bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Open Skill Visuomotor Choice Reaction Time Training on Unanticipated Jump-Landing Stability and Quality: A Randomized Controlled Trial
Authors: Friebe David , Engeroff Tobias , Giesche Florian , Niederer Daniel
Published: July 2021

Adapting movements rapidly to unanticipated external stimuli is paramount for athletic performance and to prevent injuries. We investigated the effects of a 4-week open-skill choice-reaction training intervention on unanticipated jump-landings. Physically active adults (n = 37; mean age 27, standard deviation 2.7 years, 16 females, 21 males) were randomly allocated to one of two interventions or a control group (CG). Participants in the two intervention groups performed a 4-week visuomotor open skill choice reaction training, one for the upper and one for the lower extremities. Before and after the intervention, two different types of countermovement jumps with landings in split stance position were performed. In the (1) pre-planned condition, we informed the participants regarding the landing position (left or right foot in front position) before the jump. In the (2) unanticipated condition, this information was displayed after take-off (350–600 ms reaction time before landing). Outcomes were landing stability [peak vertical ground reaction force (pGRF) and time to stabilization (TTS)], and landing-related decision-making quality (measured by the number of landing errors). To measure extremity-specific effects, we documented the number of correct hits during the trained drills. A two-factorial (four repeated measures: two conditions, two time factors; three groups) ANCOVA was carried out; conditions = unanticipated versus pre-planned condition, time factors = pre versus post measurement, grouping variable = intervention allocation, co-variates = jumping time and self-report arousal. The training improved performance over the intervention period (upper extremity group: mean of correct choice reaction hits during 5 s drill: +3.0 hits, 95% confidence interval: 2.2–3.9 hits; lower extremity group: +1.6 hits, 0.6–2.6 hits). For pGRF (F = 8.4, p < 0.001) and landing errors (F = 17.1, p < 0.001) repeated measures effect occurred. Significantly more landing errors occurred within the unanticipated condition for all groups and measurement days. The effect in pGRF is mostly impacted by between-condition differences in the CG. No between-group or interaction effect was seen for these outcomes: pGRF (F = 0.4, p = 0.9; F = 2.3, p = 0.1) landing errors (F = 0.5, p = 0.6; F = 2.3, p = 0.1). TTS displayed a repeated measures (F = 4.9, p < 0.001, worse values under the unanticipated condition, improvement over time) and an interaction effect (F = 2.4, p = 0.03). Healthy adults can improve their choice reaction task performance by training. As almost no transfer to unanticipated landing successfulness or movement quality occurred, the effect seems to be task-specific. Lower-extremity reactions to unanticipated stimuli may be improved by more specific training regimens.
Localized Modification of Water Molecule Transport After Focused Ultrasound-Induced Blood–Brain Barrier Disruption in Rat Brain
Authors: Han Mun , Seo Hyeon , Choi Hyojin , Lee Eun-Hee , Park Juyoung
Published: July 2021

Interstitial solutes can be removed by various overlapping clearance systems, including blood–brain barrier (BBB) transport and glymphatic clearance. Recently, focused ultrasound (FUS)-induced BBB disruption (BBBD) has been applied to visualize glymphatic transport. Despite evidence that FUS–BBBD might facilitate glymphatic transport, the nature of fluid movement within the sonication region is yet to be determined. In this study, we sought to determine whether FUS–BBBD may facilitate the local movement of water molecules. Two different FUS conditions (0.60–0.65 MPa and 0.75–0.80 MPa) were used to induce BBBD in the caudate-putamen and thalamus regions of healthy Sprague–Dawley rats. The water diffusion caused by FUS–BBBD was analyzed using the apparent diffusion coefficient (ADC), axial diffusivity, radial diffusivity (RD), and fractional anisotropy, obtained at 5 min, 24 and 48 h, as well as the water channel expression of aquaporin-4 (AQP-4) immunostaining at 48 h after FUS-induced BBBD. In addition, hematoxylin and eosin histopathology and Fluoro-Jade C (FJC) immunostaining were performed to analyze brain damage. The signal changes in ADC and RD in the sonication groups showed significant and transient reduction at 5 min, with subsequent increases at 24 and 48 h after FUS-induced BBBD. When we applied higher sonication conditions, the ADC and RD showed enhancement until 48 h, and became comparable to contralateral values at 72 h. AQP-4 expression was upregulated after FUS-induced BBBD in both sonication conditions at 48 h. The results of this study provide preliminary evidence on how mechanical forces from FUS alter water dynamics through diffusion tensor imaging (DTI) measures and AQP4 expression.
N-Terminally Truncated and Pyroglutamate-Modified Aβ Forms Are Measurable in Human Cerebrospinal Fluid and Are Potential Markers of Disease Progression in Alzheimer’s Disease
Authors: Domingo Guido , Benussi Luisa , Saraceno Claudia , Bertuzzi Michela , Nicsanu Roland , Longobardi Antonio , Bellini Sonia , Cagnotto Alfredo , Salmona Mario , Binetti Giuliano , Ghidoni Roberta
Published: July 2021

Alzheimer’s disease (AD) is a pathology characterized by the accumulation in the brain of intracellular and extracellular amyloid-β (Aβ) aggregates, especially of Aβ1–40 and Aβ1–42 peptides. It is known that N-terminally truncated or modified Aβ forms also exist in AD brains and cerebrospinal fluid (CSF), and they play a key role in the pathogenesis of the disease. Herein, we developed an antibody-free method based on Solid-Phase Extraction and Electrospray Ionization Liquid Chromatography Mass Spectrometry for the identification and quantitation in human CSF of Aβ isoforms. In human CSF, we could detect and quantify a panel of 19 Aβ isoforms, including N-terminally truncated and pyroglutamate-modified forms, never quantified before in CSF. Among these, we identified novel N-terminally truncated Aβ species: four bound to copper and two phosphorylated forms, which were found to be the most common proteoforms in human CSF along with Aβ1–40, Aβ3–40, and AβpE11–42. We tested the newly developed and validated method in a pilot study on CSF from elderly individuals with subjective memory complaints (SMCs, n = 9), mild cognitive impairment (MCI, n = 18), and AD (n = 15); along with Aβ1–42, five N-terminally truncated forms (Aβ11–40, Aβ3–42, AβpE11–42, AβpE3–40, and Aβ4–40 Cu2+) are altered in AD/MCI. Thus, we demonstrated that N-terminally truncated and pyroglutamate-modified Aβ can be quantified in human CSF, and five of them, along with Aβ1–42, are potential markers of AD progression. The described method could represent a useful tool for patients’ stratification and monitoring. Moreover, the newly identified Aβ CSF species might represent new potential therapeutic targets.
Targeted Next-Generation Sequencing of Circulating Tumor DNA, Bone Marrow, and Peripheral Blood Mononuclear Cells in Pediatric AML
Authors: Ruan Min , Liu Lipeng , Qi Benquan , Chen Xiaoyan , Chang Lixian , Zhang Aoli , Liu Fang , Wang Shuchun , Liu Xiaoming , Chen Xiaojuan , Zhang Li , Guo Ye , Zou Yao , Zhang Yingchi , Chen Yumei , Liu LiXia , Cao Shanbo , Lou Feng , Wang Chengcheng , Zhu Xiaofan
Published: July 2021

Background

The aim of the study was to validate the diagnostic role of circulating tumor DNA (ctDNA) in genetics aberration on the basis of next-generation sequencing (NGS) in pediatric acute myeloid leukemia (AML).

Methods

Bone marrow (BM) and peripheral blood (PB) were collected from 20 AML children at the time of initial diagnosis, and a ctDNA sample was isolated from PB. Detection of mutation was performed on ctDNA, BM, and peripheral blood mononuclear cell (PBMC) by NGS based on a 185-gene panel.

Results

Among 185 genes sequenced by the NGS platform, a total of 82 abnormal genes were identified in 20 patients. Among them, 61 genes (74.39%) were detected in ctDNA, PBMC, and BM samples, while 11 (13.41%) genes were found only in ctDNA and 4 (4.88%) were detected only in the BM sample, and 2 (2.44%) were detected only in PBMC. A total of 239 mutations were detected in three samples, while 209 in ctDNA, 180 in bone marrow, and 184 in PBMC. One hundred sixty-four mutations in ctDNA were shared by matched BM samples, and the median variant allelic frequency (VAF) of these mutations was 41.34% (range, 0.55% to 99.96%) and 44.36% (range, 0.56% to 99.98%) in bone marrow and ctDNA. It was found that 65.79% (75/114) of mutations with clinical significance were detected in three samples, with 9 mutations detected both in ctDNA and BM, and 2 mutations detected both in PBMC and BM. The consistency of mutations with clinical significance between ctDNA and BM was 77.06% (84/109). Among the 84 mutations with clinical significance detected in both sources, the concordance of VAF assessment by both methods was high (R2 = 0.895).

Conclusion

This study demonstrates that ctDNA was a reliable sample in pediatric AML and can be used for mutation detection. Consistency analysis showed that ctDNA can mirror the genomic information from BM. In addition, a subset of mutations was exclusively detected in ctDNA. These data support the fact that monitoring ctDNA with next-generation sequencing-based assays can provide more information about gene mutations to guide precision treatment in pediatric AML.
Exploring the Pharmacological Mechanism of Radix Salvia Miltiorrhizae in the Treatment of Radiation Pneumonia by Using Network Pharmacology
Authors: Li Peng , Xia Xiaochun , Zhou Jundong , Wu Jinchang
Published: July 2021

Background

Radiation pneumonia (RP) is the most common complication of radiotherapy to the thorax and seriously affects the survival rate and quality of life of patients. Radix Salviae Miltiorrhizae (RSM) is an ancient Chinese medicine, whose main pharmacological effect is to promote blood circulation and remove stasis. A growing number of studies have proved that RSM has a good effect on RP. However, the underlying mechanism is still unclear and needs to be fully elucidated.

Methods

The effective components and predictive targets of RSM were analyzed by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the related targets of RP were predicted by GeneCards database. The common targets of the two targets mentioned above were analyzed by protein-protein interaction on the STRING website, GO and KEGG analysis on the DAVID website, visualization by CytoScape3.7.0, and screening for Hubber gene by cytoHubber plug-in.

Results

A search of the TCMSP database revealed that RSM contains 65 chemical constituents and 165 potential protein targets. A total of 2,162 protein targets were found to be associated with RP. The top 10 hub genes were obtained by MCC algorithm for 70 common genes, including TP53, CASP3, MAPK1, JUN, VEGFA, STAT3, PTGS2, IL6, AKT1, and FOS. By analyzing the Gene Ontology, The anti-radiation pneumonia effect of RSM is that it performs molecular functions (protein homodimerization activity) in the nucleus through three biological processes (positive regulation of transcription from RNA polymerase II promoter,Extrinsic apoptotic signaling pathway in absence of ligand and lipopolysaccharide-mediated signaling pathway). Through KEGG analysis, the mechanism of RSM treatment of radiation pneumonia may be through PI3K-Akt, HIF-1, TNF signaling pathways.

Conclusions

Through network pharmacology analysis, we found the possible target genes of RSM on RP and revealed the most likely signaling pathway, providing theoretical basis for further elucidating the potential mechanism of RSM on RP.
Involvement and Targeted Intervention of Mortalin-Regulated Proteome Phosphorylated-Modification in Hepatocellular Carcinoma
Authors: Yang Ye , Jin Ming , Dai Yi , Shan Wenqi , Chen Shuai , Cai Rong , Yang Haojun , Tang Liming , Li Lei
Published: July 2021

Objectives

To reveal the mechanisms of the effects of mortalin in hepatocellular carcinoma (HCC) and to identify potential novel chemical inhibitors of mortalin.

Materials and Methods

For the experiments, three HCC cell lines (HepG2 cells, Hep3B cells, and sorafenib-resistant HuH7 cells) and xenografted nude mice were used. For the clinical analysis, cohorts of 126 patients with HCC and 34 patients with advanced recurrent HCC receiving sorafenib therapy were examined.

Results

Mortalin regulated the phosphorylation-modification of cancer-associated proteins and also regulated angiogenesis-related secretome to cause angiogenesis and sorafenib resistance in HCC cells. Two molecular mechanisms were identified. In one, via phosphatidylinositol 3-kinase (PI3K)/Akt signaling, mortalin regulated nuclear factor (NF)-κB and then activated vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR)2 and granulocyte-macrophage colony-stimulating factor (GM-CSF), leading to neovascularization. In the other, mortalin regulated PI3K/Akt/β-catenin and then regulated Bcl-XL and Bcl-2, leading to the antiapoptosis effect of HCC. Treatment of the sorafenib-resistant xenografts with sorafenib in combination with mortalin knockdown facilitated the sorafenib-mediated inhibition of tumor growth and angiogenesis and increased apoptosis. Mortalin was a potential risk factor for HCC, predicting poor prognosis and sorafenib resistance. Finally, we showed that caffeic acid (C9H8O4) could bind to and induce the ubiquitination-mediated degradation of mortalin, which in turn blocked the abovementioned signaling pathways, leading to the inhibition of angiogenesis and the reversal of sorafenib resistance.

Conclusions

Mortalin, which regulates the phosphorylation of cancer-associated proteins, caused angiogenesis and sorafenib resistance, and was a competitive risk factor for HCC. Caffeic acid can therefore be considered a novel chemical inhibitor that targets the action of mortalin and a potential treatment for HCC.
Beyond BRCA Status: Clinical Biomarkers May Predict Therapeutic Effects of Olaparib in Platinum-Sensitive Ovarian Cancer Recurrence
Authors: Nakanishi Kazuho , Yamada Takashi , Ishikawa Gen , Suzuki Shunji
Published: July 2021

The purpose of this study was to investigate the predictors of the effect of olaparib on platinum-sensitive recurrent ovarian cancer with unknown germline BRCA mutations. We retrospectively examined 20 patients with platinum-sensitive ovarian cancer who were treated at the Nippon Medical School Chiba Hokusoh Hospital, Japan, from 2018 to 2020. We found that the median progression-free survival was 11.4 months (95% Confidence interval (CI): 3.8–Not Available (NA)) in the group with NLPN score [recurrent neutrophil-lymphocyte ratio (rNLR) × number of previous regimens] >7.51, and median progression-free survival was not reached in the group with NLPN score <7.51 (95% CI: 21.8–NA) (p = 0.0185). There was a clear correlation between the degree of dose reduction of olaparib and recurrence (p = 0.00249). Our results show that NLPN scores lower than 7.51 are associated with a favorable outcome of olaparib treatment for platinum-sensitive recurrent ovarian cancer. In cases with a high rNLR, it may be necessary to start olaparib treatment as early as possible to obtain low NLPN scores. Our results imply that the effectiveness of olaparib can be determined after recurrence and before platinum treatment begins. As newer drugs for ovarian cancer are developed, the measurement of biomarker levels at the start of treatment for recurrent ovarian cancer, as shown in our study, may provide strong support for cancer treatment protocols.
Early Serum Infliximab Levels in Pediatric Ulcerative Colitis
Authors: deBruyn Jennifer C. C. , Jacobson Kevan , El-Matary Wael , Wine Eytan , Carroll Matthew W. , Goedhart Caitlin , Panaccione Remo , Wrobel Iwona T. , Huynh Hien Q.
Published: July 2021

Background: Data on serum infliximab concentrations during induction in pediatric ulcerative colitis are limited. The study aim is to evaluate the relationship between serum infliximab concentrations during induction and short-term clinical remission in children with ulcerative colitis.

Methods: We carried out a prospective, multi-center cohort study in pediatric patients with ulcerative colitis. Serum infliximab concentrations were collected at peak dose #1, week 1, trough pre-dose #2, and trough pre-dose #3. Infliximab dosing was left to investigator discretion. Clinical remission was defined by pediatric ulcerative colitis activity index <10 at week 8.

Results: Twenty-four of thirty-four subjects (71%) achieved clinical remission at week 8. The median infliximab concentrations were 33.0 μg/mL (interquartile range: 26.5–52.1 μg/mL) pre-dose #2 and 22.5 μg/mL (interquartile range:15.9–32.3 μg/mL) pre-dose #3. Trough pre-dose #2 infliximab concentration yielded area under receiver operator characteristic curve 0.7, 95% CI: 0.5–0.9 in predicting week 8 clinical remission; a cut-off of 33.0 μg/mL yielded 62.5% sensitivity, 66.7% specificity. Trough pre-dose #3 infliximab concentrations were lower for subjects <10 years compared to ≥ 10 years [median 15.9 μg/mL, interquartile range (IQR) 8.5–21.8 μg/mL vs. 27.7 μg/mL, IQR 17.2–46.7 μg/mL, p = 0.01] and correlated with baseline weight (Spearman's rank correlation coefficient 0.45, p = 0.01). The median half-life following first IFX dose was 6.04 days (IQR 5.3–7.9 days).

Conclusions: Infliximab concentrations ≥33 μg/mL prior to the second dose were associated with week 8 clinical remission. As young age and low body weight impact infliximab concentration, prospective studies with proactive adjustment in pediatric patients with ulcerative colitis should be carried out. Clinicians caring for children with UC should diligently adjust and monitor infliximab to optimize response.
Case Report: Improved Height in a Patient With Myhre Syndrome Using a Combination of Growth Hormone and Letrozole
Authors: Wu Hui , Wang Xinli , Cui Yunpu , Wang Xuemei
Published: July 2021

Myhre syndrome is a rare disorder caused by a heterozygous mutation in the SMAD4 gene. Affected patients may exhibit dysmorphic facial features, intrauterine growth retardation, short stature, obesity, muscle hypertrophy, thickened skin, limited joint movement, hearing impairment, and varying degrees of psychomotor developmental disorder. Serious complications of the cardiovascular and respiratory system may be seen later in life. We report the case of a Chinese boy with Myhre syndrome presenting with a novel symptom of giant testicles where treatment with growth hormone combined with letrozole successfully improved his short stature. This case shows that letrozole combined with growth hormone can improve height in children with Myhre syndrome without adverse effects.
Re-evaluating Renal Angina Index: An Authentic, Evidence-Based Instrument for Acute Kidney Injury Assessment: Critical Appraisal
Authors: Raina Rupesh , Sethi Sidharth Kumar , Mawby Isabelle , Datla Nikhil , Kumar Nikhita , Agarwal Nirav , Tibrewal Abhishek , Chakraborty Ronith
Published: July 2021

Background/Introduction: Renal angina index (RAI) used to calculate and accurately predict risk for the development of acute kidney injury (AKI) has been heavily explored. AKI is traditionally diagnosed by an increase in serum creatinine (SCr) concentration or oliguria, both of which are neither specific nor sensitive, especially among children. An RAI score may be calculated by combining objective signs of kidney dysfunction (such as SCr) and patient context, such as AKI risk factors, thus potentially serving as a more accurate indicator for AKI.

Objective: Due to the propitious and novel nature of RAI, this editorial commentary aims to analyze the current literature on RAI and determine how well RAI serves as a predictor of AKI outcomes.

Method: A comprehensive literature search was conducted in PubMed/Medline and Google Scholar between January 2012 and July 2020. Literature included the prognostic aspect of early prediction of AKI in the pediatric and adult population via RAI.

Results: The initial literature search included 149 studies, and a total of 10 studies reporting the outcomes of interest were included. The overall sample size across these studies was 11,026. The predictive ability of RAI had a pooled (95% CI) sensitivity of 79.21%, specificity of 73.22%, and negative predictive value of 94.83%.

Conclusion: RAI shows benefit in the prediction of AKI among adult and pediatric populations. However, there is a lack of sufficient data, and further prospective studies are needed in pediatric populations to use RAI as a principal AKI indicator among clinicians.
Clinical Evidence-Guided Anti-rheumatoid Arthritis Study of Shuji Tablet in Adjuvant-Induced Arthritis Rats and Mechanism Exploration via Network Pharmacological Approach
Authors: Dai Weibo , Yang Jing , Cao Haili , Wang Zhuqiang , Li Guangru , Zhong Xiwen , Peng Weiwen , Chen Chang , Liu Xin , Zeng Congyan , Hu Xianjing
Published: July 2021

Background: Rheumatoid arthritis (RA) is a kind of chronic autoimmune disease with several tissues damaged. Shuji tablet (SJT) is a prescription approved for treating lumbago and leg pain in the clinic. However, the efficacy of SJT against RA is still unknown. This study aims to evaluate the therapeutic effect of SJT on adjuvant-induced arthritis (AIA) rats and explore the mechanism via a network pharmacological approach.

Methods: AIA rats were treated with SJT for 30 days at the dosages of 3.6, 1.8, and 0.9 g/kg, respectively, and the anti-RA effect was determined by measuring paw swelling, systemic symptoms score, arthritis index, and histopathological change. ELISA assay was used to evaluate the level of inflammatory cytokines in serum. The mechanism exploration and target prediction of SJT against RA were performed via a network pharmacological approach.

Results: SJT showed excellent alleviation on AIA rats, with evidence of reducing paws swelling, decreasing systemic symptoms score, and arthritis index. Furthermore, SJT significantly reduced the serum cytokines of IL-6, IL-1β, TNF-α in AIA rats. Histopathological examination showed SJT remarkably reduced synovial hyperplasia, cartilage damage, and inflammatory infiltration in the secondary-side paws. According to network pharmacological analysis, 208 candidate compounds and 445 potential targets of SJT were identified, and 4465 RA therapy-related targets were searched out. Subsequently, 292 target genes of SJT were speculated to be associated with RA treatment, among which the top 5 “response values” targets were STAT3, AKT1, JUN, HSP90AA1, TNF. GO and KEGG enrichment analysis suggested that 45 signaling pathways were associating with SJT treating RA. The top 10 signaling pathways were PI3K-Akt, MAPK, AGE-RAGE pathway in diabetic complications, Ras, HIF-1, TNF, Chemokine, IL-17, FoxO, and Rap1.

Conclusion: Our experimental study showed that SJT significantly alleviated rheumatoid arthritis of AIA rats. Network pharmacology showed that the key targets of SJT against RA probably were STAT3, AKT1, JUN, HSP90AA1, TNF, and the potential mechanism was associated with modulation on the signaling pathways of PI3K-Akt, MAPK, Ras, AGE-RAGE, HIF-1, TNF, chemokine, IL-17, FoxO, Rap 1. Our study strongly provides evidence for Shuji tablet in RA therapy and would enlarge its application in the clinic.
The Controversy About the Effects of Different Doses of Corticosteroid Treatment on Clinical Outcomes for Acute Respiratory Distress Syndrome Patients: An Observational Study
Authors: Yang Jia-Wei , Jiang Ping , Wang Wen-Wen , Wen Zong-Mei , Mao Bei , Lu Hai-Wen , Zhang Li , Song Yuan-Lin , Xu Jin-Fu
Published: July 2021

Background: Corticosteroid usage in acute respiratory distress syndrome (ARDS) remains controversial. We aim to explore the correlation between the different doses of corticosteroid administration and the prognosis of ARDS.

Methods: All patients were diagnosed with ARDS on initial hospital admission and received systemic corticosteroid treatment for ARDS. The main outcomes were the effects of corticosteroid treatment on clinical parameters and the mortality of ARDS patients. Secondary outcomes were factors associated with the mortality of ARDS patients.

Results: 105 ARDS patients were included in this study. Corticosteroid treatment markedly decreased serum interleukin-18 (IL-18) level (424.0 ± 32.19 vs. 290.2 ± 17.14; p = 0.0003) and improved arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) (174.10 ± 65.28 vs. 255.42 ± 92.49; p < 0.0001). The acute physiology and chronic health evaluation (APACHE II) score (16.15 ± 4.41 vs. 14.88 ± 4.57, p = 0.042) decreased significantly on the seventh day after systemic corticosteroid treatment. Interestingly, the serum IL-18 decreased significantly (304.52 ± 286.00 vs. 85.85 ± 97.22, p < 0.0001), whereas the improvement of PaO2/FiO2 (24.78 ± 35.03 vs. 97.17 ± 44.82, p < 0.001) was inconspicuous after systemic corticosteroid treatment for non-survival patients, compared with survival patients. Furthermore, the receiver operating characteristic (ROC) model revealed, when equivalent methylprednisolone usage was 146.5 mg/d, it had the best sensitivity and specificity to predict the death of ARDS. Survival analysis by Kaplan–Meier curves presented the higher 45-day mortality in high-dose corticosteroid treatment group (logrank test p < 0.0001). Multivariate Cox regression analyses demonstrated that serum IL-18 level, APACHE II score, D-dimer, and high-dose corticosteroid treatment were associated with the death of ARDS.

Conclusion: Appropriate dose of corticosteroids may be beneficial for ARDS patients through improving the oxygenation and moderately inhibiting inflammatory response. The benefits and risks should be carefully weighed when using high-dose corticosteroid for ARDS.

Trial registration: This work was registered in ClinicalTrials.gov. Name of the registry: Corticosteroid Treatment for Acute Respiratory Distress Syndrome. Trial registration number: NCT02819453. URL of trial registry record: https://register.clinicaltrials.gov.
Long-Term Outcomes After In-Hospital Cardiac Arrest: Does Pre-arrest Skeletal Muscle Depletion Matter?
Authors: Hong Seok-In , Kim Kyung Won , Ko Yousun , Kim Youn-Jung , Huh Jin Won , Hong Sang-Bum , Kim Won Young
Published: July 2021

Background: Skeletal muscle depletion is prevalent in elderly patients and is associated with unfavorable outcomes in patients with chronic diseases. However, the relationship between skeletal muscle mass and neurological outcomes following in-hospital cardiac arrest (IHCA) has not been evaluated. The aim of this study was to investigate whether skeletal muscle status before cardiac arrest is an independent factor affecting neurological outcomes in patients with IHCA.

Methods: We reviewed a prospectively enrolled registry of IHCA patients. Consecutive adult patients (>18 years) admitted to a tertiary care hospital from 2013 to 2019 were included in the study. Of these, 421 patients who underwent abdominopelvic computed tomography within 3 months of cardiac arrest were included. Skeletal muscle index (SMI) was measured at the third lumbar vertebra, and skeletal muscle depletion was defined using sex- and body mass index-specific cutoffs of SMI. The primary outcome was a Cerebral Performance Category score of 1 or 2 at 6 months after cardiac arrest, which was considered a good neurological outcome.

Results: Of the 421 patients, 248 (58.9%) had skeletal muscle depletion before IHCA. The patients without skeletal muscle depletion showed significantly better neurological outcomes at 6 months after cardiac arrest than those with pre-arrest muscle depletion (20.8 vs. 10.9%, p = 0.004). The absence of skeletal muscle depletion was significantly associated with good neurological outcomes in a multivariable logistic analysis (OR = 3.49, 95% confidence intervals: 1.83–6.65, p < 0.001), along with the absence of diabetes, presence of active cancer, shockable rhythm, and short resuscitation duration.

Conclusion: Pre-arrest skeletal muscle depletion was associated with long-term mortality and poor neurological outcomes after IHCA. Skeletal muscle depletion may be used as a tool to identify at-risk patients who may benefit from aggressive treatments.
Development of Novel Fractal Method for Characterizing the Distribution of Blood Flow in Multi-Scale Vascular Tree
Authors: Li Peilun , Pan Qing , Jiang Sheng , Yan Molei , Yan Jing , Ning Gangmin
Published: July 2021

Blood perfusion is an important index for the function of the cardiovascular system and it can be indicated by the blood flow distribution in the vascular tree. As the blood flow in a vascular tree varies in a large range of scales and fractal analysis owns the ability to describe multi-scale properties, it is reasonable to apply fractal analysis to depict the blood flow distribution. The objective of this study is to establish fractal methods for analyzing the blood flow distribution which can be applied to real vascular trees. For this purpose, the modified methods in fractal geometry were applied and a special strategy was raised to make sure that these methods are applicable to an arbitrary vascular tree. The validation of the proposed methods on real arterial trees verified the ability of the produced parameters (fractal dimension and multifractal spectrum) in distinguishing the blood flow distribution under different physiological states. Furthermore, the physiological significance of the fractal parameters was investigated in two situations. For the first situation, the vascular tree was set as a perfect binary tree and the blood flow distribution was adjusted by the split ratio. As the split ratio of the vascular tree decreases, the fractal dimension decreases and the multifractal spectrum expands. The results indicate that both fractal parameters can quantify the degree of blood flow heterogeneity. While for the second situation, artificial vascular trees with different structures were constructed and the hemodynamics in these vascular trees was simulated. The results suggest that both the vascular structure and the blood flow distribution affect the fractal parameters for blood flow. The fractal dimension declares the integrated information about the heterogeneity of vascular structure and blood flow distribution. In contrast, the multifractal spectrum identifies the heterogeneity features in blood flow distribution or vascular structure by its width and height. The results verified that the proposed methods are capable of depicting the multi-scale features of the blood flow distribution in the vascular tree and further are potential for investigating vascular physiology.
RNA Sequencing Reveals Dynamic Carbohydrate Metabolism and Phytohormone Signaling Accompanying Post-mowing Regeneration of Forage Winter Wheat (Triticum aestivum L.)
Authors: Cui Guibin , Zhao Mei , Tan Hongbin , Wang Zhulin , Meng Min , Sun Fengli , Zhang Chao , Xi Yajun
Published: July 2021

Winter wheat (Triticum aestivum L.) is used as fresh green winter forage worldwide, and its ability to regenerate after mowing determines whether it can be used for forage production; however, the molecular mechanism of regeneration is poorly understood. This study identified long-chain coding and non-coding RNAs in the wheat cultivar “XN9106,” which is cultivated for forage and grain production separately in winter and summer, and analyzed their function during post-mowing regeneration. The results showed that the degradation of carbohydrate plays an important role in regeneration, as demonstrated by decreased carbohydrate content. The increased gene expression of enzymes including β-amylase, β-fructofuranosidase, sucrose synthase, sucrose-6-phosphate synthase, trehalose-6-phosphate synthase, and trehalose-6-phosphate phosphatase in mowed seedlings suggests regeneration is fueled by degraded carbohydrates that provide energy and carbon skeletons for the Krebs cycle and amino acid synthesis. The decreased auxin content relieved the inhibition of cytokinin synthesis, that controls the transition from cell division to cell expansion and stimulates cell expansion and differentiation during the cell expansion phase, and eventually accelerate post-mowing regeneration of seedlings. Additionally, differentially expressed long-chain non-coding RNAs (lncRNAs) might participate in the regulation of gene expression related to carbohydrate metabolism and hormone signal transduction. This study demonstrated the responses of key mRNAs and lncRNAs during post-mowing regeneration of winter wheat and revealed the importance of carbohydrate and hormone during regeneration, providing valuable information for genetic improvement of forage wheat.
Overexpression of F-Box Nictaba Promotes Defense and Anthocyanin Accumulation in Arabidopsis thaliana After Pseudomonas syringae Infection
Authors: Romero-Pérez Andrea , Ameye Maarten , Audenaert Kris , Van Damme Els J. M.
Published: July 2021

Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) is a well-known pathogen and model organism used to study plant-pathogen interactions and subsequent plant immune responses. Numerous studies have demonstrated the effect of Pst DC3000 on Arabidopsis plants and how type III effectors are required to promote bacterial virulence and pathogenesis. F-Box Nictaba (encoded by At2g02360) is a stress-inducible lectin that is upregulated in Arabidopsis thaliana leaves after Pst DC3000 infection. In this study, a flood inoculation assay was optimized to check the performance of transgenic Arabidopsis seedlings with different expression levels of F-Box Nictaba after bacterial infection. Using a combination of multispectral and fluorescent imaging combined with molecular techniques, disease symptoms, transcript levels for F-Box Nictaba, and disease-related genes were studied in Arabidopsis leaves infected with two virulent strains: Pst DC3000 and its mutant strain, deficient in flagellin ΔfliC. Analyses of plants infected with fluorescently labeled Pst DC3000 allowed us to study the differences in bacterial colonization between plant lines. Overexpression plants showed a reduced bacterial content during the later stages of the infection. Our results show that overexpression of F-Box Nictaba resulted in reduced leaf damage after bacterial infections, whereas knockdown and knockout lines were not more susceptible to Pseudomonas infection than wild-type plants. In contrast to wild-type and knockout plants, overexpressing lines for F-Box Nictaba revealed a significant increase in anthocyanin content, better efficiency of photosystem II (Fv/Fm), and higher chlorophyll content after Pst DC3000 infection. Overexpression of F-Box Nictaba coincided with increased expression of salicylic acid (SA) related defense genes, confirming earlier data that showed that F-Box Nictaba is part of the SA-dependent defense against Pst DC3000 infection. Knockout lines yielded no discernible effects on plant symptoms after Pseudomonas infection suggesting possible gene redundancy between F-Box Nictaba genes.
Hybridization With an Invasive Plant of Xanthium strumarium Improves the Tolerance of Its Native Congener X. sibiricum to Cadmium
Authors: Xue Chenyang , Gao Yingmei , Qu Bo , Tai Peidong , Guo Cheng , Chang Wenyue , Zhao Guanghui
Published: July 2021

Hybridization is one of the important factors influencing the adaptive evolution of invasive plants. According to previous studies, hybridization with an invasive plant reduces the adaptability of its native congener to environment. However, in this study, the hybridization with an invasive plant of Xanthium strumarium (LT) improves the tolerance and accumulation of its native congener Xanthium sibiricum (CR) to cadmium (Cd). Under Cd stress, X. sibiricum♀ × X. strumarium♂ (ZCR) showed higher biomass and Cd accumulation. Compared with CR, ZCR has longer vegetative and reproductive growth time. Moreover, ZCR adopted more reasonable biomass allocation strategy. ZCR increased the proportion of reproductive allocation and ensured its own survival with the increase of Cd stress. Furthermore, ZCR increased the translocation of Cd to aboveground parts and changed the distribution of Cd. A large amount of Cd is stored in senescent leaves and eliminated from the plant when the leaves fall off, which not only reduces the Cd content in the plant, but also reduces the toxicity of Cd in the normal leaves. Transcriptome analysis shows a total of 2055 (1060 up and 995 down) differentially expressed genes (DEGs) were detected in the leaves of Cd-stressed ZCR compared with CR, while only 792 (521 up and 271 down) were detected in X. strumarium♀ × X. sibiricum♂ (ZLT) compared with LT. A large number of DGEs in ZCR and ZLT are involved in abscisic acid (ABA) synthesis and signal transduction. The genes induced by ABA in ZCR, including CNGC5/20, CPK1/28, CML, PTI1-like tyrosine-protein kinase 3, respiratory burst oxidase homolog protein C, and WRKY transcription factor 33 were found differentially expressed compared CR. carotenoid cleavage dioxygenase 4, NCED1/2, phytoene synthase 2, and CYP707A involved in ABA synthesis and decomposition in ZLT were found differentially expressed compared LT. We speculated that ABA played an important role in Cd transportation of hybrids and Cd distribution in senescent and normal leaves. The results demonstrate that hybridization with an invasive plant improves the adaptability of the hybrid to Cd stress and may enhance the extinction risk of native congener in pollution environment.
Ethylene Signaling Facilitates Plant Adaption to Physical Barriers
Authors: Liu Simu , Chen Hui
Published: July 2021

The morphological changes are usually observed in the terrestrial plants to respond to physical barriers. The phytohormone ethylene plays an essential role in the morphological development of plants encountering exogenous mechanical impedance, which enables plants to grow optimally in response to physical barriers. Ethylene is shown to regulate these developmental processes directly or in concert with other phytohormones, especially auxin. In this mini review, the involvement of ethylene action in seedling emergence from the soil, root movement within the soil, and parasitic plant invasion of the host plant are described.
Diethyl Aminoethyl Hexanoate Priming Ameliorates Seed Germination via Involvement in Hormonal Changes, Osmotic Adjustment, and Dehydrins Accumulation in White Clover Under Drought Stress
Authors: Hassan Muhammad Jawad , Geng Wan , Zeng Weihang , Raza Muhammad Ali , Khan Imran , Iqbal Muhammad Zafar , Peng Yan , Zhu Yongqun , Li Zhou
Published: July 2021

Drought is a serious outcome of climate change reducing the productivity of forage species under arid and semi-arid conditions worldwide. Diethyl aminoethyl hexanoate (DA-6), a novel plant growth regulator, has proven to be involved in the amelioration of critical physiological functions in many agricultural crops under various abiotic stresses, but the role of the DA-6 in improving seed germination has never been investigated under drought stress. The present study was carried out to elucidate the impact of the DA-6 priming on seeds germination of white clover under drought stress. Results showed that seed priming with the DA-6 significantly mitigated the drought-induced reduction in germination percentage, germination vigor, germination index, seed vigor index, root length, shoot length, and fresh weight after 7 days of seed germination. The DA-6 significantly increased the endogenous indole-3-acetic acid, gibberellin, and cytokinin content with marked reduction in abscisic acid content in seedlings under drought stress. In addition, the DA-6 significantly accelerated starch catabolism by enhancing the activities of hydrolases contributing toward enhanced soluble sugars, proline content and ameliorated the antioxidant defense system to enhance the ability of reactive oxygen species scavenging under drought stress. Furthermore, exogenous DA-6 application significantly increased dehydrins accumulation and upregulated transcript levels of genes encoding dehydrins (SK2, Y2SK, or DHNb) during seeds germination under water deficient condition. These findings suggested that the DA-6 mediated seeds germination and drought tolerance associated with changes in endogenous phytohormones resulting in increased starch degradation, osmotic adjustment, antioxidants activity, and dehydrins accumulation during seed germination under water deficient condition.
The Influence of Entrepreneurial Policy on Entrepreneurial Willingness of Students: The Mediating Effect of Entrepreneurship Education and the Regulating Effect of Entrepreneurship Capital
Authors: Zelin Zhuo , Caihong Chen , XianZhe Chen , Xiang Min
Published: July 2021

With the transformation and development of the social economy of the country, innovation, and entrepreneurship have been a wide concern in all sectors of the society. In contrast, the entrepreneurial success rate of college students in China is low, and the willingness of students to start a business is generally not high. As a leading element, entrepreneurship policy plays an important role in creating an enabling social environment for entrepreneurship and promoting innovation and entrepreneurship. The influence of entrepreneurship policy on the entrepreneurial will of college students is not only reflected in the improvement of entrepreneurship environment but also in the reform and development of innovation and entrepreneurship education in colleges and universities. This study conducted a survey of fresh graduates from 1,231 colleges and universities in 31 provinces across the country to examine the path and influence the mechanism of entrepreneurship policy on entrepreneurial willingness, and the subsequent regression analysis results show that the entrepreneurship policy and entrepreneurship willingness are positively related, and entrepreneurship education, as a “bridge,” presents a partial intermediary role in the relationship. In addition, the study also found that the entrepreneurship capital of college students has a moderating effect on the path of entrepreneurship education–entrepreneurship willingness, that is, the higher the entrepreneurship capital of students is, the higher the entrepreneurship willingness will be generated after they receive entrepreneurship education.
“I’m Never Going to Be in Phantom of the Opera”: Relational and Emotional Wellbeing of Parkinson’s Carers and Their Partners in and Beyond Dancing
Authors: Sundström Moa , Jola Corinne
Published: July 2021

The caregiving of people who suffer from Parkinson’s predominantly falls on their life partners. Living with and caring for somebody with Parkinson’s can cause a range of emotional, psychological, and financial pressures. Whilst an increasing number of alternative treatments for Parkinson’s is available, such as dancing, the focus is predominantly on the motor and emotional improvements of the person suffering from Parkinson’s. For caregivers, however, dancing can be a double-edged sword: Although dancing can offer an opportunity to enjoy a social event with their partner; attending dance classes puts additional responsibilities on the carer. The present study thus aimed at exploring the experiences of participants with Parkinson’s who attended dance classes as well as the experiences of their care-partners in and around these classes along with their view on everyday life changes experienced since dancing. Six couples were interviewed individually where one partner had Parkinson’s. The interviews were also analyzed separately using inductive thematic analysis. In line with existing programmes that offer dance for people with Parkinson’s, the classes used a mixture of ballroom, ballet, contemporary, and creative dance styles; supported and influenced by an instructors’ extensive knowledge of the abilities and needs of those with Parkinson’s. A recurring challenge for Parkinson’s sufferers relates to “who is in control?” based on the many unknown changes of Parkinson’s; as well as seeing/being seen. Yet frustrations were oftentimes counteracted with humour. Also, when dancing, participants with Parkinson’s reported enjoying playful interactions. Caregivers’ themes focussed on theirs and their partners’ wellbeing regarding social contacts and openness, as well as issues surrounding their responsibilities as carers. Whilst some identified dance movements that help them in everyday tasks, they and their care-partners question the impact of dance on their motor control. Yet, participants unanimously agree that dance provides relevant opportunities for social contact and comparison. Nevertheless, the care-partners’ concerns remain about the burden of increasing responsibility for the wellbeing of both partners but they also reported enjoying dancing with their partner. Experiencing their loved ones as more cheerful after starting dance classes is recognised an important positive and impactful outcome of dancing together.
Bullying in the Russian Secondary School: Predictive Analysis of Victimization
Authors: Avanesian Garen , Dikaya Liudmila , Bermous Alexander , Kochkin Sergey , Kirik Vladimir , Egorova Valeria , Abkadyrova Irina
Published: July 2021

Background: Bullying has been recognized as an important risk factor for personal development in adolescence. Although numerous studies report high prevalence of bullying in Russian schools, limited research was based on the large-scale, nationally representative analysis, which highlights the lack of findings applicable to the national context.

Objective: This study aims to address the following research questions: (1) What is the bullying victimization prevalence in Russian secondary schools? (2) What is the socio-demographic profile of the bullying victims? (3) To what extent do learning outcomes in core subject domains predict bullying? (4) How does psychological climate at school affect the occurrence of bullying? (5) Which emotional states do bullying victims typically display? (6) Which psychosocial traits are the most common for bullying victims?

Data and Methods: The study adopts the statistical analysis of the Programme for International Student Assessment (PISA) data in Russia. The final sample consists of 6,249 children aged 15 years who answered the bullying questions. K-means clustering approach was adopted to identify schoolchildren who should be classified as bullying victims amongst those who have reported bullying. Logistic regression was used to estimate the probability change of bullying under different psychosocial factors and examine the effect of bullying on the emotional states of the victims.

Results: The results of the study reveal that 16% of children are victims of bullying in the Russian secondary school. Bullying is strongly associated with learning outcomes in reading, thus outlining that low performers are at risk of severe victimization. Bullying is also contingent on the psychological climate and tends to develop more frequently in a competitive environment. The findings outline that bullying increases negative feelings such as misery, sadness, and life dissatisfaction amongst its victims, making a substantial footprint on their lives. Logically, bullying victims are less likely to feel happy and joyful. Finally, it was revealed that bullying victims do not tend to share negative attitudes to the per se, which identifies directions for future research in this domain.

Implications: Instead of dealing with the consequences of bullying, prevention strategies should aim at facilitating a positive environment at school, thus addressing the problem.