bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coagulopathy Induced by Veno-Arterial Extracorporeal Membrane Oxygenation Is Associated With a Poor Outcome in Patients With Out-of-Hospital Cardiac Arrest
Authors: Tsuchida Takumi , Wada Takeshi , Gando Satoshi 
Published: April 2021

Background: In recent years, the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiopulmonary arrest who do not respond to conventional resuscitation, has increased. However, despite the development of VA-ECMO, the outcomes of resuscitated patients remain poor. The poor prognosis may be attributed to deterioration owing to the post-cardiac arrest syndrome (PCAS); this includes the systemic inflammatory response and coagulation activation caused by the extracorporeal circulation (VA-ECMO circuit) itself. This study aimed to evaluate the coagulofibrinolytic changes caused by VA-ECMO and to identify predictive factors of poor prognosis.Methods: We analyzed 151 cases of PCAS with witnessed cardiac arrest. As biomarkers, platelet counts, prothrombin time ratio, fibrin/fibrinogen degradation products, fibrinogen, antithrombin, and lactate were recorded from blood samples from the time of delivery to the third day of hospitalization. The maximum (max) and minimum (min) values of each factor during the study period were calculated. To evaluate the impact of VA-ECMO on patients with PCAS, we performed propensity score matching between the patients who received and did not receive VA-ECMO. Sub-analysis was performed for the group with VA-ECMO.Results: There were significant differences in all baseline characteristics and demographics except the time from detection to hospital arrival, percentage of cardiopulmonary resuscitations (CPR) by witnesses, and the initial rhythm between the groups. Propensity score matching adjusted for prehospital factors demonstrated that the patients who received VA-ECMO developed significantly severe coagulation disorders. In a sub-analysis, significant differences were noted in the prothrombin time ratio min, fibrinogen max, antithrombin max, and lactate min between survivors and non-survivors. In particular, the prothrombin time ratio min and antithrombin max were strongly correlated with poor outcome.Conclusion: In the present study, significant coagulopathy was observed in patients who received VA-ECMO for CPR. In particular, in patients receiving VA-ECMO, the minimum prothrombin time ratio and maximum antithrombin by day 3 of hospitalization were strongly correlated with poor outcomes. These results suggest that VA-ECMO-induced coagulopathy can be a promising therapeutic target for patients resuscitated by VA-ECMO.
Tremor-Suppression Orthoses for the Upper Limb: Current Developments and Future Challenges
Authors: Nguyen Hoai Son , Luu Trieu Phat 
Published: April 2021

Introduction: Pathological tremor is the most common motor disorder in adults and characterized by involuntary, rhythmic muscular contraction leading to shaking movements in one or more parts of the body. Functional Electrical Stimulation (FES) and biomechanical loading using wearable orthoses have emerged as effective and non-invasive methods for tremor suppression. A variety of upper-limb orthoses for tremor suppression have been introduced; however, a systematic review of the mechanical design, algorithms for tremor extraction, and the experimental design is still missing.Methods: To address this gap, we applied a standard systematic review methodology to conduct a literature search in the PubMed and PMC databases. Inclusion criteria and full-text access eligibility were used to filter the studies from the search results. Subsequently, we extracted relevant information, such as suppression mechanism, system weights, degrees of freedom (DOF), algorithms for tremor estimation, experimental settings, and the efficacy.Results: The results show that the majority of tremor-suppression orthoses are active with 47% prevalence. Active orthoses are also the heaviest with an average weight of 561 ± 467 g, followed by semi-active 486 ± 395 g, and passive orthoses 191 ± 137 g. Most of the orthoses only support one DOF (54.5%). Two-DOF and three-DOF orthoses account for 33 and 18%, respectively. The average efficacy of tremor suppression using wearable orthoses is 83 ± 13%. Active orthoses are the most efficient with an average efficacy of 83 ± 8%, following by the semi-active 77 ± 19%, and passive orthoses 75 ± 12%. Among different experimental setups, bench testing shows the highest efficacy at 95 ± 5%, this value dropped to 86 ± 8% when evaluating with tremor-affected subjects. The majority of the orthoses (92%) measured voluntary and/or tremorous motions using biomechanical sensors (e.g., IMU, force sensor). Only one system was found to utilize EMG for tremor extraction.Conclusions: Our review showed an improvement in efficacy of using robotic orthoses in tremor suppression. However, significant challenges for the translations of these systems into clinical or home use remain unsolved. Future challenges include improving the wearability of the orthoses (e.g., lightweight, aesthetic, and soft structure), and user control interfaces (i.e., neural machine interface). We also suggest addressing non-technical challenges (e.g., regulatory compliance, insurance reimbursement) to make the technology more accessible.
The Clinical Effect of Repetitive Transcranial Magnetic Stimulation on the Disturbance of Consciousness in Patients in a Vegetative State
Authors: Zhang Xiao-Hua , Han Ping , Zeng Yuan-Yuan , Wang Yu-Long , Lv Hui-Lan 
Published: April 2021

ObjectiveTo explore the effect of combining repetitive transcranial magnetic stimulation (rTMS) and conventional rehabilitation on the recovery of consciousness in patients in a persistent vegetative state (PVS).MethodsA total of 48 patients in a PVS were randomly divided into a treatment and control group. Patients in the treatment group were treated with rTMS to stimulate the dorsolateral prefrontal cortex, and patients in the control group were treated with false stimulation. All patients were evaluated using scales and neuroelectrophysiological assessment before treatment, after 30 days of treatment, and following 60 days of treatment.ResultsBased on the Coma Recovery Scale-Revised (CRS-R) and electroencephalogram (EEG) grading indexes, the treatment group was significantly higher than those of the control group after 30 and 60 days of treatment. The average difference in the three measurements between the two groups before treatment, at 30 days, and 60 days was 0.04, 1.54, and 2.09 for CRS-R and 0.08, −0.83, and −0.62 for EEG indexes, respectively. The latency periods of each wave of the brainstem auditory evoked potentials (BAEPs) in the treatment group were shorter than those in the control group after 30 and 60 days of treatment. In both groups, the BAEP scores after 30 days of treatment were significantly higher than the scores before treatment, and the scores after 60 days of treatment were higher than the scores after 30 days.ConclusionIn patients in a PVS, rTMS assists in the recovery of consciousness function.
Auricular Vagus Neuromodulation—A Systematic Review on Quality of Evidence and Clinical Effects
Authors: Verma Nishant , Mudge Jonah D. , Kasole Maïsha , Chen Rex C. , Blanz Stephan L. , Trevathan James K. , Lovett Eric G. , Williams Justin C. , Ludwig Kip A. 
Published: April 2021

Background: The auricular branch of the vagus nerve runs superficially, which makes it a favorable target for non-invasive stimulation techniques to modulate vagal activity. For this reason, there have been many early-stage clinical trials on a diverse range of conditions. These trials often report conflicting results for the same indication.Methods: Using the Cochrane Risk of Bias tool we conducted a systematic review of auricular vagus nerve stimulation (aVNS) randomized controlled trials (RCTs) to identify the factors that led to these conflicting results. The majority of aVNS studies were assessed as having “some” or “high” risk of bias, which makes it difficult to interpret their results in a broader context.Results: There is evidence of a modest decrease in heart rate during higher stimulation dosages, sometimes at above the level of sensory discomfort. Findings on heart rate variability conflict between studies and are hindered by trial design, including inappropriate washout periods, and multiple methods used to quantify heart rate variability. There is early-stage evidence to suggest aVNS may reduce circulating levels and endotoxin-induced levels of inflammatory markers. Studies on epilepsy reached primary endpoints similar to previous RCTs testing implantable vagus nerve stimulation therapy. Preliminary evidence shows that aVNS ameliorated pathological pain but not evoked pain.Discussion: Based on results of the Cochrane analysis we list common improvements for the reporting of results, which can be implemented immediately to improve the quality of evidence. In the long term, existing data from aVNS studies and salient lessons from drug development highlight the need for direct measures of local neural target engagement. Direct measures of neural activity around the electrode will provide data for the optimization of electrode design, placement, and stimulation waveform parameters to improve on-target engagement and minimize off-target activation. Furthermore, direct measures of target engagement, along with consistent evaluation of blinding success, must be used to improve the design of controls—a major source of concern identified in the Cochrane analysis. The need for direct measures of neural target engagement and consistent evaluation of blinding success is applicable to the development of other paresthesia-inducing neuromodulation therapies and their control designs.
Comparison of Antioxidant and Antibacterial Activities of Camellia Oil From Hainan With Camellia Oil From Guangxi, Olive Oil, and Peanut Oil
Authors: Wang Lanying , Ahmad Shakil , Wang Xi , Li Hua , Luo Yanping 
Published: May 2021

Background/Aim: Camellia oil from Hainan (SY) is a unique vegetable oil in Hainan, China, due to the geographical environment and oil extraction only through simple physical treatments. To compare SY with camellia oil from Guangxi (SC), olive oil (GL), and peanut oil (HS), this study analyzed the antioxidant and antibacterial activity of four vegetable oils.Methods: Using Gallic acid, BHT as the control, Saccharomyces cerevisiae as the model organism, the antioxidant activities of vegetable oils were measured in vitro and in vivo, and the antibacterial activity was measured with the minimum inhibitory concentration (MIC) method.Results: The major contents of SY, SC, and HS were oleic Acid; the major content of GL was squalene. The highest total flavonoids content of SY was 39.50 ± 0.41 mg RE/g DW; and the highest total phenolic content of SC was 47.05 ± 0.72 mg GAE/g DW. SY exhibited the strongest scavenging activity of hydroxyl radical (HO·) and superoxide anions (O2-·), the IC50 value were 2.06 mg/mL, 0.62 mg/mL, respectively; and SC showed the strongest DPPH· and ABTS· scavenging activity and the reducing abilities. SY showed excellent effect on survival rate, protection rate, flavonoids uptake of S. cerevisiae cells, decreased MDA content and ROS level, inhibited CAT, POD, and GR enzyme activity. The absorption of SC total phenols was the highest by cells. The activity showed GL had a broad-spectrum antibacterial activity.Conclusion: Thus, SY shows potential antioxidant activity and provides an important reference value for people to choose edible vegetable oils.
Efficacy and Safety of Pyrotinib Versus T-DM1 in HER2+ Metastatic Breast Cancer Patients Pre-Treated With Trastuzumab and a Taxane: A Bayesian Network Meta-Analysis
Authors: Liao Hao , Huang Wenfa , Liu Yaxin , Pei Wendi , Li Huiping 
Published: May 2021

PurposeTo compare the efficacy and safety between pyrotinib (Pyr) and trastuzumab emtansine (T-DM1) in pre-treated human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) patients.MethodsA comprehensive literature search of the PubMed, EMBASE, and Web of Science was performed in August 2020. Randomized clinical trials comparing the efficacy and safety between different anti-HER2 regimens in patients pre-treated with trastuzumab (Tra) and a taxane in metastatic settings (≤second-line treatment) were included. A fixed effects network meta-analysis based on the Bayesian inferential framework was conducted for progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grade ≥3 adverse events (AEs). Values of surface under cumulative ranking probability curve (SUCRA) were calculated to offer a ranking of all regimens.ResultsTwelve studies with 4,353 subjects were identified. Nine regimens were included into the network: T-DM1, lapatinib-capecitabine (Lap-Cap), Tra-Cap, Cap, neratinib (Ner), pertuzumab (Per)-Tra-Cap, Pyr-Cap, atezolizumab (Ate)-T-DM1, and Ner-Cap. For PFS, Pyr-Cap was more favorable than T-DM1 (hazard ratio, 95% confidence interval: 0.77, 0.70–0.86), Lap-Cap (0.64, 0.59–0.69), Tra-Cap (0.63, 0.56–0.70), Cap (0.50, 0.45–0.56), Ner (0.59, 0.51–0.69), Per-Tra-Cap (0.68, 0.59–0.79), and Ner-Cap (0.72, 0.64–0.81). For OS, Pyr-Cap showed further improvement than Lap-Cap (hazard ratio, 95% confidence interval: 0.71, 0.52–0.99), Cap (0.68, 0.49–0.96), and Ner (0.65, 0.45–0.94). For ORR, Pyr-Cap was significantly superior than Cap (odds ratio, 95% confidence interval: 7.87, 1.22–56.51). No significant difference was observed in grade ≥3 AEs among all the regimens. Pyr-Cap ranked in the highest in PFS, OS, ORR, and grade ≥3 AEs (SUCRA = 99.4, 89.7, 86.4, and 89.3%).ConclusionsThese results indicate that Pyr may be more effective than T-DM1 in HER2+ MBC patients pre-treated with Tra and a taxane. However, it may be associated with more grade ≥3 AEs.
Necrotizing Enterocolitis and Intestinal Microbiota: The Timing of Disease and Combined Effects of Multiple Species
Authors: Fu Xin , Li Siwen , Jiang Yanfang , Hu Xintong , Wu Hui 
Published: May 2021

Background:The purpose of this study was to investigate the relationship between intestinal microbiota and necrotizing enterocolitis (NEC).Methods:16S rRNA gene sequencing was used to compare the microbial composition of feces. The first sample was collected within 48 h after birth, then once per week until the NEC diagnosis, and finally 1–2 weeks after treatment or 28 days after birth.Results:The alpha diversity of the microbiota in the NEC group was higher than that in the control group. Beta diversity analysis showed that the control group had a higher similarity at the onset of NEC, while the NEC group was distributed in subgroups. Linear discriminant analysis effect size and taxonomic composition analyses indicated that the abundance of Bacteroides and Actinobacteria in NEC infants at birth was much higher than that in the control group, and this trend continued until NEC occurred. At this time, Rhizobiales, Dysgonomonas, Ochrobactrum, Ralstonia, Pelomonas, Acinetobacter, etc., were also more abundant in NEC infants. The upregulated different metabolic pathways in the NEC group were mainly concentrated on degradation/utilization/assimilation, biosynthesis, and generation of precursor metabolites and energy.Conclusions:1. The microbial community differs according to the time of NEC diagnosis (bounded by 20 days).2. No single microorganism is related to NEC, and the combined effect of multiple species is of great significance in the occurrence of NEC. Premature infants are easily affected by bacteria living in the environment, and compared with ordinary premature infants, NEC infants have a higher abundance of waterborne bacteria. Therefore, attention should be paid to the contamination of water sources and various ventilator pipelines for premature infants hospitalized in the neonatal intensive care unit.3. An in-depth study of the mode of microbial colonization in premature infants combined with the different functions of various metabolic pathways involved in different microorganisms may be able to identify the cause of NEC.
Health Insurance and Out-Of-Pocket Expenditure on Health and Medicine: Heterogeneities along Income
Authors: Al-Hanawi Mohammed Khaled , Mwale Martin Limbikani , Qattan Ameerah M. N. 
Published: April 2021

Background: Achieving universal health coverage is an important objective enshrined in the 2015 global Sustainable Development Goals. However, the rising cost of healthcare remains an obstacle to the attainment of the universal health coverage. Health insurance is considered an option to reduce out-of-pocket (OOP) expenditure on health and medicine. Nevertheless, the relationship between insurance and the OOP along welfare distributions is not well understood. This study investigates the heterogeneous association between health insurance and OOP expenditure on health and medicine, along income, using data from the Kingdom of Saudi Arabia.Methods: This study used data of 8655 individuals drawn from the Saudi Family Health Survey conducted in 2018. The study adopts Tobit models to account for possible corner solution due to individuals with zero expenditure on health. We minimize the confounding effects of non-random selection into the insurance program by estimating the Tobit equations on a sample weighted by inverse propensity scores of insurance participation. In addition, we test whether the health insurance differently relates to OOP on health and medicine amongst people with access to free medical care as opposed to those without this privilege. The study estimates separate models for OOP expenditure on health and on medicines.Results: Health insurance reduces OOP expenditure on health by 2.0% and OOP expenditure on medicine by 2.4% amongst the general population while increasing the OOP expenditure on health by 0.2% and OOP expenditure on medicine by 0.2%, once income of the insured rises. The relationship between the insurance and OOP expenditure is robust only amongst the citizens, a sub-sample that also has access to free public healthcare. Specifically, the insurance reduces OOP expenditure on health by 3.6% and OOP on medicine by 5.2% and increases OOP expenditure on health by 0.4% and OOP expenditure on medicine by 0.5% once income of the insured increases amongst Saudi citizens. In addition, targeting medicines can lead to greater changes in OOP. The relationship between insurance and OOP is stronger for medicine relative to that observed on health expenditure.Conclusion: Our findings suggest that insurance induces different effects along the income spectrum. Hence, policy needs to be aware of the possible welfare distribution impacts of upscaling or downscaling the coverage of insurance amongst the populations, while pursuing universal healthcare coverage.
Profiling Ribonucleotide and Deoxyribonucleotide Pools Perturbed by Remdesivir in Human Bronchial Epithelial Cells
Authors: Li Yan , Zhang Hui-Xia , Luo Wen-Di , Lam Christopher Wai Kei , Wang Cai-Yun , Bai Li-Ping , Wong Vincent Kam Wai , Zhang Wei , Jiang Zhi-Hong 
Published: April 2021

Remdesivir (RDV) has generated much anticipation for its moderate effect in treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the unsatisfactory survival rates of hospitalized patients limit its application to the treatment of coronavirus disease 2019 (COVID-19). Therefore, improvement of antiviral efficacy of RDV is urgently needed. As a typical nucleotide analog, the activation of RDV to bioactive triphosphate will affect the biosynthesis of endogenous ribonucleotides (RNs) and deoxyribonucleotides (dRNs), which are essential to RNA and DNA replication in host cells. The imbalance of RN pools will inhibit virus replication as well. In order to investigate the effects of RDV on cellular nucleotide pools and on RNA transcription and DNA replication, cellular RNs and dRNs concentrations were measured by the liquid chromatography-mass spectrometry method, and the synthesis of RNA and DNA was monitored using click chemistry. The results showed that the IC50 values for BEAS-2B cells at exposure durations of 48 and 72 h were 25.3 ± 2.6 and 9.6 ± 0.7 μM, respectively. Ten (10) μM RDV caused BEAS-2B arrest at S-phase and significant suppression of RNA and DNA synthesis after treatment for 24 h. In addition, a general increase in the abundance of nucleotides and an increase of specific nucleotides more than 2 folds were observed. However, the variation of pyrimidine ribonucleotides was relatively slight or even absent, resulting in an obvious imbalance between purine and pyrimidine ribonucleotides. Interestingly, the very marked disequilibrium between cytidine triphosphate (CTP) and cytidine monophosphate might result from the inhibition of CTP synthase. Due to nucleotides which are also precursors for the synthesis of viral nucleic acids, the perturbation of nucleotide pools would block viral RNA replication. Considering the metabolic vulnerability of endogenous nucleotides, exacerbating the imbalance of nucleotide pools imparts great promise to enhance the efficacy of RDV, which possibly has special implications for treatment of COVID-19.
Crocetin and Its Glycoside Crocin, Two Bioactive Constituents From Crocus sativus L. (Saffron), Differentially Inhibit Angiogenesis by Inhibiting Endothelial Cytoskeleton Organization and Cell Migration Through VEGFR2/SRC/FAK and VEGFR2/MEK/ERK Signaling Pathways
Authors: Zhao Chen , Kam Hio-Tong , Chen Yan , Gong Guiyi , Hoi Maggie Pui-Man , Skalicka-Woźniak Krystyna , Dias Alberto Carlos Pires , Lee Simon Ming-Yuen 
Published: April 2021

Crocetin and crocin are two important carotenoids isolated from saffron (Crocus sativus L.), which have been used as natural biomedicines with beneficial effects for improving the suboptimal health status associated with abnormal angiogenesis. However, the anti-angiogenic effects and underlying mechanisms of the effects of crocetin and crocin have not been investigated and compared. The anti-angiogenic effects of crocetin and crocin were tested on human umbilical vein endothelial cells (HUVECs) in vitro, and in zebrafish in vivo. In vivo, crocetin (20 μM) and crocin (50 and 100 μM) significantly inhibited subintestinal vein vessels formation, and a conversion process between them existed in zebrafish, resulting in a difference in their effective concentrations. In the HUVEC model, crocetin (10, 20 and 40 μM) and crocin (100, 200 and 400 μM) inhibited cell migration and tube formation, and inhibited the phosphorylation of VEGFR2 and its downstream pathway molecules. In silico analysis further showed that crocetin had a higher ability to bind with VEGFR2 than crocin. These results suggested that crocetin was more effective than crocin in inhibiting angiogenesis through regulation of the VEGF/VEGFR2 signaling pathway. These compounds, especially crocetin, are potential candidate natural biomedicines for the management of diseases associated with abnormal blood vessel growth, such as age-related macular degeneration.