiaojing
Published: May 2022

Neuropathic pain is a chronic debilitating condition with a high comorbidity with depression. Clinical reports and animal studies have suggested that both the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC) are critically implicated in regulating the affective symptoms of neuropathic pain. Neuropathic pain induces differential long-term structural, functional, and biochemical changes in both regions, which are thought to be regulated by multiple waves of gene transcription. However, the differences in the transcriptomic profiles changed by neuropathic pain between these regions are largely unknown. Furthermore, women are more susceptible to pain and depression than men. The molecular mechanisms underlying this sexual dimorphism remain to be explored. Here, we performed RNA sequencing and analyzed the transcriptomic profiles of the mPFC and ACC of female and male mice at 2 weeks after spared nerve injury (SNI), an early time point when the mice began to show mild depressive symptoms. Our results showed that the SNI-induced transcriptomic changes in female and male mice were largely distinct. Interestingly, the female mice exhibited more robust transcriptomic changes in the ACC than male, whereas the opposite pattern occurred in the mPFC. Cell type enrichment analyses revealed that the differentially expressed genes involved genes enriched in neurons, various types of glia and endothelial cells. We further performed gene set enrichment analysis (GSEA), which revealed significant de-enrichment of myelin sheath development in both female and male mPFC after SNI. In the female ACC, gene sets for synaptic organization were enriched, and gene sets for extracellular matrix were de-enriched after SNI, while such signatures were absent in male ACC. Collectively, these findings revealed region-specific and sexual dimorphism at the transcriptional levels induced by neuropathic pain, and provided novel therapeutic targets for chronic pain and its associated affective disorders.
Immunomodulatory and Anticancer Activities of Barley Bran Grown in Jordan: An in vitro and in vivo Study
Authors: Abuarab Sara Feras , Talib Wamidh H.
Published: May 2022

The Mediterranean diet is regarded as one of the most healthful dietary patterns in the world, owing to a combination of foods high in antioxidants and anticancer constituents. Barley bran is one of the components of the Mediterranean diet. It has nutritional and beneficial effects in different pathological conditions. Many studies were achieved to assess the nutritious values of barley bran, but there is no research indicating immunomodulatory and anticancer activities of barley bran grown in Jordan. The present study aims to examine and assess the potential immunomodulatory and anti-tumor activities of ethanol, n-hexane, aqueous/methanol, and water extracts obtained from barley bran. The Maceration method was utilized to prepare ethanol, n-hexane, aqueous/methanol, and water extracts. Various phytochemical groups were determined by using qualitative phytochemical tests. The antiproliferative activity of extracts was determined against MCF-7, HCT-116, A549, and EMT6/p by the MTT assay. The Folin-Ciocalteu reagent was used to detect the total phenolic content in extracts. Furthermore, immunomodulatory activity was assessed by determining the effect of extracts on splenocytes proliferation in the presence and absence of mitogens. The nitro blue tetrazolium assay and the neutral red method were used to assess the effect of each extract on the phagocytic activity of macrophages and pinocytosis, respectively. For the in vivo part, three different concentrations (10, 20, and 30% w/v) of barley bran were used to test the prophylactic effect in four Balb/C mice groups inoculated with EMT6/p cell-line subcutaneously. Also, serum samples were collected to assess the effect on cytokines (IFN-gamma, IL-2, IL-4, and IL-10). Barley bran extracts inhibited cancer cell proliferation. According to immunoassays, n-hexane and aqueous/methanol extracts could significantly rise lymphocyte proliferation and pinocytosis activity of macrophages. The activity of phagocytosis was increased by n-hexane and ethanol extracts. For the in vivo part, the average tumor size and weight of mice given the 30% barley bran group was significantly reduced (p < 0.05) compared with the control group. During our study, higher levels of TH1 cytokines (IFN- γ, IL-2) and lower levels of TH2 cytokine (IL-4) and T regulatory cytokine (IL-10) were obtained due to consumption of barley bran in food. Barley bran can be used as a prophylactic agent because it has anti-cancer and immunomodulatory activities.
Changes in the Leptin to Adiponectin Ratio Are Proportional to Weight Loss After Meal Replacement in Adults With Severe Obesity
Authors: Rafey Mohammed Faraz , Abdalgwad Razk , O'Shea Paula Mary , Foy Siobhan , Claffey Brid , Davenport Colin , O'Keeffe Derek Timothy , Finucane Francis Martin
Published: May 2022

Hypocaloric diets are known to induce changes in adipokine secretion, but the influence of a low energy liquid diet (LELD) on the leptin: adiponectin ratio (LAR), a measure of insulin resistance and cardiovascular risk, has not previously been investigated in patients with severe obesity. We conducted a prospective, single-center cohort study of adults with severe obesity (defined as body mass index (BMI) ≥40 kgm−2, or ≥35 kgm−2 with co-morbidities) who completed a 24-week milk-based LELD. We measured leptin, adiponectin and LAR at the start and on completion of the programme. Of 120 patients who started, 52 (43.3 %) completed the programme. Their mean age was 50.3 ± 11.2 (range 18–74) years, 29 (55.8 %) were female and 20 (38.5 %) had type 2 diabetes mellitus (T2DM). Weight decreased from 148.2 ± 39.6 to 125.4 ± 34.8 kg and BMI decreased from 52.4 ± 11.1 to 44.3 ± 9.8 kgm−2, respectively (all p < 0.001). In patients with T2DM, HbA1c decreased from 60.0 ± 17.4 to 47.5 ± 15.5 mmol/mol (p < 0.001). Leptin decreased (from 87.2 [48.6, 132.7] to 39.1 [21.0, 76.4] ng/ml) and adiponectin increased (from 5.6 [4.5, 7.5] to 7.1 [5.5, 8.5] μg/ml), with a reduction in LAR from 15 [8.4, 22.4] to 5.7 [3.0, 9.1] ng/μg (all p < 0.001), indicating decreased insulin resistance. The percentage weight lost was associated with the percentage reduction in LAR (ß = 2.9 [1.7, 4.1], p < 0.001) and this association was stronger in patients with T2DM. Patients with severe obesity who completed a milk-based LELD had a substantial reduction in LAR, consistent with decreased insulin resistance and cardiovascular risk, proportional to weight loss.
Experimental and Clinical Studies on the Effects of Natural Products on Noxious Agents-Induced Lung Disorders, a Review
Authors: Saadat Saeideh , Beigoli Sima , Khazdair Mohammad Reza , Amin Fatemeh , Boskabady Mohammad Hossein
Published: May 2022

The harmful effects of various noxious agents (NA) are well-known and there are reports regarding the induction of various lung disorders due to exposure to these agents both in animal and human studies. In addition, various studies have shown the effects of natural products (NP) on NA-induced lung disorders. The effects of various NP, including medicinal plants and their derivatives, on lung injury induced by NA, were reviewed in this study. The improving effects of various NP including medicinal plants, such as Aloe vera, Anemarrhena asphodeloides, Avena sativa, Crocus sativus, Curcuma longa, Dioscorea batatas, Glycyrrhiza glabra, Gentiana veitchiorum, Gentiopicroside, Houttuynia cordata, Hibiscus sabdariffa, Hochu-ekki-to, Hippophae rhamnoides, Juglans regia, Melanocarpa fruit juice, Mikania glomerata, Mikania laevigata, Moringa oleifera, Myrtus communis L., Lamiaceae, Myrtle, Mosla scabra leaves, Nectandra leucantha, Nigella sativa, Origanum vulgare L, Pulicaria petiolaris, Paulownia tomentosa, Pomegranate seed oil, Raphanus sativus L. var niger, Rosa canina, Schizonepeta tenuifolia, Thymus vulgaris, Taraxacum mongolicum, Tribulus Terrestris, Telfairia occidentalis, Taraxacum officinale, TADIOS, Xuebijing, Viola yedoensis, Zataria multiflora, Zingiber officinale, Yin-Chiao-San, and their derivatives, on lung injury induced by NA were shown by their effects on lung inflammatory cells and mediators, oxidative stress markers, immune responses, and pathological changes in the experimental studies. Some clinical studies also showed the therapeutic effects of NP on respiratory symptoms, pulmonary function tests (PFT), and inflammatory markers. Therefore, the results of this study showed the possible therapeutic effects of various NP on NA-induced lung disorders by the amelioration of various features of lung injury. However, further clinical studies are needed to support the therapeutic effects of NP on NA-induced lung disorders for clinical practice purposes.
Gut Microbiota of Individuals Could Be Balanced by a 14-Day Supplementation With Laminaria japonica and Differed in Metabolizing Alginate and Galactofucan
Authors: Zhang Xueqian , Su Changyu , Cao Cui , Gong Guiping , Huang Linjuan , Wang Zhongfu , Song Shuang , Zhu Beiwei
Published: May 2022

Laminaria japonica is rich in alginate (Alg) and galactofucan (GF) which have both been reported to regulate gut microbiota composition. To reveal the effect of L. japonica on human gut microbiota, the fecal microbiota of 12 volunteers before and after 14-day L. japonica intake was sequenced and compared, and the capabilities of the gut microbiota to utilize Alg and GF were also investigated. The 16S rRNA gene sequencing results demonstrated that Firmicutes/Bacteroidetes ratio could be balanced by L. japonica supplementation. The ability of gut microbiota to utilize Alg was significantly enhanced by L. japonica supplementation. Furthermore, the multiple linear regression analysis suggested that bacteria from Bacteroidaceae and Ruminococcaceae were positively correlated with Alg utilization while those from Erysipelotrichaceae, Bacteroidaceae, and Prevotellaceae participated in GF degradation. Moreover, the production of acetic acid and the total short-chain fatty acids (SCFAs) in fermentation were consistent with the consumption of Alg or GF, and propionic acid content was positively correlated with Alg consumption. In addition, the percentage of monosaccharides in the consumed GF after the fermentation suggested that gut microbiota from individuals could consume GF with different monosaccharide preferences. These findings shed a light on the impacts of dietary L. japonica on human health.
The Utility of Euroflow MRD Assessment in Real-World Multiple Myeloma Practice
Authors: Turner Rose , Kalff Anna , Bergin Krystal , Gorniak Malgorzata , Fleming Shaun , Spencer Andrew
Published: May 2022

Measurable residual disease (MRD) is being recognised as an optimal method for assessing depth of response, identifying higher risk of relapse, and guiding response-based treatment paradigms for multiple myeloma (MM). Although MRD negativity is increasingly replacing complete response as the surrogate endpoint in clinical trials, its role in real-world practice is less established. We retrospectively analyzed EuroFlow MRD results from patients with newly diagnosed MM (NDMM) who underwent bortezomib, cyclophosphamide and dexamethasone (VCD) induction and high dose melphalan conditioned autologous stem cell transplant (ASCT) at the Alfred Hospital between January 2016 and December 2020. Next generation flow MRD evaluation was performed 3 months following ASCT using the standardised EuroFlow platform. 112 patients with available MRD data were identified to have received VCD induction followed by ASCT. Post ASCT MRD was undetectable in 28.6% of patients. Those who achieved MRD negativity had significantly longer progression free survival (PFS) than those with persisting MRD (24-month PFS of 85% [95% CI: 72.4-99.9%] vs 63% [95% CI: 52.9-75.3%], p = 0.022). Maintenance therapy was associated with improved PFS regardless of MRD status (24-month PFS of 100% [95% CI: NA, p = 0.02] vs 73% [95% CI: 53.1-99.6%] in MRD negative, and 75% [95% CI: 64.2-88.6%] vs 36% [95% CI: 20.9-63.2%, p = 0.00015] in MRD positive patients). Results from this retrospective study of real-world practice demonstrate that Euroflow MRD analysis following standard VCD induction and ASCT in NDMM is feasible and allows more accurate prognostication, providing a platform for response adaptive therapies.
Guiding Value of Circulating Tumor Cells for Preoperative Transcatheter Arterial Embolization in Solitary Large Hepatocellular Carcinoma: A Single-Center Retrospective Clinical Study
Authors: Zhang Qiao , Xia Feng , Mo Ali , He Weiming , Chen Jiazhen , Zhang Weiqiao , Chen Weiqiang
Published: May 2022

Background

Large hepatocellular carcinoma (LHCC) is highly malignant and prone to recurrence, leading to a poor long-term prognosis for patients. There is an urgent need for measures to intervene in postoperative recurrence. Preoperative Transcatheter Arterial Embolization (TACE) is an effective treatment. However, there is a lack of reliable preoperative indicators to guide the application of preoperative TACE. We, therefore, investigated whether the preoperative status of circulating tumor cells (CTCs) could be used to guide preoperative TACE for HCC treatment.

Methods

This study recruited 361 HCC patients and compared recurrence-free survival (RFS) and overall survival (OS) in patients treated with TACE prior to surgery and those not treated with TACE. Patients were divided into CTC-positive group and CTC-negative group according to CTC status, and the effect of preoperative TACE on RFS and OS was compared in each subgroup.

Results

In CTC-positive patients, preoperative TACE reduces early recurrence and improves long-term survival. However, HCC patients did not benefit from preoperative TACE for the overall population and CTC-negative patients.

Conclusions

Preoperative CTC testing is a reliable indicator of whether HCC patients received TACE preoperatively. CTC positivity was associated with early tumor recurrence, and preoperative TACE could reduce early recurrence and long-term prognosis in CTC-positive patients.
Slow Shallow Energy States as the Origin of Hysteresis in Perovskite Solar Cells
Authors: van Heerden Rik , Procel Paul , Mazzarella Luana , Santbergen Rudi , Isabella Olindo
Published: May 2022

Organic-inorganic metal halide perovskites have attracted a considerable interest in the photovoltaic scientific community demonstrating a rapid and unprecedented increase in conversion efficiency in the last decade. Besides the stunning progress in performance, the understanding of the physical mechanisms and limitations that govern perovskite solar cells are far to be completely unravelled. In this work, we study the origin of their hysteretic behaviour from the standpoint of fundamental semiconductor physics by means of technology computer aided design electrical simulations. Our findings identify that the density of shallow interface defects at the interfaces between perovskite and transport layers plays a key role in hysteresis phenomena. Then, by comparing the defect distributions in both spatial and energetic domains for different bias conditions and using fundamental semiconductor equations, we can identify the driving force of hysteresis in terms of slow recombination processes and charge distributions.