bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug-Related Problems of Children With Chronic Diseases in a Chinese Primary Health Care Institution: A Cross-Sectional Study
Authors: Ni Xiao-Feng , Yang Chun-Song , Zeng Li-Nan , Li Hai-Long , Diao Sha , Li De-Yuan , Wu Jin , Liu Yuan-Chun , Jia Zhi-Jun , Cheng Guo , Zhang Ling-Li
Published: July 2022

Introduction: Drug-related problems (DRPs) refer to events or circumstances involving drug therapy that actually or potentially interfere with desired health outcomes. DRPs might be severe for children with chronic diseases managed at primary health care institutions, but the relevant research is scarce.

Objective: In this cross-sectional study, we aimed to explore the prevalence, types, causes, and influencing factors of DRPs in children with chronic diseases in a Chinese primary health care institution.

Methods: We recruited children with chronic diseases who visited the pediatric outpatient department in a primary health care institution from July 1 to 12 October 2021. Clinical pharmacists identified DRPs through medication therapy reviews, classified the types and causes of DRPs, and distinguished the manifested DRPs that affected the outcome and potential DRPs that were going to affect the outcome.

Results: A total of 188 children with chronic diseases was included, and 584 DRPs were identified in 89.89% of participants. The most common type of DRPs was “treatment effectiveness” (a manifested problem or potential problem with the effect of the pharmacotherapy; 83.56%), of which 67.29% were potential DRPs. The second common type was “treatment safety” (patient suffers or could suffer from an adverse drug event; 14.21%), of which 89.16% were potential DRPs. The most common cause of DRPs was related to the process of use (42.24%), such as “patient uses/takes less drug than prescribed or does not take the drug at all,” “patient stores drug inappropriately,” and “patient administers/uses the drug in a wrong way.” The second common cause was related to the process of dispensing (29.83%), such as “necessary information not provided or incorrect advice provided” and “prescribed drug is not available.” The third common cause was related to the process of prescribing (26.21%), such as “drug dose is too low” and “no or incomplete drug treatment despite an existing indication.” The number of combined medications was an influencing factor for the frequency of DRPs (p < 0.05).

Conclusion: This cross-sectional study showed that the current situation regarding DRPs among children with chronic diseases managed in the primary health care institution was serious. The types of DRPs were mainly related to treatment effectiveness, and improper usage of medications was one of the main causes of DRPs. The number of combined drugs was the influencing factor for the frequency of DRPs. In the future, pharmacists should consider formulating pharmaceutical intervention strategies for this specific group according to the characteristics of DRPs.
Effects of Glycolysis-Related Genes on Prognosis and the Tumor Microenvironment of Hepatocellular Carcinoma
Authors: Zheng Ju-Yan , Liu Jun-Yan , Zhu Tao , Liu Chong , Gao Ying , Dai Wen-Ting , Zhuo Wei , Mao Xiao-Yuan , He Bai-Mei , Liu Zhao-Qian
Published: July 2022

Background: Hepatocellular carcinoma (HCC) is a common and deadly malignancy worldwide. Current treatment methods for hepatocellular carcinoma have many disadvantages; thus, it is urgent to improve the efficacy of these therapies. Glycolysis is critical in the occurrence and development of tumors. However, survival and prognosis biomarkers related to glycolysis in HCC patients remain to be fully identified.

Methods: Glycolysis-related genes (GRGs) were downloaded from “The Molecular Signatures Database” (MSigDB), and the mRNA expression profiles and clinical information of HCC patients were obtained from TCGA. Consensus clustering was performed to classify the HCC patients into two subgroups. We used the least absolute shrinkage and selection operator (LASSO) regression analysis to construct the risk signature model. Kaplan–Meier (K-M) survival analysis was performed to evaluate the prognostic significance of the risk model, and the receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction accuracy. The independent prediction ability of the risk model was validated by univariate and multivariate Cox regression analyses. The differences of immune infiltrates and relevant oncogenic signaling between different risk groups were compared. Finally, biological experiments were performed to explore the functions of screened genes.

Results: HCC patients were classified into two subgroups, according to the expression of prognostic-related GRGs. Almost all GRGs categorized in cluster 2 showed upregulated expressions, whereas GRGs in cluster 1 conferred survival advantages. GSEA identified a positive correlation between cluster 2 and the glycolysis process. Ten genes were selected for risk signature construction. Patients were assigned to high-risk and low-risk groups based on the median risk score, and K-M survival analysis indicated that the high-risk group had a shorter survival time. Additionally, the risk gene signature can partially affect immune infiltrates within the HCC microenvironment, and many oncogenic pathways were enriched in the high-risk group, including glycolysis, hypoxia, and DNA repair. Finally, in vitro knockdown of ME1 suppressed proliferation, migration, and invasion of hepatocellular carcinoma cells.

Conclusion: In our study, we successfully constructed and verified a novel glycolysis-related risk signature for HCC prognosis prediction, which is meaningful for classifying HCC patients and offers potential targets for the treatment of hepatocellular carcinoma.
Integrated Plasma Metabolomics and Gut Microbiota Analysis: The Intervention Effect of Jiawei Xiaoyao San on Liver Depression and Spleen Deficiency Liver Cancer Rats
Authors: Li Zhuoxian , Zhao Youxing , Cheng Jinlai , Xu Lijing , Wen Xiaoyu , Sun Yuhao , Xia Meng , He Yining
Published: July 2022

Primary liver cancer is the third most common malignancy, and hepatocellular carcinoma is its main subtype, with a high recurrence rate and high mortality. Intestinal microflora and metabolic disorders are present in most HCC patients. Traditional Chinese medicine (TCM) plays an important role in the composition of intestinal microorganisms and the transformation of active metabolites. Many scholars are trying to develop related drugs to assist in the treatment of liver cancer. In the preliminary study of the research group, it was found that the Jiawei Xiaoyao San has a certain therapeutic effect on liver cancer, but the specific mechanism is still unclear. Therefore, this study constructed a liver cancer rat model with liver stagnation and spleen deficiency, to explore the regulatory effect of Jiawei Xiaoyao San on plasma metabolites and intestinal microflora and to find the potential mechanism of Jiawei Xiaoyao San in the treatment of liver cancer. Plasma samples and fecal samples were collected from liver cancer rats with liver depression and spleen deficiency for microbiome 16S rDNA sequencing and metabolic ESI-QTRAP-MS/MS analysis. Various bioinformatics methods were used to analyze the dataset individually and in combination. The analysis and identification of plasma metabolomics showed that the intervention effect of Jiawei Xiaoyao San on liver cancer rats with liver depression and spleen deficiency was related to 11 differential metabolites and signal pathways such as primary bile acid biosynthesis, phenylalanine metabolism, pantothenate and COA biosynthesis, metabolic pathways, cholesterol metabolism, and bile secretion. Combined with fecal microbiological analysis, it was found that Jiawei Xiaoyao San could significantly change the composition of intestinal flora in liver cancer rates, increase beneficial bacteria, and reduce the composition of harmful bacteria. This study provides some experimental basis for the traditional Chinese medicine theory and clinical application of Jiawei Xiaoyao San in the adjuvant treatment of liver cancer. The potential mechanism may be to regulate metabolism and intestinal flora to play the role of regulating liver depression, activating blood, and detoxifying, to achieve the purpose of adjuvant treatment of liver cancer.
Herbal medicine for the treatment of chronic rhinosinusitis: A systematic review and meta-analysis
Authors: Lee Boram , Kwon Chan-Young , Park Man Young
Published: July 2022

Objectives: Chronic rhinosinusitis (CRS) is a disease with a high prevalence and a high socioeconomic burden. This study aimed to conduct a comprehensive systematic review to update the evidence on the use of herbal medicine (HM) for CRS treatment.

Methods: A total of 14 electronic databases for randomized controlled trials (RCTs) evaluating the effects of HM on the treatment of CRS were searched for articles published before July 2021. The primary outcome was CRS severity post-treatment, measured with the Visual Analogue Scale (VAS) and Total Effective Rate (TER). The risk of bias of the included studies and the quality of evidence of the main findings were assessed using the Cochrane Collaboration’s risk of bias tool and the Grading of Recommendations, Assessment, Development, and Evaluations tool.

Results: A total of 80 RCTs were included. Compared to placebo, HM significantly improved CRS severity as measured by TER and VAS. When HM was compared with conventional treatment (CT) as monotherapy or adjuvant therapy, CRS severity measured by TER and VAS, quality of life, Lund-Kennedy endoscopy score, Lund-Mackay computed tomography score, and nasal mucociliary function were significantly improved in the HM group. No serious adverse events associated with HM were reported. The risk of bias was generally unclear, and the quality of evidence ranged from moderate to low.

Conclusion: This review found some limited clinical evidence that HM or HM combined with CT may be more effective and safer than CT alone in treating CRS. However, the methodological quality of the included studies was generally low, and the quality of the evidence needs to be improved.
Traditional Chinese Medicine in the Treatment of Chronic Kidney Diseases: Theories, Applications, and Mechanisms
Authors: Wang Yunlai , Feng Ye , Li Manman , Yang Mo , Shi Gaoxiang , Xuan Zihua , Yin Dengke , Xu Fan
Published: July 2022

Chronic kidney disease (CKD) is a common and progressive disease that has become a major public health problem on a global scale. Renal fibrosis is a common feature in the pathogenesis of CKD, which is mainly related to the excessive accumulation and deposition of extracellular matrix caused by various inflammatory factors. No ideal treatment has yet been established. In recent years, based on the traditional Chinese medicine (TCM) theory of CKD and its molecular mechanism, clinical evidence or experimental studies have confirmed that a variety of Chinese materia medica (CMM) and their effective components can delay the progress of CKD. TCM believes that the pathogenesis of CKD is the deficiency in the root and excess in the branch, and the deficiency and excess are always accompanied by the disease. The strategies of TCM in treating CKD are mainly based on invigorating Qi, tonifying the kidneys, promoting blood circulation, removing stasis, eliminating heat and dampness, removing turbidity, and eliminating edema, and these effects are multitargeted and multifunctional. This review attempts to summarize the theories and treatment strategies of TCM in the treatment of CKD and presents the efficacy and mechanisms of several CMMs supported by clinical evidence or experimental studies. In addition, the relationship between the macroscopic of TCM and the microscopic of modern medicine and the problems faced in further research were also discussed.
Clostridium butyricum Protects Against Pancreatic and Intestinal Injury After Severe Acute Pancreatitis via Downregulation of MMP9
Authors: Yan Qingqing , Jia Lin , Wen Biyan , Wu Yao , Zeng Yanbo , Wang Qing
Published: July 2022

Background:Evidence have shown that gut microbiota plays an important role in the development of severe acute pancreatitis (SAP). In addition, matrix metalloproteinase-9 (MMP9) plays an important role in intestinal injury in SAP. Thus, we aimed to determine whether gut microbiota could regulate the intestinal injury during SAPviamodulating MMP9.

Methods:In this study, the fecal samples of patients with SAP (n= 72) and healthy controls (n= 32) were analyzed by 16S rRNA gene sequencing. In addition, to investigate the association between gut microbiota and MMP9 in intestinal injury during SAP, we established MMP9 stable knockdown Caco2 and HT29 cellsin vitroand generated a MMP9 knockout (MMP9−/−) mouse model of SAPin vivo.

Results:We found that the abundance ofClostridium butyricum(C.butyricum) was significantly decreased in the SAP group. In addition, overexpression of MMP9 notably downregulated the expressions of tight junction proteins and upregulated the expressions of p-p38 and p-ERK in Caco2 and HT29 cells (p< 0.05). However, C.butyricumor butyrate treatment remarkably upregulated the expressions of tight junction proteins and downregulated the expressions of MMP9, p-p38 and p-ERK in MMP9-overexpressed Caco2 and HT29 cells (p< 0.05). Importantly, C.butyricumor butyrate could not affect the expressions of tight junction proteins, and MMP9, p-p38 and p-ERK proteins in MMP9-knockdown cells compared with MMP9-knockdown group. Consistently, C.butyricumor butyrate could not attenuate pancreatic and intestinal injury during SAP in MMP9−/− mice compared with the SAP group.

Conclusion:Collectively, C.butyricumcould protect against pancreatic and intestinal injury after SAPviadownregulation of MMP9in vitroandin vivo.
Role of 5HT1A Receptors in the Neuroprotective and Behavioral Effects of Cannabidiol in Hypoxic–Ischemic Newborn Piglets
Authors: Barata Lorena , de Hoz-Rivera María , Romero Angela , Martínez María , Silva Laura , Villa María , Campa Leticia , Jiménez-Sánchez Laura , Martínez-Orgado José
Published: July 2022

Background: Hypoxic–ischemic (HI) insults have important deleterious consequences in newborns, including short-term morbidity with neuromotor and cognitive disturbances. Cannabidiol (CBD) has demonstrated robust neuroprotective effects and shows anxiolytic/antidepressant effects as well. These effects are thought to be related to serotonin 5-HT1A receptor (5HT1AR) activation. We hereby aimed to study the role of 5HT1AR in the neuroprotective and behavioral effects of CBD in HI newborn piglets.

Methods: 1-day-old piglets submitted to 30 min of hypoxia (FiO2 10%) and bilateral carotid occlusion were then treated daily with vehicle, CBD 1 mg/kg, or CBD with the 5HT1AR antagonist WAY 100635 1 mg/kg 72 h post-HI piglets were studied using amplitude-integrated EEG to detect seizures and a neurobehavioral test to detect neuromotor impairments. In addition, behavioral performance including social interaction, playful activity, hyperlocomotion, and motionless periods was assessed. Then, brain damage was assessed using histology (Nissl and TUNEL staining) and biochemistry (proton magnetic resonance spectroscopy studies.

Results: HI led to brain damage as assessed by histologic and biochemistry studies, associated with neuromotor impairment and increased seizures. These effects were not observed in HI piglets treated with CBD. These beneficial effects of CBD were not reversed by the 5HT1AR antagonist, which is in contrast with previous studies demonstrating that 5HT1AR antagonists eliminated CBD neuroprotection as assessed 6 h after HI in piglets. HI led to mood disturbances, with decreased social interaction and playfulness and increased hyperlocomotion. Mood disturbances were not observed in piglets treated with CBD, but in this case, coadministration of the 5HT1AR antagonist eliminates the beneficial effects of CBD.

Conclusion: CBD prevented HI-induced mood disturbances in newborn piglets by acting on 5HT1AR. However, 5HT1AR activation seems to be necessary for CBD neuroprotection only in the first hours after HI.
Neuroprotective Effects and Mechanisms of Senegenin, an Effective Compound Originated From the Roots of Polygala Tenuifolia
Authors: Chen Zhe , Yang Yu , Han Ying , Wang Xijun
Published: July 2022

Senegenin is the main bioactive ingredient isolated from the dried roots of Polygala tenuifolia Willd. In recent years, senegenin has been proved to possess a variety of pharmacological activities, such as anti-oxidation, anti-inflammation, anti-apoptosis, enhancement of cognitive function. Besides, it has a good development prospect for the treatment of neurodegenerative diseases, depression, osteoporosis, cognitive dysfunction, ischemia-reperfusion injury and other diseases. However, there is no systematic literature that fully demonstrates the pharmacological effects of senegenin. In order to meet the needs of new drug research and precise medication, this review summarized the neuroprotective effects, mechanisms and gastrointestinal toxicity of senegenin based on the literatures published from the past 2 decades. In addition, an in-depth analysis of the existing problems in the current research as well as the future research directions have been conducted in order to provide a basis for the clinical application of this important plant extract.
Pharmacological Inhibition of STING/TBK1 Signaling Attenuates Myeloid Fibroblast Activation and Macrophage to Myofibroblast Transition in Renal Fibrosis
Authors: Zeng Haimei , Gao Ying , Yu Wenqiang , Liu Jiping , Zhong Chaoqun , Su Xi , Wen Shihong , Liang Hua
Published: July 2022

Renal fibrosis is an important pathological biomarker of chronic kidney disease (CKD). Stimulator of interferon genes/TANK binding kinase 1 (STING/TBK1) axis has been identified as the main regulator of innate immune response and closely related to fibrotic disorder. However, the role of STING/TBK1 signaling pathway in kidney fibrosis is still unknown. In this study, we investigated the effect of pharmacological inhibition of STING/TBK1 signaling on renal fibrosis induced by folic acid (FA). In mice, TBK1 was significantly activated in interstitial cells of FA-injured kidneys, which was markedly inhibited by H-151 (a STING inhibitor) treatment. Specifically, pharmacological inhibition of STING impaired bone marrow-derived fibroblasts activation and macrophage to myofibroblast transition in folic acid nephropathy, leading to reduction of extracellular matrix proteins expression, myofibroblasts formation and development of renal fibrosis. Furthermore, pharmacological inhibition of TBK1 by GSK8612 reduced myeloid myofibroblasts accumulation and impeded macrophage to myofibroblast differentiation, resulting in less deposition of extracellular matrix protein and less severe fibrotic lesion in FA-injured kidneys. In cultured mouse bone marrow-derived monocytes, TGF-β1 activated STING/TBK1 signaling. This was abolished by STING or TBK1 inhibitor administration. In addition, GSK8612 treatment decreased levels of α-smooth muscle actin and extracellular matrix proteins and prevents bone marrow-derived macrophages to myofibroblasts transition in vitro. Collectively, our results revealed that STING/TBK1 signaling has a critical role in bone marrow-derived fibroblast activation, macrophages to myofibroblasts transition, and kidney fibrosis progression.
The circRNA-miRNA/RBP regulatory network in myocardial infarction
Authors: Zhang Lei , Zhang Yuan , Yu Fei , Li Xin , Gao Huijuan , Li Peifeng
Published: July 2022

Myocardial infarction (MI) is a serious heart disease that causes high mortality rate worldwide. Noncoding RNAs are widely involved in the pathogenesis of MI. Circular RNAs (circRNAs) are recently validated to be crucial modulators of MI. CircRNAs are circularized RNAs with covalently closed loops, which make them stable under various conditions. CircRNAs can function by different mechanisms, such as serving as sponges of microRNAs (miRNAs) and RNA-binding proteins (RBPs), regulating mRNA transcription, and encoding peptides. Among these mechanisms, sponging miRNAs/RBPs is the main pathway. In this paper, we systematically review the current knowledge on the properties and action modes of circRNAs, elaborate on the roles of the circRNA-miRNA/RBP network in MI, and explore the value of circRNAs in MI diagnosis and clinical therapies. CircRNAs are widely involved in MI. CircRNAs have many advantages, such as stability, specificity, and wide distribution, which imply that circRNAs have a great potential to act as biomarkers for MI diagnosis and prognosis.
Hu’po Anshen Decoction Accelerated Fracture-Healing in a Rat Model of Traumatic Brain Injury Through Activation of PI3K/AKT Pathway
Authors: Shen Jing , Li Yan-Ze , Yao Sai , Zhu Zhou-Wei , Wang Xiang , Sun Hui-Hui , Ji Wei-Feng
Published: July 2022

Hu’po Anshen decoction (HPASD) is a traditional Chinese medicine formula comprising five herbal medicines for the treatment of concussion and fracture healing, but its pharmacological mechanism is still unclear. Ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC/Q-TOF MS) was used to analyze the main active components of HPASD. Rats were randomly assigned to fracture group, fracture combined with traumatic brain injury (TBI) group (FBI) and FBI combined with HPASD treatment group (FBIH). Rats in the FBIH group were given oral doses of HPASD (2.4 g/kg, 4.8 g/kg and 9.6 g/kg) for 14 or 21 consecutive days. The fracture callus formation and fracture sites were determined by radiographic analysis and micron-scale computed tomography (micro-CT) analysis. Hematoxylin and eosin (H&E) staining and a three-point bending test were applied to assess histological lesions and biomechanical properties, respectively. The levels of cytokines-/protein-related to bone formation and differentiation as well as PI3K/AKT pathway-related proteins were determined by Enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription-polymerase chain reaction (qRT-PCR), or western blot assays, respectively. UPLC-Q/TOF-MS-based serum metabolomic analysis was also performed to investigate the therapeutic effects of HPASD in the treatment of FBI. UPLC/Q-TOF MS analysis showed the chemical components in HPASD, including flavonoids, amino acids, saponins, and phenylpropanoid constituents, etc. HPASD dose-dependently promoted callus formation, increased bone density, improved mechanical parameters and morphological scores, and facilitated the expressions of VEGF, PDGF, bFGF, VEGFA, CoL1A1, RUNX2, BMP2, and Aggrecan, inhibited the expression of MMP13, and activated PI3K/AKT pathway. Metabolomics analysis revealed abnormalities of malate-aspartate shuttle and glucose-alanine. HPASD accelerates fracture healing by promoting bone formation and regulating the malate-aspartate shuttle and glucose-alanine cycle, which might be associated with the activation of the PI3K/AKT pathway.
Numerical Computation for Modified Cross Model Fluid Flow Around the Circular Cylinder with Symmetric Trapezoidal Cavities
Authors: Mahmood Rashid , Siddique Imran , Khan Ilyas , Badran Mohamed , Mehrez Sadok , Majeed Afraz Hussain , Naaz Sehrish
Published: July 2022

This manuscript explores the flow features of the Modified Cross Model in a channel with symmetric trapezoidal cavities in the presence of a circular obstacle. The non-dimensional governing equations and model for different parameters are evaluated via a Galerkin Finite Element Method The system of non-linear algebraic equations is computed by adopting the Newton method. A space involving the quadratic polynomials (P2) has been selected to compute for the velocity profile while the pressure profile is approximated by a linear (P1) finite element space of functions. Simulations are performed for a wide range of physical parameters such as modified parameter (from 0.0 to 0.5), power-law index (from 0.5 to 1.5), relaxation parameter (from 1 to 3), and Reynolds number (from 10 to 40). For the case of a modified parameter (b) and relaxation parameter (λ), it is observed that the drag coefficient (CD) shows an increasing trend while the lift coefficient (CL) is changing sign at lower values of (λ), and then becomes positive at λ=3.
Ultra-Wideband Vertically Polarized Omnidirectional Antenna With Dual Metal Loops
Authors: Peng Jian Dong , Fu Dong Qiang , Ye Liang Hua , Shi Xinrong
Published: July 2022

An ultra-wideband vertically polarized monopole antenna having excellent omnidirectional radiation pattern is proposed. It consists of a four-sector monopole, dual metal loops and a metal reflector. The four-sector monopole is employed as radiator and excited by a 50 Ω coaxial cable to realize vertical-polarized omnidirectional radiation pattern and good impedance matching. Then two metal loops surrounding the monopole are used to further enhance the impedance matching and improve the gain variation. The antenna has an ultrawide bandwidth of 103% (1.63–5.1 GHz) for return loss > 15 dB. It also obtains a steady gain of 3.25 ± 1.35 dBi and a very small gain variation of less than 0.9 dBi within the ultrawide band. These performances indicate that the proposed antenna is competitive for 2G/3G/4G/5G indoor mobile communications.
Flow reversal in distal collaterals as a possible mechanism of delayed intraparenchymal hemorrhage after flow diversion treatment of cerebral aneurysms
Authors: Hadad Sara , Pradhan Aseem , Kadirvel Ramanathan , Kallmes David , Cebral Juan R. , Mut Fernando
Published: July 2022

Background and Purpose: Delayed intraparenchymal hemorrhages (DIPHs) are one of the most serious complications of cerebral aneurysm treatment with flow diverters (FD), yet their causes are largely unknown. This study analyzes distal hemodynamic alterations induced by the treatment of intracranial aneurysms with FDs.

Methods: A realistic model of the brain arterial network was constructed from MRA images and extended with a constrained constructive optimization technique down to vessel diameters of approximately 50μm. Different variants of the circle of Willis were created by alternatively occluding communicating arteries. Collateral vessels connecting different arterial trees were then added to the model, and a distributed lumped parameter approach was used to model the pulsatile blood flow in the arterial network. The treatment of an ICA aneurysm was modeled by changing the local resistance, flow inertia, and compliance of the aneurysmal segment.

Results: The maximum relative change in distal pressure induced by the aneurysm treatment was below 1%. However, for certain combinations of the circle of Willis and distal collateralization, important flow reversals (with a wall shear stress larger than approximately 1.0 dyne/cm2) were observed in collateral vessels, both ipsilaterally and contralaterally to the treated aneurysm.

Conclusion: This study suggests the hypothesis that flow diverters treatment of intracranial aneurysms could cause important flow reversal in distal collaterals. Flow reversal has previously been shown to be pro-inflammatory and pro-atherogenic and could therefore have a detrimental effect on these collateral vessels, and thus could be a suitable explanation of DIPHs, while the small distal pressure increase is not.
Heme Biosynthetic Gene Expression Analysis With dPCR in Erythropoietic Protoporphyria Patients
Authors: Granata Francesca , Brancaleoni Valentina , Barman-Aksözen Jasmin , Scopetti Margherita , De Luca Giacomo , Fustinoni Silvia , Motta Irene , Di Pierro Elena , Graziadei Giovanna
Published: July 2022

Background: The heme biosynthesis (HB) involves eight subsequent enzymatic steps. Erythropoietic protoporphyria (EPP) is caused by loss-of-function mutations in the ferrochelatase (FECH) gene, which in the last HB step inserts ferrous iron into protoporphyrin IX (PPIX) to form heme.

Aim and method: The aim of this work was to for the first time analyze the mRNA expression of all HB genes in peripheral blood samples of patients with EPP having the same genotype FECH c.[215dupT]; [315-48T > C] as compared to healthy controls by highly sensitive and specific digital PCR assays (dPCR).

Results: We confirmed a decreased FECH mRNA expression in patients with EPP. Further, we found increased ALAS2 and decreased ALAS1, CPOX, PPOX and HMBS mRNA expression in patients with EPP compared to healthy controls. ALAS2 correlated with FECH mRNA expression (EPP: r = 0.63, p = 0.03 and controls: r = 0.68, p = 0.02) and blood parameters like PPIX (EPP: r = 0.58 p = 0.06).

Conclusion: Our method is the first that accurately quantifies HB mRNA from blood samples with potential applications in the monitoring of treatment effects of mRNA modifying therapies in vivo, or investigation of the HB pathway and its regulation. However, our findings should be studied in separated blood cell fractions and on the enzymatic level.
Effect of Modulated Electromyostimulation on the Motor System of Elderly Neurological Patients. Pilot Study of Russian Currents Also Known as Kotz Currents
Authors: Amirova Liubov , Avdeeva Maria , Shishkin Nikita , Gudkova Anna , Guekht Alla , Tomilovskaya Elena
Published: July 2022

In this brief report, we present preliminary findings from a study of the use of electromyostimulation (EMS) in neurological patients. Assuming the approach to be sufficiently effective, we decided to investigate the motor system of elderly neurological patients before and after a course of Russian currents EMS, which were developed for Soviet athletes and cosmonauts. To this point, 19 patients—EMS (n = 11) and control (n = 8)—have successfully completed the study. The study included patients aged 60–90 years with confirmed walking and balance disorders with a history of chronic cerebral ischemia. Patients in the experimental group underwent a course of modulated EMS of the hip and shin muscles from 3 to 9 procedures. Preliminary results of the study showed good patient acceptance of EMS. After the course, the EMS group showed a significant improvement from baseline in the Tinetti Test (+1.4 points, p = 0.0045), Rivermead Mobility Index (+0.5 points, p = 0.0022), and Timed Up and Go Test (−1.2 s, p = 0.0053). There was also a significant improvement in balance quality of 8.6% (p = 0.04). Shin muscle strength, although trending positively, did not change significantly. There was also no change in hip and shin muscles’ tone. No significant changes were observed in the control group in the same tests. It can be concluded that stimulation of the hip and shin muscles with Russian (Kotz) currents has a positive effect on the motor system of elderly neurological patients. Significant effects with a course of short duration indicate that this EMS regimen is promising.
Hypoxic Training Ameliorates Skeletal Muscle Microcirculation Vascular Function in a Sirt3-Dependent Manner
Authors: Ma Chunwei , Zhao Yongcai , Ding Xiaoqing , Gao Binghong
Published: July 2022

Hypoxic training improves the microcirculation function of human skeletal muscle, but its mechanism is still unclear. Silent information regulator 2 homolog 3 (Sirt3) can improve mitochondrial function and oxidative status. We aimed to examine the role of Sirt3 in the process of hypoxic training, which affects skeletal muscle microcirculation. C57BL/6 mice were assigned to control (C), hypoxic training (HT), Sirt3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP), and 3-TYP + hypoxic training (3-TYP + HT) groups (n = 6/group). Sirt3 inhibition was induced by intraperitoneal injection of Sirt3 inhibitor 3-TYP. After 6 weeks of intervention, microcirculatory capillary formation and vasomotor capacity were evaluated using immunofluorescence, Western blot, biochemical tests, and transmission electron microscopy (TEM). Laser Doppler flowmetry was used to evaluate skeletal muscle microcirculation blood flow characteristics. Six weeks of hypoxic training enhanced skeletal muscle microcirculation function and increased microcirculatory vasodilation capacity and capillary formation. After the pharmacological inhibition of Sirt3, the reserve capacity of skeletal muscle microcirculation was reduced to varying degrees. After the inhibition of Sirt3, mice completed the same hypoxic training, and we failed to observe the microcirculation function adaptation like that observed in hypoxic training alone. The microcirculation vasodilation and the capillaries number did not improve. Hypoxic training improved skeletal muscle microcirculation vasodilation capacity and increased skeletal muscle microcirculation capillary density. Sirt3 is involved in the adaptation of skeletal muscle microcirculation induced by hypoxic training.
Training Convolutional Neural Networks on Simulated Photoplethysmography Data: Application to Bradycardia and Tachycardia Detection
Authors: Sološenko Andrius , Paliakaitė Birutė , Marozas Vaidotas , Sörnmo Leif
Published: July 2022

Objective: To develop a method for detection of bradycardia and ventricular tachycardia using the photoplethysmogram (PPG).

Approach: The detector is based on a dual-branch convolutional neural network (CNN), whose input is the scalograms of the continuous wavelet transform computed in 5-s segments. Training and validation of the CNN is accomplished using simulated PPG signals generated from RR interval series extracted from public ECG databases. Manually annotated real PPG signals from the PhysioNet/CinC 2015 Challenge Database are used for performance evaluation. The performance is compared to that of a pulse-based reference detector.

Results: The sensitivity/specificity were found to be 98.1%/97.9 and 76.6%/96.8% for the CNN-based detector, respectively, whereas the corresponding results for the pulse-based detector were 94.7%/99.8 and 67.1%/93.8%, respectively.

Significance: The proposed detector may be useful for continuous, long-term monitoring of bradycardia and tachycardia using wearable devices, e.g., wrist-worn devices, especially in situations where sensitivity is favored over specificity. The study demonstrates that simulated PPG signals are suitable for training and validation of a CNN.
Relative Handgrip Strength is Inversely Associated with Hypertension in Consideration of Visceral Adipose Dysfunction: A Nationwide Cross-Sectional Study in Korea
Authors: Park Jae Ho , Lim Nam-Kyoo , Park Hyun-Young
Published: July 2022

This study investigated the associations of relative handgrip strength (rHGS) and hypertension. Individual differences in visceral adipose dysfunction (VAD) were evaluated to verify whether rHGS was associated with a reduction in the risk of hypertension, even in individuals with VAD. We included 77,991 participants (50,616 women) from nationwide cohorts in Korea. Participants were categorized into three groups based on sex-specific tertiles of rHGS (Low, Mid, and High). The visceral adiposity index (VAI) was used to evaluate VAD. The multiple logistic regression model was used to assess the risk of hypertension. High rHGS is associated with reduction of hypertension risk in 38 and 26% of men and women, respectively, although rHGS was significantly low in women compared to men. The benefit of rHGS was observed from middle-aged to older participants in both sexes. High rHGS is associated with risk reduction for hypertension in both VAD and non-VAD groups. In the VAD group, compared to Low rHGS, High rHGS was associated with 32 and 22% risk reductions in hypertension in men and women, respectively, and these associations remained significant even when classified according to age, such as in middle-aged and older subgroups. Therefore, the present study suggests that high levels of rHGS are significantly associated with a reduced risk of hypertension even in participants with VAD. Thus, maintaining a higher level of rHGS may be associated with protective benefits against hypertension.
Long Bone Mineral Loss, Bone Microstructural Changes and Oxidative Stress After Eimeria Challenge in Broilers
Authors: Tompkins Y. H. , Teng P. , Pazdro R. , Kim W. K.
Published: July 2022

The objective of this study was to evaluate the impact of coccidiosis on bone quality and antioxidant status in the liver and bone marrow of broiler chickens. A total of 360 13-day old male broilers (Cobb 500) were randomly assigned to different groups (negative control, low, medium-low, medium-high, and highest dose groups) and orally gavaged with different concentrations of Eimeria oocysts solution. Broiler tibia and tibia bone marrow were collected at 6 days post-infection (6 dpi) for bone 3-D structural analyses and the gene expression related to osteogenesis, oxidative stress, and adipogenesis using micro-computed tomography (micro-CT) and real-time qPCR analysis, respectively. Metaphyseal bone mineral density and content were reduced in response to the increase of Eimeria challenge dose, and poor trabecular bone traits were observed in the high inoculation group. However, there were no significant structural changes in metaphyseal cortical bone. Medium-high Eimeria challenge dose significantly increased level of peroxisome proliferator-activated receptor gamma (PPARG, p < 0.05) and decreased levels of bone gamma-carboxyglutamate protein coding gene (BGLAP, p < 0.05) and fatty acid synthase coding gene (FASN, p < 0.05) in bone marrow. An increased mRNA level of superoxide dismutase type 1 (SOD1, p < 0.05) and heme oxygenase 1 (HMOX1, p < 0.05), and increased enzyme activity of superoxide dismutase (SOD, p < 0.05) were found in bone marrow of Eimeria challenged groups compared with that of non-infected control. Similarly, enzyme activity of SOD and the mRNA level of SOD1, HMOX1 and aflatoxin aldehyde reductase (AKE7A2) were increased in the liver of infected broilers (p < 0.05), whereas glutathione (GSH) content was lower in the medium-high challenge group (p < 0.05) compared with non-challenged control. Moreover, the mRNA expression of catalase (CAT) and nuclear factor kappa B1 (NFKB1) showed dose-depend response in the liver, where expression of CAT and NFKB1 was upregulated in the low challenge group but decreased with the higher Eimeria challenge dosage (p < 0.05). In conclusion, high challenge dose of Eimeria infection negatively affected the long bone development. The structural changes of tibia and decreased mineral content were mainly located at the trabecular bone of metaphyseal area. The change of redox and impaired antioxidant status following the Eimeria infection were observed in the liver and bone marrow of broilers.
A review of remote sensing for potato traits characterization in precision agriculture
Authors: Sun Chen , Zhou Jing , Ma Yuchi , Xu Yijia , Pan Bin , Zhang Zhou
Published: July 2022

Potato is one of the most significant food crops globally due to its essential role in the human diet. The growing demand for potato, coupled with severe environmental losses caused by extensive farming activities, implies the need for better crop protection and management practices. Precision agriculture is being well recognized as the solution as it deals with the management of spatial and temporal variability to improve agricultural returns and reduce environmental impact. As the initial step in precision agriculture, the traditional methods of crop and field characterization require a large input in labor, time, and cost. Recent developments in remote sensing technologies have facilitated the process of monitoring crops and quantifying field variations. Successful applications have been witnessed in the area of precision potato farming. Thus, this review reports the current knowledge on the applications of remote sensing technologies in precision potato trait characterization. We reviewed the commonly used imaging sensors and remote sensing platforms with the comparisons of their strengths and limitations and summarized the main applications of the remote sensing technologies in potato. As a result, this review could update potato agronomists and farmers with the latest approaches and research outcomes, as well as provide a selective list for those who have the intentions to apply remote sensing technologies to characterize potato traits for precision agriculture.
Scrutinizes the Sustainable Role of Halophilic Microbial Strains on Oxygen-Evolving Complex, Specific Energy Fluxes, Energy Flow and Nitrogen Assimilation of Sunflower Cultivars in a Suboptimal Environment
Authors: Ali Fiza , Wei Xiangying , Siddiqui Zamin Shaheed , Chen Jianjun , Ansari Hafiza Hamna , Wajid Danish , Shams Zafar Iqbal , Abbasi Muhammad Waseem , Zafar Urooj
Published: July 2022

Environmental extremes such as hypersaline conditions are significant threats to agricultural productivity. The sustainable use of halophilic microbial strains was evaluated in plant in a salt stress environment. Oxygen-evolving complex (OEC), energy compartmentalization, harvesting efficiencies (LHE), specific energy fluxes (SEF), and nitrogen assimilation of oilseed crops (Sunflower cultivars) in a suboptimal environment was examined. Plants were grown in a plastic pot (15 ×18 cm2) containing sterilized (autoclaved at 120°C for 1 h) soil. Twenty-five ml suspension (107 CFU/ml) each of Bacillus cereus strain KUB-15 and KUB-27 (accession number NR 074540.1) and Bacillus licheniformis strain AAB9 (accession number MW362506), were applied via drenching method. Month-old plants were subjected to salt stress via gradual increment method. The energy compartmentalization of microbial inoculated plants exposed to salt stress revealed higher photosystem II (PSII) activity at the donor side, lesser photo-inhibition, and increased performance of oxygen-evolving complex compared to control. High potassium (K+) and low sodium (Na+) ions in treated leaves with the activated barricade of the antioxidant system stimulated by Bacillus strains favored enhanced photochemical efficiency, smooth electron transport, and lesser energy dissipation in the stressed plants. Moreover, the results reveal the increased activity of nitrite reductase (NiR) and nitrate reductase (NR) by microbial inoculation that elevated the nitrogen availability in the salt-stressed plant. The current research concludes that the application of bio-inoculants that reside in the hyper-saline environment offers substantial potential to enhance salt tolerance in sunflowers by modulating their water uptake, chlorophyll, nitrogen metabolism, and better photochemical yield.
Algorithm for appearance simulation of plant diseases based on symptom classification
Authors: Yang Meng , Ding Shu
Published: July 2022

Plant disease visualization simulation belongs to an important research area at the intersection of computer application technology and plant pathology. However, due to the variety of plant diseases and their complex causes, how to achieve realistic, flexible, and universal plant disease simulation is still a problem to be explored in depth. Based on the principles of plant disease prediction, a time-varying generic model of diseases affected by common environmental factors was established, and interactive environmental parameters such as temperature, humidity, and time were set to express the plant disease spread and color change processes through a unified calculation. Using the apparent symptoms as the basis for plant disease classification, simulation algorithms for different symptom types were propose. The composition of disease spots was deconstructed from a computer simulation perspective, and the simulation of plant diseases with symptoms such as discoloration, powdery mildew, ring pattern, rust spot, and scatter was realized based on the combined application of visualization techniques such as image processing, noise optimization and texture synthesis. To verify the effectiveness of the algorithm, a simulation similarity test method based on deep learning was proposed to test the similarity with the recognition accuracy of symptom types, and the overall accuracy reaches 87%. The experimental results showed that the algorithm in this paper can realistically and effectively simulate five common plant disease forms. It provided a useful reference for the popularization of plant disease knowledge and visualization teaching, and also had certain research value and application value in the fields of film and television advertising, games, and entertainment.
Quantitative Trait Loci Mapping Analysis for Cold Tolerance Under Cold Stress and Brassinosteroid-Combined Cold Treatment at Germination and Bud Burst Stages in Rice
Authors: Guo Zhifu , Wang Haotian , Yao Jialu , Cheng Yishan , Zhang Wenzhong , Xu Zhengjin , Li Maomao , Huang Jing , Zhao Minghui
Published: July 2022

Low temperature is one of the major abiotic stresses limiting seed germination and early seedling growth in rice. Brassinosteroid (BR) application can improve cold tolerance in rice. However, the regulatory relationship between cold tolerance and BR in rice remains undefined. Here, we constructed a population of 140 backcross recombinant inbred lines (BRILs) derived from a cross between a wild rice (Dongxiang wild rice, DXWR) and a super rice (SN265). The low-temperature germination rate (LTG), survival rate (SR), plant height (PH), and first leaf length (FLL) were used as indices for assessing cold tolerance under cold stress and BR-combined cold treatment at seed germination and bud burst stages. A high-resolution SNP genetic map, covering 1,145 bin markers with a distance of 3188.33 cM onto 12 chromosomes, was constructed using the GBS technique. A total of 73 QTLs were detected, of which 49 QTLs were identified under cold stress and 24 QTLs under BR-combined cold treatment. Among these, intervals of 30 QTLs were pairwise coincident under cold stress and BR-combined cold treatment, as well as different traits including SR and FLL, and PH and FLL, respectively. A total of 14 candidate genes related to cold tolerance or the BR signaling pathway, such as CBF/DREB (LOC_Os08g43200), bHLH (LOC_Os07g08440 and LOC_Os07g08440), WRKY (LOC_Os06g30860), MYB (LOC_Os01g62410 and LOC_Os05g51160), and BRI1-associated receptor kinase 1 precursor (LOC_Os06g16300), were located. Among these, the transcript levels of 10 candidate genes were identified under cold stress and BR-combined cold treatment by qRT-PCR. These findings provided an important basis for further mining the genes related to cold tolerance or the BR signaling pathway and understanding the molecular mechanisms of cold tolerance in rice.
What kind of science for dual diagnosis? A pragmatic examination of the enactive approach to psychiatry
Authors: Larsen Jonathan Led , Johansen Katrine Schepelern , Mehlsen Mimi Yung
Published: July 2022

The recommended treatment for dual diagnosis - the co-occurrence of substance use and another mental disorder - requires seamless integration of the involved disciplines and services. However, no integrative framework exists for communicating about dual diagnosis cases across disciplinary or sectoral boundaries. We examine if Enactive Psychiatry may bridge this theoretical gap. We evaluate the enactive approach through a two-step pragmatic lens: Firstly, by taking a historical perspective to describe more accurately how the theoretical gap within the field of dual diagnosis initially developed. Secondly, by applying the Enactive Psychiatry approach to data from a longitudinal study on the trajectory of cannabis use in psychosis disorders. By applying the theory rather than simply presenting it, we position ourselves better to evaluate whether it may assist the purpose of achieving a more expedient pragmatic “grip” on the field of dual diagnosis. In our discussion, we suggest that this may very well be the case. Finally, we consider the enactive approach as one of a small handful of new theories of mental disorders that draw on systems thinking and ecological psychology, and discuss whether they have the potential for a wider progressive problemshift within psychiatry. The case in favor of such potential, we argue, is less strong unless the role of complexity, similar to that seen within the dual diagnosis field, may be demonstrated for other fields of clinical practice.